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Almström, Markus, Johannes Jacks, Pia Malmquist, Per-Arne Lönnqvist, Boye Lagerbon Jensen, Mattias Carlström, Rafael Tomas Krmar et al. « Low Plasma Sodium Concentration Predicts Perforated Acute Appendicitis in Children : A Prospective Diagnostic Accuracy Study ». European Journal of Pediatric Surgery 30, no 04 (25 avril 2019) : 350–56. http://dx.doi.org/10.1055/s-0039-1687870.
Résumé :
Introduction Early differentiation between perforated and nonperforated acute appendicitis (AA) in children is of major benefit for the selection of proper treatment. Based on pilot study data, we hypothesized that plasma sodium concentration at hospital admission is a diagnostic marker for perforation in children with AA. Materials and Methods This was a prospective diagnostic accuracy study, including previously healthy children, 1 to 14 years of age, with AA. Blood sampling included plasma sodium concentration, plasma glucose, base excess, white blood cell count, plasma arginine vasopressin (AVP), and C-reactive protein. Results Eighty children with histopathologically confirmed AA were included in the study. Median plasma sodium concentration on admission in patients with perforated AA (134 mmol/L, [interquartile range 132–136]) was significantly lower than in children with nonperforated AA (139 mmol/L, [137–140]). The receiver operating characteristic curve of plasma sodium concentration identifying patients with perforated AA showed an area under the curve of 0.93 (95% confidence interval, 0.87–0.99), with a sensitivity and specificity of 0.82 (0.70–0.90) and 0.87 (0.60–0.98), respectively. Plasma sodium concentrations ≤136 mmol/L resulted in an odds ratio of 31.9 (6.3–161.9) for perforation. The association between low plasma sodium concentration and perforated AA was confirmed in a multivariate logistic regression analysis. Median plasma AVP on admission was higher in patients with perforated (8.6 pg/mL [5.0–14.6]) as compared with nonperforated AA (3.4 pg/mL [2.5–6.6]). Conclusion In children with AA, there is a strong association between low plasma sodium concentration and perforation, a novel and not previously described finding.
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Mattheussen, M., K. Mubagwa, B. F. Rusy, H. Van Aken et W. Flameng. « Potentiated state contractions in isolated hearts : effects of ischemia and reperfusion ». American Journal of Physiology-Heart and Circulatory Physiology 264, no 5 (1 mai 1993) : H1663—H1673. http://dx.doi.org/10.1152/ajpheart.1993.264.5.h1663.
Résumé :
To investigate mechanisms underlying the contractile dysfunction during myocardial "stunning," potentiated contractions were studied in Langendorff-perfused rabbit hearts paced at 2.5 Hz. Isovolumetric left ventricular pressure (LVP) and the first derivative of LVP (dP/dt) were measured via a balloon. Potentiated contractions, elicited after 3 s of rest (postrest potentiation, PRP) or with paired pulses (paired-pulse potentiation, PPP) were first characterized in nonischemic conditions. Exposure to 5 nM ryanodine changed PRP into postrest depression [control, 134 +/- 1.7% (SE); ryanodine, 65 +/- 3.4%; n = 5] but did not decrease PPP (control, 125 +/- 7.2%; ryanodine, 141 +/- 14.5%). When sarcolemmal Ca2+ influx was decreased by 0.2-2 microM verapamil, PRP increased (control, 136 +/- 3.7%; 1 microM verapamil, 214 +/- 23.8%; n = 5), whereas PPP was maintained (control, 134 +/- 8.0%; 1 microM verapamil, 154 +/- 11.5%). During ischemia, both PRP and PPP were increased above preischemic values (from 128 +/- 1.9 to 355 +/- 60.4% and from 122 +/- 5.4 to 313 +/- 37.4%, respectively, n = 5). Changes of potentiation of dP/dt were qualitatively similar to those of LVP. On reperfusion, rest potentiation transiently decreased (PRP of dP/dt: 127 +/- 6% preischemia vs. 112 +/- 3% at 2 min postischemia; n = 6). However, PPP increased during the first 20 min of reperfusion (PPP of dP/dt: 184 +/- 22% preischemia vs. 236 +/- 34% postischemia; n = 6). This transient depression of PRP during reperfusion suggests an impairment of sarcoplasmic reticulum function in stunned myocardium, at least during the early phase of reperfusion.
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Derakhshande-Rishehri, Seyede-Masome, Marjan Mansourian, Roya Kelishadi et Motahar Heidari-Beni. « Association of foods enriched in conjugated linoleic acid (CLA) and CLA supplements with lipid profile in human studies : a systematic review and meta-analysis ». Public Health Nutrition 18, no 11 (7 novembre 2014) : 2041–54. http://dx.doi.org/10.1017/s1368980014002262.
Résumé :
AbstractObjectiveThe present study aimed to review the association of conjugated linoleic acid (CLA) consumption in two forms, foods enriched in CLA and CLA supplements, with serum lipid profile in human studies.DesignSystematic review and meta-analysis.SettingSearch process was conducted in PubMed, Cochrane Library, Google Scholar, Scopus and Science Direct. Clinical trials that investigated the association of CLA intakes either in the form of supplements or enriched foods with lipid profile in healthy adults were included. All outcomes were recorded as continuous variables, and the effect size was measured by analysis of the mean and standard deviation before and after the intervention for case and control groups.SubjectsHealthy adult population.ResultsCLA supplementation was associated with a significant decrease in LDL cholesterol (mean difference=−0·218; 95 % CI −0·358, −0·077;P=0·002), a non-significant decrease in HDL cholesterol (mean difference=−0·051; 95 % CI −0·188, 0·086;P=0·468), a non-significant increase in total cholesterol (mean difference=0·009; 95 % CI −0·128, 0·146;P=0·896) and a non-significant decrease in TAG (mean difference=−0·065; 95 % CI −0·20, 0·07;P=0·344). Foods enriched with CLA were associated with significantly decreased LDL cholesterol (mean difference=−0·231; 95 % CI −0·438, −0·024;P=0·028), non-significantly increased HDL-C (mean difference=0·075; 95 % CI −0·121, 0·270;P=0·455), non-significantly decreased total cholesterol (mean difference=−0·158; 95 % CI −0·349, 0·042;P=0·124) and non-significantly decreased TAG (mean difference=−0·078; 95 % CI −0·274, 0·117;P=0·433).ConclusionsAccording to our analysis, consumption of foods enriched with CLA or CLA supplements has favourable effects on LDL cholesterol levels.
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Zylbersztejn, Ania, Ruth Gilbert, Anders Hjern et Pia Hardelid. « Origins of disparities in preventable child mortality in England and Sweden : a birth cohort study ». Archives of Disease in Childhood 105, no 1 (26 juin 2019) : 53–61. http://dx.doi.org/10.1136/archdischild-2018-316693.
Résumé :
ObjectiveTo compare mortality in children aged <5 years from two causes amenable to healthcare prevention in England and Sweden: respiratory tract infection (RTI) and sudden unexpected death in infancy (SUDI).DesignBirth cohort study using linked administrative health databases from England and Sweden.Setting and participantsSingleton live births between 2003 and 2012 in England and Sweden, followed up from age 31 days until the fifth birthday, death or 31 December 2013.Main outcome measuresThe main outcome measures were HR for RTI-related mortality at 31–364 days and at 1–4 years and SUDI mortality at 31–364 days in England versus Sweden estimated using Cox proportional hazards models. We calculated unadjusted HRs and HRs adjusted for birth characteristics (gestational age, birth weight, sex and congenital anomalies) and socioeconomic factors (maternal age and socioeconomic status).ResultsThe English cohort comprised 3 928 483 births, 768 RTI-related deaths at 31–364 days, 691 RTI-related deaths at 1–4 years and 1166 SUDIs; the corresponding figures for the Swedish cohort were 1 012 682, 131, 118 and 189. At 31–364 days, unadjusted HR for RTI-related death in England versus Sweden was 1.52 (95% CI 1.26 to 1.82). After adjusting for birth characteristics, the HR reduced to 1.16 (95% CI 0.96 to 1.40) and for socioeconomic factors to 1.11 (95% CI 0.92 to 1.34). At 1–4 years, unadjusted HR was 1.58 (95% CI 1.30 to 1.92) and decreased to 1.32 (95% CI 1.09 to 1.61) after adjusting for birth characteristics and to 1.30 (95% CI 1.07 to 1.59) after further adjustment for socioeconomic factors. For SUDI, the respective HRs were 1.59 (95% CI 1.36 to 1.85) in the unadjusted model, and 1.40 (95% CI 1.20 to 1.63) after accounting for birth characteristics and 1.19 (95% CI 1.02 to 1.39) in the fully adjusted model.ConclusionInterventions that improve maternal health before and during pregnancy to reduce the prevalence of adverse birth characteristics and address poverty could reduce child mortality due to RTIs and SUDIs in England.
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O'Doherty, J. V., et T. F. Crosby. « Blood metabolite concentrations in late pregnant ewes as indicators of nutritional status ». Animal Science 66, no 3 (juin 1998) : 675–83. http://dx.doi.org/10.1017/s1357729800009243.
Résumé :
AbstractIn a feeding experiment β-hydroxybutyrate (BHB), glucose, albumin, total protein, globulin and urea concentrations in the plasma of twin-bearing ewes were analysed. Mature Suffolk cross ewes were given either formic acid (FA)-treated grass silage or grasslmolassed sugar-beet pulp (MSBP) silage in late pregnancy. The experiment commenced on day 91 of pregnancy and the dietary treatments were FA-treated silage (Tl), FA-treated silage + soya-bean meal (SBM) (T2), MSBP silage (T3), MSBP silage + SBM (T4), FA-treated silage + MSBP (T5), FA-treated silage + MSBP + SBM (T6) or FA-treated silage + 150 g crude protein (CP) per kg concentrate (T7). SBM was given only in the last 22 days of pregnancy aiming for a total CP intake of 220 g per ewe per day. Blood samples were collected by jugular venipuncture from each ewe 3 h following consumption of the morning dietary allowance on days 121, 128, 135 and 142 of pregnancy. Daily metabolizable energy (ME) intakes of 6·8, 11·4, 9·6, 12·8, 10·5, 13·7 and 14·7 (s.e. 0·58) MJ per ewe were recorded for Tl to T7 respectively over the last 3 weeks of pregnancy. Respective CP intakes of 72, 213, 110, 225, 109, 215 and 175 (s.e. 5·64) g per ewe were recorded for Tl to T7 respectively over the last 3 weeks of pregnancy. BHB concentrations (mmol/l) on day 121 of pregnancy of 1·18, 1·25, 0·52, 0·52, 0·56, 0·39 and 0·45 (s.e. 0·17), on day 128 of pregnancy of 1·17, 0·94, 0·52, 0·51, 0·72, 0·62 and 0·39 (s.e. 0·20), on day 135 of pregnancy of 1·53, 0·68, 0·68, 0·66, 0·71, 0·62 and 0·46 (s.e. 0·20) and on day 142 of pregnancy of 1·43, 0·60, 0·62, 0·56, 0·62, 0·56 and 0·63 (s.e. 0·20) were recorded for Tl to T7 respectively. There was a quadratic relationship between plasma BHB concentration and ME intake on days 121 (R2 = 0·538, P < 0·001), 128 (R2 = 0·324, P < 0·001), 135 (R2 = 0·429, P < 0·001)) and 142 (R2 = 0·344, P < 0·002) of pregnancy. There was a positive relationship between plasma glucose concentration and ME intake on day 222 (R2 = 0·208, P < 0·002), 228 (R2 = 0·203, P < 0·05), and 135 (R2 = 0·160, P < 0·02) of pregnancy. Albumin concentrations (gll) on day 128 of pregnancy of 21·8, 21·7, 23·6, 22·9, 22·5, 22·9 and 24·3 (s.e. 0-75), on day 135 of 20·9, 23·6, 24·2, 24·1, 22·4, 24·1 and 23·8 (s.e. 0·75), and on day 142 of 16·9, 22·6, 20·7, 22·2, 20·4, 22·7 and 21·1 (s.e. 1·05) were recorded for Tl to T7 respectively. Plasma albumin concentrations were significantly affected by SBM supplementation (P < 0·05). Despite the lower than generally recommended energy concentrations in T2 to T7, the concentrations of plasma BHB were within the normal range for healthy sheep.
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Lines, A., S. B. Hooper et R. Harding. « Lung liquid production rates and volumes do not decrease before labor in healthy fetal sheep ». Journal of Applied Physiology 82, no 3 (1 mars 1997) : 927–32. http://dx.doi.org/10.1152/jappl.1997.82.3.927.
Résumé :
Lines, A., S. B. Hooper, and R. Harding. Lung liquid production rates and volumes do not decrease before labor in healthy fetal sheep. J. Appl. Physiol. 82(3): 927–932, 1997.—Previous studies have suggested that the volume and production rate of fetal lung liquid decrease late in gestation, before the onset of labor, in preparation for the clearance of lung liquid at birth. In contrast, our earlier studies have not shown a decrease in lung liquid volume near term, although these studies were not continued to the onset of labor. Our aim was to determine the changes in lung liquid volume and production rate in fetal sheep during the last 2 wk of gestation up to the onset of labor at term (∼147 days). In eight chronically catheterized fetal sheep, the volume and production rate of fetal lung liquid were measured at 130, 135, and 140 days of gestation and then on every 2nd day until the onset of labor. Labor was detected by monitoring uterine muscle activity and intrauterine pressure changes. On the day of labor onset, which occurred at 147 ± 1 days of gestation, fetuses weighed 5.0 ± 0.2 kg. The volume of fetal lung liquid was 40.4 ± 2.7 ml/kg at 19 ± 1 days before labor onset and had not significantly changed by 0.7 ± 0.2 days (44.8 ± 5.1 ml/kg) before labor. Similarly, lung liquid production rates at 19 ± 1 days before labor (5.1 ± 1.8 ml ⋅ h−1 ⋅ kg−1) were not significantly different from those at 0.7 ± 0.2 days before labor (3.4 ± 0.7 ml ⋅ h−1 ⋅ kg−1). We conclude that, in healthy ovine fetuses, lung liquid volumes and production rates do not decrease before the onset of labor. Our results indicate that the entire volume of fetal lung liquid (∼222.5 ± 36.6 ml) must be cleared after the onset of labor.
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Marincowitz, Carl, Omar Bouamra, Tim Coates, Dhushy Kumar, David Lockey, Virginia Newcombe, Lyndon Mason, David Yates, Julian Thompson et Fiona Lecky. « 1427 The effect of the COVID-19 pandemic on major trauma presentations and patient outcomes in English hospitals ». Emergency Medicine Journal 39, no 12 (22 novembre 2022) : A960.2—A964. http://dx.doi.org/10.1136/emermed-2022-rcem2.2.
Résumé :
Aims, Objectives and BackgroundThere is evidence that COVID-19 ‘lockdowns’ may have contributed to increased non-accidental injury, domestic violence and self-harm related to deteriorating mental health. Internationally, there is also evidence that the diversion of health care resources may led to worse outcomes for patients presenting with major trauma. There has been no previous national evaluation of ‘lockdown’ measures impact on the characteristics, treatment pathways and outcomes of trauma patients in EnglandWe aimed to assess the impact of successive lockdowns on the volume, demographics, injury mechanism, severity, treatment and outcomes of major trauma in England.Method and DesignDemographic characteristics and clinical pathways of TARN eligible patients in the first lockdown (24th March to 3rd July 2020 inclusive) and second lock down (1st November 2020 to 16th May 2021 inclusive) were compared to equivalent pre-COVID-19 periods in 2018–2019.A segmented regression model predicting the weekly risk adjusted survival was estimated and a discontinuity in the gradient (trend) or intercept (level) of the fitted model was tested for at the weekly time point of implementation of each lockdown.Abstract 1427 Figure 1Strobe diagram for inclusion of study populationAbstract 1427 Figure 2Interrupted time series analysis assessing the impact of COVID restrictions on likelihood of survival (red horizontal lines indicate introduction and relaxation of ‘lockdown’ measures)Abstract 1427 Table 1Comparison of demographics ‘lockdown’ and pre-COVID periodsPeriodPeriod24Mar19 – 03Jul19 (comparator)24Mar20 – 03Jul20 (lockdown 1)Absolute change [percentage point change (95%CI)] p-value01Nov18 – 16May19 (comparator)01Nov20 – 16May21 (lockdown 1)Absolute change [percentage point change (95%CI)] p-valueTotal2224317510-4733 (-21%)p<0.0001‡41016382622754 (–6.7%)p<0.0001‡Age (years), Median (IQR)67.6 (46.5–83.1)70.9 (50.3–84.2)3.3 (2.4 to 4.2)p<0.000169.1 (48.7–83.6)73.1 (53.3–85.1)4 (3.5 to 4.2)<0.0001Age bands, n(%)Age< 1138 (0.6%)130 (0.7%)-8 [0.1(-0.04 to 0.030)] p=0.14281 (0.7%)234 (0.6%)-47 [0.1 (-0.2 to 0.04)]p=0.1979Age <16942 (4.2%)674 (3.8%)-268 [-0.4 (-0.8 to 0]p=0.05311444 (3.5%)1218 (3.2%)-226 [-0.3(-0.6 to – 0.1)p=0.0084Age 16 – 649561 (43%)6974 (39.8%)-2587 [-3.2(-4.1 to -2.2)P<0.000117173 (41.9%)13980 (36.5%)-3193 [-5.3(-6 to -5)]p<0.0001Age 65 and over11740 (52.8%)9862 (56.3%)-1878 [3.5 (2.5 to 4.5)]p<0.000122399 (54.6%)23064 (60.3%)665 [5.7(5 to 6.3)]P<0.0001Age 85 and over4610 (20.7%)4047 (23.1%)-563 [2.4(1.6 to 3.2)]p<0.00018903 (21.7%)9731 (25.4%)828 [3.7 (3.1 to 4.3)]p<0.0001Male, n(%)12316 (55.4%)9512 (54.3%)-2804 [-1 (-2 to -0.6)]p=0.037322146 (54%)19769 (51.7%)-2377 [-2.3 (-3 to -1.6)]<0.0001CCI*, n(%)CCI 09359 (42.1%)6220 (35.5%)-3139 [ -6.5 (-7.5 to -5.6)] p<0.000116665 (40.6%)12806 (33.5%)-3859 [-7.1(-7.8 to -6.5)]p<0.0001CCI 1 – 58538 (38.4%)6896 (39.4%)-1642 [1 (0.3 to 2)]p=0.042615899 (38.8%)15667 (40.9%)-232 [2.2 (1.5 to 2.9)]p<0.0001CCI 6 – 103032 (13.6%)3061 (17.5%)29 [3.8 (3.2 to 4.6)]p<0.00015987 (14.6%)6863 (17.9%)876 [3.3(2.8 to 3.8)]p<0.0001CCI > 10927 (4.2%)1024 (5.8%)97 [1.7(1.2 to 2.1)]p<0.00011648 (4%)2410 (6.3%)762 [2.3(2 to 2.6)]p<0.0001Not recorded387 (1.7%)309 (1.8%)-88 [0.2 (-0.2 to 0.3)]p=0.8513817 (2%)516 (1.3%)-301 [-0.6(-0.8 to -0.5)]p<0.0001MOI**: RTC, n(%)Car occupant1247 (30.7%)551 (20.4%)-696 [-10.4(-12.4 to -8.2)]p<0.00012485 (35.2%)1551 (31.3%)-934 [-3.9(-5.6 to -2.2)]p<0.0001Pedestrian661 (16.3%)288 (10.6%)-373 [-5.6 (-7.2 to -4)]p<0.00011629 (23.1%)962 (19.4%)-667 [-3.7(-5.1 to -2.2)]p<0.0001Motorcycles1196 (29.4%)711 (26.3%)-485 [-3.2(-5.3 to -1)]p<0.00011524 (21.6%)976 (19.7%)-548[ -1.9(-3.3 to -0.4)]p<0.0001Cyclist912 (22.4%)1139 (42.1%)227 [19.6(17.4 to 21.9)]p<0.00011315 (18.6%)1396 (28.2%)81 [9.5(8 to 11.1)]p<0.0001Other11 (0.3%)<9 ()-10 [ -0.2(-0.4 to -0.06)p=0.025131 (0.4%)10 (0.2%)-21 [-0.23(-0.4 to -0.04)]p=0.0281MOI: Intentional, n(%)Intentional assault130 (0.6%)88 (0.5%)-42 [-0.08 (-0.2 to 0.06)]p=0.2724227 (0.6%)175 (0.5%)-52 [-0.1(-0.2 to 0.002)]P=0.0570Self harm276 (1.2%)284 (1.6%)8 [0.4 (0.1 to 0.6)]p=0.0014525 (1.3%)562 (1.5%)37 [0.2 (0.02 to 0.3)]p=0.0223NAI63 (0.3%)27 (0.2%)-36 [-0.1(-0.2 to -0.03)]p=0.007297 (0.2%)90 (0.2%)-7 [-0.001(-0.07 to 0.07)]p=0.9701Shooting34 (0.2%)40 (0.2%)6 [0.08(-0.01 to 0.2)]p=0.082680 (0.2%)56 (0.1%)-24 [ -0.05(-0.1 to 0.001)]p=0.0979Stabbing450 (2%)312 (1.8%)-138 [-0.2(-0.5 to 0.03)]p=0.0816791 (1.9%)589 (1.5%)-202 [-0.4 (-0.6 to -0.2)]p<0.0001Blows1174 (5.3%)647 (3.7%)-527 [-1.6(-1.9 to -1.2)]p<0.00012059 (5%)1299 (3.4%)-760 [-1.6(-1.9 to -1.3)]p<0.0001Unintentional, n(%)Falls>2m2055 (9.2%)1757 (10%)-298 [0.8(0.2 to 1.4)]P=0.00753740 (9,1%)3528 (9.2%)-212 [0.1(-0.3 to 0.5)]p=0.6181Falls<2m13384 (60.2%)11314 (64.6%)-2070 [4.4 (3.5 to 5.4)]p<0.000125505 (62.2%)26203 (65.8%)698 [6.3 (5.6 to 6.9)]p<0.0001Sport449 (2%)320 (1.8%)-129 [-0.2 (-0.5 to 0.01]p=0.1697615 (1.5%)489 (1.3%)-126 [-0.2 (-0.4 to -0.006)]p=0.0079GCS bands , n(%)Mild19609 (88.2%)15449 (88.2%)4160 [0.1 (-0.6 to 0.7)]p=0.826435831 (87.4%)34051 (89%)-1780 [1.6 (1.2 to 2.1)]p<0.0001Moderate689 (3.1%)625 (3.6%)-64 [0.5(0.1 to 0.8)]p=0.00901333 (3.2%)1127 (2.9%)-206 [-0.3 (-0.5 to -0.06)]p=0.0135Severe955 (4.3%)765 (4.4%)-190 [0.1 (-0.3 to 0.5)]p=0.71361886 (4.6%)1464 (3.8%)-422 [-0.8(-1 to -0.5)]p<0.0001Not recorded990 (4.5%)671 (3.8%)-319 [ -0.6(-1 to -0.2)]p=0.00221966 (4.8%)1620 (4.2%)-346 [-0.6(-0.8 to -0.3)]p=0.0002ISS***, median (IQR)9 (9–18)9 (9–18)09 (9–18)9 (9–17)0ISS bands, n(%)ISS 1 – 84545 (20.4%)3062 (17.5%)-1483 [-3 (-4 to -2)]p=<0.00018266 (20.2%)7838 (20.5%)-428 [0.3(-0.2 to 0.9)]p=0.2457ISS 9 – 159290 (41.8%)7728 (44.1%)-1562 [2.4(1.4 to 3.3)]p<0.000117207 (42%)16969 (44.3%)-233 [2.4(1.7 to 3.1)]p<0.0001ISS >158408 (37.8%)6720 (38.4%)-1688 [5.6(-0.4 to 1.5)]p=0.239115543 (37.9%)13455 (35.2%)-2088 [-2.7 (-3.4 to -2)]p<0.0001ISS >253995 (18%)3127 (17.9%)-868 [-0.1(-0.9 to 0.7 )]p=0.79217521 (18.3%)6201 (16.2%)-1320 [-2.1(-2.6 to -1.6)]p<0.0001Body regions, n(%)Head AIS 3+5911 (26.6%)4670 (26.7%)-1241 [0.1 (-0.8 to 1)]p=0.830111128 (27.1%)9629 (25.2%)-1499 [ -2(-2.6 to -1.3)]p<0.0001Face AIS 3+63 (0.3%)41 (0.2%)-22 [-0.05 (-0.1 to 0.05)]p=0.341699 (0.2%)69 (0.2%)-30 [-0.06 (-0.1 to 0)]p=0.0618Chest AIS 3+4787 (21.5%)3915 (22.4%)-872 [8.3 (0.2 to 1.6)]<0.04508515 (20.8%)8075 (21.1%)-440 [0.3 (-0.2 to 0.9)]p=0.2337Abdomen AIS 3+872 (3.9%)690 (3.9%)-182 [0.02 (-0.3 to 0.4)]p=0.91771465 (3.6%)1179 (3.1%)-286 [-0.5 (-0.7 to -0.2)]p=0.0001Spine AIS 3+1985 (8.9%)1561 (8.9%)-424 [-0.01(-0.6 to 0.5)]p=0.97443784 (9.2%)3459 (9%)-325 [-0.2(-0.6 to 0.2)]p=0.3654Pelvis AIS 3+758 (3.4%)600 (3.4%)-158 [0.02(-0.3 to 0.4)]p=0.91841501 (3.7%)1386 (3.6%)-115 [-0.04(-0.3 to 0.2)]p=0.7802Limb AIS 3+5707 (25.7%)4892 (27.9%)-815 [2.3 (1.4 to 3.2)]p<0.000110719 (26.1%)10122 (26.5%)-597 [0.3(-0.3 to 0.9)]p=0.3053Other AIS 3+217 (1%)199 (1.1%)-18 [0.2 (-0.04 to 0.3)]p=0.1176375 (0.9%)396 (1%)21 [0.1 (-0.01 to 0.2]p=0.0836Polytrauma1622 (7.3%)1350 (7.7%)-272 [0.4 (-0.1 to 0.9)]p=0.11602984 (7.3%)2429 (6.3%)-555 [-0.9(-1.2 to 0.6)]p<0.0001*CCI Charlson Comorbidity Index**MOI Mechanism of injury***ISS Injury Severity Score‡chi square test for uniform distributionAbstract 1427 Table 2Comparison care pathways ‘lockdown’ and pre-COVID periodsPeriodPeriod24Mar19 – 03Jul19 (comparator)24Mar20 – 03Jul20 (lockdown 1)Absolute Change01Nov18 – 16May19 (comparator)01Nov20 – 16May21 (lockdown 2)Absolute Change1stHospital MTC9908 (44.5%)7376 (42.1%)-2532 [-2.4 (-3.4 to -1.4)]p<0.000118099 (44.1%)15928 (41.6%)-2171 [-2.5 (-3.2 to -1.8)]p<0.0001Treated at MTC11176 (50.2%)8256 (47.2%)-2920 [-3 (-4 to -2)]p<0.000120395 (49.7%)17852 (46.7%)-2543[-3 (-4 to -2.4)]p<0.0001Consultant ED8140 (36.6%)5562 (31.8%)-2578 [-4.8(-5.8 to -3.9)]p<0.000114779 (36%)12577 (32.9%)-2202 [-3.2 (-3.8 to -2.5)]p<0.0001CT within 1 hr5062 (31.9%)3992 (30.9%)-1070 [-0.9(-2 to 0.1)]p=0.09449203 (31.6%)7776 (27.1%)-1427 [-4(-5 to -3.7)]p<0.0001Whole body CT3348 (15.1%)3210 (18.3%)-138 [3 (2 to 4)]p<0.00016040 (14.7%)6417 (16.8%)377 [2 (1.5 to 2.5)]p<0.0001ICU stay3092 (13.9%)2208 (12.6%)-884 [-1.3(-1.9 to -0.6) ]p=0.00025591 (13.6%)3850 (10.1%)-1741 [-3.6(-4 to -3)]p<0.0001Mortality*1417 (7.1%)1316 (8.3%)-101 [1.2 (0.6 to 1.7)]p<0.00012916 (7.9%)2858 (8.1%)-58 [0.2 (-0.1 to 0.6)] p=0.2040Discharge destination, n(%)Home (own)13800 (62%)10484 (59.9%)-3316 [-2(-3.1 to -1.2)]p<0.000124961 (60.9%)23368 (61.1%)-1593 [-0.7 (-1.4 to -0.05)]p=0.0340Home (relative/carer)473 (2.1%)372 (2.1%)-101 [0 (-0.3 to 0.3)]p=0.9890974 (2.4%)852 (2.2%)-122 [-0.1(-0.4 to 0.06)]p=0.1653Mortuary*1501 (6.7%)1323 (7.6%)-178 [0.8(0.3 to 1.3)]p=0.00193086 (7.5%)2977 (7.8%)-109 [0.1 (-0.3 to 0.5)]p=0.5113No fixed abode75 (0.3%)47 (0.3%)-28 (-37.3%)107 (0.3%)87 (0.2%)-20 (-18.7%)Not Known87 (0.4%)39 (0.2%)-48 (-55.2%)101 (0.2%)95 (0.2%)-6 (-5.9%)Nursing Home1190 (5.3%)1063 (6.1%)-127 [0.7(0.3 to 1.2)]p=0.00202448 (6%)2231 (5.8%)-217 [-0.2(-0.6 to 0.1)]p=0.1620Other Acute hospital2425 (10.9%)1736 (9.9%)-689 [-0.1(-1.6 to -0.4)]p=0.00144346 (10.6%)3313 (8.7%)-1033 [-0.1(-0.5 to 0.2)]p=0.4115Other institution526 (2.4%)516 (2.9%)-10 [0.6 (0.3 to 0.9)]p=0.0003980 (2.4%)870 (2.3%)-110 [-0.1 (-0.3 to 0.1)]p=0.2817Rehabilitation2077 (9.3%)1871 (10.7%)-206 [1.3(0.7 to 1.9)]p<0.00013851 (9.4%)4274 (11.2%)423 [ 1.7(1.3 to 2.2)]p<0.0001Social care63 (0.3%)50 (0.3%)-13 [0 (-0.1 to 0.1)]p=0.9657121 (0.3%)103 (0.3%)-18 [-0.2(-0.1 to 0.5)]p=0.4939*These totals do not correspond as mortality includes deaths in the community and is censored at 30 daysResults and ConclusionThe first ‘lockdown’ had a larger associated reduction in total trauma volume (-21%) compared to the pre-COVID period than the second ‘lockdown’ (-6.7%). Trauma volume increased for those 65 and over (3%) and 85 and over (9.3%) during the second ‘lockdown’.There was a reduction in likelihood of survival (-1.71; 95% CI:-2.76 to -0.66) associated with the immediate introduction of the first ‘lockdown’. However, this was followed by a trend of improving survival (0.25; 95% CI: 0.14 to 0.35) and likelihood of survival returned to pre-pandemic levels by the end of the first ‘lockdown’ period.Future research is needed understand the initial reduction in likelihood of survival after major trauma observed with the implementation of the first ‘lockdown’ to prevent this occurring if measures re-introduced.
8
Jwo, Ching Song, Lung Yue Jeng, Ho Chang et Sih Li Chen. « Research of Vacuum Pump with Nano-Lubricant ». Key Engineering Materials 364-366 (décembre 2007) : 867–72. http://dx.doi.org/10.4028/www.scientific.net/kem.364-366.867.
Résumé :
This study used the Al2O3 nano-lubricant produced from the direct synthesis method was used as the experimental samples and the ultrasonic vibration was used for dispersing the nanoparticles into three types of the weight fraction (0.1, 0.2, 0.3%wt). The base solvent was the lubricant of vacuum pump. The objectives of this study were to discuss the dependence of operating temperature of vacuum pump under the various weight fraction of Al2O3 nanoparticles. In this experiment we added Al2O3 nano-lubricant into the direct drive oil sealed rotary vacuum pump, and used the thermocouple measure the temperature on the four test points (cylinder, in-lubricant, case of vacuum pump and discharge pipeline). The results show that the cylinder temperature was reduced by 1.3% and increased by 0.4%, 1.8%, the lubricant temperature was increased by 5.3%, 0.5% and 1.9%, the case surface temperature was reduced by 1.7%, 1.4% and 1.5%, and discharge pipeline temperature was reduced by 0.6%, 2.1% and 3.8% respectively when the sample fractions were 0.1%, 0.2% and 0.3%wt. From the results, it could be realized that the nano-lubricant has more effects on increasing the performance of heat sink than conventional lubricant.
9
Phan, Kevin, Khushdeep S. Vig, Yam Ting Ho, Awais K. Hussain, John Di Capua, Jun S. Kim, Samuel J. W. White, Nathan J. Lee, Parth Kothari et Samuel K. Cho. « Age Is a Risk Factor for Postoperative Complications Following Excisional Laminectomy for Intradural Extramedullary Spinal Tumors ». Global Spine Journal 9, no 2 (13 août 2018) : 126–32. http://dx.doi.org/10.1177/2192568218754512.
Résumé :
Study Design: Retrospective analysis. Objective: The incidence of intradural extramedullary (IDEM) spinal tumors is increasing. Excisional laminectomy for removal and decompression is the standard of care, but complications associated with patient age are unreported in the literature. Our objective is to identify if age is a risk factor for postoperative complications after excisional laminectomy of IDEM spinal tumors. Methods: A retrospective analysis was performed on the 2011 to 2014 ACS-NSQIP (American College of Surgeons National Surgical Quality Improvement Program) database for patients undergoing excisional laminectomy of IDEM spinal tumors. Age groups were determined by interquartile analysis. Chi-squared tests, t tests, and multivariate logistic regression models were employed to identify independent risk factors. Institutional review board approval was not needed. Results: A total of 1368 patients met the inclusion criteria for the study. Group 1 (age ≤ 44) contained 372 patients, group 2 (age 45-54) contained 314 patients, group 3 (age 55-66) contained 364 patients, and group 4 (age > 66) contained 318 patients. The univariate analysis showed that mortality and unplanned readmission were highest among patients in group 4 (1.26%, P = .011, and 10.00%, P = .039, respectively). Postoperative wound complications were highest among patients in group 1 (2.15%, P = .009), and postoperative venous thromboembolism and cardiac complications were highest among patients in group 3 (4.4%, P = .007, and 1.10%, P = .032, respectively). Multivariate logistic regression revealed that elderly age was an independent risk factor for postoperative venous thromboembolism (group 3 vs group 1; odds ratio = 6.739, confidence interval = 1.522-29.831, P = .012). Conclusions: This analysis revealed that increased age is an independent risk factor for postoperative venous thromboembolism in patients undergoing excisional laminectomy for IDEM spinal tumors.
10
Wang, Wen, Linghua Wang, Säm Krucker et Robert F. Wimmer-Schweingruber. « Energy Spectrum of Solar Energetic Electron Events over 25 Years ». Astrophysical Journal 948, no 1 (1 mai 2023) : 51. http://dx.doi.org/10.3847/1538-4357/acbea2.
Résumé :
Abstract We investigate the peak flux energy spectrum of 458 solar energetic electron (SEE) events with a clear velocity dispersion detected at energies from ≤4.2 to ≥108 keV by Wind/3DP from 1994 December through 2019 December, utilizing a pan-spectrum fitting method. According to the fitted spectral parameters, these 458 events are self-consistently classified into five spectral types: 304 downward double-power-law (DDPL) events, 32 upward double-power-law (UDPL) events, 23 single-power-law (SPL) events, 44 Ellison–Ramaty (ER) events, and 55 logarithmic–parabola (LP) events. The DDPL events can be further divided into two types: 231 DDPL E B ≥ 20 keV events and 73 DDPL E B < 20 keV events, since their break energy E B exhibits a double-peak distribution separated by a dip at ∼20 keV. The DDPL E B < 20 keV ( DDPL E B ≥ 20 keV ) events show a power-law spectral index of 2.0 − 0.2 + 0.2 ( 2.1 − 0.3 + 0.3 ) at energies below E B = 5.6 − 2.4 + 2.3 ( 61 − 12 + 23 ) keV and an index of 3.3 − 0.3 + 0.5 ( 3.9 − 0.7 + 0.6 ) at energies above. The UDPL events have a spectral index of 3.0 − 0.3 + 0.3 at energies below E B = 5.1 − 1.8 + 4.2 keV and an index of 2.2 − 0.3 + 0.2 at energies above. The SPL events exhibit a spectral index of 2.8 − 0.2 + 0.5 . The ER events show a spectral index of 1.9 − 0.3 + 0.3 at energies below E c = 31 − 11 + 19 keV. The LP events are characterized by a spectral slope of 1.8 − 0.3 + 0.4 ( 3.6 − 0.5 + 0.7 ) at 2.8 keV (108 keV). The six spectral types also behave differently in the relationship between spectral parameters and in solar cycle variations. The spectral shape of most SEE events appears to be unrelated to the estimated electron path lengths. These results suggest that the formation of SEE events can involve complex processes/sources.
11
Nielson, D. W. « Electrolyte composition of pulmonary alveolar subphase in anesthetized rabbits ». Journal of Applied Physiology 60, no 3 (1 mars 1986) : 972–79. http://dx.doi.org/10.1152/jappl.1986.60.3.972.
Résumé :
We measured the concentration of Na+, K+, Ca2+, and Cl- in the aqueous subphase of the alveolar lining by puncturing the most superficial alveoli of the exposed lungs of anesthetized rabbits with ion-selective microelectrodes and a nonselective KCl microelectrode. A buffered electrolyte solution bathed the lung surface to keep it moist and warm (38 +/- 1 degrees C) and to serve as a reference for each measurement of ionic concentration. The serum and alveolar concentrations (meq/l) were Na+ 134 +/- 6 and 135 +/- 5, K+ 3.4 +/- 0.2 and 7.3 +/- 0.7, Ca2+ 3.1 +/- 0.2 and 3.2 +/- 0.4, and Cl- 106 +/- 7 and 103 +/- 5 (mean +/- SD). Only K+ was significantly different (P less than 0.001). There was a small electrical potential difference between the alveolar lumen and the pleural surface (-3.5 +/- 0.8 mV, lumen negative) that was significantly different from zero (P less than 0.001). Although it is not possible to measure ion fluxes with these techniques, the results are consistent with active transport of one or more of the ions studied.
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Heimlich, Jonathan Brett, Godwin Chipoka, Portia Kamthunzi, Yuri D. Fedoriw, Nigel S. Key, Kenneth I. Ataga et Satish Gopal. « Establishing Sickle Cell Diagnostics and Characterizing a Pediatric Sickle Cell Disease Cohort in Malawi ». Blood 126, no 23 (3 décembre 2015) : 2070. http://dx.doi.org/10.1182/blood.v126.23.2070.2070.
Résumé :
Abstract Sickle cell disease (SCD) is highly prevalent in sub-Saharan Africa; however, there are relatively few studies describing the clinical profile for children with laboratory-confirmed SCD. Prior to December 2014, neither neonatal screening nor standardized methods for SCD diagnosis were routinely available in Malawi, as hemoglobin electrophoresis and alternative diagnostic methods were absent. We describe implementation of hemoglobin electrophoresis for children with clinically suspected SCD at Kamuzu Central Hospital, one of two national teaching hospitals in Malawi. Children with clinically suspected SCD were recruited January - May 2015 and underwent comprehensive clinical and laboratory characterization. 137 total patients were recruited and 117 were confirmed to have HbSS disease. Among children who were being cared for as SCD prior to enrollment, 86% had HbSS suggesting generally accurate clinical diagnosis by local providers. Baseline clinical parameters and self-reported SCD complications for the study population are displayed in Table 1. Of those with confirmed SCD, median age was 7.3 years (IQR 2.7-10.4) with 53% males. Prior malaria was reported by 39% of patients, and was higher in the 0-5 age group compared with the over 5 age group (46% vs. 31%, p=0.03). The most commonly reported SCD complications were anemia (72%), joint pain (56%), jaundice (52%), and acute pain episodes (50%). Children with confirmed SCD had median hemoglobin of 7.3 g/dL (IQR 6.9-7.9), total bilirubin of 1.7 mg/dL (IQR 1.1-2.6) and lactate dehydrogenase of 658 IU/L (IQR 527-773). Urinalysis demonstrated 26% of patients with blood and 7% with proteinuria by dipstick. As of May 2015, more than 250 samples for enrolled children as well as routine clinical care had been batch-processed weekly with an average turn-around time of 36 hours for results. Three Malawian laboratory technicians were trained to perform hemoglobin electrophoresis, all of whom have been performing the test independently since April 2015. Our findings highlight a need for wider implementation of resource-appropriate diagnostics as an essential foundation for care and research. Children had substantial clinical and laboratory evidence of SCD-related morbidity. Earlier diagnosis can improve care for this population by facilitating earlier therapeutic interventions, as well as providing a basis for research to better understand SCD-related morbidity in sub-Saharan Africa. These efforts can ultimately inform management strategies to improve outcomes and increase life expectancy among children with SCD in Malawi. Table 1. All (n=117) Male (n= 62) Female (n=55) p value Age years, median (IQR) 7.3 (2.7-10.4) 5.3 (2.3-9.4) 8.9 (4.2-11.9) 0.004 Height cm, median (IQR, n) 115 (88-131, 60) 111 (89-128, 36) 119.5 (93-140, 24) 0.21 Weight kg, median (IQR, n) 19 (13-27, 108) 16.5 (12-23.6, 58) 21 (14-30, 50) 0.01 Blood Pressure Systolic mmHg, median (IQR, n) 103 (98-110, 83) 101 (94-108, 43) 103 (99-110, 40) 0.37 Blood Pressure Diastolic mmHg, median (IQR, n) 60 (55-65, 83) 58 (53-65, 43) 61 (56-68, 40) 0.13 Heart Rate BPM, median (IQR, n) 104 (91-118, 114) 105 (94-123, 61) 104 (88-112, 53) 0.15 O2 Saturation %, median (IQR, n) 93 (88-97, 108) 91 (85-96, 59) 95 (91-98, 49) 0.004 % Hypoxemic (SPO2 < 90%), n (%) 36 (30.7) 26 (41.9) 10 (18.2) 0.005 Body Temperature Celsius, median (IQR, n) 37 (36.7-37.4, 91) 37 (36.7-37, 46) 37 (36.4-37.2, 45) 0.22 Positive History of: Malaria, n (%) 45 (38.5) 22 23 0.34 0-5 years, n (%) 25 (46.3) - - 0.03 6-18 years, n (%) 20 (31.7) - - Pneumonia, n (%) 29 (24.8) 10 (16.1) 19 (34.5) 0.02 HIV, n (%) 0 0 0 - Anemia, n (%) 84 (71.8) 49 (79.0) 35 (63.6) 0.06 Pallor, n (%) 16 (13.7) 7 (11.3) 9 (16.4) 0.43 Jaundice, n (%) 61 (52.1) 33 (53.2) 28 (50.9) 0.82 Received Blood Transfusion, n (%) 87 (74.4) 47 (75.8) 40 (72.7) 0.47 Days since last transfusion, median (IQR) 316 (133-1144) 240 (111-410) 577 (180-1784) 0.03 Pain episodes, n (%) 58 (49.6) 27 (43.5) 31 (56.4) 0.16 Joint pain, n (%) 66 (56.4) 33 (53.2) 33 (60.0) 0.34 Dactylitis, n (%) 41 (35.0) 19 (30.6) 22 (40.0) 0.29 Leg ulcers, n (%) 5 (4.3) 5 (8.1) 0 0.03 Stroke, n (%) 10 (8.5) 5 (8.1) 5 (9.1) 0.84 Nocturnal Enuresis, n (%) 24 (20.5) 12 (19.4) 12 (21.8) 0.74 Disclosures No relevant conflicts of interest to declare.
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Luong, Huu Thanh, Thuy Nga Vu, Thi Thuy Ha, Kieu Bang Tam Nguyen et Thi Hong Van Dao. « Effects of some microelements on antifungal activity and biomass of the Actinomyces producing Validamycin-A ». Journal of Vietnamese Environment 9, no 3 (20 juillet 2018) : 128–31. http://dx.doi.org/10.13141/jve.vol9.no3.pp128-131.
Résumé :
Validamycin A (Val-A) is an aminoglycoside's antibiotic with anti-fungal activity. Val-A synthesized by Streptomyces hygroscopicus strain depending on the growth and development of this actinomyces. In this study, the effects of Mn and Zn on the antifungal activity and biomass of the Streptomyces hygroscopicus were conducted. The results showed that micronutrients Mn, Zn had significant effects on biomass as well as antifungal activity of strain Streptomyces hygroscopicus-DA15. With the addition of Mn at a concentration of 1μg/l of the nutrient medium, biomass of Streptomyces hygroscopicus was 2.85 ± 0.02 g/ml, the anti-fungal Rhizoctonia solani (R. solani) round diameter reached 3.5 ± 0.2 cm. With the addition of Zn = 3 µg/l of the nutrient medium, biomass of Streptomyces hygroscopicus DA15 was 4.5 ± 0.02 g/ml, the anti-fungal R. solani diameter reached 3.4 ± 0.2 cm.
Validamycin A (val-A) là một loại kháng sinh có khả năng kháng nấm, được tổng hợp bởi xạ khuẩn Streptomyces hygroscopicus và phụ thuộc vào quá trình sinh trưởng, phát triển của xạ khuẩn. Bài báo này đánh giá ảnh hưởng của nguyên tố vi lượng Mn, Zn đến hoạt tính kháng nấm Rhizoctonia solani (R. solani) và sinh khối của chủng Streptomyces hygroscopicus DA15. Khi bổ sung Mn vào môi trường nuôi cấy với nồng độ 1μg/l, sinh khối của Streptomyces hygroscopicus-DA15 đạt 2,85±0,02g/ml, đường kính vòng kháng nấm đạt 3,5±0,2cm. Bổ sung Zn vào môi trường nuôi cấy với hàm lượng Zn=3µg/l, sinh khối của Streptomyces hygroscopicus DA15 đạt 4,5±0,02g/ml và đường kính vòng kháng nấm đạt 3,4±0,2cm.
14
Hauswirth, C., J. Fitschen, E. Martin, G. Oetting, H. Hundeshagen et Ch Ehrenheim. « Zum genetischen Risiko nach hochdosierter Radiojodtherapie unter Berücksichtigung der Gonadendosis ». Nuklearmedizin 36, no 05 (1997) : 157–66. http://dx.doi.org/10.1055/s-0038-1629786.
Résumé :
Zusammenfassung Ziel der vorliegenden Arbeit ist die Abschätzung des genetischen Risikos nach hochdosierter Radiojodtherapie unter besonderer Berücksichtigung der individuell erreichten Gonadendosis. Methode: Mittels eines Erhebungsbogens wurden die Daten von insgesamt 364 Patientinnen und Patienten mit einem differenzierten Schilddrüsenkarzinom im gebärbzw. zeugungsfähigen Alter bezüglich ihrer Nachkommen ausgewertet. 45 Patienten (41 Frauen und vier Männer) aus dieser Gruppe hatten insgesamt 56 Kinder. Der Verlauf von Schwangerschaft, Geburt und Kindesentwicklung wurde erfaßt. Ergebnisse: Im Rahmen der Therapie und Nachsorge waren insgesamt zwischen 4,144 und 35,15 GBq I-131 verabreicht worden; die individuell auf der Grundlage des MIRD-Modells errechnete Gonadendosis lag zwischen 0,2 und 2,2 Sv (im Mittel 0,51 Sv). Der Abstand zwischen der letzten I-131 Applikation und einer Geburt betrug mindestens 9 Monate und höchstens 14 Jahre. Bezüglich Schwangerschaftsverlauf und Geburt wurden zwei Frühaborte, eine Extrauteringravidität und eine Plazentainsuffizienz mit nachfolgender Frühgeburt ermittelt. In einem Fall trat eine chromosomale Translokation 7/14 als genetischer Defekt auf, die zur Interruptio führte. Die Entwicklung der ausgetragenen Kinder verlief bis auf das Auftreten einer Neurodermitis in zwei Fällen, multipler Allergien in einem anderen Fall und eines frühzeitigen Fontanellenverschlusses bei einem Kind unauffällig. Schlußfolgerung: Unter der Annahme einer Verdoppelung der Häufigkeit spontaner Mutationen bei einer erzielten Gonadendosis von 1 Sv erhöht sich das Risiko irgendeiner angeborenen Erkrankung bei unseren Patienten im Mittel rechnerisch um rund 13%; tatsächlich lag der Anteil genetischer Defekte in unserem Kollektiv mit 1,8% (1/57) im Bereich des natürlichen Risikos. Unter Berücksichtigung der Literatur ließ sich damit bisher bei insgesamt 408 Kindern keine Zunahme genetisch bedingter Erkrankungen oder angeborener Anomalien feststellen.
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Kantarjian, Hagop M., Richard A. Larson, Francois Guilhot, Stephen G. O’Brien et Brian J. Druker. « Declining Rates of Adverse Events (AEs), Rare Occurrence of Serious AEs (SAEs), and No Unexpected Long-Term Side Effects at 5 Years in Patients with Newly Diagnosed Chronic Myeloid Leukemia (CML) in Chronic Phase (CP) Initially Treated with Imatinib (IM) in the International Randomized Study of Interferon vs STI571 (IRIS). » Blood 108, no 11 (1 novembre 2006) : 2136. http://dx.doi.org/10.1182/blood.v108.11.2136.2136.
Résumé :
Abstract The IRIS trial compared interferon alfa + cytarabine (IFN+Ara-C) and imatinib (IM) in patients (pts) with newly diagnosed CML-CP. Among 553 pts randomized to receive 400 mg IM, 157 (28%) discontinued for reasons which included AEs or deaths unrelated to CML and treatment (6%) and unsatisfactory therapeutic effect (11%). Only 2.4% discontinued due to drug-related AEs. The average daily dose was 389±71 mg, suggesting that no major dose modifications were required due to toxicity. In pts still on IM, the average doses was 382±50 mg. Average duration of exposure is 50 mos (median 60 mos). Table 1 summarizes the most frequently reported non-hematologic AEs (regardless of relationship to study drug) in pts who started IM therapy and those who were still on IM at 2 and 4 years (n=456 and 409 respectively). Table 1. AEs (≥ 20%) on First-Line Imatinib Therapy AE All grades N= 551 (%) All grades, after 2 yrs N = 456 (%) All grades, after 4 yrs N = 409 (%) Grades 3/4 N= 551 (%) Fluid retention 61.7 20.2 5.6 2.5 – Superficial edema 59.9 18.2 5.1 1.5 – Other fluid retention events 6.9 2.4 0.7 1.3 Nausea 49.5 15.4 3.4 1.3 Muscle cramps 49.2 22.8 7.3 2.2 Musculoskeletal pain 47.0 20.8 6.1 5.4 Diarrhea 45.4 23.0 5.1 3.3 Rash and related terms 40.1 13.8 2.4 2.9 Fatigue 38.8 11.4 2.9 1.8 Headache 37.0 12.1 3.4 0.5 Abdominal pain 36.5 15.4 3.4 4.2 Joint pain 31.4 9.2 2.0 2.5 Nasopharyngitis 30.5 14.3 3.7 0 Hemorrhage 28.9 14.3 5.1 1.8 Myalgia 24.1 4.6 1.5 1.5 Vomiting 22.5 9.2 3.7 2.0 Upper respiratory tract infection 21.2 11.2 2.7 0.2 Cough 20.0 7.7 3.4 0.2 Hematologic toxicities were the most frequently occurring grade 3/4 AEs (Table 2). Table 2. Grade 3/4 laboratory abnormalities on First-line Imatinib Overall N = 551 (%) After 2 years N= 456 (%) After 4 years N= 409 (%) Hematologic – Neutropenia 16.7 7 1.0 – Thrombocytopenia 8.9 1.5 0.2 – Anemia 4.4 1.8 0.5 Biochemical – ↑ SGOT/SGPT 5.3 0.4 0 – ↑Total bilirubin 1.1 0.4 0.2 The most frequent reported AEs as well as grade 3/4 hematological and biochemical toxicities were observed at decreasing frequencies throughout therapy. After 4 years, 8% of pts experienced an SAE, compared with 14%, 12%, 7.5%, and 9% during year one through four of therapy. Overall, only 6% of pts had SAEs considered related to study drug (1.5% pts after 4 years of IM). Congestive heart failure/cardiac dysfunction (incl. pulmonary edemas) were reported for 3% of pts (<1% grade 3/4) and pleural effusion in 1% (<1% grade 3/4). Despite much shorter average exposure (12 mos), similar % of these AEs were noted for IFN+Ara-C. Although it should be considered that pts more likely to experience grade 3/4 events may have discontinued from the study prematurely, the 5-year data with IM in pts with newly diagnosed CML-CP show declining frequencies of AEs and SAEs over time. Occurrence of SAEs and laboratory abnormalities with long-term follow-up was rare. No unexpected long-term side effects were noted. These results confirm the IM tolerability and safety profile for durations exceeding 4 years.
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McCartney, Christopher R., Melissa Gilrain, Jessica A. Lundgren, Su Hee Kim et Christine Michele Burt Solorzano. « Assessment of Estradiol-Induced Gonadotropin Surge Generation : Preliminary Results From a Protocol of Graded Transdermal Estradiol Dosing ». Journal of the Endocrine Society 5, Supplement_1 (1 mai 2021) : A729—A730. http://dx.doi.org/10.1210/jendso/bvab048.1484.
Résumé :
Abstract In normally-cycling women, high midcycle estradiol (E2) concentrations (> 200-300 pg/ml) derived from the dominant follicle trigger an approximately 10-fold increase in LH and 4-fold increase in FSH levels—the gonadotropin surge—over about 48 hours. In prenatally-androgenized female rats and sheep (animal models with polycystic ovary syndrome [PCOS]-like features), high-dose estrogen fails to initiate gonadotropin surges. However, it remains unclear whether E2-induced gonadotropin surge generation is defective in PCOS. Baird et al., induced LH surges in 12 women with PCOS and 6 normally-cycling controls (studied in the early follicular phase) with 3 days of high-dose oral ethinyl E2, and the LH peak magnitude was similar in both groups (JCEM 1977;45:798-801). However, the dose of ethinyl E2 in this study (200 mcg/day) was markedly supraphysiological, and the dosing schedule did not mimic the normal, gradual increase in E2 levels observed in normal follicular phases. To further assess potential impairments in E2 augmentation of gonadotropin secretion in PCOS, we developed a study protocol involving graded transdermal E2 dosing (with dose adjustments as needed) to gradually achieve serum E2 concentrations approximating 300-400 pg/ml. Herein we present our early experience with this protocol in six normally-cycling, non-hyperandrogenic women: median (range) age 23.1 (19.8–29.0) years, body mass index 20.7 (19.2–27.2) kg/m2, calculated serum free testosterone 2.7 (2.4–5.3) pg/ml. Study subjects began transdermal E2 on cycle day 4 with the following dose-escalation protocol: 0.2 mg/d x 1 day, then 0.3 mg/d x 1 day, then 0.4 mg/d x 1 day, then 0.5 mg/d. Daily serum E2 measurements informed dose adjustments (e.g., a measured E2 level > 400 pg/ml prompted a dose reduction; a measured E2 level < 250 pg/ml while on the 0.5 mg/d dose prompted a dose increase to 0.6 mg/d). In these six women, daily E2 values (pg/ml) were as follows: baseline 31 (17–36) (median [IQR]) on cycle day 4 (the morning of E2 initiation); 205 (135–240) on day 5; 159 (135–270) on day 6; 263 (202–363) on day 7; 276 (239–351) on day 8; 328 (307–367) on day 9; 333 (269–402) on day 10; and 328 (253–354) on day 11. Median transdermal E2 doses (mg/d) on days 5 through 11 were 0.2, 0.3, 0.4, 0.35, 0.4, 0.4, and 0.4, respectively. Morning serum LH concentrations (median [IQR]) were 5.2 (3.5–6.1) IU/L immediately before E2 initiation (cycle day 4), decreased to a nadir of 1.5 (1.0–2.4) IU/L after 2 days of E2 (cycle day 6), thereafter increasing 8.1-fold to a peak of 12.1 (8.1–18.3) IU/L after 5 days of E2 (cycle day 9). FSH similarly changed from baseline median 3.5 (3.4–4.2) IU/L to nadir median of 1.6 (1.2–1.8) IU/L after 2 days of E2, thereafter increasing again to 3.5 (2.6–4.0) IU/L after 5 days of E2. We conclude that this experimental protocol may be useful to investigate potential defects in E2-induced LH surge generation in PCOS.
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Ha, Heon-Young, Jae Jang, Tae-Ho Lee, Chihyoung Won, Chang-Hoon Lee, Joonoh Moon et Chang-Geun Lee. « Investigation of the Localized Corrosion and Passive Behavior of Type 304 Stainless Steels with 0.2–1.8 wt % B ». Materials 11, no 11 (25 octobre 2018) : 2097. http://dx.doi.org/10.3390/ma11112097.
Résumé :
The pitting corrosion resistance and passive behavior of type 304 borated stainless steels (Febalance–18Cr–12Ni–1.5Mn–(0.19, 0.78, and 1.76 wt %)B) manufactured through conventional ingot metallurgy were investigated. The alloys were composed of an austenitic matrix and Cr2B phase, and the volume fraction of Cr2B increased from 1.68 to 22.66 vol % as the B content increased from 0.19 to 1.76 wt %. Potentiodynamic polarization tests measured in aqueous NaCl solutions revealed that the pitting corrosion resistance was reduced as the B content increased and the pits were initiated at the matrix adjacent to the Cr2B phase. It was found that the reduced resistance to pitting corrosion by B addition was due to the formation of more defective and thinner passive film and increased pit initiation sites in the matrix.
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Tilchenko, D. A., E. Yu Bibik, K. A. Frolov, V. V. Dotsenko, S. G. Krivokolysko, G. A. Batishcheva et E. S. Ketova. « The effect of new partially hydrogenated pyridines, cyanothioacetamide derivatives, on the liver morphological parameters in rats with dexamethasone-induced diabetes mellitus ». Journal of Siberian Medical Sciences 7, no 1 (2023) : 118–31. http://dx.doi.org/10.31549/2542-1174-2023-7-1-118-131.
Résumé :
Introduction. On the basis of the Chemex Scientific Lab of the Vladimir Dahl Lugansk State University we have synthesized and selected 4 samples of partially hydrogenated pyridine derivatives via in silico screening, containing a furan fragment in the fourth position (codenamed cv-150, cv-140, cv-083 and jen09-039), the effect of which on the course of dexamethasone-induced diabetes mellitus (DM) is of interest. Aim. To study the morphological parameters of the liver of dexamethasone-induced diabetic rats during a period of pronounced senile changes in the setting of pharmacological treatment with new partially hydrogenated pyridines, cyanothioacetamide derivatives. Materials and methods. The experiment was carried out with 92 18-month-old albino male rats, by administering per os 4 samples of 1,4-dihydropyridine at a dose of 1 mg/kg to each individual group of animals with dexamethasone-induced diabetes mellitus. Simultaneously, a control group (dexamethasone-induced diabetes) and a group of intact animals (without steroid-induced diabetes) were used. Dexamethasone was administered for 13 days. The intact and control group of animals consisted of 12 individuals. Four experimental groups of animals consisted of 17 individuals in each group. Animals of the experimental groups received one of the study compounds cv-150, cv-140, cv-083 and jen09-039 via gastric tube at a dose of 1 mg/kg body weight for 21 days. Results. During the experiment, 10 animals died from late complications of DM. Death was recorded in the control and experimental groups treated with cv-083 and jen09-039 compounds. The most pronounced hepatomegaly was found in animals of the control group, the absolute liver weight averaged 16.43 g (3.4% of body weight) with indicators in intact animals group of 14.44 g (2.8% of body weight). The liver weight of rats treated with the cv-150 compound was 12.90 g (2.74% of body weight). The minimal number of pathological changes of the liver was detected in animals receiving partially hydrogenated pyridine cv-083 – 28.6%. The maximum number of pathological changes was registered in control animals receiving dexamethasone without pharmacological treatment – 88.9%. No liver changes were detected in intact rats. Conclusion. Positive metabolic and psychosomatic changes were observed during the experiment in groups of animals treated with cv-150 and cv-140 compounds. There was no mortality in these experimental groups. According to necroptic study, hepatoprotective activity was found in these compounds. The result of using the cv-083 compound is questionable. The jen09-039 compound did not have any positive effect on the course of dexamethasone-induced diabetes.
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Dominietto, Alida, Teresa Lamparelli, Anna Maria Raiola, Maria Teresa Van Lint, Francesca Gualandi, Giovanni Berisso, Stefania Bregante et al. « Transplant-related mortality and long-term graft function are significantly influenced by cell dose in patients undergoing allogeneic marrow transplantation ». Blood 100, no 12 (1 décembre 2002) : 3930–34. http://dx.doi.org/10.1182/blood-2002-01-0339.
Résumé :
We have studied the impact of cell dose on short- and long-term graft function and outcome in 905 patients undergoing an unmanipulated allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling (n = 735), a one-antigen mismatched related donor (n = 35), or a matched unrelated donor (n = 135). Median number of nucleated cells infused was 3.4 × 108/kg (25th percentile 2.4 × 108/kg, 75th percentile 5 × 108/kg). Patients were stratified according to cells infused in 3 groups: ≤ 2.4 × 108/kg (n = 247; low dose); >2.4 × 108/kg and ≤ 5 × 108/kg (n = 452; intermediate dose); and >5 × 108/kg (n = 206; high dose). Patients receiving high cell dose had significantly higher platelet counts on days +20, +50, +100, +180, and +365 after BMT (P< .01) and higher white blood cell counts on days +50, +100, and +180 after BMT (P < .01) as compared with other patients. The actuarial 5-year transplant-related mortality (TRM) was 41% versus 36% versus 28% (P = .01); overall survival was 45% versus 51% versus 56% (P = .0008); and disease-free survival was 41% versus 42% versus 48%, respectively, (P = .04) in patients receiving low, intermediate, or high cell dose. The cell dose effect was more pronounced in patients older than 30 years of age, with advanced disease, with chronic myeloid leukemia, and with alternative donors. In multivariate Cox analysis on TRM, cell dose was a significant predictor (P = .002; relative risk 0.6) together with donor type (P = .0001), year of transplantation (P = .0001), conditioning regimen (P = .02), and recipient age (P = .02). In conclusion, transplantation of high marrow cell dose is associated with reduced transplant mortality and improved survival and results in improved graft function both short and long term.
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Guglielmelli, Paola, Flavia Biamonte, Johannah Score, Claire Hidalgo-Curtis, Francisco Cervantes, Margherita Maffioli, Tiziana Fanelli et al. « Prognostic Impact of EZH2 and ASXL1 Mutation in Myelofibrosis ». Blood 118, no 21 (18 novembre 2011) : 2811. http://dx.doi.org/10.1182/blood.v118.21.2811.2811.
Résumé :
Abstract Abstract 2811 Among chronic myeloproliferative neoplasms (MPN) myelofibrosis (MF) has the worst prognosis. The International Prognostic Score System-IPSS reliably discriminates four categories of patients (pts) with different survival (OS); however, the possibility to identify pts with very high-risk disease, based on intrinsic characteristics of the underlying disease, would be particularly useful for therapeutic choices that include early stem cell transplantation. Several studies have addressed the prognostic value of molecular abnormalities harbored by MF pts, but a part from a negative role of low JAK2V617F allele burden on survival independently reported by the Mayo Clinic and our own group, none of them impacted significantly on survival. Here we have genotyped at diagnosis 370 pts with primary MF (PMF) and 148 with post-polycythemia vera/essential thrombocythemia MF (PPV/PET-MF) for mutations of EZH2 and ASXL1. EZH2 is the catalytic component of polycomb repressive complex 2 involved in trimethylation of H3 lysine 27, while ASXL1 is a member of enhancer of trithorax and polycomb group required for repression of HOX genes through deubiquitination of histone H2A. All 20 EZH2 exons were screened by high-resolution melting followed by direct sequencing whereas direct sequencing was used for ASXL1 exon 12 genotype. Pts median FU was 39 mo (1–340); 128 pts died (25.9%), 81 (18.3%) because of leukemia (AL). Among PMF pts survival differed significantly according to the IPSS category and was also predicted by the lowest V617F quartile. EZH2 mutation. We found 22 PMF (6%), 1 PPV-MF (1.2%) and 6 PET-MF (9.4%) mutated pts, harboring 25 different mutations, 20 exonic (heterozygous in 83%), 5 intronic. Concurrent JAK2 V617F, MPL W515L/K, IDH1/2, TET2, CBL and ASXL1 mutations were found in 41.4%, 0%, 0%, 6.9%, 3.4% and 20.7% of EZH2 -mutated pts. In multivariate analysis EZH2 mutation was associated with leukocytosis (12.3±13.2 vs 18.7±11.5×10e9/L) in PMF pts, but no additional clinical/hematological correlation was discovered. EZH2 mut pts clustered preferentially in the IPSS high-risk category (52.6%; P=.002). More EZH2 mut than wt PMF pts died (51.9% vs 24.4%; P<.001); median OS was shorter in EZH2 mut pts (32 vs 137 mo, P=.001). Leukemia occurred in 31.8% of EZH2 mutated and 17.6% of wt pts; leukemia-free survival (LFS) was shorter in EZH2 mut PMF pts (25.7 vs 63.6 mo; P=.028). ASXL1 mutation. In a total number of 334 evaluated patients we found 38 different mutations in 49 pts (14.7%), 35 PMF (15%), 5 PPV-MF (8.6 %) and 9 PET-MF (21.4%). Mutations were frameshift, non sense and missense mutations, heterozygous in 46 of 49 cases. Co-expression of JAK2 V617F, MPL W515L/K and EZH2 mutation was found in 55.1%, 4.1% and 12.2%, respectively. Co-espression of ASXL1 and IDH1/2, TET2 or CBL was observed in two, one and one of the evaluable subjects, respectively. ASXL1 mutation was associated with leucocytosis (P=.006), a blast count >1% (43.8% vs 16.6%, P<.0001) and constitutional symptoms (P=.027). ASXL1 mutated pts clustered preferentially in the IPSS high-risk category (46.4%; P<.0001). OS was significantly shortened in ASXL1 mutated PMF patients (median= 87.6 mo vs 264; P=.004); leukemia occurred in 34.9% of ASXL1 mutated and 15.2% of wt pts (P=.002). LFS was shorter in ASXL1 mutated PMF patients [137 mo than wt 264 mo, (P=.01)]. According to EZH2 and ASXL1 mutational status, median OS was significantly shorter in double EZH2/ASXL1 mutated PMF pts compared with single EZH2 or ASXL1 mutated or WT patients (34 vs 116 vs 198 vs 272 mo, respectively. P<.0001). On multivariate analysis, OS was predicted by IPSS score (P<.001), ASXL1 (P=.016) and EZH2 mutational status (P=.011). Leukemia-free survival (LFS) was shorter in double EZH2/ASXL1 mutated PMF pts compared with single EZH2 or ASXL1 mutated or WT patients (25 vs 153 vs 138 vs 264 mo; P=.002), but the low number of cases (n=6) prevented multivariate analysis. No impact of EZH2 or ASXL1 mutations on OS or LFS was seen in PPV/PET-MF. Overall, these results showed that mutations in genes involved in epigenetic gene regulation such as EZH2 and ASXL1 negatively impact on OS and LFS in pts with PMF, suggesting that screening for these mutations might be useful for risk stratification and treatment decisions. Disclosures: Barosi: Novartis: Membership on an entity's Board of Directors or advisory committees. Vannucchi:Novartis: Honoraria.
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Harshman, Lauren Christine, Yu-Hui Chen, Glenn Liu, Michael Anthony Carducci, David Frazier Jarrard, Robert Dreicer, Noah M. Hahn et al. « Lower PSA at 7 months is prognostic for improved overall survival (OS) in metastatic hormone sensitive prostate cancer (mHSPC) treated with ADT with and without docetaxel (D). » Journal of Clinical Oncology 35, no 6_suppl (20 février 2017) : 137. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.137.
Résumé :
137 Background: Prior work from SWOG 9346 revealed that PSA ≤ 0.2 ng/dL at 7 months (mo) is prognostic for longer OS with ADT alone. We sought to evaluate if this optimal decline remained predictive of better OS when D was added to ADT for initial mHSPC treatment. Methods: We performed a landmark survival analysis at 7 mo using the E3805 database (NCT00309985). Inclusion required at least 7 mo of followup and PSA levels at 7 mo from ADT initiation. Survival was defined from ADT start or randomization to death. SWOG 9346 PSA nadirs of ≤ 0.2, > 0.2-4 and > 4 were used as classifiers. Results: 719 patients were eligible for analysis: 358 treated with ADT plus D and 361 with ADT alone. Median follow-up was 23.1 mo. On multivariable analysis (MVA), achieving a PSA ≤ 0.2 at 7 mo was more likely if the patient received D and had lower volume disease, prior local therapy, and lower baseline PSAs (all p ≤ 0.01). Across all patients, median OS was significantly longer if PSA at 7 mo reached ≤ 0.2 compared to > 4 (p < 0.0001) (Table). On MVA, PSA ≤ 0.2 at 7 mo and low volume disease were prognostic of longer OS (all p < 0.01). On ADT, 28.8% achieved a PSA ≤ 0.2 at 7 mo vs. 45.3% on ADT+D. Patients on ADT alone who achieved a PSA nadir ≤ 0.2 had the best survival. These patients were more likely to have low volume disease (56.7%) compared to the ADT + D pts (46.3%). Conclusions: Achieving PSA ≤ 0.2 at 7 mo remains prognostic for longer OS with ADT for mHSPC, whether administered alone or with D. Adding D to ADT increased the likelihood of a lower PSA and improved survival. Partial support and drug supply by Sanofi. Clinical trial information: NCT00309985. [Table: see text]
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Lammers-van der Holst, H. M., Y. Zhang, L. K. Barger, J. C. Wise, A. S. Murphy, B. M. Desnoyers, S. Qadri, J. M. Ronda et J. F. Duffy. « 0382 Sex Differences in Sleep and Quality of Life in Healthcare Shift Workers ». Sleep 43, Supplement_1 (avril 2020) : A146—A147. http://dx.doi.org/10.1093/sleep/zsaa056.379.
Résumé :
Abstract Introduction Shift work is associated with insufficient and disrupted sleep and impaired quality of life due to misalignment between the timing of internal biological clock and work/sleep schedule. There are reported sex differences in the circadian timing system, in sleep, and in reported sleep complaints, but how these impact female shift workers remains unclear. Furthermore, relatively little is known about sex differences in quality of life in shift workers. The objective of this study is to investigate sex differences in sleepiness, insomnia and quality of life in healthcare shift workers. Methods Forty women (31 ± 6.4 yo) and 70 men (31.2 ± 6.7 yo) who work at least 4 night shifts a month, completed the Shift Worker Sleep and Health Survey. This REDcap administered survey included the Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), and Functional Outcomes of Sleep Questionnaire (FOSQ-10). Independent samples T-tests were carried out using SAS. Results Women reported significantly higher scores on the ESS compared to men (13 ± 4 vs. 11 ± 3.4, respectively; t(108)=-2.74,P=0.007), as on the ISI (13 ± 5.2 vs. 9.8 ± 5.4; t(108)=-3.05,P=0.003), indicating greater levels of daytime sleepiness and insomnia-like symptoms in female shift workers. In addition, women scored significantly lower on the FOSQ-10 than men (13.9 ± 2.9 vs. 15.3 ± 2.5; t(108)=2.68,P=0.009), suggesting a lower functional status related to activities of daily living in female shift workers. Conclusion These preliminary analyses suggest that in this group of healthcare shift workers, women are less tolerant to irregular work hours compared to men, in terms of sleep, sleepiness and quality of life. Our future goal is to understand how sleep quality and duration, daytime sleepiness, and quality of life interact, and what role sex plays in those interactions. Support The study was supported by NIH grant R01 AG044416.
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Powles, Thomas, Ajjai Shivaram Alva, Mustafa Ozguroglu, Peter H. O'Donnell, Yohann Loriot, Tibor Csoszi, Jacqueline Vuky et al. « Post hoc pooled analysis of first-line (1L) pembrolizumab (pembro) for advanced urothelial carcinoma (UC) : Outcomes by response at week nine in KEYNOTE-052 and KEYNOTE-361. » Journal of Clinical Oncology 40, no 6_suppl (20 février 2022) : 519. http://dx.doi.org/10.1200/jco.2022.40.6_suppl.519.
Résumé :
519 Background: Pembro is a 1L treatment for cisplatin-ineligible pts with UC. This post hoc landmark analysis evaluated clinical outcomes by response at 9 wk to 1L pembro monotherapy in pts with advanced/unresectable or metastatic UC from the single-arm phase 2 KEYNOTE-052 (NCT02335424) and the randomized phase 3 KEYNOTE-361 (NCT02853305) trials. Methods: Cisplatin-ineligible pts with advanced UC were enrolled in KEYNOTE-052 and received pembro (200 mg Q3W for ≤2 y). Platinum-eligible pts with advanced UC who had not previously received systemic chemotherapy (chemo) were enrolled in KEYNOTE-361 and randomly assigned 1:1:1 to receive pembro (200 mg Q3W for ≤2 y), pembro + chemo (1000 mg/m2 gemcitabine on d1 and d8 + cisplatin [70 mg/m2] or carboplatin [AUC 5] on d1 of each 3-wk cycle), or chemo. The primary analysis group included pembro monotherapy–treated pts; the sensitivity analysis group included pembro monotherapy–treated pts from KEYNOTE-052 and the choice of carboplatin subpopulation of pembro monotherapy–treated pts from KEYNOTE-361. Landmark analyses of OS by pts with CR, PR, SD, or PD per RECIST v1.1 by BICR at first imaging assessment (wk 9) were pooled for the ITT populations. Duration of CR/PR/SD and OS were estimated using the Kaplan-Meier method. Data cutoffs were Sep 26, 2020 (KEYNOTE-052) and Apr 29, 2020 (KEYNOTE-361). Results: The primary analysis group included 681 pembro-treated pts (KEYNOTE-052, N = 374; KEYNOTE-361, N = 307); the sensitivity analysis group included 544 pembro-treated pts (KEYNOTE-052, N = 374; KEYNOTE-361, N = 170). Median time from randomization to cutoff was 51.9 mo (range, 22.0-65.3) and 53.7 mo (range, 22.0-65.3) for the primary and sensitivity analysis groups, respectively. Twenty-five pts (4.6%) had CR and 135 (24.6%) had PR (primary group); 17 pts (3.9%) had CR and 105 (24.1%) had PR (sensitivity group). Median DOR was 25.9 mo for pts with CR/PR at wk 9; pts with CR/PR or SD at wk 9 had longer OS than pts with PD at wk 9 (Table). Conclusions: In this post hoc analysis, pts with advanced UC in KEYNOTE-052 and KEYNOTE-361 with CR/PR at wk 9 had better clinical outcomes with pembro monotherapy than pts with SD or PD; 1L pembro monotherapy continues to show efficacy in advanced UC. Clinical trial information: NCT02335424 and NCT02853305. [Table: see text]
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Rodriguez, Lisette Patricia, Vida Farhangi, Julaine Braham, Robert A. Smith et Wilhelmine Wiese-Rometsch. « In-Hospital Glycemic Dysregulation Associated With Worse Outcomes in COVID-19 ». Journal of the Endocrine Society 5, Supplement_1 (1 mai 2021) : A346. http://dx.doi.org/10.1210/jendso/bvab048.705.
Résumé :
Abstract Introduction: Evidence establishes that COVID-19 patients with DM2 are at increased risk for severe disease and worse outcomes. Peer reviewed data is sparse comparing glycemic control and clinical outcomes among COVID-19 patients with vs. without DM2, and thus we sought to address this gap. Methods: We selected patients at least 18 years old who expired or were discharged between March 16, 2020 through September 15, 2020. Principal analysis compared glycemic patterns among patients with DM2 vs. non-DM2. Median, coefficient of variation (CV), maximum and minimum glucose parameters were computed to characterize longitudinal glycemic patterns. Logistic regression modeling identified significant (p<.05) associations between composite outcome vs. glycemic parameters and putative risks for progression to severe COVID-19. Receiver operating characteristic (ROC) curve identified cut points for glycemic parameters. Cox regression models were employed to control for significant confounders. Continuous data summarized as median was compared using Kruskal-Wallis test. Discrete data were compared with Pearson’s chi-square test. Two-tailed p<.05 was significant. Results: Among 494 patients, 157 (32%) had DM2 with no intergroup differences in age (68 [56–79]), sex (52% male, 48% female), or race (68% Caucasian, 19% Other, 13% African American). Insulin was administered to DM2 (93%) and non-DM2 (54%) patients (p<.0001). Comorbidities were more prevalent in DM2, including cardiovascular (68% vs. 54%, p=.003), renal (72% vs. 52%, p<.0001) and obesity (51% vs. 38%, p<.0001). Markers including D-dimer (0.98 [0.61–1.95] mg/L), lactate dehydrogenase (308 [230–392] U/L), ferritin (436 [174–856] ng/mL), and triglycerides (172 [109–239] mg/dL), were not different in DM2 vs. non-DM2 (p>.05). CRP was greater in patients with (8.6 [3.6–14.6]) vs. without (6.1 [2.0–12.6]) DM2 (p=.005). Baseline glucose in DM2 (163 [121–253] mg/dL) vs. non-DM2 (107 [96–124] mg/dL) was significantly greater, with former an independent predictor of composite outcome (p=.0005). Cox modeling of other glucose parameters in DM2 vs. non-DM2 demonstrated various impact regarding risk for composite outcome including median (155 [128–209], p=.46) vs. (103 [94–118], p=.09); coefficient of variation (28 [19–38], p=.08) vs. (15 [9–20], p=.002); maximum (252 [187–362], p=.0005) vs. (129 [110–156], p=.002); and minimum (99 [79–128], p=.95) vs. (89 [81–98], p=.02). The unified baseline glucose cut point for composite outcome risk controlled for significant covariates was 138 gm/dL (p<.0001), which included respectively 20% and 10% of patients with and without DM2. Conclusion: Glycemic dysregulation in COVID-19 patients is independently associated with ICU admission and/or hospital mortality. Presence of DM2 amplifies glycemic dysregulation, but risk stratification appears warranted in all COVID-19 patients.
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Tang, Junwang. « (Invited, Digital Presentation) Methane Conversion to High Value Chemicals By Photocatalysis ». ECS Meeting Abstracts MA2022-02, no 48 (9 octobre 2022) : 1815. http://dx.doi.org/10.1149/ma2022-02481815mtgabs.
Résumé :
As underlined in the COP26, methane as a greenhouse gas is nearly 80 time more potent than CO2 while its reserve is much more than the sum of coal, oil and natural gas. Thus methane conversion not only involves the environmental issue but also is related to high-value chemical production /clean energy supply, which has been attracting substantial interest over the last decades. However CH4 activation is energy intensive and kinetically very challenging so that methane activation is regarded as the “holy grail” in the catalytically chemical process. [1] Photocatalysis provides a cost efficient potential to activation of such small molecule under very mild conditions, while to achieve the potential is a huge challenge.[2] Stimulated by our research outcomes on the charge dynamics in inorganic semiconductor photocatalysis, which reveal that the low reaction efficiency is due to both fast charge recombination and large bandgap of an inorganic semiconductor [3,4], together with the recent findings on atomic catalysis [5], we developed novel material strategies for photocatalytic methane conversion to methanol. Highly dispersed atomic level iron species immobilised on a TiO2 photocatalyst show an excellent activity for methane conversion, resulting into ~97% selectivity towards alcohols operated under ambient conditions by a one-step chemical process [6]. Such photocatalyst is also very stable, promising an attractive industrial process of methane upgrade. The dominating function of the iron species has also been investigated in detail. Furthermore, we designed a flow system for relatively efficient methane to C2, achieving the benchmark results in this area.[7] In addition, C1 oxygenates can be produced with nearly 100% by photocatalytic methane conversion due to the synergy between Au and Cu cocatalysts loaded on ZnO.[8] References ： Li, X. Wang, C., Tang, J. Nature Reviews Materials , 2022, Doi: 1038/s41578-022-00422-3. Wang Y., Suzuki H., Xie, J., Tomita, O., Martin, D. J., Higashi, M., Kong, D., Abe R. Tang, J., Chem. Rev., 2018, 118: 5201-5241. Tang, J. Durrant J. R., Klug, R ., J. Am. Chem. Soc ., 2008, 130(42) : 13885-13891. Miao, T., Wang, C., Xiong, L., Li, X., Xie, X., Tang, J., ACS Catalysis , 2021, 11, 8226-8238. Wang, A. Li J., Zhang. T., Nat . Rev. Chem ., 2018, 2; 65-81. Xie, J., Jin, R. ,Li, A., Bi, Y., Sankar, G. , Ma , Tang, J. Nature Catalysis , 2018, 1: 889-896. Li, X., Xie J.,Rao, H., Wang, , Tang, J., Angewandte Chemie International Edition , 2020, 132: 19870-19875. Luo, L., Gong, Z., Xu, Y., Ma, J., Liu, H., Xing, J., Tang, J., Journal of the American Chemical Society , 2022, 144, 2, 740–750.
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Maksymowych, W. P., U. Weber, X. Baraliakos, P. Machado, S. Juhl Pedersen, J. Sieper, S. Wichuk et al. « POS0032 SCORING MRI STRUCTURAL LESIONS IN SACROILIAC JOINTS OF PATIENTS WITH AXIAL SPONDYLOARTHRITIS : HOW MANY SLICES ARE OPTIMAL ? » Annals of the Rheumatic Diseases 80, Suppl 1 (19 mai 2021) : 221.1–221. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3427.
Résumé :
Background:There is no international consensus on the optimal number of slices for evaluation of MRI structural lesions in the SIJ. An “all slice” method evaluates lesions from the most anterior slice, defined as the first slice with vertical height of ≥1cm of the SIJ joint cavity, up to the most posterior slice, defined as the most posterior slice where ≥1cm vertical height of the cartilaginous portion is still visible. The SPARCC method scores the transitional slice between cartilaginous and ligamentous compartments as the first slice and then an additional 4 slices anterior to the transitional slice.Objectives:We aimed to investigate inter-reader reliability, the extent of detection of lesions, and frequency of cases with a positive MRI for structural lesions when using an “all slice” approach versus the SPARCC scoring of 5 central slices.Methods:MRI T1W images with DICOM series were available from 148 cases who had MRI performed in the ASAS-Classification Cohort. Seven central readers recorded MRI lesions in an eCRF that recorded global assessments of presence/absence of changes suggestive of axSpA and structural lesions typical of axSpA. Structural lesions per the ASAS definitions were also recorded in consecutive semicoronal slices using the “all slice” approach, but also recording the transitional slice, according to their presence/absence in SIJ quadrants (erosion, fat lesion, sclerosis) or halves (backfill, ankylosis). Structural lesion frequencies were assessed descriptively according to majority agreement (≥4/7) of central readers and also any 2 central readers. Reliability for detection of MRI lesions was compared between central and local readers using the ICC.Results:The mean (SD) (range) number of anterior and posterior slices peripheral to the 5 central slices was 1.0 (1.0) (0-4) and 2.2 (1.8) (0-6) per case, respectively. There were 2 cases (1.4%) where ≥2 readers scored structural lesions in peripheral slices but not in the 5 central slices. The mean percentage of the total structural lesion score that was captured by the 5 central slices was >75% for all types of lesions except ankylosis (59%) (Table 1). Inter-reader reliability was greater for all lesions when assessing the 5 central slices and especially for erosion and backfill (Table 1).Conclusion:The major component of structural lesion data is captured by assessment of 5 slices, which includes the transitional slice and the subsequent 4 anterior slices. Moreover, reliability for detection of structural lesions is substantially worse in peripheral slices.MRI Lesion“All slice”Central 5 slicesPeripheral slicesP value central vs peripheral slicesP value“all slice” vs central slicesMean (SD) Lesion Score Per CaseErosion2.4 (4.5) (0-22.9)1.8(3.4) (0-17.1)0.6 (1.4) (0-10.1)<0.001< 0.001Fat lesion2.5 (5.9) (0-34.0)1.8 (4.5) (0-25.1)0.7 (1.8) (0-9.9)< 0.001<0.001Sclerosis2.0 (4.9) (0-39.0)1.5 (3.6) (0-26.1)0.5 (1.5) (0-12.9)< 0.001<0.001Backfill0.5 (1.5) (0-12)0.4 (1.2) (0.0-9.3)0.1 (0.4) (0-2.7)< 0.0010.84Ankylosis0.5 (3.4) (0-30.7)0.3 (2.3) (0-20.0)0.2 (1.2) (0-11.3)0.100.18Mean (SD) (Range) % of Total Lesion Score in Central vs Peripheral slicesErosion100%76.4% (28.9%) (0-100%)23.6% (28.9%) (0-100%)<0.001NAFat lesion100%75.4% (26.5%) (0-100%)24.6% (26.5%) (0-100%)<0.001NASclerosis100%79.5% (22.9%) (0-100%)20.5% (22.9%) (0-100%)<0.001NABackfill100%86.0% (20.2%) (0-100%)14.0% (20.2%)(0-100%)<0.001NAAnkylosis100%59.0% (36.4%) (0-100%)41.0% (36.4%) (0-100%)0.56NAICC of 7 readers (Mean (SD) (Range))MRI lesionAll slicesCentral 5 slicesPeripheral slicesErosion0.54 (0.15) (0.28-0.84)0.58 (0.13) (0.34-0.85)0.40 (0.17) (0.10-0.66)Fat lesion0.61 (0.18) (0.30-0.89)0.63 (0.16) (0.35-0.88)0.52 (0.20) (0.19-0.82)Sclerosis0.73 (0.18) (0.36-0.94)0.73 (0.16) (0.36-0.91)0.67 (0.19) (0.27-0.94)Backfill0.37 (0.21) (0.10-0.85)0.39 (0.19) (0.14-0.83)0.18 (0.23) (0.0-0.80)Ankylosis0.97 (0.02) (0.91-0.99)0.99 (0.01) (0.97-1.0)0.85 (0.10) (0.62-0.98)Disclosure of Interests:None declared.
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De Lima, José Ayron Moraes, Elizanilda Ramalho Do Rêgo, Joabe Freitas Crispim, Witalo da Silva Sales, Eliane Cristina Arcelino, Mailson Monteiro Do Rêgo, Angela Maria dos Santos Pessoa et Sabrina Trajano Pereira Da Silva. « Diversidade e seleção em população segregante de pimenteiras ornamentais (Capsicum annuum L.) ». OBSERVATÓRIO DE LA ECONOMÍA LATINOAMERICANA 21, no 12 (4 décembre 2023) : 23486–99. http://dx.doi.org/10.55905/oelv21n12-002.
Résumé :
O crescente interesse por pimenteiras ornamentais é motivado pela grande variedade observada em uma série de características, incluindo tamanho, folhagem, cor do fruto e arquitetura apropriada. Por meio da caracterização morfológica, é possível acessar a diversidade genética de um acervo de um banco de germoplasma que estão disponíveis para uso em programas de melhoramento genético. Portanto, o presente trabalho teve como objetivo avaliar a diversidade genética dentro em geração F2 em pimenteira ornamental (Capsicum annuum L) e indicar genótipos para a abertura de linha em geração F3. O experimento foi realizado em casa de vegetação, no Laboratório de Biotecnologia Vegetal, do Centro de Ciências Agrárias da Universidade Federal da Paraíba (CCA-UFPB), no município de Areia – PB. Os tratamentos foram constituídos de 354 progênies de uma geração F2 de pimenteiras ornamentais (Capsicum annuum L.), pertencentes ao Banco de Germoplasma do gênero Capsicum da UFPB, UFPB390 x UFPB137 seguindo o método do pedigree. Para a caracterização morfoagronômica, foram considerados 20 caracteres quantitativos. A análise de diversidade foi por meio de distância euclidiana média padronizada com posterior agrupamento de Tocher. Além disto, foi realizada a análise de importância de caracteres pelo método de Singh. Todas as análises foram realizadas com o programa computacional Genes. O método de otimização de Tocher, baseado na Distância Euclidiana Média Padronizada, separou os genótipos em 9 grupos. Pelo método de Singh (1981), determinou-se que nove das vinte características contribuíram com 70,80% da divergência genética total, sendo elas o peso do fruto, largura da copa, comprimento do fruto, número de sementes por fruto, comprimento do pedicelo e menor diâmetro do fruto. As demais características (onze) contribuíram com apenas 24,83%, destacando-se os caracteres, diâmetro do caule, maior diâmetro do fruto e peso da matéria fresca que menos contribuíram, sendo 0,72%, 0,560% e 0,55% respectivamente. As plantas 1, 3, 13, 17, 53, 105, 132, 139, 164, 296, 188, 324, 354. são indicadas para seleção para uso em programas de melhoramento genético visando uso para ornamental porque apresentam particularidade nas características desejaveis para uso em ornamental e pertencerem a diferentes grupos.
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Jasonsmith, J. F., W. Maher, A. C. Roach et F. Krikowa. « Selenium bioaccumulation and biomagnification in Lake Wallace, New South Wales, Australia ». Marine and Freshwater Research 59, no 12 (2008) : 1048. http://dx.doi.org/10.1071/mf08197.
Résumé :
Selenium concentrations were measured in water, sediments and organisms inhabiting a freshwater coal power station cooling reservoir. Se concentrations found were: water, 1.9 ± 2 μg L–1; sediment, 7 ± 1 μg g–1; phytoplankton, 3.4 μg g–1; zooplankton, 5.3 μg g–1; epiphytic algae, 1.3 ± 0.2 μg g–1; benthic algae, 8 ± 2 μg g–1; macrophyte leaves, 2.7–2.8 μg g–1; macrophyte roots, 0.5–6.5 μg g–1; detritus, 10 μg g–1; Oligochaeta, 11 μg g–1; Corbiculidae, 1.1 μg g–1; Insects, 3.7–8.3 μg g–1; Gastropoda, 3.2 μg g–1; Crustacea, 3.1–6 μg g–1; whole fish, 2.2–13 μg g–1; and fish liver, 134–314 μg g–1. Bioconcentration factors were similar to those found in aquatic ecosystems with comparable Se concentrations in the water column. A food web was constructed with four main food chains (phytoplankton, epiphytic algae, benthic algae and sediment/detrital), with fish fed from multiple pathways. Biomagnification only occurs along food chains for flathead gudgeons and rainbow trout. Se concentrations in food sources were above the 3 μg g–1 dietary Se level considered to induce teratogenesis in fish spawning. Flathead gudgeons were found to be suffering teratogenesis and rainbow trout showed no evidence of teratogenesis.
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Carrenho-Sala, L. C., A. Garcia-Guerra, R. V. Sala, M. Fosado, D. C. Pereira, A. Lopez, J. F. Moreno et M. C. Wiltbank. « 102 UNILATERAL AND BILATERAL TRANSFER OF 2IN VITRO-PRODUCED EMBRYOS INCREASES PREGNANCY LOSS BETWEEN 30 AND 60 DAYS ». Reproduction, Fertility and Development 29, no 1 (2017) : 159. http://dx.doi.org/10.1071/rdv29n1ab102.
Résumé :
Fertility of in vitro-produced embryos is affected by embryo stage and quality. Embryos quality 1 and stage 7 result in higher fertility than embryos of earlier stages and/or lower quality. The objective was to evaluate the effect of unilateral and bilateral transfer of 2 in vitro-produced embryos of earlier stages and/or poor quality on fertility. Heifers were synchronized using a 5-day CIDR Synch or 2 prostaglandin F2α injections 14 days apart followed by oestrus detection. Embryo transfer was performed 7 ± 1 day after gonadotropin-releasing hormone/oestrus and heifers were assigned randomly to 1 of 3 groups: single embryo ipsilateral to the corpus luteum (single; n = 188); 2 embryos in the uterine horn ipsilateral to the corpus luteum (unilateral; n = 138); 2 embryos bilaterally (bilateral; n = 128). Embryos stage 4 to 8 and quality 1 or 2 were randomly assigned to treatment groups. All embryos were 7-day fresh in vitro-produced embryos, and pregnancy diagnosis was performed by ultrasonography on Days 32 and 60. Data were analysed by logistic regression. Conception rates on Days 32 and 60 were not different (P > 0.10) between heifers receiving a single embryo [Day 32 = 30.9% (58/188) and Day 60 = 25% (47/188)] or those receiving 2 embryos [Day 32 = 36.5% (97/266) and Day 60 = 22.2% (59/266)]. However, pregnancy loss between Days 32 and 60 was greater (P < 0.01) in heifers with 2 embryos (39.2%; 38/97) than in those with a single embryo (18.9%; 11/58). Conception rate on Day 32 was not different between groups (P = 0.4) and was 30.9% (58/188) for single, 36.9% (51/138) for unilateral, and 35.9% (46/128) for bilateral. Similarly, there was no difference (P = 0.8) in conception rates on Day 60, single = 25% (47/188), unilateral = 23.9% (33/138), and bilateral= 20.3% (26/128). However, there was an effect of group on pregnancy loss between Days 32 and 60 (P = 0.04). Losses were higher (P = 0.01) in the bilateral group [43.5% (20/46)] compared with the single group [18.9% (11/58)], and the unilateral group was intermediate [35.3% (18/51)] and tended to be different from the single group (P = 0.1). Interestingly, when pregnancy loss was compared between heifers with twin or single pregnancies, as determined by ultrasonography, and regardless of the number of embryos transferred or their location, twin pregnancies had a greater pregnancy loss [62.1% (18/29)] compared with single pregnancies [24.6% (31/126); P < 0.01]. For twin bearing heifers, as determined by ultrasonography on Day 32, pregnancy loss did not differ between unilateral (62.5%; 10/16) and bilateral (61.5%; 8/13) transfers (P = 0.9). Similarly, there was no difference (P = 0.2) for heifers with single embryo pregnancies: single (18.9%; 11/58), unilateral (22.9%; 8/35), bilateral (36.4%; 12/33), although bilateral transfer of 2 embryos tended to be higher than single (P = 0.07). Transfer of 2 low quality in vitro-produced embryos results in similar conception rates, although pregnancy losses are greater. Interestingly, only 30% (29/97) of the pregnancies from heifers that received 2 embryos contained twins, indicating the loss of one of the embryos before Day 32. Furthermore, the increased losses observed with the transfer of 2 embryos were attributed to those heifers in which twin pregnancies were diagnosed on Day 32 regardless of distribution.
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Hill, Timothy A., Jennette A. Sakoff, Phillip J. Robinson et Adam McCluskey. « Parallel Solution-Phase Synthesis of Targeted Tyrphostin Libraries with Anticancer Activity ». Australian Journal of Chemistry 58, no 2 (2005) : 94. http://dx.doi.org/10.1071/ch04143.
Résumé :
The combination of semi-automation, an elegant synthesis, and parallel solution-phase synthesis approaches has allowed the development of five targeted, symmetrical tyrphostin compound libraries. These libraries on average are comprised of 12 compounds. Notwithstanding this, low micromolar potent growth inhibitors against HT29 (colorectal carcinoma) and G401 (renal carcinoma) cell lines were discovered. Additionally, significant SAR data was obtained. We noted that the most potent growth inhibitory activity was consistently observed for those analogues that possessed a 2-chlorophenyl (for 10: GI50 HT29 5.5 ± 0.4 μM, GI50 G401 2.6 ± 0.4 μM; for 23: GI50 HT29 2.4 ± 0.2 μM, GI50 G401 1.9 ± 1 μM; for 34: GI50 HT29 8.8 ± 3.1 μM, GI50 G401 6.2 ± 2.9 μM; for 46: GI50 HT29 5.2 ± 0.9 μM, GI50 G401 3.7 ± 0.6 μM; for 57: GI50 HT29 4.6 ± 0.8 μM, GI50 G401 2.1 ± 0.2 μM), a 3-chlorophenyl (for 11: GI50 HT29 3.8 ± 0.7 μM, GI50 G401 1.7 ± 0.7 μM; for 48: GI50 HT29 5.9 ± 0.1 μM, GI50 G401 3.4 ± 0.6 μM; for 58: GI50 HT29 4.8 ± 0.9 μM, GI50 G401 3.4 ± 0.2 μM), or a 3-methoxyphenyl substituent (for 13: GI50 HT29 7.4 ± 3.8 μM, GI50 G401 2.8 ± 0.5 μM; for 26: GI50 HT29 4.5 ± 0.5 μM, GI50 G401 4.9 ± 1 μM; for 37: GI50 HT29 3.7 ± 0.2 μM, GI50 G401 1.6 ± 0.2 μM; for 49: GI50 HT29 3.7 ± 0.4 μM, GI50 G401 3.4 ± 0.2 μM; for 60: GI50 HT29 4.1 ± 0.6 μM, GI50 G401 1.8 ± 0.3 μM). Finally, we noted that increasing the distance between the terminal aromatic rings had only a minimal effect on the 2-, 3-chlorophenyl, and 3-methoxyphenyl analogues, but did have a favourable effect on OH, COOH, and multiply substituted analogues.
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Gogate, Anagha, Amanda Crosbie, Trong Kim Le, Ying Zhang, Rolee Das et Catherine Davis. « Abstract P3-12-15 : Clinical characteristics, treatment patterns, and survival outcomes in women with early triple-negative (TN) or hormone receptor-positive/human epidermal growth factor receptor-2 negative (HR+/HER2−) breast cancer (BC) in the real-world (RW) setting ». Cancer Research 82, no 4_Supplement (15 février 2022) : P3–12–15—P3–12–15. http://dx.doi.org/10.1158/1538-7445.sabcs21-p3-12-15.
Résumé :
Abstract Background: BC remains the most commonly diagnosed cancer for women. TNBC is an aggressive form with a poorer prognosis compared with other subtypes. Neoadjuvant therapy (NAT) is the standard-of-care approach to shrink tumors in the breast and axilla and to improve patient outcomes. Few RW studies exist of US patients with early BC (eBC); this study aimed to describe clinical parameters by receipt of systemic therapy and to assess overall survival (OS) and progression-free survival (PFS) after NAT and adjuvant therapy (AT) in women with early HR+/HER2− or TNBC using RW evidence in the US. Methods: This retrospective observational study used the Flatiron Health nationwide electronic health record-derived de-identified database, including women ([pts], age ≥18 years) diagnosed with early HR+/HER2− BC or TNBC between 01/01/2011 and 05/31/2018. The primary outcome was to describe pt demographics, clinical characteristics, and treatment patterns. Secondary outcomes included OS and PFS. Results: Of the pts identified for inclusion (N = 5,299), 13.3% (n = 707) were diagnosed with early TNBC and 86.7% (n = 4,592) with HR+/HER2− eBC, of whom 34.7% (n = 245) and 10.9% (n = 502), respectively, did not receive systemic therapy (Table). Systemically treated pts with TNBC vs HR+/HER2− tended to be younger (59.0 years vs 64.0 years); were represented by a higher proportion of Black women (18.0% vs 7.2%); had a greater proportion presenting with invasive ductal carcinoma (IDC) (91.6% vs 78.2%); had a higher proportion with progression to metastasis (19.0% vs 5.7%) and presented with a more aggressive disease (Grade 3) at diagnosis (79.0% vs 18.4%). Most pts (98.4%) received surgery, predominantly breast-conserving surgery (BCS; unilateral lumpectomy: 62.8%); however, 17.8% received bilateral mastectomies. Overall, 9.1% of pts received NAT. More pts with TNBC vs HR+/HER2− received NAT (34.0% vs 7.9%) and achieved a pathologic complete response (pCR; 36.3% vs 6.2%). Consistent with treatment guidelines, pts with TNBC were treated with chemotherapy (CT)-doublet or single-agent regimens and pts with HR+/HER2− received hormone and CT-based regimens. Duration of NAT was similar for both subtypes (3.3 months) but was shorter for AT in pts with TNBC vs HR+/HER2− (3.4 vs 38.2 months). From initial diagnosis, the 36-month survival probability [standard error] was lower for systemically treated pts with TNBC vs HR+/HER2− (85.7% [1.8%] vs 95.6% [0.3%]) and from start of therapy by line setting (NAT: 80.6% [3.5%] vs 91.9% [1.7%]; AT: 84.7% [2.2%] vs 95.8% [0.4%]). Similarly, the 36-month PFS probability was lower for pts with TNBC vs HR+/HER2− from diagnosis (77.9% [2.1%] vs 93.3% [0.4%]) and from start of therapy by line setting (NAT: 68.7% [4.1%] vs 85.2% [2.1%]; AT: 79.5% [2.5%] vs 93.5% [0.4%]). Conclusion: This analysis of US RWE further confirms early TNBC to be a particularly aggressive form of BC, with poorer survival compared with pts with HR+/HER2− eBC. While these RW data indicate BCS is becoming more routine, almost one-fifth of pts still receive bilateral mastectomies. Overall, these data confirm there remains a high unmet need to reduce the need for aggressive treatments while further improving outcomes in pts with early TNBC and HR+/HER2− BC. Table: Patient demographics, clinical characteristics, OS and PFSPatient selection criteriaNumber of patients, n (%)SubgroupsEarly HR+/HER2− BC4,592 (86.7)Patients who received systemic therapy4,090 (89.1)Early TNBC707 (13.3)Patients who received systemic therapy462 (65.3)All patients [1] (N = 5,299), n (%)Systemically treated patients with early HR+/HER2− BC (n = 4,090), n (%)Systemically treated patients with early TNBC (n = 462), n (%)Patient demographicsMedian age (years)64.064.059.0RaceBlack or African American449 (8.5)294 (7.2)83 (18.0)White3,602 (68.0)2,835 (69.3)283 (61.3)Asian139 (2.6)111 (2.7)9 (1.9)Hispanic or Latino15 (0.3)12 (0.3)1 (0.2)Clinical characteristicsHistology at initial diagnosisIDC4,222 (79.7)3,197 (78.2)423 (91.6)ILC684 (12.9)612 (15.0)7 (1.5)Infiltrating ductal mixed and infiltrating lobular mixed132 (2.5)108 (2.6)3 (0.6)Mucinous adenocarcinoma97 (1.8)88 (2.2)0 (0.0)Other [2]122 (2.3)63 (1.5)26 (5.6)Unknown/ND42 (0.8)22 (0.5)3 (0.6)Tumor grade at initial diagnosisGrade 11,350 (25.5)1,161 (28.4)5 (1.1)Grade 22,462 (46.5)2,098 (51.3)88 (19.0)Grade 31,374 (25.9)752 (18.4)365 (79.0)Unknown/ND113 (2.1)79 (1.9)4 (0.9)Surgery at initial diagnosisYes5,215 (98.4)4,032 (98.6)450 (97.4)Surgery type [3]Unilateral lumpectomy3,277 (62.8)2,568 (63.7)241 (53.6)Unilateral mastectomy1,168 (22.4)883 (21.9)128 (28.4)Bilateral lumpectomy75 (1.4)61 (1.5)5 (1.1)Bilateral mastectomy927 (17.8)713 (17.7)89 (19.8)Treatment line settingNumber of patients who received NAT481 (9.1)324 (7.9)157 (34.0)Number of patients who received AT4,263 (80.4)3,949 (96.6)314 (68.0)pCR to NATAchieved pCR77 (16.0)20 (6.2)57 (36.3)OSFrom initial diagnosis: survival probability at Month 36, % (SE)94.0 (0.4)95.6 (0.3)85.7 (1.8)From NAT: survival probability at Month 36, % (SE)88.3 (1.6)91.9 (1.7)80.6 (3.5)From AT: survival probability at Month 36, % (SE)94.9 (0.4)95.8 (0.4)84.7 (2.2)PFSFrom initial diagnosis: progression-free probability at Month 36, % (SE)91.3 (0.4)93.3 (0.4)77.9 (2.1)From NAT: progression-free probability at Month 36, % (SE)79.9 (2.0)85.2 (2.1)68.7 (4.1)From AT: progression-free probability at Month 36, % (SE)92.5 (0.4)93.5 (0.4)79.5 (2.5)Duration of treatment, Months (n)Median duration of NAT3.3 (481)3.3 (324)3.3 (157)Median duration of AT35.3 (4263)38.2 (3,949)3.4 (314)[1] All patients includes both patients systemically treated and systemically untreated. [2] Other includes Inflammatory, Papillary, Metaplastic, Medullary and Tubular histologies. [3] Patient may have received more than one surgery. AT, adjuvant therapy; IDC, invasive ductal carcinoma; NAT, neoadjuvant therapy; ND, not documented; SE, standard error. Citation Format: Anagha Gogate, Amanda Crosbie, Trong Kim Le, Ying Zhang, Rolee Das, Catherine Davis. Clinical characteristics, treatment patterns, and survival outcomes in women with early triple-negative (TN) or hormone receptor-positive/human epidermal growth factor receptor-2 negative (HR+/HER2−) breast cancer (BC) in the real-world (RW) setting [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-15.
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Joseph, S. A., et D. W. Walker. « Monoamine concentrations in cerebrospinal fluid of fetal and newborn sheep ». American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 266, no 2 (1 février 1994) : R472—R480. http://dx.doi.org/10.1152/ajpregu.1994.266.2.r472.
Résumé :
Monoamine concentrations were measured in cisternal cerebrospinal fluid (CSF) of unanesthetized fetal (115-135 days gestation) and newborn (2-34 days old) sheep. Norepinephrine (NE) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations decreased with gestational age; NE CSF concentrations were significantly higher in the newborn (336.4 +/- 61.7 pg/ml; n = 5) compared with the 131- to 135-day-gestation fetuses (104.0 +/- 46.3 pg/ml, n = 3; P < 0.05). Dopamine (DO), homovanillic acid (HVA), and serotonin (5-HT) concentrations in fetal CSF did not change with gestational age, and epinephrine (Epi) was undetectable in most fetal and newborn samples. Hypoxia, induced by giving the ewe 9% O2 in N2 to breathe for 30 min, resulted in a 10.78 +/- 3.94-fold (n = 5) increase of NE concentration in fetal CSF (P < 0.05); DO and DOPAC concentrations did not change. Hypoxia did not increase NE concentrations in CSF of newborn lambs. Inhibition of prostaglandin (PG) synthesis by intravenous infusion of indomethacin significantly reduced plasma prostaglandin E2 concentrations from 7.8 +/- 1.0 (n = 6) to 2.5 +/- 0.2 nmol/l (n = 3; P < 0.05), and was associated with an increase of CSF DOPAC concentrations from 2,156.3 +/- 504.5 (n = 9) to 5,453.6 +/- 1,091.3 pg/ml (n = 5; P < 0.05); NE and DO concentrations did not change significantly. These results show that catecholamines and indoleamines are released in the brain and enter the CSF of fetal sheep from at least 115 days gestation. The data also show that concentrations of some monoamines in CSF are changed by fetal hypoxia or prostaglandin synthesis.
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Redeker, I., S. Moustakis, S. Tsiami, X. Baraliakos, I. Andreica, B. Buehring, J. Braun et U. Kiltz. « AB0823 TREATMENT WITH ADALIMUMAB IN PATIENTS WITH CHRONIC INFLAMMATORY RHEUMATIC DISEASES : A STUDY OF TREATMENT TRAJECTORIES ON A PATIENT LEVEL IN CLINICAL PRACTICE ». Annals of the Rheumatic Diseases 80, Suppl 1 (19 mai 2021) : 1435.2–1436. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1838.
Résumé :
Background:There is evidence that drug retention rates to adalimumab (ADA) in patients (pts.) with chronic inflammatory rheumatic diseases (CIRD) are impaired by loss of efficacy and adverse events, and that about 50% of users had discontinued ADA within 5 years (1). With the introduction of ADA biosimilars in October 2018, non-medical switching from originator to ADA biosimilars is now increasingly part of daily practice in rheumatologic care.Objectives:The aim was to study treatment trajectories over two years in pts. with CIRD receiving originator ADA.Methods:Pts. with CIRD on originator ADA who switched to ADA biosimilar from October 2018 onwards were identified and followed until 2020. Disease activity (ASDAS), physical function (HAQ, BASFI), and changes in treatment were documented every 3 months. The four predefined treatment trajectories “continued ADA biosimilar therapy”, “back-switch to originator ADA therapy”, “switch to other biological (b) disease modifying anti-rheumatic drug (DMARD) therapy”, and “stopped bDMARD therapy /death /drop out” were used to compare characteristics of pts. with different trajectories.Results:A total of 111 CIRD pts. on treatment with originator ADA were switched to ADA biosimilar (Table 1). The majority of pts. 75 continued therapy with ADA biosimilar (Figure 1 next page) while 16% switched back to originator ADA, 7% switched to a different bDMARD, and 9% either stopped treatment (n=9) or died (n=1). Pts. who continued ADA biosimilar were more frequently male, older or with a longer disease duration than those who switched therapy back to originator ADA and those who switched to a different bDMARD (Table 1). The previous duration on originator ADA treatment was increased in patients who continued ADA biosimilar compared to those who switched therapy back to originator ADA and those who switched to a different bDMARD. There was more functional impairment (HAQ, BASFI) and higher disease activity (ASDAS) in pts. who switched compared to those who continued ADA biosimilar therapy (Table 1). Treatment with csDMARDs and glucocorticoids was increased in pts. who continued ADA biosimilar therapy, while pts. who switched therapy had more previous bDMARD therapies (Table 1).Table 1.Characteristics of patients at baseline for the entire group and stratified by treatment trajectoryTotal groupN=111 (100%)Treatment trajectorycontinued ADA biosimilar therapyN=75 (67.6%)back-switch to originator ADA therapyN=18 (16.2%)switch to different bDMARD therapyN=8 (7.2%)no bDMARD therapy /death /drop outN=10 (9.0%)Age, y51.2 (14.5)51.5 (13.6)50.6 (16.8)43.5 (9.5)56.4 (19.0)Women, No. (%)46 (41.4)27 (36.0)9 (50.0)6 (75.0)4 (40.0)RA23 (20.7)17 (22.7)2 (11.1)1 (12.5)3 (30.0)axSpA68 (61.3)47 (62.7)11 (61.1)6 (75.0)4 (40.0)PsA15 (13.5)7 (9.3)4 (22.2)1 (12.5)3 (30.0)Other diagnoses5 (4.5)4 (5.3)1 (5.6)0 (0.0)0 (0.0)Disease duration, median (IQR), y5.0 (2.0-8.0)5.0 (2.0-9.0)3.5 (2.0-6.0)2.0 (1.0-5.5)4.5 (2.0-8.0)Duration previous originator ADA therapy40.7 (27.7)45.3 (27.8)35.0 (25.2)20.3 (24.7)32.3 (25.1)DAS283.0 (1.0)2.9 (1.0)3.4 (1.0)-3.3 (1.2)CRP, median (IQR), mg/L0.2 (0.1-0.3)0.1 (0.1-0.2)0.2 (0.0-0.5)0.2 (0.2-1.3)0.3 (0.2-0.4)HAQ score1.3 (0.8)1.1 (0.7)1.7 (0.8)-1.8 (1.0)ASDAS2.2 (1.1)2.0 (1.0)3.0 (1.2)2.7 (0.9)2.3 (0.2)BASFI3.5 (2.6)3.0 (2.5)5.4 (2.4)3.4 (1.6)5.4 (1.6)+values are given as mean (SD)Conclusion:Two thirds of pts. who switched to ADA biosimilar remained on this therapy for 2 years. As many as 16% of pts. switched back to ADA originator. Whether or to what degree this was influenced by nocebo effects needs further study. The same is true for the effect of functional impairment – it would be interesting to know whether this was due to inflammation or structural damage.References:[1]Neovius M et al. Ann Rheum Dis 2015; 74:354-360[2]The study was funded by Hexal Germany.Figure 1.Treatment trajectories of ADA therapy in patients with CIRD during two years ADA: adalimumab; bDMARD: biological disease modifying anti-rheumatic drug.Disclosure of Interests:None declared
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Lee, Donna, et Preeti Kishore. « Pituitary Metastasis Presenting With Central Diabetes Insipidus and Panhypopituitarism ». Journal of the Endocrine Society 5, Supplement_1 (1 mai 2021) : A601. http://dx.doi.org/10.1210/jendso/bvab048.1225.
Résumé :
Abstract Background: Metastatic involvement of the pituitary gland and infundibular stalk is rare, accounting for about 2% of all diagnosed pituitary masses. Although primary tumors from almost every organ have been reported, breast and lung cancers are the most common primary tumors to metastasize to the pituitary gland. The clinical presentation varies and can include headache, visual impairment, diabetes insipidus, and panhypopituitarism. The posterior lobe of the pituitary is more susceptible to metastatic involvement than the anterior lobe due to its direct blood supply from the systemic circulation, whereas the anterior lobe is supplied by the hypophyseal portal system. Additionally, the smaller posterior lobe can be destroyed with less metastatic volume, allowing for earlier manifestation of symptoms. Clinical Case: An 81-year-old woman with a history of Stage IIA ER+ IDC of the left breast status post lumpectomy and axillary lymph node dissection in 1999 followed by mastectomy in 2009 due to local recurrence presented with confusion for two weeks. At the time, she had known lung metastases and was on palliative chemotherapy. CT head showed a 1.8 cm and 2.3 cm calvarial lytic lesion in the right occipital bone and at the vertex, respectively. MRI brain/pituitary revealed a well-circumscribed, enhancing suprasellar mass measuring 9 x 10 mm likely involving the pituitary infundibulum and hypothalamus with mass effect on the optic chiasm. Laboratory results were consistent with secondary adrenal insufficiency, central hypothyroidism, and hypogonadotropic hypogonadism. Prolactin was mildly elevated due to stalk effect. The patient also had hypernatremia and inappropriately low urine osmolality, which nearly tripled after administration of desmopressin, confirming central diabetes insipidus. She was subsequently started on hydrocortisone, levothyroxine, and desmopressin. Laboratory Results: Prolactin 30.47 (reference range 4.79-23.3 mIU/mL), IGF-1 88 (17-193 ng/mL), 7am ACTH 3.4 (7.2-63.3 pg/mL), 7am cortisol 0.6 (6.2-29 µg/dL), TSH 3.03 (0.47-6.9 U/L), FT4 0.351 (0.75-2 ng/dL), FSH 0.2 (25.8-134.8 mIU/mL), LH <0.1 (7.7-58.5 mIU/mL), estradiol <5 (5-138 pg/mL); before desmopressin: Na 154 (reference range 135-145 mEq/L), urine osm 162 (50-1,200 mOsm/kg); after desmopressin: Na 143 (reference range 135-145 mEq/L), urine osm 469 (50-1,200 mOsm/kg) Conclusion: While pituitary metastases remain rare, their prevalence is expected to increase due to more sensitive biochemical tests and imaging techniques coupled with advances in cancer therapy that help patients with metastatic disease live longer. Interesting in our case is the patient’s age, which is significantly older than the median age reported in the literature, and her presentation with total anterior and posterior pituitary insufficiency after a prolonged oncologic course marked by progression of disease.
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Klein Goldewijk, Kees, Arthur Beusen, Jonathan Doelman et Elke Stehfest. « Anthropogenic land use estimates for the Holocene – HYDE 3.2 ». Earth System Science Data 9, no 2 (1 décembre 2017) : 927–53. http://dx.doi.org/10.5194/essd-9-927-2017.
Résumé :
Abstract. This paper presents an update and extension of HYDE, the History Database of the Global Environment (HYDE version 3.2). HYDE is an internally consistent combination of historical population estimates and allocation algorithms with time-dependent weighting maps for land use. Categories include cropland, with new distinctions for irrigated and rain-fed crops (other than rice) and irrigated and rain-fed rice. Grazing lands are also provided, divided into more intensively used pasture and less intensively used rangeland, and further specified with respect to conversion of natural vegetation to facilitate global change modellers. Population is represented by maps of total, urban, rural population, population density and built-up area. The period covered is 10 000 before Common Era (BCE) to 2015 Common Era (CE). All data can be downloaded from https://doi.org/10.17026/dans-25g-gez3. We estimate that global population increased from 4.4 million people (we also estimate a lower range < 0.01 and an upper range of 8.9 million) in 10 000 BCE to 7.257 billion in 2015 CE, resulting in a global population density increase from 0.03 persons (or capita, in short cap) km−2 (range 0–0.07) to almost 56 cap km−2 respectively. The urban built-up area evolved from almost zero to roughly 58 Mha in 2015 CE, still only less than 0.5 % of the total land surface of the globe. Cropland occupied approximately less than 1 % of the global land area (13 037 Mha, excluding Antarctica) for a long time period until 1 CE, quite similar to the grazing land area. In the following centuries the share of global cropland slowly grew to 2.2 % in 1700 CE (ca. 293 Mha, uncertainty range 220–367 Mha), 4.4 % in 1850 CE (578 Mha, range 522–637 Mha) and 12.2 % in 2015 CE (ca. 1591 Mha, range 1572–1604 Mha). Cropland can be further divided into rain-fed and irrigated land, and these categories can be further separated into rice and non-rice. Rain-fed croplands were much more common, with 2.2 % in 1700 CE (289 Mha, range 217–361 Mha), 4.2 % (549 Mha, range 496–606 Mha) in 1850 CE and 10.1 % (1316 Mha, range 1298–1325 Mha) in 2015 CE, while irrigated croplands used less than 0.05 % (4.3 Mha, range 3.1–5.5 Mha), 0.2 % (28 Mha, range 25–31 Mha) and 2.1 % (277 Mha, range 273–278 Mha) in 1700, 1850 and 2015 CE, respectively. We estimate the irrigated rice area (paddy) to be 0.1 % (13 Mha, range 9–16 Mha) in 1700 CE, 0.2 % (28 Mha, range 26–31 Mha) in 1850 CE and 0.9 % (118 Mha, range 117–120 Mha) in 2015 CE. The estimates for land used for grazing are much more uncertain. We estimate that the share of grazing land grew from 5.1 % in 1700 CE (667 Mha, range 507–820 Mha) to 9.6 % in 1850 CE (1192 Mha, range 1068–1304 Mha) and 24.9 % in 2015 CE (3241 Mha, range 3211–3270 Mha). To aid the modelling community we have divided land used for grazing into more intensively used pasture, less intensively used converted rangeland and less or unmanaged natural unconverted rangeland. Pasture occupied 1.1 % in 1700 CE (145 Mha, range 79–175 Mha), 1.9 % in 1850 CE (253 Mha, range 218–287 Mha) and 6.0 % (787 Mha, range 779–795 Mha) in 2015 CE, while rangelands usually occupied more space due to their occurrence in more arid regions and thus lower yields to sustain livestock. We estimate converted rangeland at 0.6 % in 1700 CE (82 Mha range 66–93 Mha), 1 % in 1850 CE (129 Mha range 118–136 Mha) and 2.4 % in 2015 CE (310 Mha range 306–312 Mha), while the unconverted natural rangelands occupied approximately 3.4 % in 1700 CE (437 Mha, range 334–533 Mha), 6.2 % in 1850 CE (810 Mha, range 733–881 Mha) and 16.5 % in 2015 CE (2145 Mha, range 2126–2164 Mha).
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Lorenz, John N., Patrick J. Schultheis, Timothy Traynor, Gary E. Shull et Jürgen Schnermann. « Micropuncture analysis of single-nephron function in NHE3-deficient mice ». American Journal of Physiology-Renal Physiology 277, no 3 (1 septembre 1999) : F447—F453. http://dx.doi.org/10.1152/ajprenal.1999.277.3.f447.
Résumé :
The Na/H exchanger isoform 3 (NHE3) is expressed in the proximal tubule and thick ascending limb and contributes to the reabsorption of fluid and electrolytes in these segments. The contribution of NHE3 to fluid reabsorption was assessed by micropuncture in homozygous ( Nhe3 −/−) and heterozygous ( Nhe3 +/−) knockout mice, and in their wild-type (WT, Nhe3 +/+) littermates. Arterial pressure was lower in the Nhe3 −/−mice (89 ± 6 mmHg) compared with Nhe3 +/+ (118 ± 4) and Nhe3 +/−(108 ± 5). Collections from proximal and distal tubules demonstrated that proximal fluid reabsorption was blunted in both Nhe3 +/− and Nhe3 −/−mice (WT, 4.2 ± 0.3; Nhe3 +/−, 3.4 ± 0.2; and Nhe3 −/−, 2.6 ± 0.3 nl/min; P < 0.05). However, distal delivery of fluid was not different among the three groups of mice (WT, 3.3 ± 0.4 nl/min; Nhe3 +/−, 3.3 ± 0.2 nl/min; and Nhe3 −/−, 3.0 ± 0.4 nl/min; P < 0.05). In Nhe3 −/−mice, this compensation was largely attributable to decreased single-nephron glomerular filtration rate (SNGFR): 10.7 ± 0.9 nl/min in the Nhe3 +/+ vs. 6.6 ± 0.8 nl/min in the Nhe3 −/−, measured distally. Proximal-distal SNGFR differences in Nhe3 −/−mice indicated that much of the decrease in SNGFR was due to activation of tubuloglomerular feedback (TGF), and measurements of stop-flow pressure confirmed that TGF is intact in Nhe3 −/−animals. In contrast to Nhe3 −/−mice, normalization of early distal flow rate in Nhe3 +/−mice was not related to decreased SNGFR (9.9 ± 0.7 nl/min), but rather, to increased fluid reabsorption in the loop segment ( Nhe3 +/+, 2.6 ± 0.2; Nhe3 +/−, 3.6 ± 0.5 nl/min). We conclude that NHE3 is a major Na/H exchanger isoform mediating Na+ and fluid reabsorption in the proximal tubule. In animals with NHE3 deficiency, normalization of fluid delivery to the distal tubule is achieved through alterations in filtration rate and/or downstream transport processes.
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Urude, R. O., G. A. Amuga, R. J. Ombugado, W. A. ,. Oyibo et J. O. Nebe. « The effect of physico chemical parameter on the distribution of fresh water snails in the Federal Capital Territory, Abuja, Nigeria ». Nigerian Journal of Parasitology 42, no 2 (15 octobre 2021) : 302–10. http://dx.doi.org/10.4314/njpar.v42i2.15.
Résumé :
Some species of freshwater snails are known to be intermediate hosts of biomedical importance. This study was conducted to identify some physico-chemical parameters of water bodies associated with the distribution of freshwater snail species in the Federal Capital Territory, Abuja. Eight water bodies in four locations were surveyed for the presence of freshwater snails. Five physico chemical parameters (pH, temperature, dissolved oxygen content, salinity and water speed) were measured using standard water meters. A correlation matrix between the water parameters and the snail species were analysed. A total of 1,225 freshwater snails belonging to eight species and families were collected in the study area. These were Bulinus truncatus 304 (24.8%), B. umbilicatus 162 (13.2%), B. globosus 138 (11.3%), Biomphalaria pfeifferi 138 (11.3%), Aplexa waterloti 190 (15.5%), Physa acuta 96 (7.8%), Lymnea natalensis (15.8%). and Melanoides tuberculata 3 (0.2%). Three of these snail species {B. globosus, B. Pfeffeiri and L. natalensis} which are known intermediate hosts of schistosomes were reasonably present in the study area. Out of the five water parameters investigated, two (Dissolved oxygen content and salinity) were found to significantly associated with the distribution of freshwater snail species in the area (P<0.05). The study recommends freshwater snail control intervention to interrupt the transmission and spread of human and animal diseases in the area.
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PHILLIPS, DAVID, KATHRYN BRIDGER, IAN JENSON et JOHN SUMNER. « An Australian National Survey of the Microbiological Quality of Frozen Boneless Beef and Beef Primal Cuts ». Journal of Food Protection 75, no 10 (1 octobre 2012) : 1862–66. http://dx.doi.org/10.4315/0362-028x.jfp-12-135.
Résumé :
The fourth national baseline microbiological survey of Australian beef was conducted in 2011, including frozen boneless beef and, for the first time, samples from selected beef primal cuts. Cartons of frozen boneless beef (n = 1,165) sampled at 29 boning (fabrication) plants were found to have a mean total viable count of 2.2 log CFU/g, and the mean count for the 2.1% of samples with detectable Escherichia coli was 1.3 log CFU/g. The mean total viable counts for striploins (longissimus dorsi, n = 572) and outsides (biceps femoris, n = 572) were 1.3 and 1.5 log CFU/cm2 respectively. E. coli isolates were obtained from 10.7 and 25.2% of striploins and outsides, respectively, with mean counts of −0.5 and −0.3 log CFU/cm2 on positive samples. E. coli O157:H7, Salmonella, and Campylobacter were not isolated from any primal cut samples, and Salmonella was not isolated from any of the boneless product (E. coli O157:H7 and Campylobacter were not tested for). Listeria spp. were not detected in any of the boneless product, and one Listeria isolate was obtained on 1 (0.2%) of 572 striploin samples. Coagulase-positive staphylococci were isolated from 3.4% of boneless beef samples, 7.7% of beef striploins, and 8.4% of beef outsides, with positive samples having mean log counts of 1.9 CFU/g, 0.2 CFU/cm2, and 0.2 CFU/cm2, respectively.
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Sagatys, Elizabeth, Lynn Moscinski, Sophie Dessureault, Eduardo Sotomayor et Hernani Cualing. « Analysis of T-Cell Subpopulations in the Lymph Nodes of Patients with Mantle Cell Lymphoma. » Blood 110, no 11 (16 novembre 2007) : 1580. http://dx.doi.org/10.1182/blood.v110.11.1580.1580.
Résumé :
Abstract Mantle cell lymphoma (MCL) is an aggressive and incurable B-cell NHL characterized by a high relapse rate. Novel treatments capable of providing and/or sustaining more durable responses in MCL patients are clearly needed. Manipulation of the immune system to unleash its protective effect might induce durable responses in MCL. To effectively harness the immune system against MCL, it is important to understand how T-cells interact with malignant B-cells that reside where immune responses are normally initiated. In the present study, we evaluated the number and phenotype of T-cells present in the lymph nodes of 14 patients with MCL. Given the increasingly important role of T regulatory cells (Tregs) and the paucity of information regarding their role in MCL, we also evaluated if T-cells infiltrating the lymph node of MCL patients co-express CD4 and FoxP3. Our patients consisted of 1 woman and 13 men, age range from 49–78 (mean age 65), 6 previously treated with chemotherapy, and 8 de novo. There was heterogeneity in the CD3+ T cell populations in our patients (range 2.7–55% [mean 15.8%]). Double staining with CD4/FoxP3 (range 0.2–3.4% [mean 1.7%]) and CD8/FoxP3 (range 0–3.2% [mean 1.4%]) showed significant heterogeneity in both populations (Table 1). A significant portion of FoxP3 positive, CD4/CD8 negative cells were seen in several cases (range 0–16% [mean 4.9%]). Flow cytometry was run on all 14 cases to evaluate the T cell populations. Spearman non-Gaussian regression analysis (using GraphPad™ software) comparing the CD4/FoxP3+ and CD8/FoxP3+ cells to the total CD8 cells showed a negative correlation by both immunohistochemical and flow, confirming that as the Treg population increases the CD8 population decreases (Table 2). Correlating CD4 Treg with CD8 by flow cytometry and IHC indicated an inverse correlation in 7 of 14 cases. Only 1 case had a positive correlation. The remaining cases had no correlation. These findings suggest increasing FoxP3 populations in MCL could result in a decrease in CD8+ T cell immune response against the malignant cells. Future studies including the characterization of the non-CD4/CD8 FoxP3+ cells may help clarify the role of Tregs in MCL. Table 1: MCL T cell Populations CD3+ FLOW (%) Total FoxP3 IHC (%) CD4/FoxP3+ IHC (%) CD8/FoxP3+ IHC (%) CD4+ IHC (%) CD8+ IHC (%) CD4+ FLOW (%) CD8+ FLOW (%) 6.5 3.2 1.8 0.4 6.4 7.8 2 4 43 12.8 0.6 1 10.6 19.2 16 27 16 4.4 0.2 0.8 8.8 15.4 5 11 11 3.6 1.4 0 6.2 1.8 8 3 8.4 3.4 0.8 1.4 17.6 11.2 1.6 3.9 10 7.8 1.8 0.6 13.6 9.2 7.5 2.5 26 12.4 3.4 2.4 15.8 16.8 20 0.1 6.3 8.2 2.2 3.2 11.6 11 1.7 3.7 55 8.6 3.4 1 21 21.6 30 25 12 10.8 2.4 2 16.8 17 5.1 6 8.4 4.6 1.6 1.2 17.6 18 5.1 3.2 5.4 9.6 1.8 1.8 13.6 16 3.6 0.3 2.7 2.2 0.8 1.4 3.8 3.4 0.8 1.9 11 19 1.2 1.8 22 8.6 7.6 3.6 Table 2: Spearman Rank Correlation Group Spearman Rank Correlation 95% Confidence Interval CD4/FoxP3+ vs. CD8 (IHC) 0.2788 −0.3115 to 0.7138 CD4/FoxP3+ vs. CD8 (FLOW) −0.2614 −0.7045 to 0.3284 CD8/FoxP3+ vs. CD8 (IHC) 0.2558 −0.3337 to 0.7105 CD8/FoxP3+ vs. CD8 (FLOW) −0.2196 −0.6815 to 0.3673 CD4/FoxP3+ vs. CD4 (IHC) 0.3448 −0.2440 to 0.7479 CD4/FoxP3+ vs. CD4 (FLOW) 0.3636 −0.2237 to 0.7572 CD8/FoxP3+ vs. CD4 (IHC) 0.4044 −0.1777 to 0.7769 CD8/FoxP3+ vs. CD4 (FLOW) −0.2243 −0.6841 to 0.3630
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Nigro, Giovanni, Stuart P. Adler, Stefania Lasorella, Giulia Iapadre, Maria Maresca, Arianna Mareri, Claudia Di Paolantonio et al. « High-Dose Cytomegalovirus (CMV) Hyperimmune Globulin and Maternal CMV DNAemia Independently Predict Infant Outcome in Pregnant Women With a Primary CMV Infection ». Clinical Infectious Diseases 71, no 6 (20 octobre 2019) : 1491–98. http://dx.doi.org/10.1093/cid/ciz1030.
Résumé :
Abstract Background After primary maternal cytomegalovirus (CMV) infection during pregnancy, infants are at risk for disease. Methods Factors predictive of infant outcome were analyzed in a database of 304 pregnant women with primary infection. These women were enrolled between 2010 and 2017 and delivered 281 infants, of whom 108 were CMV infected. Long term follow-up occurred for 173 uninfected and 106 infected infants at age 4 years (range, 1–8 years). One hundred fifty-seven women were treated with an average of 2 doses (range, 1–6 doses) of high-dose hyperimmune globulin (HIG: 200 mg/kg/infusion). We used a regression model to define predictors of fetal infection, symptoms at birth, and long-term sequelae; 31 covariates were tested. Results Four factors predicted fetal infection: a 1.8-fold increase (30% vs 56%) in the rate of congenital infection without HIG (adjusted odds ratio [AOR], 5.2; P < .0001), a 1.8-fold increase (32% vs 56%) associated with maternal viral DNAemia prior to HIG administration (AOR, 3.0; P = .002), abnormal ultrasounds (AOR, 59; P = .0002), and diagnosis of maternal infection by seroconversion rather than avidity (AOR, 3.3; P = .007). Lack of HIG and abnormal ultrasounds also predicted symptoms (P = .001). Long-term sequelae were predicted by not receiving HIG (AOR, 13.2; P = .001), maternal infection in early gestation (odds ratio [OR], 0.9; P = .017), and abnormal ultrasounds (OR, 7.6; P < .003). Prevalence and copy/number of DNAemia declined after HIG. Conclusions Maternal viremia predicts fetal infection and neonatal outcome. This may help patient counseling. High-dose HIG may prevent fetal infection and disease and is associated with the resolution of DNAemia.
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Balaji, Aanika, Stephanie Leigh Alden, Howard Li, Kabeer Munjal, Evan J. Lipson, Jarushka Naidoo, Laura Cappelli et al. « Incidence, risk factors, and outcomes of immune-related adverse events (irAEs) in a prospective, pan-tumor population. » Journal of Clinical Oncology 41, no 16_suppl (1 juin 2023) : 2662. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.2662.
Résumé :
2662 Background: IrAEs associated with immune checkpoint inhibitors (ICIs) can result in morbidity and mortality. The incidence, spectrum, and risk factors for irAEs are usually reported from retrospective studies and clinical trials, which typically exclude patients (pts) with pre-existing autoimmune disease (AD). The prevalence and risk factors for irAEs in a diverse, pan-tumor, real-world setting is not well understood. Methods: From 06/2021 to 2/2023, we prospectively enrolled pts receiving ICIs (alone or in combination as standard-of-care) at a tertiary care center in this imCORE network study. Univariate and multivariate logistic regressions and survival curves were used to interrogate risk factors for irAE development and the relationship between irAEs, graded using CTCAE v5.0, and clinical response by RECIST 1.1. Results: 132 pts with prior ICI therapy were prospectively followed. Median age was 65 years (IQR 56-72), 35% were female, 69% were white, and 24% were black. Most common tumor histologies were: hepatocellular, renal cell, bladder, non-small cell lung, and head and neck carcinoma. 23% (n=30/132) received dual ICI (nivolumab+ipilimumab). In the whole cohort, 36.4% (n=48/132) of pts developed any-grade irAE and 10.6% (n=14/132) developed a severe irAE (grades 3-5). There were 2 fatal irAEs (n=1 hepatitis, n=1 myocarditis) representing 1.5% of the total cohort. The median time to first irAE was 1.8 months (mos; IQR 1.2-3.1) for anti-PDL1 monotherapy, 1.2 mos (IQR 0.7-2.2) for dual ICI, 4.4 mos (0.2-8.7) for PDL1+chemotherapy, and 2.1 mos (1.3-3.1) for PDL1+other. A subgroup of pts (10.6%; n=14/132) had pre-existing AD and 50% (n=7/14) had ever received immunosuppression for their AD. Among pts with AD, the incidence of irAEs was 57% (n=8/14) vs 33.9% (n=40/118) among those without AD. Antitumor response for pts with AD was 27.3% vs 25.8% those without AD. Receipt of dual ICI therapy was associated with increased risk of any-grade irAE (OR 2.87 p=0.02) and severe irAE (OR 40.9 p=0.004). Pts with any grade irAEs were significantly more likely to experience a partial/complete response vs pts without irAEs (OR 4.14 p=0.02) and this relationship was preserved after adjustment for single vs dual ICI. Pts who did not develop irAEs had an overall response rate (ORR) of 18.2%, mPFS of 3.5 mos (IQR 1.6-7.3), and mOS 7.3 mos (IQR 3.8-9.9) vs pts who developed any grade irAE who had an ORR of 37.8%, mPFS of 5.9 mos (IQR 3.3-8.8), and mOS 8.6 mos (IQR 4.9-11.4). Conclusions: In this pan-tumor, prospective cohort study of pts receiving ICI therapy in a real world setting, we identified that pts with pre-existing AD and those on dual ICI had increased risk of irAE development. This signals the need for closer monitoring, early recognition, and management of irAEs in these pts. In addition, pts who developed irAEs were more likely to experience partial or complete response in a diverse tumor cohort.
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Vassilakos, George, Rob S. James et Valerie M. Cox. « Effect of stimulation frequency on force, net power output, and fatigue in mouse soleus muscle in vitro ». Canadian Journal of Physiology and Pharmacology 87, no 3 (mars 2009) : 203–10. http://dx.doi.org/10.1139/y09-002.
Résumé :
The effects of electrical stimulation frequency on force, work loop power output, and fatigue of mouse soleus muscle were investigated in vitro at 35 °C. Increasing stimulation frequency did not significantly affect maximal isometric tetanic stress (overall mean ± SD, 205 ± 16.6 kN·m–2 between 70 and 160 Hz) but did significantly increase the rate of force generation. The maximal net power output during work loops significantly increased with stimulation frequency: 18.2 ± 3.7, 22.5 ± 3.3, 26.8 ± 3.7, and 28.6 ± 3.4 W·kg–1 at 70, 100, 130, and 160 Hz, respectively. The stimulation frequency that was used affected the pattern of fatigue observed during work loop studies. At stimulation frequencies of 100 and 130 Hz, there were periods of mean net negative work during the fatigue tests due to a slowing of relaxation rate. In contrast, mean net work remained positive throughout the fatigue test when stimulation frequencies of 70 and 160 Hz were used. The highest cumulative work during the fatigue test was performed at 70 and 160 Hz, followed by 130 Hz, then 100 Hz. Therefore, stimulation frequency affects power output and the pattern of fatigue in mouse soleus muscle.
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Min, Hyang K., Hyun Y. Ko, Jin T. Kim, Lise Bankir et Sung W. Lee. « Low hydration status may be associated with insulin resistance and fat distribution : analysis of the Korea National Health and Nutrition Examination Survey (KNHANES) 2008–2010 ». British Journal of Nutrition 124, no 2 (19 mars 2020) : 199–208. http://dx.doi.org/10.1017/s0007114520001063.
Résumé :
AbstractWe aimed to identify the association of hydration status with insulin resistance (IR) and body fat distribution. A total of 14 344 adults participated in the Korea National Health and Nutrition Examination Survey 2008–2010. We used urine specific gravity (USG) to indicate hydration status, and HOMA-IR (homoeostasis model assessment of IR) and trunk:leg fat ratio (TLR) as primary outcomes. In multivariate logistic regression, the OR per 0·01 increase in USG for high IR was 1·303 (95 % CI 1·185, 1·433; P < 0·001). In multivariate generalised additive model plots, increased USG showed a J-shaped association with logarithmic HOMA-IR, with the lowest Akaike’s information criterion score of USG 1·030. Moreover, increased USG was independently associated with increased trunk fat, decreased leg fat and increased TLR. In mediation analysis, the proportion of mediation effects of USG on TLR via IR was 0·193 (95 % CI 0·132, 0·285; P < 0·001), while the proportion of mediation effects of USG on IR via TLR was 0·130 (95 % CI 0·086, 0·188; P < 0·001). Increased USG, a sign of low hydration status and presumably high vasopressin, was associated with IR and poor fat distribution. Direct effect of low hydration status may be more dominant than indirect effect via IR or fat distribution. Further studies are necessary to confirm our findings.
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Choi, Rihwa, Sang Gon Lee et Eun Hee Lee. « Exploring Utilization and Establishing Reference Intervals for the Apolipoprotein B Test in the Korean Population ». Diagnostics 13, no 20 (12 octobre 2023) : 3194. http://dx.doi.org/10.3390/diagnostics13203194.
Résumé :
We investigated the reference intervals for Apolipoprotein B (ApoB), a valuable biomarker for cardiovascular diseases, in Korean adults who had undergone health check-ups and showed normal lipid levels under traditional lipid tests, including total cholesterol, triglyceride, and high-density lipoprotein cholesterol, along with ApoB. We compared the findings with different cutoffs for ApoB from international clinical guidelines. Among a total of 264,105 traditional lipid test sets, only 464 (0.2%) included ApoB tests, indicating underutilization of this test in health check-up clinics in Korea. From these 464 samples, 334 ApoB results (164 men and 170 women) with normal traditional lipid test results were used to establish reference intervals. Using the parametric method (mean ± 2 SD), the reference intervals ranged from 46 to 134 mg/dL for men and 49 to 129 mg/dL for women. Employing the non-parametric method (central 95th percentile value), the reference intervals ranged from 50 to 131 mg/dL for men and 51 to 127 mg/dL for women. The prevalence of high ApoB did not significantly differ by sex when considering the established reference intervals for each sex and the cutoffs recommended by international clinical guidelines. This study enhances knowledge on ApoB reference intervals in the Korean population, and it will in aid test result interpretation for clinicians and laboratories.
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Popovych, O. M., I. M. Budzulyak, O. V. Popovych, B. I. Rachiy, R. V. Ilnytskyi, L. S. Yablon et O. V. Morushko. « Synthesis and Electrochemical Properties of Nanocrystalline Nickel Molybdate ». Physics and Chemistry of Solid State 22, no 1 (13 mars 2021) : 123–31. http://dx.doi.org/10.15330/pcss.22.1.123-131.
Résumé :
We have obtained nanocrystalline hydrate and alpha phase of nickel molybdate by a hydrothermal technique. On the basis of the obtained cyclic voltammetry data, we have evaluated the contribution of faradaic and non-faradaic processes to the total capacitance of molybdates under study. It was found that the specific capacitance of hydrate NiMoO4·H2O is 621 F/g at a scan rate of 1 mV / s and the specific capacitance of the α-NiMoO4 is 281 F/g. Cathodes for hybrid supercapacitors were formed on the basis of the obtained nickel molybdates. As a result of electrochemical studies, it was found that the specific capacitance of hybrid supercapacitor based on NiMoO4·H2O/C was 256 F/g at the current of 0.2 A/g, while the specific energy was 80 W h/kg and specific power – 304 W/kg and these results are higher below in the α-NiMoO4 /C-based hybrid supercapacitor.
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Marrero-Gonzalez, Alejandro R., Anna Crawford, Fitzgerald Draper, Andrea Incudine, Stacy Tessler Lindau et Evan M. Graboyes. « Abstract 1016 : Food insecurity among patients with cancer in the US ». Cancer Research 84, no 6_Supplement (22 mars 2024) : 1016. http://dx.doi.org/10.1158/1538-7445.am2024-1016.
Résumé :
Abstract Introduction: Food insecurity (FI) is common among cancer patients and can lead to decreased treatment adherence, worse quality of life, and increased recurrence and mortality. Although some studies suggest that patients with cancer are particularly susceptible to FI, these studies have been limited by their small sample size, narrow sampling of cancer types and stages, and limited geographic scope. To address this gap, this study leverages data from a supportive care organization to characterize FI prevalence and associated risk factors in a nationwide sample of patients with diverse types of cancer. Methods: This cross-sectional study included adults with cancer undergoing treatment referred to Family Reach, a national organization that provides financial support to cancer patients and their families, from 2020-2023. The primary outcome was FI, defined as a self-reported concern that the family would run out of food before getting enough money to buy more. Estimates of FI were provided for the cohort stratified by cancer type; multivariable logistic regression was used to evaluate the association of cancer type (primary independent variable) with FI, adjusted for oncologic and demographic covariates. Results: Of 6,615 patients with cancer, 62.9% reported FI. Across cancer types, FI prevalence ranged from 56% (brain) to 68% (gynecologic). FI did not vary significantly by cancer type on multivariable logistic regression adjusted for oncologic, geographic, and demographic factors (Table 1). A variety of demographic factors were associated with FI (Table 1). Table 1. Characteristics of Patients with Cancer With Food Insecurity Referred to Family Reach and Factors Associated with Food Insecurity Using Multivariable Logistic Regression Analysis. Outcome N (%) aOR (95% CI) Outcome N (%) aOR (95% CI) Outcome N (%) aOR (95% CI) Cancer Type Age, y Region of US • Breast 1,348 (32.4) Ref - • 18-64 3,887 (93.3) Ref - • Pacific 465 (11.2) Ref - • Brain 118 (2.8) 0.84 (0.61 - 1.16) • ≥65 279 (6.7) 0.38 (0.3 - 0.48) • Mountain 246 (5.9) 0.94 (0.71 - 1.23) • Gastrointestinal 500 (12) 1.13 (0.92 - 1.38) Gender • West South Central 489 (11.7) 1.09 (0.87 - 1.38) • Genitourinary 115 (2.8) 1.1 (0.78 - 1.55) • Male 1,298 (31.2) Ref - • West North Central 213 (5.1) 1.09 (0.82 - 1.44) • Gynecologic 274 (6.6) 1.21 (0.95 - 1.54) • Female 2,859 (68.6) 1.04 (0.91 - 1.19) • East South Central 302 (7.2) 1.6 (1.21 - 2.13) • Head and Neck 82 (2) 1.08 (0.72 - 1.62) • Other 9 (0.2) 1.07 (0.25 - 4.6) • East North Central 466 (11.2) 1.02 (0.81 - 1.29) • Hematologic 958 (30) 0.95 (0.79 - 1.15) Race and Ethnicity • South Atlantic 941 (22.6) 1.14 (0.93 - 1.4) • Lung 247 (5.9) 0.99 (0.77 - 1.26) • Non-Hispanic White 1,725 (41.4) Ref - • Middle Atlantic 851 (20.4) 0.76 (0.62 - 0.94) • Melanoma/Sarcoma 200 (4.8) 0.97 (0.74 - 1.28) • Non-Hispanic Black 1,249 (30) 1.6 (1.4 - 1.83) • New England 193 (4.6) 1 (0.74 - 1.36) • Other 324 (7.8) 1 (0.79 - 1.25) • Hispanic White 832 (20) 1.63 (1.36 - 1.96) Preferred Language Stage • Asian or Pacific Islander 130 (3.1) 1.1 (0.82 - 1.49) • English 3,686 (88.5) Ref - • I 415 (10) Ref - Health Insurance • Spanish 328 (7.9) 1.69 (1.26 - 2.28) • II 652 (15.7) 1.01 (0.81 - 1.25) • Private/commercial 718 (17.2) Ref - • Other 61 (1.5) 1.26 (0.81 - 1.98) • III 814 (19.5) 1.11 (0.9 - 1.37) • Self-pay 240 (5.8) 2.35 (1.74 - 3.16) • IV 1,254 (30.1) 1.07 (0.87 - 1.32) • Medicaid 1,588 (38.1) 1.87 (1.62 - 2.16) • Not applicable 1,031 (24.7) 0.87 (0.69 - 1.08) • Medicare 536 (12.9) 2.23 (1.81 - 2.76) Relapsed • Medicare + Medicaid 122 (2.9) 2.98 (2.06 - 4.3) • Yes 631 (15.1) Ref - • Other 782 (18.8) 1.45 (1.23 - 1.7) • No 3,535 (84.9) 1.11 (0.95 - 1.29) Employment • Dual employment 1,343 (32.2) Ref - • Single employment 2,428 (58.3) 1.24 (1.1 - 1.38) • Dual unemployment 261 (6.3) 1.7 (1.31 - 2.21) Conclusion: Nearly two-thirds of patients with cancer served by a large national cancer support organization reported FI. FI was common across all types of cancer and was associated primarily with demographic characteristics. These FI prevalence and risk factor data can be used by researchers, clinicians, and community-based organizations to understand and address FI among patients with cancer. Citation Format: Alejandro R. Marrero-Gonzalez, Anna Crawford, Fitzgerald Draper, Andrea Incudine, Stacy Tessler Lindau, Evan M. Graboyes. Food insecurity among patients with cancer in the US [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1016.
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Mathioudakis, Nestoras Nicolas, Estelle Everett, Shuvodra Routh, Peter J. Pronovost, Hsin-Chieh Yeh, Sherita Hill Golden et Suchi Saria. « Development and validation of a prediction model for insulin-associated hypoglycemia in non-critically ill hospitalized adults ». BMJ Open Diabetes Research & ; Care 6, no 1 (mars 2018) : e000499. http://dx.doi.org/10.1136/bmjdrc-2017-000499.
Résumé :
ObjectiveTo develop and validate a multivariable prediction model for insulin-associated hypoglycemia in non-critically ill hospitalized adults.Research design and methodsWe collected pharmacologic, demographic, laboratory, and diagnostic data from 128 657 inpatient days in which at least 1 unit of subcutaneous insulin was administered in the absence of intravenous insulin, total parenteral nutrition, or insulin pump use (index days). These data were used to develop multivariable prediction models for biochemical and clinically significant hypoglycemia (blood glucose (BG) of ≤70 mg/dL and <54 mg/dL, respectively) occurring within 24 hours of the index day. Split-sample internal validation was performed, with 70% and 30% of index days used for model development and validation, respectively.ResultsUsing predictors of age, weight, admitting service, insulin doses, mean BG, nadir BG, BG coefficient of variation (CVBG), diet status, type 1 diabetes, type 2 diabetes, acute kidney injury, chronic kidney disease (CKD), liver disease, and digestive disease, our model achieved a c-statistic of 0.77 (95% CI 0.75 to 0.78), positive likelihood ratio (+LR) of 3.5 (95% CI 3.4 to 3.6) and negative likelihood ratio (−LR) of 0.32 (95% CI 0.30 to 0.35) for prediction of biochemical hypoglycemia. Using predictors of sex, weight, insulin doses, mean BG, nadir BG, CVBG, diet status, type 1 diabetes, type 2 diabetes, CKD stage, and steroid use, our model achieved a c-statistic of 0.80 (95% CI 0.78 to 0.82), +LR of 3.8 (95% CI 3.7 to 4.0) and −LR of 0.2 (95% CI 0.2 to 0.3) for prediction of clinically significant hypoglycemia.ConclusionsHospitalized patients at risk of insulin-associated hypoglycemia can be identified using validated prediction models, which may support the development of real-time preventive interventions.
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Hunter, Sandra K., Romuald Lepers, Carol J. MacGillis et Roger M. Enoka. « Activation among the elbow flexor muscles differs when maintaining arm position during a fatiguing contraction ». Journal of Applied Physiology 94, no 6 (1 juin 2003) : 2439–47. http://dx.doi.org/10.1152/japplphysiol.01038.2002.
Résumé :
Twenty-four men ( n = 11) and women ( n = 13) supported an inertial load equivalent to 20% of the maximum voluntary contraction force with the elbow flexor muscles for as long as possible while maintaining a constant elbow angle at 90°. Endurance time did not differ on the three occasions that the task was performed (320 ± 149 s; P > 0.05), and there was no difference between women (360 ± 168 s) and men (273 ± 108 s; P = 0.11). The rate of increase in average electromyogram (EMG) for the elbow flexor muscles was similar across sessions ( P > 0.05). However, average EMG during the fatiguing task increased for the long head of biceps brachii, brachioradialis, and brachialis ( P < 0.05) but not for the short head of biceps brachii. Furthermore, the average EMG for the brachialis was greater at the start and end of the contraction compared with the other elbow flexor muscles. The rate of bursts in EMG activity increased during the fatiguing contraction and was greater in brachialis (1.0 ± 0.2 bursts/min) compared with the other elbow flexor muscles (0.5 ± 0.1 bursts/min). The changes in the standard deviation of acceleration, mean arterial pressure, and heart rate during the fatiguing contractions were similar across sessions. These findings indicate that the EMG activity, which reflects the net excitatory and inhibitory input received by the motoneurons in the spinal cord, was not adaptable over repeat sessions for the maintain-position task. Furthermore, these results contrast those from a previous study (Hunter SK and Enoka RM. J Appl Physiol 94: 108–118, 2003) when the goal of the isometric contraction was to maintain a constant force. These results, from a series of studies on the elbow flexor muscles, indicate that the type of load supported during the fatiguing contraction influences the extent to which endurance time can change with repeat performances of the task.
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Hassan, F. A., Сh Alali et L. R. Gainullina. « Increasing the efficiency of wind farms ». iPolytech Journal 26, no 2 (4 juillet 2022) : 217–27. http://dx.doi.org/10.21285/1814-3520-2022-2-217-227.
Résumé :
This work evaluates variables affecting wind parameters in order to maximally reduce turbulence and trace. In addition, the position of each wind turbine in a farm and the limits of wind turbines are determined in order to determine an optimal distance between them. To this end, a 150 MW wind farm operating 60 wind turbines was studied. The speed and direction of wind was studied using a wind-measuring installation. An optimal mode of operating a wind farm was calculated using the WindFarmer software produced by DNV GL (Norway). Experiments conducted on a site in the south-east of the Republic of Tatarstan showed its suitability for the construction of a wind power plant: the proximity of electrical networks and the absence of large buildings and forests. The wind shear at different heights (at the levels of anemometers) was found to be 0.2. Wind turbines were selected based on a calculation of power factors, which comprised 47 % for Siemens Gamesa SG 3.4-132 3.465MW, 45 % for Vestas V126-3.45 HTq and 29% for Lagerwey L100-2.5 MW. The conducted analysis of the main external factors (ground profile, average wind speed, distance to electrical networks, etc.) affecting the selection of an optimal site for a wind power plant, as well as the calculation of an average wind shear of 0.2, confirmed the suitability of the site under study. According to the calculated capacity factor, Lagerwey L100 and Siemens Gamesa SG 3.4-132 turbines showed the lowest (2.5 MW) and highest (3.465 MW) values, respectively. However, from an economic point of view, a balance between the turbine’s capacity factor and its cost should be achieved.
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Bizino, Maurice B., Ingrid M. Jazet, Paul de Heer, Huub J. van Eyk, Ilona A. Dekkers, Patrick C. N. Rensen, Elisabeth H. M. Paiman, Hildebrandus J. Lamb et Johannes W. Smit. « Placebo-controlled randomised trial with liraglutide on magnetic resonance endpoints in individuals with type 2 diabetes : a pre-specified secondary study on ectopic fat accumulation ». Diabetologia 63, no 1 (5 novembre 2019) : 65–74. http://dx.doi.org/10.1007/s00125-019-05021-6.
Résumé :
Abstract Aims/hypothesis The aim of this work was to assess the effect of liraglutide on ectopic fat accumulation in individuals with type 2 diabetes mellitus. Methods This study is a pre-specified subanalysis of the MAGNetic resonance Assessment of VICTOza efficacy in the Regression of cardiovascular dysfunction In type 2 diAbetes mellitus (MAGNA VICTORIA) study, with primary endpoints being the effects of liraglutide on left ventricular diastolic and systolic function. The MAGNA VICTORIA study was a single-centre, parallel-group trial in 50 individuals with type 2 diabetes mellitus (BMI >25 kg/m2) who were randomly assigned (1:1, stratified for sex and insulin use) to receive liraglutide 1.8 mg once daily or placebo for 26 weeks, added to standard care. Participants, study personnel and outcome assessors were blinded to treatment allocation. The secondary endpoints of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT) and epicardial fat were measured with MRI. Hepatic triacylglycerol content (HTGC) and myocardial triacylglycerol content (MTGC) were quantified with proton MR spectroscopy. Between-group differences (change from baseline) were tested for significance using ANCOVA. Mean differences with 95% CIs were reported. Results The trial was completed in 2016. Twenty-four participants were randomised to receive liraglutide and 26 to receive placebo. One patient in the liraglutide group withdrew consent before having received the study drug and was not included in the intention-to-treat analysis. Liraglutide (n = 23) vs placebo (n = 26) significantly reduced body weight (liraglutide 98.4 ± 13.8 kg to 94.3 ± 14.9 kg; placebo 94.5 ± 13.1 kg to 93.9 ± 13.2 kg; estimated treatment effect −4.5 [95% CI −6.4, −2.6] kg). HbA1c declined in both groups without a significant treatment effect of liraglutide vs placebo (liraglutide 66.7 ± 11.5 mmol/mol to 55.0 ± 13.2 mmol/mol [8.4 ± 1.1% to 7.3 ± 1.2%]; placebo 64.7 ± 10.2 mmol/mol to 56.9 ± 6.9 mmol/mol [8.2 ± 1.0% to 7.5 ± 0.7%]; estimated treatment effect −2.9 [95% CI −8.1, 2.3] mmol/mol or −0.3 [95% CI −0.8, 0.2]%). VAT did not change significantly between groups (liraglutide 207 ± 87 cm2 to 203 ± 88 cm2; placebo 204 ± 63 cm2 to 200 ± 55 cm2; estimated treatment effect −7 [95% CI −24, 10] cm2), while SAT was reduced by a significantly greater extent with liraglutide than with placebo (liraglutide 361 ± 142 cm2 to 339 ± 131 cm2; placebo 329 ± 107 cm2 to 333 ± 125 cm2; estimated treatment effect −29 [95% CI −51, −8] cm2). Epicardial fat did not change significantly between groups (liraglutide 8.9 ± 4.3 cm2 to 9.1 ± 4.7 cm2; placebo 9.6 ± 4.1 cm2 to 9.6 ± 4.6 cm2; estimated treatment effect 0.2 [95% CI −1.5, 1.8] cm2). Change in HTGC was not different between groups (liraglutide 18.1 ± 11.2% to 12.0 ± 7.7%; placebo 18.4 ± 9.4% to 14.7 ± 10.0%; estimated treatment effect −2.1 [95% CI −5.3, 1.0]%). MTGC was not different after treatment with liraglutide (1.5 ± 0.6% to 1.2 ± 0.6%) vs placebo (1.3 ± 0.5% to 1.2 ± 0.6%), with an estimated treatment effect of −0.1 (95% CI −0.4, 0.2)%. There were no adjudicated serious adverse events. Conclusions/interpretation Compared with placebo, liraglutide-treated participants lost significantly more body weight. Liraglutide primarily reduced subcutaneous fat but not visceral, hepatic, myocardial or epicardial fat. Future larger studies are needed to confirm the results of this secondary endpoint study. Trial registration ClinicalTrials.gov NCT01761318. Funding This study was funded by Novo Nordisk A/S (Bagsvaerd, Denmark).