Journal articles on the topic '863/.64'

Background With growing numbers of adults turning to the internet to get answers for health-related questions, online communities provide platforms with participatory networks to deliver health information and social support. However, to optimize the benefits of these online communities, these platforms must market effectively to attract new members and promote community growth. Objective The aim of this study was to assess the engagement results of Facebook advertisements designed to increase membership in the LungCancer.net online community. Methods In the fall of 2017, a series of 5 weeklong Facebook advertisement campaigns were launched targeting adults over the age of 18 years with an interest in lung cancer to increase opt ins to the LungCancer.net community (ie, the number of people who provided their email to join the site). Results The advertisements released during this campaign had a sum reach of 91,835 people, and 863 new members opted into the LungCancer.net community by providing their email address. Females aged 55 to 64 years were the largest population reached by the campaign (31,401/91,835; 34.29%), whereas females aged 65 and older were the largest population who opted into the LungCancer.net community (307/863; 35.57%). A total of US $1742 was invested in the Facebook campaigns, and 863 people opted into LungCancer.net, resulting in a cost of US $2.02 per new member. Conclusions This research demonstrates the feasibility of using Facebook advertising to promote and grow online health communities. More research is needed to compare the effectiveness of various advertising approaches. Public health professionals should consider Facebook campaigns to effectively connect intended audiences to health information and support.

ImportanceLimited evidence supports the performance of human papillomavirus (HPV) DNA testing as a primary screening method, followed by triage with visual inspection with acetic acid, in areas with limited health care resources, as suggested by the 2021 World Health Organization guidelines.ObjectiveTo evaluate the performance of visual inspection with acetic acid and Lugol iodine as a triage method for detecting cervical precancerous lesions among HPV-positive women in 1 visit.Design, Setting, and ParticipantsThis cohort study examined the implementation of a government-led cervical cancer screening program conducted from January 1, 2016, to December 31, 2020, in Ordos City, China. Female residents, aged 35 to 64 years, who understood the screening procedures and voluntarily participated were included in the study. Women were excluded if they reported never having had sexual intercourse, were pregnant, had a hysterectomy, or had ever undergone treatment for cervical lesions. Statistical analysis was conducted from December 2022 to December 2023.ExposuresThe program used the careHPV DNA assay as the primary screening method, and immediate triage was performed by visual inspection if HPV screening results were positive, with a 5-year screening interval. A colposcopy was performed for the women who had suspected cancer on visual inspection results or who were HPV positive and had abnormal visual inspection results, all in 1 visit.Main Outcomes and MeasuresThe rate of compliance with colposcopy and the detection rate of cervical intraepithelial neoplasia grade 2 or higher (CIN2+).ResultsThe study included 187 863 women (median age, 46 years [IQR, 40-52 years]) who participated in the program and had valid HPV test results. The overall prevalence of HPV positivity was 12.8% (24 070 of 187 863), and the adherence to triage with visual inspection among HPV-positive women was 93.9% (22 592 of 24 070). Among HPV-positive women, the rate of compliance with colposcopy was 65.6% (2714 of 4137), and the CIN2+ detection rate was 2.8% (643 of 22 592).Conclusions and RelevanceThe findings of this cohort study suggest that the implementation of HPV testing, visual inspection, and colposcopy within 1 visit may mitigate losses to follow-up, detect precancerous lesions, and hold significant implications for screening in comparable areas with limited health care resources.

The objective of this work is to determine the epidemiological profile of Acinetobacter b aumannii (A.baumannii ) bacteremia in the microbiology laboratory of CHU Mohammed VI of Oujda and its antibiotic resistance rates. This is a retrospective and descriptive study of 27 months from June 24, 2016to September 19, 2018 including all positive blood cultures processed in the microbiology laboratory in accordance with REMIC (reference in medical microbiology)and EUCAST(European Committee on Antimicrobial Susceptibility Testing). Contaminated blood cultures were excluded. As results we collected 863 positive blood cultures, A. baumannii accounted for 7.41% (n = 64). 67% (n =43) of the strains were isolated from patients hospitalized in intensive care (adults, children and newborns). The two main risk factors described in patients with our series were wearing of intravascular device in 55% (n=35) Immunosuppression in 22% n=14). A. baumannii bacteremia was associated with care in 37.5% (n=24). 75% (n=48) of A. baumannii isolates were resistant to carbapenems. No strain of A. baumannii was resistant to colistin. In light of these results strengthening the control and prevention measures for healthcare associated infections would be the most reliable way to limit the spread of A. baumannii in our establishment.

AbstractPurposeThe purpose of this study is to examine the association between non-psychotic serious mental disorders and earnings in the general population of Belgium on both the individual- and society-level.Subjects and methodsData stem from a cross-sectional population study of the non-institutionalized adult (between 18 and 64) population from Belgium (N = 863). The third version of the Composite International Diagnostic Interview (CIDI-3.0) was administered to assess 12-month non-psychotic serious mental disorders and annual earnings. Multivariate approaches were used to estimate the observed and estimated annual earnings for persons with serious mental disorders, controlling for sociodemographic variables and alcohol disorders.ResultsOn the individual-level, 12-month serious mental disorders significantly predicted the probability of having any earnings (OR = 0.32; 95%CI = 0.14–0.74). Respondents with serious mental disorders had 12-month earnings of 5969€ less than expected in the absence of serious mental disorders. Taking into account the prevalence of serious mental disorders (i.e. 4.9%), the society-level effects of serious mental disorders in 2002 can be estimated at about 1797 million € per year for the Belgian general population.DiscussionNon-psychotic serious mental disorders had considerable impact on annual earnings.ConclusionThis is the first study in Belgium that addresses the association between mental illness and earnings. Serious mental disorders are associated with individual- and societal-level impairments and loss of human capital.

This research aimed to design a scale for measuring pre-service teachers’ environmental consciousness. A systematic literature review was carried out to develop initial items for measuring pre-service teachers’ environmental consciousness. A total of 64 items were finalized for the scale under five parts, with seventeen items under knowledge, attitude, pedagogies, beliefs, and practices of pre-service teachers regarding environmental consciousness. Through a survey, this scale was administered to 362 pre-service teachers from public sector universities offering teacher education programs in Punjab. The validity of the scale is ensured through expert opinion, and reliability (inter-item consistency) is confirmed through Cronbach’s alpha test. The reliability value was found to be .863 for items on the scale. Validity and reliability were statistically tested by conducting exploratory factor analysis. Values of factor loading range from a maximum of .800 to .501. After exploratory factor analysis, a total of 23 items were removed, and the final scale consisted of 41 items. The final scale indicates appropriate reliability and validity regarding five factors related to environmental consciousness. Theoretically, this scale contributes significantly to identifying and measuring the environmental consciousness of pre-service teachers. The scale for environmental consciousness of pre-service teachers could be useful for understanding the environment and also helpful in investigating relation relationship among different variables regarding environmental consciousness.

Purpose – The purpose of this paper is to review the evidence of alcohol use disorders within the different stages of the criminal justice system in the UK. Furthermore it reviewed the worldwide evidence of alcohol brief interventions in the various stages of the criminal justice system. Design/methodology/approach – A rapid systematic review of publications was conducted from the year 2000 to 2014 regarding the prevalence of alcohol use disorders in the various stages of the criminal justice system. The second part of the work was a rapid review of effectiveness studies of interventions for alcohol brief interventions. Studies were included if they had a comparison group. Worldwide evidence was included that consisted of up to three hours of face-to-face brief intervention either in one session or numerous sessions. Findings – This review found that 64-88 per cent of adults in the police custody setting; 95 per cent in the magistrate court setting; 53-69 per cent in the probation setting and 5,913-863 per cent in the prison system and 64 per cent of young people in the criminal justice system in the UK scored positive for an alcohol use disorder. There is very little evidence of effectiveness of brief interventions in the various stages of the criminal justice system mainly due to the lack of follow-up data. Social implications – Brief alcohol interventions have a large and robust evidence base for reducing alcohol use in risky drinkers, particularly in primary care settings. However, there is little evidence of effect upon drinking levels in criminal justice settings. Whilst the approach shows promise with some effects being shown on alcohol-related harm as well as with young people in the USA, more robust research is needed to ascertain effectiveness of alcohol brief interventions in this setting. Originality/value – This paper provides evidence of alcohol use disorders in the different stages of the criminal justice system in the UK using a validated tool as well as reviewing the worldwide evidence for short ( < three hours) alcohol brief intervention in this setting.

Background: Neutrophils are an essential part of innate immunity and play a crucial role in controlling infection caused by Neisseria meningitidis. The Moraxella catarrhalis ubiquitous surface protein A1 (UspA1)-based recombinant polypeptide binds to the carcinoembryonic antigen-related cellular adhesion molecule (CEACAM) 1 receptor on host cells and blocks binding of the mucosal pathogens to human epithelial cells and T cells. Aim of the study: Since the CEACAM1 receptor is expressed on neutrophils, the aim of this study was to investigate the effect of CEACAM1-binding recombinant polypeptide on the ability of neutrophils to kill Neisseria meningitidis. Methods: The effect of CEACAM1-binding recombinant polypeptide on the phagocytic killing of Neisseria meningitidis by neutrophils was assessed by incubation of neutrophils with CEACAM1-binding recombinant polypeptide (UspA1 527–665) or with CEACAM1-non-binding polypeptide control (UspA1 659–863) for one hour before infection with Neisseria meningitidis. The surviving bacteria were released and counted. Results: 30 minutes after infection of neutrophils with Neisseria meningitidis, the survival of bacteria in presence of CEACAM1-binding recombinant polypeptide was 64% compared to 52% with control peptide and 43% without peptide. However, one-hour after infection, the surviving bacteria was 32% in presence of CEACAM1-binding recombinant polypeptide compared to 18% with control peptide and 22% without peptides. Conclusion: Although CEACAM1-binding polypeptide reduced the killing of Neisseria meningitidis by neutrophils, it did not entirely stop phagocytosis and killing of bacteria.

Abstract Platt, T., Sathyendranath, S., and Fuentes-Yaco, C., 2007. Biological oceanography and fisheries management: perspective after 10 years. – ICES Journal of Marine Science, 64: 863–869. Despite 100 years of research into the relationship between oceanographic factors and fish recruitment, it has proved very difficult to demonstrate causal connections between properties of the marine ecosystem and the success of fisheries. Some authors have been led to conclude that such causal connections, therefore, do not exist: a corollary would be that biological oceanography is of limited relevance to fisheries issues. However, it would be premature to dismiss biological oceanography as a tool in fisheries management. If we have not been able to implicate ecosystem factors as a significant source of variance in fish recruitment, it may be because the search has been conducted at an inappropriate scale, a consequence of the limitations of ships as oceanographic platforms. The advent of remotely sensed data from satellites greatly extends the scales of time and space at which synoptic oceanography can be carried out. Access to such data allows a wider range of hypotheses to be tested, than is possible with ships alone, on the relationship between ecosystem factors and recruitment. Applications in both the Atlantic and Pacific have demonstrated strong fluctuations between years in the timing and the intensity of phytoplankton dynamics, with implications for recruitment and growth of exploited populations of fish and invertebrates. The results provide essential intelligence for those charged with stewardship of the marine environment.

Abstract Background The incidence of depression is higher in women; women are more often on sick leave due to depression, and more women than men use antidepressants. The objective of this study was to explore possible gender differences in buying prescribed antidepressants during the first 21 days of a new sick-leave spell due to depressive episode. Methods Included were all individuals living in Sweden in working age (18–64 years old) who in 2010 or 2011 began a new sick-leave spell due to depressive episode (ICD-10 F32) lasting at least 21 days (n = 44 863). Register data on sociodemographics, morbidity and dispensed prescription medication were used to investigate associations between gender and buying prescribed antidepressants in the total group and in subgroups, using multiple logistic regression models. Results The study population consisted of 69.5% women. Within the first 21 days of the sick-leave spell, 48.0% of the men and 42.1% of the women had dispensed prescribed antidepressants. In the adjusted multiple logistic regression model, men had an odds ratio of 1.28 (95% confidence interval 1.23–1.33) as compared with women, for buying prescribed antidepressants. Conclusions In this nationwide register study, nearly half of the women and men on sick leave with depressive episode bought prescribed antidepressants during the first three weeks of the sick-leave spell. In the adjusted models, men were more likely to do this. Further studies are needed to elucidate the reasons for this gender difference.

Para sobresalir entre la abundancia de ofertas de medios y contenidos que se presenta en el mercado informativo actual, las empresas periodísticas deben intensificar acciones que les permitan fortalecer su identidad. Ésta se construye sobre los valores de la organización, los cuales, además de generar visibilidad para la marca, deben ser fuente de motivación para los periodistas. En este artículo se analiza la manera en la que se transmiten los elementos sobre los cuales se construye la identidad en un grupo de empresas informativas colombianas y el grado en el que estos son conocidos y compartidos por los directores de contenido de las mismas entidades. Se toman como punto de referencia los estudios sobre comunicación corporativa, según los cuales, la organización busca transmitir una idea integrada sobre lo que es y lo que hace, mediante la divulgación de atributos que terminan por arraigarse en el comportamiento de los empleados. En el artículo se aportan perspectivas a la discusión sobre la formación de la identidad en organizaciones que trabajan con personas talentosas, creativas y críticas, rasgos particulares que presenta el perfil profesional de los periodistas.

8552 Background: Forodesine is a potent inhibitor of purine nucleoside phosphorylase (PNP) that leads to T-cell selective intracellular accumulation of dGTP, resulting in apoptosis. Methods: An open-label dose escalation study of oral forodesine (40–320 mg/m2 daily) for 4 wks with extended therapy was performed to determine the maximum tolerated and/or optimal biologic dose (OBD). Additional subjects were accrued at an OBD (80 mg/m2) to further assess safety and clinical efficacy. Subjects with refractory CTCL, stages IB-IV were eligible. The primary efficacy endpoint (objective response rate [ORR]) was defined as ≥ 50% improvement by a severity-weighted assessment tool (mSWAT). Results: The overall intent to treat response rate was 17 of 64 (27%) subjects or 14 of 36 (39%) at the OBD. As of October 2008, nine of 64 subjects (14%) have received forodesine treatment for >12 months. This cohort of 9 subjects is further examined. Six discontinued treatment (median time on treatment 440 days): 4 for progressive disease, 1 withdrew consent, and 1 due to an adverse event (Diffuse Large B-cell Lymphoma). Three are continuing on therapy for 416, 710, and 863 days. Median age was 68 years (range 42, 81), and all but one was ≥ stage III. They had received a median of 3 prior systemic therapies including 8 of 9 with prior bexarotene. Five of 9 subjects had a response (2 with complete response, 3 with partial response, and 4 with stable disease). Related AEs were experienced by 7 of 9 subjects. The most frequent were nausea (44%), fatigue, peripheral edema, dyspnea, and urinary casts (all 22%). Grade 3 or higher related AEs were experienced by 2 of 9 subjects (Diffuse Large B-Cell Lymphoma as previously mentioned and peripheral edema). There were no hematologic or infection AEs related to forodesine. Grade 3 lymphopenia and CD4 count < 200 were noted in 8 of 9 and 4 of 9 subjects respectively. The risk of any infection AE regardless of cause in these 9 subjects was 15 per 100 person-months of forodesine exposure compared to 59 in all other subjects (n=55). Conclusions: Forodesine has an acceptable safety profile and efficacy in these CTCL subjects treated for 12 months or longer. [Table: see text]

ImportanceSeveral pharmacotherapies have been authorized to treat nonhospitalized persons with symptomatic COVID-19. Longitudinal information on the use of these therapies is needed.ObjectiveTo analyze trends and factors associated with prescription of outpatient COVID-19 pharmacotherapies within the Veterans Health Administration (VHA).Design, Setting, and ParticipantsThis cohort study evaluated nonhospitalized veterans in VHA care who tested positive for SARS-CoV-2 from January 2022 through January 2023 using VHA and linked Community Care and Medicare databases.ExposuresDemographic characteristics, underlying medical conditions, COVID-19 vaccination, and regional and local systems of care, including Veterans Integrated Services Networks (VISNs).Main Outcomes and MeasuresMonthly receipt of any COVID-19 pharmacotherapy (nirmatrelvir-ritonavir, molnupiravir, sotrovimab, or bebtelovimab) was described. Multivariable logistic regression was used to identify factors independently associated with receipt of any vs no COVID-19 pharmacotherapy.ResultsAmong 285 710 veterans (median [IQR] age, 63.1 [49.9-73.7] years; 247 358 males [86.6%]; 28 444 Hispanic [10.0%]; 61 269 Black [21.4%] and 198 863 White [69.6%]) who tested positive for SARS-CoV-2 between January 2022 and January 2023, the proportion receiving any pharmacotherapy increased from 3285 of 102 343 veterans (3.2%) in January 2022 to 5180 of 21 688 veterans (23.9%) in August 2022. The proportion declined to 2194 of 10 551 veterans (20.8%) by January 2023. Across VISNs, the range in proportion of patients who tested positive who received nirmatrelvir-ritonavir or molnupiravir during January 2023 was 41 of 692 veterans (5.9%) to 106 of 494 veterans (21.4%) and 2.1% to 120 of 1074 veterans (11.1%), respectively. Veterans receiving any treatment were more likely to be older (adjusted odds ratio [aOR] for ages 65-74 vs 50-64 years, 1.18; 95% CI, 1.14-1.22; aOR for ages ≥75 vs 50-64 years, 1.19; 95% CI, 1.15-1.23) and have a higher Charlson Comorbidity Index score (aOR for CCI ≥6 vs 0, 1.52; 95% CI, 1.44-1.59). Compared with White veterans, Black veterans (aOR, 1.06; 95% CI, 1.02-1.09) were more likely to receive treatment, and compared with non-Hispanic veterans, Hispanic veterans (aOR 1.06; 95% CI, 1.01-1.11) were more likely to receive treatment.Conclusions And RelevanceThis study found that prescription of outpatient COVID-19 pharmacotherapies in the VHA peaked in August 2022 and declined thereafter. There were large regional differences in patterns of nirmatrelvir-ritonavir and molnupiravir use.

Abstract Background External validation of risk models is critical for risk-stratified breast cancer prevention. We used the Individualized Coherent Absolute Risk Estimation (iCARE) as a flexible tool for risk model development and comparative model validation and to make projections for population risk stratification. Methods Performance of two recently developed models, one based on the Breast and Prostate Cancer Cohort Consortium analysis (iCARE-BPC3) and another based on a literature review (iCARE-Lit), were compared with two established models (Breast Cancer Risk Assessment Tool and International Breast Cancer Intervention Study Model) based on classical risk factors in a UK-based cohort of 64 874 white non-Hispanic women (863 patients) age 35–74 years. Risk projections in a target population of US white non-Hispanic women age 50–70 years assessed potential improvements in risk stratification by adding mammographic breast density (MD) and polygenic risk score (PRS). Results The best calibrated models were iCARE-Lit (expected to observed number of cases [E/O] = 0.98, 95% confidence interval [CI] = 0.87 to 1.11) for women younger than 50 years, and iCARE-BPC3 (E/O = 1.00, 95% CI = 0.93 to 1.09) for women 50 years or older. Risk projections using iCARE-BPC3 indicated classical risk factors can identify approximately 500 000 women at moderate to high risk (&gt;3% 5-year risk) in the target population. Addition of MD and a 313-variant PRS is expected to increase this number to approximately 3.5 million women, and among them, approximately 153 000 are expected to develop invasive breast cancer within 5 years. Conclusions iCARE models based on classical risk factors perform similarly to or better than BCRAT or IBIS in white non-Hispanic women. Addition of MD and PRS can lead to substantial improvements in risk stratification. However, these integrated models require independent prospective validation before broad clinical applications.

Abstract This study evaluated the effect of replacing soybean meal (SBM) with DDGS and crystalline amino acids on growth and carcass lean. Pigs (n = 512; 38.51±0.13 kg BW) were blocked by BW and sex and placed in 64 pens (4 gilts and barrows per pen). Treatments were arranged as a 2×4 factorial with DDGS included at 0 or 25% and L-lysine-HCl (LYS) added at 0, 0.2, 0.4, and 0.6%. Dietary SBM inclusion declined as LYS increased from 32.06 to 13.14% (Phase 1) and 28.25 to 9.40% (Phase 2) for control diets. It declined from 27.85 to 8.89% (Phase 1) and 24.05 to 5.10% (Phase 2) for DDGS diets. Diets contained 1.00 (Phase 1, 21 days) and 0.90% (Phase 2, 18 days) SID lysine and were balanced for ideal protein and net energy. During Phase 1, DDGS decreased ADG (P = 0.06; 786 vs. 821 g/d). Increasing LYS increased (quadratic, P ≤ 0.05) ADG and ADFI with the greatest response at 0.4% LYS. G:F decreased (linear, P = 0.035) with increasing LYS. During Phase 2, increasing LYS in control, but not DDGS diets, decreased (linear, P &lt; 0.005) ADG and ADFI. G:F declined (P = 0.054) with DDGS inclusion (370 vs. 383 g/kg). Overall, ADG decreased (linear, P = 0.005) as LYS increased in control (959, 929, 908, 860 g/d), but not DDGS diets (863, 908, 931, 832 g/d). ADFI decreased (linear, P = 0.014) with increasing LYS in control (2270, 2198, 2186, 2130 g/d), but increased (quadratic, P = 0.039) in DDGS diets (2112, 2207, 2324, 2103 g/d). DDGS reduced (P≤0.03) ADG (883 vs. 914 g/d), G:F (405 vs. 417 g/kg) and LEA (34.5 vs. 35.3 cm2), while increasing LYS decreased (linear, P &lt; 0.005) G:F (417, 419, 409, 401 g/kg) and LEA (35.34, 35.17, 35.46, 33.64 cm2). Displacement of SBM with DDGS reduced growth and LYS addition negatively affected growth and G:F for diets with SBM, but not DDGS.

Purpose. To study the preferences of ophthalmologists in the implementation of therapeutic and diagnostic measures in children with myopia and habitually excessive tension of accommodation (HETA) as part of a routine clinical practice. Material and methods. The study was conducted based on outpatient ophthalmologists’ offices. The analysis involved 64 medical questionnaires received from 32 doctors from 23 cities of Russia (2 questionnaires of the same type were filled in, each for 20 patients) and information about 1280 clinical cases of myopia or habitually excessive tension of accommodation, documented in the medical records of children aged 5 to 17 years, diagnosed with myopia (863 children, 67.4% of the surveyed) or habitually excessive tension of accommodation (417 children, 32.6%). Data was sourced from medical treatment records and a survey of doctors’ opinions. Results. In the structure of juvenile myopia, the most commonly observed degrees are mild (49.36%) and moderate (37.31%). The recentness of myopia is proportional to its degree. Most often, for treating juvenile myopia and HETA, doctors combine a drug therapy aimed at improving accommodation (96.5%) with functional methods of treatment. Phenylephrine hydrochloride preparations such as Irifrin® and Irifrin® BK (28.44 and 33.13%, respectively), as well as the combined preparation Midrimax® (36.41%) were most often used as drug therapy. To improve accommodation, ophthalmologists of outpatient clinics more often prescribe a one-month course of drug instillations, and 50% of the respondents undergo it twice a year. However, the number of patients who rated the degree of satisfaction and adherence to therapy as high and very high turned out to be higher in cases when such courses were underwent 4 times a year, compared with the group of patients who underwent them 2 times a year. Conclusion. Convenience of use of Irifrin®, Irifrin® BK and Midrimax® drugs, combined with their availability, make it possible to recommend them for a wide clinical use – treatment of patients with myopia and habitually excessive tension of accommodation.

Abstract Abstract 1159 Poster Board I-181 Background In allogeneic SCT, genetic factors such as donor and recipient gene polymorphisms of pro- and anti-inflammatory cytokines have been associated with the incidence and severity of GVHD. However, the influence of such donor and recipient gene polymorphisms on other outcomes, such as early infection after SCT, has seldom been described. TNFαa, TNF receptorII (TNFRII), IL-10 and TGF gene contain multiple single nucleotide polymorphisms (SNPs) in the promoter and codon region. We thus studied the association of this panel of candidate gene polymorphisms with the incidence of the first episodes of early bacterial infections within 100 days after allo-HSCT. Methods A total of 138 unrelated donor/recipient pairs, who had undergone HLA-matched allo-HSCT from January 2001 to March 2009 at the First Affiliated Hospital of Zhejiang University School of Medicine, were tested for TNFαa(TNFαa-857 C>T, TNFαa-863 C>A, TNFαa-1031 T>C), TNFRII (codon196 T>G), IL-10 (IL10-1082 A>G, IL10-819 T>C, IL10-592 A>C), TGF (TGF-509 T>C, TGF+869 C>T) polymorphism allele frequencies and genotype. SNPs were analysed by Multiplex SnaPshot. We considered the first episodes of early bacterial infections within 100 days after allo-HSCT have developed when sepsis, pneumonia, or septic shock was diagnosed according to previously published criteria. Results (1) 133 patients achieved complete donor chimerism in the peripheral blood and 5 patients had graft failure. All patients achieved an absolute neutrophil count (ANC) greater than 0.5×109/L at day 13 (7∼22) and platelet recovery at day 15 (7∼64). The cumulative incidence of at least one bacterial infection was 47.8% (pneumonia and intestinal infection are the most popular) within 100 days after allo-HSCT. There is no significant difference in the time to neutrophil recovery in patients who experienced early bacterial infections with those who did not (13.6 vs 12.8,P=0.115). (2) The TNFαa-857 C/C genotype and TNFRII 196 T/T genotype of the donor were significantly associated with a higher risk of early bacterial infection ( for TNFαa-857 C/C genotype: 53.3% vs 29.0%, P=0.024 ; TNFRII 196 T/T genotype: 53.5% vs 33.3%, P=0.038); (3) The TGF-509 T/T genotype of the donor was significantly associated with a higher risk of early bacterial infection (62.5% vs 41.8, P=0.038); (4) Transplantation from donors with IL10-819 C/C genotype or IL10-592 C/C genotype were significantly associated with a higher risk of early bacterial infection (for IL10-819 C/C genotype: 71.4.1% vs 45.3%, P=0.034; IL10-592 C/C genotype: 70.0.1% vs 45.8%, P=0.055); (5) The genotypes of TNFαa-863, TNFαa-1031, IL10-1082 and TGF+869 were not found to be associated with the risk of early bacterial infection. Conclusions Recent studies have shown that the generation potential of IL-10 is influenced by the polymorphism of the IL-10 gene. The IL10-819*C allele and IL10-592 *C allele are associated with higher secretion of IL-10 than IL10-819*T allele and IL10-592*A allele. In our data, a higher risk of early bacterial infection with IL10-819 C/C and IL10-592 C/C genotype was postulated to be associated with a higher IL-10 production, which suppressed reactive T-cell response. These results, which is the first report of TNFαa, TNFRII, IL-10and TGF polymorphic features of Chinese population with the risk of early bacterial infection after HLA-matched unrelated allo-HSCT, suggest an interaction of the donor TNFαa-857C/C, TNFRII 196 T/T, IL10-819 C/C, IL10-592 C/C and TGF-509 T/T genotypes on risk of early infection. These results are helpful for predict allo-HSCT outcome, identify more suitable donors and clarify therapy on an individual patient basis. Disclosures No relevant conflicts of interest to declare.

Abstract Background Refractory acute graft versus host disease (aGVHD) is a major cause of death after allogenetic haematopoietic stem cell transplantation (allo-HSCT). This study evaluated the efficacy and safety of mesenchymal stem cells (MSCs) from bone marrow of a third-party donor to refractory aGVHD. Methods Twenty-five patients with refractory aGVHD were enrolled in this prospective study. MSCs were given at a median dose of 1×106 cells/kg once weekly until aGVHD got complete response (CR) or MSCs were infused for a total of 8 doses. In order to evaluate infections, tumor relapse and cGVHD, 25 refractory aGVHD patients with MSCs treatment was matched with grade II-IV aGVHD patient without MSCs in the corresponding period Results After a total of 112 doses of MSCs were administered, with a median of 4 (range:2-12) doses per patient, the overall response (OR) rate for aGVHD was 72%,including CR in 56% and partial response (PR) in 16%. The efficacy of MSCs to aGVHD was significantly related with the severity and the number of involved organs of aGVHD, but unrelated with the onset timing of MSC. The incidence of CMV and EBV infections, including viremia and associated disease, was not different between MSCs and non-MSCs groups during aGVHD treatment and follow-up. At a median follow-up time of 126 (range: 49–1067) days post-transplantation, only two patients relapsed in MSCs group, compared with four relapsed in the control group. Tumor relapse was not different between the two groups (P=0.771). No toxic side effects and other secondary tumors were observed after MSCs treatment except for one EBV-associated post-transplant lymphoproliferative disorders (PTLD). The incidence of cGVHD in MSCs group, especially extensive cGVHD, was lower than that in non-MSCs group (25.0% Vs 68%, P=0.001; 20.0% Vs 64%, P=0.043, respectively). The ratio of CD3+CD4+/CD3+CD8+ T cells and the proportion of CD4+CD25+ regulatory T cells (Tregs) at 8 weeks after MSCs were higher than that before treatment (P=0.037 and P=0.020, respectively), and there were not different from the healthy people at 36 weeks after treatment. Conclusions MSCs derived from bone marrow of third-party donors are effective to refractory aGVHD. It might not increase the risks of infections, tumor relapse, but reduce the incidence and severity of cGVHD. Disclosures: Liu: Science and Technology Program of Guangzhou of China (11A72121174): Research Funding; National Natural Science Foundation of China (Grant No.81000231, No.81270647): Research Funding; National Public Health Grand Research Foundation (Grant No. 201202017): Research Funding; 863 Program (No. 2011AA020105): Research Funding.

Background2,261,419 women were diagnosed with breast cancer worldwide in 2020. For postmenopausal women with hormone sensitive disease, aromatase inhibitors (AI) are recommended for their mortality benefit. However, AI bone loss (AIBL) is a recognised adverse event with resultant increase in fracture risk. In 2017, a consensus statement of 7 international bone and cancer societies was published proposing an algorithm based on clinical risk factors and different bone mineral density (BMD) threshold for bone active therapeutic intervention.ObjectivesTo determine the real-world impact of the 2017 consensus guidelines on AIBL and whether bone sparing therapy utilising proposed risk stratification model is effective in fracture prevention.MethodsOver a 7-year study period, 1001 women were prescribed AI at our university teaching hospital. The new guidelines were adopted in July 2017. We split the participants in two groups: 361 (36%) women had commenced their AI prior to the adoption of guidelines and 640 (64%) were in the post implementation group.First group were offered bone active treatment based on NOS 2009 guidelines whereas the second group followed the 2017 consensus guidelines. Women with osteoporosis were all offered treatment, however the difference in guideline is pertinent to osteopenia and we compared the results of that group.Results1001 women were included. Mean age was 64 years (range 29-93). 929 (93%) were Caucasian, 57 (6%) were Asian and 15 (1%) were Afro-Caribbean. 723 women (72%) had invasive ductal carcinoma and 863 women (86%) were postmenopausal. At diagnosis, 428 women (43%) had node positive disease and 35 women (4%) had metastases. 91 women (9%) had sustained fractures prior to their cancer diagnosis.276 women (28%) were offered oral bisphosphonates based on DEXA result, with 58 (6%) offered parenteral therapy.First group: 361 women had a baseline DEXA with a mean left neck of femur (LNOF) BMD of 0.888 g/cm2 (range 0.552-1.222). 143 (40%) women had a normal DEXA, 174 (48%) had osteopenia and 44 (12%) had osteoporosis.Of the women with osteopenia, 44 (25%) women were offered treatment and 33 women had a repeat DEXA after a mean of 4 years. In the treatment group, LNOF mean BMD remained relatively unchanged from 0.814 g/cm2 to 0.812 g/cm2 at the repeat DEXA (p= 0.94).Of the 174 women with osteopenia, 22 (13%) women had a fracture.Second group: 640 women had a baseline DEXA with a mean LNOF BMD of 0.888 g/cm2 (range 0.512-1.390). 216 (33%) women were normal, 322(50%) had osteopenia and 107 (17%) had osteoporosis.Of the women with osteopenia, 127 (39%) women were offered treatment and 56 women had a repeat DEXA after a mean of 3 years. In the treatment group, LNOF mean BMD remained relatively unchanged from 0.822 g/cm2 to 0.829 g/cm2 at the repeat DEXA (p= 0.6169).Of the 322 women with osteopenia, 8 (2.5%) women had a fracture.ConclusionOur study provides real world evidence of the success of 2017 consensus statement in lowering fracture risk. Though there has been data for positive impact on BMD decline with this approach, evidence for fracture prevention has been limited. This study showcases the success of lowering bone active therapy threshold employing alternative risk modelling strategy for women with breast cancer commenced on AI. A significant reduction in fractures pre (13%) and post guidelines change (2.5%) was demonstrated (absolute risk reduction of 10.5%) which has implications for healthcare systems worldwide as we have demonstrated this approach can reduce morbidity.References[1]https://www.wcrf.org/dietandcancer/worldwide-cancer-data/. Accessed: 26.01.2022.[2]Reid DM, Doughty J, Eastell R, et al. Guidance for the management of breast cancer treatment-induced bone loss: a consensus position statement from a UK Expert Group. Cancer Treat Rev. 2008;34 Suppl 1:S3-S18.[3]Hadji P, Aapro MS, Body JJ, et al. Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG. J Bone Oncol. 2017;7:1-12.Disclosure of InterestsNone declared

Abstract Abstract 4085 Acute graft vs. host diseases (aGVHD) is a life threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT). In a large series of patients undergoing allo-HCT (n=863) we recently demonstrated that following the initiation of corticosteroids, a clinical response at day 28 was associated with an increased likelihood of overall treatment response and a reduction in treatment related mortality (TRM) (MacMillan, Blood, 2010). We have also shown that patients who have rapid lymphocyte recovery following umbilical cord blood transplantation (UCBT) have improved outcomes (Burke, BBMT, 2010). To date, no study has addressed the influence of absolute lymphocyte count (ALC) on aGVHD treatment responses. We hypothesized that high ALC might predict favorable responses to aGVHD therapy. To test this hypothesis we reviewed the ALC at the time of aGVHD diagnosis and weekly following the initiation of corticosteroid therapy (48 mg/m2 × 14 days followed by a 10% taper over 8 weeks). ALCs were collected on patients who had clinical laboratory data available in the electronic medical record and who had available data on clinical response to corticosteroid therapy. There were 211 patients transplanted at our center from 2001–2007 who fit the above criteria. Median age was 42 years (range 0.2–69 yrs). Thirty nine patients (19%) were <18 years of age and 135 (64%) were >35 years old. The majority of patients underwent UCBT (n=134, 64%) and most others received a sibling PBSC transplant (n=71, 34%). Myeloablative conditioning was used in 55% of patients. GVHD prophylaxis was mainly with CSA/MMF (n=142, 67%) or MTX/CSA (n=42, 22%). Median time to aGVHD onset was 37 days (11–92). Patterns of aGVHD included skin only (n=91, 43%), gut only (n=36, 17%) or multi-organ involvement (n=82, 39%). At the time of GVHD diagnosis, ALC was not predictive of response to therapy. Likewise, there was no association with the ALC at D7 (after the start of steroid treatment) and therapeutic response. The D14 post-treatment ALC showed an association with clinical response at D28 (a time point previously associated with long-term responses and NRM). Patients with an ALC of 0–0.14, 0.15–0.34 and >0.35 at D+14 after corticosteroid therapy had a 40%, 54% and 68% chance of a clinical response at D28 (p>0.01). This translated into a reduction in non-relapse mortality for patients with higher ALC (0–0.14 vs. >0.15; 33% [19–47%] vs 23% [17–29%], p=0.04). Subgroup analysis showed that these observations were mainly driven by the myeloablatve UCB group. Treating ALC as a continuous variable and using a repeated measures approach, we observed that for every unit increase in ALC between the day of diagnosis and D14, there was a 2.26 higher increased likelihood of having a complete clinical response at D28 (p>0.001). Similar results were seen for NRM (OR=0.89 [0.81–9.8], p=0.01). In multivariate analysis, repeated measures of ALC (from D0-14) remained significant for both D28 clinical response (p=0.001) and NRM (p=0.05). Patients with steroid refractory aGVHD (n=17) were treated with ATG. Because steroid refractory aGVHD has poor outcomes and because ATG can negatively impact ALC, we removed these patients from the analysis to determine the impact of ALC. In this subgroup analysis, ALC at D14 after aGVHD treatment remained associated with D28 clinical response in multivariate analysis (OR=3.01, 95%CI[1.24–7.35], p=0.02). Using repeated analysis, the change in ALC from aGVHD treatment day D0 to 14 was associated with D28 treatment response (OR=4.42 [1.88–10.37], p<0.001). Collectively, these results show that absolute ALC at D14 and increases in ALC from the day of treatment to day 14were associated with D28 clinical response and NRM. ALC maybe a simple and cost effective method to monitor response to aGVHD therapy. Disclosures: No relevant conflicts of interest to declare.

ABSTRACT We have examined the activation of the pituitary-adrenal axis in two lines of rats, the Roman high (RHA)- and low (RLA)-avoidance rats known to be emotionally different. These rats are selected for rapid acquisition of a conditioned avoidance response (RHA) compared with failure to acquire this response (RLA). In this study the endocrine response (ACTH, corticosterone, aldosterone) of RLA and RHA rats to two types of stress was examined: exposure to openfield stress for 10 min (Op) or exposure to ether vapours for 3 min (E). Basal plasma ACTH concentrations were lower in RLA than in RHA rats (RLA: 110·8 ± 24·5 ng/l; RHA: 252·7 ± 60·8 ng/l, P<0·05) but the absolute values of ACTH reached after both types of stress were comparable between RLA and RHA rats. Plasma corticosterone and aldosterone under resting conditions were not different between RLA and RHA rats. Plasma corticosterone was higher in RLA following openfield stress (P<0·05) while no differences between RLA and RHA were observed after ether stress (RHA: basal = 66±14·nmol/l, Op =384± 55, E= 606± 75; RLA: basal=121±52, Op = 612 ±92, E= 698 ± 89). Stressinduced increases in plasma aldosterone were higher in the RLA line after both types of stress (RHA: basal = 175±36 pmol/l, Op = 546±53, E= 563± 47; RLA: basal = 272 ± 64, Op =1246 ± 91, E= 863 ± 72). Pituitary responsiveness to exogenous corticotrophinreleasing factor (CRF) in vivo and in vitro differed in the two lines: administration of ovine CRF (10 μg/kg body weight, i.p.) resulted in significant increases in ACTH secretion but the response was significantly lower in RHA rats (RHA: 511·1 ±41·5 ng/l; RLA: 831·4 ± 70·3 ng/l, P<0·01). Dispersed pituitary cells from the RHA line exhibited a smaller response to CRF (10 nmol/l) treatment in vitro compared with cells derived from the RLA rats (RHA: 750 ± 83% of control; RLA: 1374 ±79, P<0·01) suggesting differences in pituitary sensitivity to CRF between the two lines. Additional differences at the pituitary level were observed since the type II glucocorticoid receptor population in RHA rats was higher than in RLA rats (RHA: 246±13 fmol [3H]RU28362 bound/mg protein; RLA: 173±18, P<0·01). Similarly, hippocampal type I glucocorticoid receptor population was increased in RHA rats (RHA: 172·2 ± 8·3 fmol [3H]aldosterone bound/mg protein; RLA: 116·7±7·3, P< 0·01). It is concluded that first, differences in pituitary activity between RLA and RHA rats are distinct from changes observed at the adrenal level, secondly, increased stress-induced ACTH output in the RLA line is associated with enhanced pituitary sensitivity to CRF and possibly with diminished corticosterone inhibitory feedback action on CRF and ACTH secretion, and thirdly, the possible involvement of differences in the pattern of CRF secretion between RLA and RHA rats on resting pituitary ACTH secretion cannot be excluded. Journal of Endocrinology (1989) 123, 477–485

Abstract Background: The histone deacetylase inhibitor vorinostat was approved by the United States FDA in October 2006 for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following 2 systemic therapies. Vorinostat has also demonstrated promising preclinical activity in multiple myeloma. Patients and Methods: A Phase I trial of oral vorinostat 200, 250 or 300 mg bid for 5 days each week of a 4 week cycle or 200, 300, or 400 mg bid for 14 days/3 week cycle until progressive disease or intolerable toxicity was conducted. Patients with measurable, relapsed and/or refractory multiple myeloma with adequate hematologic, hepatic, and renal function were eligible. The objectives were to determine the maximum tolerated dose (MTD) on each of the schedules and assess activity and safety. Results: Thirteen patients (median age, 63 years; median 7 prior systemic therapies) were enrolled. The MTDs were not determined due to early termination of the study due to the decision of the sponsor. One patient (250 mg bid 5 days/week) developed dose-limiting toxicity (DLT) of grade 3 fatigue. There were no other DLTs and the maximum administered doses were 250 mg bid for 5 days each week of a 4-week cycle and 200 mg bid for 14 days/3-week cycle. Common drug-related adverse experiences included fatigue (69%), anorexia (62%), dehydration (46%), diarrhea (46%), and nausea (38%) and were mostly grade ≤ 2. Of 10 evaluable patients, 1 had a minimal response and 9 had stable disease (Table 1). Conclusions: Oral vorinostat was generally well tolerated at 250 mg bid for 5 days each week of a 4 week cycle or 200 mg bid for 14 days/3 week cycle in patients with advanced multiple myeloma. Modest activity was demonstrated in relapsed and/or refractory multiple myeloma and combination studies with other anti-myeloma agents are warranted. Table 1. Clinical outcomes of patients per EBMT Criteria* Allocation Number Age Baseline Myeloma Stage Prior Systemic Therapies Prior Bone Marrow Transplant Baseline β2-microglobulin On-study Duration (days) Best Response EBMT = European Group for Blood and Marrow Transplantation; MR = Minimal Response; ND = Not Determined; NE = Not Evaluable; SD = Stable Disease. *Cohorts 3, 5, and 6 were not initiated. Cohort 1 (200 mg twice daily x 5 days/week) 1001 55 III 12 1 ND 41 NE 1002 47 II 3 1 2.0 254 SD 1003 64 III 4 0 2.6 62 SD Cohort 2 (250 mg twice daily x 5 days/week) 1004 38 I 5 0 1.7 55 SD 1005 74 III 7 1 6.7 240 MR 1006 65 ND 7 2 3.3 74 NE 1007 67 ND 1 0 10.1 118 SD 1008 42 III 5 0 4.7 109 SD 1009 50 III 5 0 1.4 123 SD Cohort 4 (200 mg twice daily x 14 days/3 weeks) 861 69 IIIa 16 1 4.6 56 SD 862 63 IIIa 20 1 3.1 25 NE 863 61 IIIa 10 1 2.7 62 SD 864 71 IIIa 16 1 11.0 155 SD

Abstract This retrospective study looked at all patients with Haemophilia A who attended Manchester Pendlebury Childrens Hospital for their first and subsequent Factor replacement therapy between January 1980 and May 2005. The aim was to determine :- Does an increased number of different products used influence inhibitor formation. Does using a B domain deleted factor (Refacto) concentrate influence inhibitor formation. Does changing from plasma derived to recombinant factor influence inhibitor formation. A total of 107 patients who received a cumulative total of 65,102 trearment days were identified and the following information was recorded for each patient :-severity of haemophilia (mild, moderate or severe) and baseline factor VIII level, date and age of first product, all types of products used, number of treatment days used of each product, detection of inhibitor and if present date of ocurrence and age of patient. The policy of the unit was to test for inhibitors every six months, pre operatively or when clinically indicated. Thirteen different products were in use during the period of the study :- AHFC(anti haemophilic factor concentrate), Cryoprecipitate, 8Y, 8SM, Alphanate, Replenate, Monoclate P, Helixate, Refacto, Recombinate, Hemophil M, Advate and Haemate P. Only 4 patients out of 107 developed inhibitors and all were exposed to less than 4 products. Inhibitor patient demographics Haemophilia type and baseline factor VIII Number of treatment days before inhibitor Products used with respective treatment days Severe (<1%) 249 Cryoprecipitate (128) 8Y(121) Severe (1%) 75 Alphanate(34) 8SM(34) Replinate(7) Moderate (2%) 39 Alphanate(30) Helixate(9) Moderate (2%) 18 Refacto(2) Helixate(16) A total of 37 patients received 6 or greater factor products. The mean number of treatment days was 1224 (median 1285, SDV 863) and the mean number of factor products used was 6.8 (median 7, SDV 0.81). In severe patients (baseline factor VIII of 2% or less) a total of 31 patients received 4 or greater factor products. The mean number of treatment days was 1512 (median 1501, SDV 776) and the mean number of factor products used was 6.45 (median 6, SDV 1.31). A total of 23 patients received 6 or greater factor products. The mean number of treatment days was 1664 (median 1525, SDV 776) and the mean number of products used was 7.04 (median 7, SDV 0.93). There were 10443 exposure days of Refacto in those patients that did not develop an inhibitor. 69 out of 103 patients were exposed to the product with a mean number of treatment days of 151 (median 43, SDV 237). In the same population 29 out of 43 severe patients (baseline factor VIII of 2% or less) were exposed to the product with a total number of exposure days of 6464 with a mean number of treatment days of 222 (median 241, SDV 241). There were only 2 exposure days of ReFacto in just one of the inhibitor patients. 64 patient changed from using plasma to recombinant products. Only one of these patients developed an inhibitor. In this study the number of different factors used, use of a B deleted domain factor and change from plasma derived to recombinant factors did not appear to be factors in the formation of inhibitors.

Abstract Abstract 863 Aims: In order to investigate the efficacy and the safety of imatinib in children and adolescents with untreated Philadelphia-positive CML, the CML working party of the Société Française des Cancers de l'enfant (SFCE) conducted an open label, multicentric phase IV study trial (Clinical Trials.gov.NCT00845221). Patients and methods. Patients less than 18 yrs of age with newly diagnosed CP CML were eligible. Imatinib was administered orally at a dose of 260 mg/m2 which is equivalent in terms of drug exposure to the total dose of 400 mg in adults. Forty four children (64% boys) with a median age of 11.5 yrs (range 10 months-17 yrs) have been enrolled from 15 French pediatric centres between July 2004 and December 2008. Side effects were reported prospectively using the NIH CTCv2.0 criteria. Results. Median follow up is currently 17 months (range:1-67). The complete hematologic response rate was 86% and 98% (ITT) at 3 months and 6 months, respectively. The rate of complete cytogenetic response (CCyR) was 62% (ITT) at 12 months. The rate of major molecular response (MMR) defined as a BCR-ABL/ABL ratio ≤ 0.1% according to the International Scale was 34% (ITT) at 12 months. The median daily dose of imatinib was close to the intended doses, 250 mg/m2 (range 176-405) with a median treatment duration of 16 months (2 w to 67 mo). Three pts (7%) had a dose reduction of more than 25% of the theoretic dose. Nine pts (20%) interrupted imatinib temporarily at least once for a median duration of dose interruption of 12 days (range 2-70). Ten pts (23%) discontinued imatinib. The reasons for discontinuation were the following: allogeneic HSCT in CCyR or MMR (2 pts) according to the investigator choice, adverse event (2 pts: muscle pain 1 pt, liver enzyme elevation 1 pt), disease progression or failure (6 pts: loss of CHR [L248V mutation] 1pt, loss of CCyR [L384M mutation] 1pt, no cytogenetic response 1 pt, no molecular response 1 pt, loss of MMR 2 pts). One of them (loss of hematologic response) transformed to blastic phase shortly after coming off study and died. Grade III or IV toxicity was recorded in 14 pts (32%). GradeIII-IV hematologic toxicity was recorded in 8 pts (18%) including neutropenia in 18% and thrombocytopenia in 5%. Nine pts (21%) developed grade III or IV non-hematologic toxicity: muscle pain (2.5%), arthralgia (5%), weight gain (13%), liver enzyme (GOT/GPT) increase (6.5%). Change of body height was observed during the first year of treatment with imatinib in the 22 pts with a sufficient follow-up: a significant decrease of height standard deviation scores (SDS) was observed with a median of the difference of -0.37 (range, -1.09 to +0.14)(p<0.0001) between the start of the treatment and 12 months later. Conclusion. Imatinib is efficient in children and adolescent with previously untreated CML in early chronic phase. However, we report for the first time, a negative impact of imatinib on the growth in a cohort of children and adolescents treated with imatinib. Disclosures: No relevant conflicts of interest to declare.

Background:Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD), and Ulcerative colitis (UC) are related to Spondyloarthritis (SpA). Ocular manifestations (OM) are well-stablished in axial SpA but not in IBD. It has been classically reported that whereas uveitis with axial SpA is predominantly anterior, unilateral, acute, and non-recurrent; in IBD it is bilateral, posterior, insidious, and chronic (1).Objectives:In a large unselected series of IBD, our aim was to assess a) epidemiology and clinical features of uveitis associated to IBD, b) to compare patients who developed uveitis and those who did not, and c) its relationship with biological treatment used in IBD.Methods:Study of all consecutive patients from a single University Hospital during the last 40 years with: a) IBD (CD and UC), and b) uveitis according to Standarization Uveitis Nomenclature (SUN) Working Group. Demographic features, clinical findings, occurrence of other extraintestinal manifestations and treatment were recorded.Results:We studied 1449 (714 women/735 men) patients with IBD, mean age of 55.2±15.9 years.Uveitis was present in 23 (1.6 %) (38 eyes) of 1448 IBD patients. The most common pattern of uveitis was typically anterior (n=18; 78.3%), unilateral (n=19; 82.6%), acute (n=19; 82.6%), and non-recurrent (n=12; 52.2%).The comparative study between patients with and without uveitis showed a significant predominance of women (Table 1) in patients with uveitis, as well as erythema nodosum, hidradenitis suppurativa and joint involvement.Regarding IBD severity, in terms of surgical interventions, and conventional and biological immunosuppressive treatments, there were no significant differences.Conclusion:Although uveitis is more infrequent in IBD than in axial SpA, it is also anterior, unilateral, acute, and non-recurrent in contrast with published data from selected series. Patients with uveitis do not seem to represent more severe phenotype of IBD.References:[1]Lyons & Rosenbaum JT. Arch Ophthalmol 1997; 115:61-4.Table 1.General features of 1448 patients with IBD with and without uveitis.Overall(n=1449)Uveitis(n=23)Non uveitis(n=1426)pMain general featuresAge, years, mean±SD55.2±15.949.1±14.655.2±15.90.8Sex, women/men, n, (% of women)714 / 735 (49.3)17 / 6 (73.9)697 / 729 (48.9)0.02*IBD duration, years, mean±SD13.2 ± 9.717.4 ± 10.213.1 ± 8.90.08IBD SeveritySurgical Interventions, n (%)289 (19.9)2 (8.7)284 (19.9)0.7Conventional Immunosuppressive drugs, n (%)878 (60.6)14 (60.9)863 (60.5)0.5Biological Therapy, n (%)384 (26.5)7 (30.4)378 (26.5))0.9TNFi monoclonal antibodies384 (26.5)7 (30.4)378 (26.5)0.9Ustekinumab27 (1.9)1 (4.3)27 (1.9)0.5Other23 (1.6)1 (4.3)22 (1.6)0.3Extraintestinal manifestationsCutaneous manifestations, n (%) (TOTAL)125 (8.6)9 (39.1)121 (8.7)0.1Erythema nodosum, n (%)26 (1.8)6 (26.1)24 (1.7)0.009*Pyoderma gangrenosum, n (%)13 (0.9)1 (4.3)13 (0.9)0.7Hidradenitis suppurativa, n (%)2 (0.1)1 (4.3)1 (0.1)0.0001*Joint involvement, n (%) (TOTAL)131 (9)10 (43.5)121 (8.5)0.0001*Axial pattern, n (%)65 (4.5)4 (17.4)58 (4.1)0.0001*Peripheral pattern, n (%)64 (4.4)4 (17.4)63 (4.4)0.9Disclosure of Interests:Lara Sanchez-Bilbao: None declared, María José García-García: None declared, David Martínez-López: None declared, Montserrat Rivero-Tirado: None declared, Beatriz Castro: None declared, Iñigo González-Mazón: None declared, Javier Crespo: None declared, Miguel A González-Gay Speakers bureau: AbbVie, Pfizer, Roche, Sanofi, Celgene and MSD., Grant/research support from: AbbVie, MSD, Jansen and Roche,, Ricardo Blanco Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD., Grant/research support from: AbbVie, MSD and Roche

BackgroundBreast cancer remains the most common cancer diagnosed in women worldwide. Aromatase inhibitors (AI) are employed for hormone sensitive disease in mainly postmenopausal women. AI related bone loss (AIBL) is a known complication; although data regarding the natural history in the real-world, long-term outcomes and the role of bone active therapy in fracture prevention is sparse.ObjectivesOur aim was to determine the real-world impact of AIBL and whether bone sparing therapy utilising standard risk stratification model is sufficient for fracture prevention.MethodsWe undertook a longitudinal study of patients prescribed AI for breast cancer over a seven-year period at our university teaching hospital. All the data was recorded electronically with full access to demographics, disease parameters, investigations and drug management. DEXA scans performed prior to initiation of AI were compared with subsequent imaging over a mean follow up of 3 years. Outcome data for cancer and all fractures was collected. Statistical analysis was done to investigate significant relationships amongst the variables of interest.Results1001 women were identified during the study period. The mean age of the cohort was 64 years (range 29-93). 929 (93%) were Caucasian, 57 (6%) were Asian and 15 (1%) were Afro-Caribbean. 723 women (72%) were diagnosed with invasive ductal carcinoma and 863 women (86%) were postmenopausal. At diagnosis, 428 women (43%) had node positive disease and 35 women (4%) had metastases. 91 women (9%) had sustained fractures prior to their breast cancer diagnosis.All women had a baseline DEXA: 496 (49.6%) had osteopenia, 151 (15%) had osteoporosis and 354 (35.4%) had a normal result. 478 (48%) of women had a repeat scan available. Overall, there was a decline (from a mean of 0.888 g/cm2 to 0.858 g/cm2, p<0.0001) in left neck of femur (LNOF) bone mineral density (BMD) over time (mean of 3 years, with a range of 1-6).334 (33%) were prescribed bone active therapy with 276 women (83%) given oral bisphosphonates. This group had an improvement in BMD by 0.4% (LNOF mean BMD of 0.785 g/cm2 at baseline compared to LNOF mean BMD of 0.788 at repeat DEXA, p=0.82).Women who were not offered any treatment (n=667, 66%), showed a significant decline in bone density with the decline being -5%. (LNOF mean BMD of 0.939 g/cm2 at baseline compared to LNOF mean BMD of 0.888 g/cm2 at repeat DEXA, p< 0.0001).The rate of fractures remained the same between the treatment (19 fractures, 5.67%) and non-treatment group (38 fractures, 5.70%)ConclusionOur study provides long term data for AIBL and confirms a significant decline in BMD over seven years. It confirms that bone sparing therapy is effective in reducing the pace of decline in BMD. However standard risk stratification model such as FRAX based intervention thresholds in mainly those with WHO defined osteoporosis (T ≤-2.5) is ineffective in fracture prevention in keeping with prior literature. Since our study period overlaps with publication of newer guidelines recommending different T score-based risk model, further studies are required to confirm their utility.References[1]https://www.wcrf.org/dietandcancer/worldwide-cancer-data/. Date accessed: 26.01.2022[2]R. Coleman, J.J. Body, M. Aapro, et al., Bone health in cancer patients: ESMO clinical practice guidelines, Ann. Oncol. 25 (Suppl 3) (2014) iii124–iii137.[3]E. Amir, B. Seruga, S. Niraula, et al., Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis, J. Natl. Cancer Inst. 103 (2011) 1299–1309.Disclosure of InterestsNone declared

Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) is the largest subtype of lymphoma, but consists of heterogeneous groups with different prognosis. Many studies conducted to determine prognosis factors of DLBCL. Recently, several studies have been reported that the elderly Epstein-Barr virus (EBV)-positive DLBCL patients showed worse prognosis than the elderly EBV-negative DLBCL. (Oyama T et al. Clin Cancer Res 2007;13:5024-5032). On the other hand, other studies reported that EBV-positivity is not a prognosis factor in young-adult DLBCL patients (Hong JY et al. Annals of Oncology 2015;26:548-555, Nicolae A et al. BLOOD 2015;126:863-872). In the present study, retrospective analyses were carried out for patients with DLBCL diagnosed between 1990 and 2007 to analyze the clinical and prognostic significance of EBV. Patients: Those who met the following criteria were included in the study: (i) pathology confirmed de novo DLBCL, according to the WHO classification; (ii) adequate amount and quality of paraffin-embedded biopsy specimens or unstained slides for EBV-encoded RNA in situ hybridization. Statistical methods: Intergroup comparisons were carried out with Fisher's exact test for categorical variables and the Mann-Whitney test for age. For survival analysis, we carried out Kaplan-Meier and multivariate proportional hazard (Cox) analyses. Statistical analyses were carried out using the software Stata SE version 14.0. Results: A total of 456 patients were included. The median follow up duration of survivor was 100 months (range, 1.9-363). There were 236 male (51.75%) and 220 female patients (48.25%) with a median age of 67 (range, 22-94) years. 246 patients (54.0%) were in advanced (III/IV) stage, 134 (29.4%) presented with poor Eastern Cooperative Oncology Group Performance Status (ECOG-PS), 275 (60.3%) with elevated lactate dehydrogenase (LDH) level, 263 (57.7%) with extranodal involvement of 1 or more sites, and 64 (14.0%) with bulky mass. As a consequence, 211 patients (46.3%) were in high/high-intermediate International Prognostic Index (IPI) categories. 5 years overall survival (OS) was 66.2%, in total. EBV was detected in samples from 47 patients (10.3 %). The positivity was 10.6% (15 / 142) in patients of 60 years or younger, and 10.2 % (32 / 314) in those older than 60 years (p = 0.51). No differences in back ground date were found between EBV - positive and negative DLBCLs regarding age (median 66.5 vs. 64.8, P = 0.17), male sex (88.1% vs. 11.9%, P = 0.16), advanced stage (88.2% vs. 11.8%, P = 0.17), poor ECOG-PS (90.3% vs. 9.7%, P = 0.47), elevated LDH (89.5% vs. 10.6%, P = 0.48), extranodal sites of one or more (90.5% vs. 9.5%, P = 0.31), bulky mass (92.2% vs. 7.8%, P = 0.33), and higher IPI categories (88.6% vs. 11.4%, P = 0.29). The prognosis was also not different between EBV-positive and negative DLBCLs. The 5 years OS was 42.6% for EBV-positive DLBCLs, and 56.4% for EBV-negative DLBCLs (P = 0.11). The same results were found for the younger (53.3% vs. 66.9%, P = 0.30) and the elderly patients (42.9% vs. 51.8%, P = 0.18). Conclusion: In this practice based, uncontrolled study, EBV-positively wad not different in younger and elderly DLBCLs. Although EBV-positive DLBCL showed worse trend of prognosis, the difference was not statistically significant. The significance of EBV in DLBCL should be reconsidered in unbiased, large-scale patient date. Figure Figure. Disclosures Suzuki: Chugai: Honoraria; Bristol-Myers Squibb: Honoraria; Kyowa Hakko kirin: Honoraria. Suzumiya:Chugai: Research Funding, Speakers Bureau; Astellas: Research Funding; Toyama Chemical: Research Funding; Eizai: Research Funding; Takeda: Speakers Bureau; Kyowa Hakko Kirin: Research Funding.

Abstract Introduction. Acute renal failure (ARF) develops in 10–15% of patients with multiple myeloma (MM). Typically, complexes of serum free light chains (sFLC) and Tamm-Horsfall protein form casts in the distal tubules that block urine flow. Many patients, subsequently, require long-term hemodialysis (HD) and may have reduced survival. In an attempt to minimise renal damage, plasma exchange (PE) has been used to reduce the pre-renal load of sFLC. Zucchelli et al., (Kidney Int1988; 33:1175–1180) showed that PE reduced HD requirements but subsequent controlled trials showed no benefit (Johnson WJ et al., Arch Intern Med1990; 150:863–869: Clarke WF et al., Haematologica2005; 90(s1) p117). The availability of sFLC immunoassays now allows an informed evaluation of the role of PE and/or HD in treating these patients. Methods. sFLC were measured in 1: 100 patients with chronic renal failure (CRF), GFR&lt; 15ml/min and not on dialysis; 2: 38 at the beginning and end of HD (dialyzer A) and 3: 25 on chronic ambulatory peritoneal dialysis (CAPD). sFLC hemofiltration efficiency was assessed, in-vitro, for three different dialyzers, using standard pump pressures and flow rates. Sera containing approximately 1,000 mg/L of monoclonal kappa (κ ) (NR &lt; 20mg/L) and lambda (λ ) FLC (NR &lt; 27mg/L) were recycled for ~45 minutes through the dialyzers and clearance rates assessed. A two-compartment, mathematical model was constructed to assess sFLC removal by HD and PE from hypothetical patients. The following parameters were considered:- sFLC concentrations in MM at clinical presentation; monomeric κ or dimeric λ clearance differences; partition of sFLC between vascular and extravascular compartments; flow of FLC between compartments; half-life of sFLC in ARF; sFLC production and tumour killing rates with chemotherapy. The model was interrogated for various dialysis times, different dialyzers and a PE protocol of 3L, x6 over 2 weeks. Results. Mean sFLC concentrations in severe CRF were: κ 93 mg/L (range 43–207); λ 64 mg/L (range 43–134). Mean sFLC before and after HD: κ 130 mg/L (range 40–567) to 49 (range 20–234); λ 100 mg/L (range 31–225) to 61 (range 24–159). Mean sFLC in CAPD patients: κ 118 mg/L (range 31–266); λ 114 mg/L (range 36–263). Clearances of sFLC by the 3 dialyzers were: A: BBraun high flux polyethersulfone 1.8sqm (HI PeS) (the dialyzer in routine use); κ 46%: λ 39%, B: Idmesa high flux polyethersulphone 2.0sqm (200MHP); κ 67%: λ 59%, C: Asahi high flux polysulphone 2.1sqm (APS 1050); κ 71%: λ 65%. Model calculations showed that sFLC reduced from a starting value of 14g/L (typical of light chain MM) to less than 0.5g/L in 14 days using PE. Membrane A, used for four hours, x3/week, was approximately 20% more efficient than PE and reduced κ sFLC approximately 50% faster than the natural clearance rate of patients in ARF. Dialyzers B and C were approximately twice as efficient. Performing initial, 16-hour dialyses daily for 3 days, with dialyzer C reduced sFLC to less than 0.5g/L in 2–3 days with ~95% of the sFLC being removed. Dimeric λ sFLC were removed ~50% more slowly. Conclusion. PE was less efficient at removing sFLC than routine HD. Prolonged HD with high-flux dialyzers removed monoclonal sFLC quickly and should be assessed in a clinical trial for patients with acute myeloma kidney. CAPD was inefficient at removing sFLC.

ImportanceData on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2–related pneumonia are scarce.ObjectiveTo evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU.Design, Setting, and ParticipantsThis retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021.ExposuresCOVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine).Main Outcomes and MeasuresThe incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders.ResultsAmong the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] age was 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dose was 0.03 (95% CI, 0.03-0.04; P &amp;lt; .001), whereas IRR of individuals who received an adenoviral vector vaccine after 120 days was 0.21 (95% CI, 0.19-0.24; P &amp;lt; .001). There were 553 patients admitted to an ICU for COVID-19 pneumonia during the study period: 139 patients (25.1%) were vaccinated and 414 (74.9%) were unvaccinated. Compared with unvaccinated patients, vaccinated patients were older (median [IQR]: 72 [66-76] vs 60 [51-69] years; P &amp;lt; .001), primarily male individuals (110 patients [79.1%] vs 252 patients [60.9%]; P &amp;lt; .001), with more comorbidities (median [IQR]: 2 [1-3] vs 0 [0-1] comorbidities; P &amp;lt; .001) and had higher ratio of arterial partial pressure of oxygen (Pao2) and fraction of inspiratory oxygen (FiO2) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P = .007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower Pao2/FiO2 at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients.Conclusions and RelevanceIn this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status. These findings suggest a substantial reduction of the risk of developing COVID-19–related severe acute respiratory failure requiring ICU admission among vaccinated people.

Abstract Abstract 3927 Poster Board III-863 In previous studies we characterized the t(X;14)(p11.4;q32) translocation in a patient with MALT lymphoma and found that GPR34, an orphan G-protein coupled receptor (GPCR), was highly expressed due to its juxtaposition to the IGHSA2 switch region. As part of a larger MALT gene expression-profiling project, we have now acquired gene expression analysis on the patient carrying the t(X;14)(p11;q32) translocation and have confirmed overexpression of GPR34. We then measured GPR34 mRNA expression in a panel of MALT lymphomas (n=17) and found that GPR34 was expressed at levels higher than that seen in normal B cells (mean, 11.3 fold; median, 5.5; range, 1.4-64 fold). When analyzed separately, 70% (12/17) had an expression level greater than 3-fold over normal B cells. Of note, in a gastric MALT lymphoma specimen, we found a 64 fold increase in GPR34 mRNA expression. FISH studies performed on this specimen showed an extra intact GPR34 signal but no translocation involving IGH or GPR34, suggesting that other mechanisms, including gene dosage effect, can upregulate GPR34. Elevated expression of GPR34 mRNA was also detected in other histologic types of NHL, but not to the extent seen in MALT lymphoma. Taken together, these data suggest that GPR34 is commonly overexpressed in MALT lymphoma and that deregulation of GPR34 expression can occur independent of a t(X;14)(p11.4;q32) translocation. The receptor encoded by GPR34 is most similar to the PY2 receptor subfamily of GPCR and GPR34 mRNA transcripts are abundant in mast cells while lower levels were detected in other immune cells including B cells. Signals from GPR34 have been briefly described and the results to date suggest that overexpression of GPR34 results in an accumulation of inositol phosphates. To further characterize the impact of GPR34 overexpression on cell signaling, HeLa cells were transduced with a retroviral expression plasmid (pBMN-GFP) that expresses GPR34 and GFP. GFP expressing cells were isolated and overexpression of GPR34 mRNA was confirmed by PCR and GPR34 protein expression was detected by flow cytometry. When normalized to the isotype control, pBMN-GPR34 cells expressed 17-fold more GPR34 on their cell surface compared to the pBMN-vector control cells. To determine which signaling pathways were affected by GPR34 overexpression, pBMN-GPR34 or pBMN-vector control cells were transfected with an AP-1, CRE, NF-κB, E2F, SRE, NFAT, or ISRE- luciferase reporter plasmid. Upon normalization with renilla, pBMN-GPR34 expressing cells had increased luciferase activity (n=3) driven by AP-1 (5.35-fold), CRE (4.7), NF-κB (2.8-fold), and E2F (2.13) when compared to pBMN-vector control cells. ISRE, NFAT, and SRE mediated luciferase expression was similar in the GPR34 and control cells. AP-1 and CRE have been implicated in a large variety of cellular processes, including transformation, and both AP-1 and CRE activity is induced upon activation of MAP kinases. To determine if MAPK activity was also upregulated in GPR34 expressing cells, we analyzed the phosphorylation status of Erk1/2 in pBMN-GPR34 cells by western blot and found that Erk1/2 was constitutively phosphorylated in GRP34 expressing cells (1.8 fold increase) compared to vector control cells. Increased phosphorylation of PKC-α/β was also detected in pBMN-GPR34 cells (3.5 fold increase compared to control cells). To determine the biologic impact of GRP34 overexpression on cell growth, the proliferation rates of pBMN-control and pBMN-GPR34 cells were compared and it was found that proliferation of GPR34 expressing cells was 2.2 times higher than that seen in control cells. Because the MAPK kinase pathway was found to be active in the pBMN-GPR34 cells, we tested the effect of the MEK inhibitor PD98059 on proliferation and saw a dose dependent decrease in proliferation of GPR34 expressing cells. These results suggest that GPR34-mediated proliferation is Erk-dependent. In summary, these data suggest that deregulation of GPR34 is commonly found in MALT lymphoma and that overexpression of GPR34 results in activation of Erk1/2, phosphorylation of PKC, and results is AP-1 and CRE mediated transcription. Additionally, our data suggest that overexpression of GPR34 results in increased cell growth that is MAPK-dependent. Taken together, this studies indicate that overexpression of a GPCR, GPR34, may be a novel mechanism by which MALT, lymphoma, and potentially other subtypes of NHL, develop. Disclosures: No relevant conflicts of interest to declare.

Heparin, an anticoagulant widely used in numerous medical applications, is considered an essential medicine by the WHO. Due to its high volume use and that it is the parent material for low molecular weight heparins, there is potential for the raw material to be in short supply. The African swine fever epidemic in China, ongoing since August 2018, has added further restraints on heparin source material supply. At present medical grade heparin in the US is only derived from porcine intestinal mucosa; however, there are explorations into using bovine, ovine, and other sources. Bovine heparin, once common place in the US pharmaceutical sector, is again under consideration by the US FDA. This study focused on the primary immunogenic activity associated with heparin, that is heparin-induced thrombocytopenia (HIT), and how the interaction of bovine heparin with functional HIT antibodies compares to that of porcine heparin. Materials and Methods Bovine unfractionated heparin from multiple manufacturers was compared to commercial medical grade porcine heparin obtained from US pharmacies. The US Pharmacopeia porcine heparin standard was used to determine potency equivalence. Antibodies to the complex of platelet factor 4/heparin (PF4/heparin) from banked clinically confirmed HIT patient apheresis fluids were combined with heparin and donor platelet rich plasma (PRP; blood collected in citrate from volunteers after signing a consent document). Heparins were tested at final concentrations of 0.1, 0.4, 0.8, 1, and 100 U/mL. The platelet activation response was determined on the BioData PAP-8 Platelet Aggregometer and quantitated in terms of primary slope (PS), area under the curve (AUC), maximum aggregation (MA), and final aggregation (FA). Characterization of the biophysical interaction between varying molar ratios of human PF4 and heparin was performed using photon correlation spectroscopy (PCS) and zeta potential (Zp) measurements of PF4/heparin complexes using Zetasizer Nano ZS instrumentation and software. Differences between bovine and porcine heparin were assessed by t-test or Mann-Whitney test. Concentration-response curves were analyzed by two-way ANOVA followed by the Holm-Sidak multiple comparison test using SigmaPlot software. Results Platelet activation to PF4/heparin antibodies at bovine and porcine heparin concentrations of 0.1 U/mL (56 ± 9 % vs. 54 ± 11 % MA) and 0.4 U/mL (59 ± 10 % vs. 65 ± 8 % MA) were the same with the expected inhibition (9 ± 4% MA) at the supra-therapeutic concentration of 100 U/mL. Consistent responses were obtained across 21 lots of bovine heparin, 30 lots of porcine heparin, and 38 platelet-HIT antibody combinations. The HIT potential of bovine heparin and porcine heparin was not statistically different (p>0.05). At higher medical use doses, the platelet aggregation response in the presence of HIT antibodies was actually lower for bovine heparin than porcine heparin (0.8 U/mL, 49 ± 10 % vs. 64 ± 9 % MA, p<0.05; and 1.0 U/mL, 45 ± 11 % vs. 62 ± 9 % MA, p<0.05). By PCS, it was observed that the maximal aggregation between PF4 and either porcine or bovine heparin occurred at comparable molar ratios (7.3 ± 1.5 vs. 6.4 ± 0). Although the porcine and bovine heparins exhibited comparable molecular weights (16,333 ± 153 vs. 16,790 ± 230 Da) and polydispersities (1.19 ± 0.02 vs. 1.15 ± 0.01), porcine heparin formed somewhat larger complexes with PF4 (1113 ± 65 nm) than did bovine heparin (863 ± 68 nm). The molar ratios of PF4 to heparin at which the charge of the complex was fully neutralized (Zp = 0) was comparable for porcine and bovine heparin (9.04 ± 0.19 vs. 9.97 ± 0.65). Consistent responses were obtained across 4 lots of bovine heparin and 3 lots of porcine heparin. Conclusions Bovine heparin and porcine heparin had the same in vitro functional platelet activation response in the presence of HIT antibodies, the same potential to form complexes with human PF4, and the same associated features that make PF4 immunogenic. This investigation demonstrates that bovine heparins should have a similar immunogenic response as porcine heparin at equi-unit dosing. Current refinements in the manufacturing process for bovine and porcine heparins have led to well-characterized and purified products which is reflected in their comparable biological behavior. Disclosures No relevant conflicts of interest to declare.

Introduction: The chronic lymphocytic leukemia (CLL) treatment landscape is rapidly evolving, and real-world (rw) outcomes of patients receiving 2L+ therapy in the current treatment paradigm are incompletely understood. This study examined the rw outcomes of patients with CLL/ small lymphocytic lymphoma (SLL) receiving 2 or more lines of therapy (LOTs) using a large, contemporary rw dataset. Methods: Patients meeting the study criteria were identified in the COTA real-world, clinical database: Aged ≥ 18 years at diagnosis with CLL/SLL who initiated 2L therapy between January 1, 2014 and June 30, 2021. The initial index date for the study was the date of 2L initiation and was updated to the start of each subsequent LOT for LOT-specific analyses. The following time to event outcomes were evaluated for the study population and by LOT using the Kaplan-Meier method: time to next treatment (TTNT: time from index to the initiation of the next LOT or death), time to treatment discontinuation (TTD: time from index to treatment discontinuation for any reason, including end of therapy as prescribed/indicated), rw duration of response (rwDOR: time from the first clinician-documented CR or PR to the first assessment of progressive disease or the initiation of next LOT among responders), rw progression-free survival (rwPFS), and rw overall survival (rwOS). For all time-to-event endpoints, patients were censored at the date of last visit. Rw overall response rate (rwORR) was the proportion of patients who had a clinician-documented PR or CR as the best response to a LOT among all patients who received that LOT. Results: A population of 1,102 patients was identified from the COTA database meeting the study criteria. Key patient and clinical characteristics included: median age at diagnosis of 64 years, 60.9% male, 88.1% treated in a community setting, 74.1% diagnosed in 2014 or earlier, 9.3% positive for TP53 mutation (55.0% unknown), and 7.8% with del(17p) mutation (66.2% unknown). Median TTNT among patients who received 2L (n=1102) was 29.3 months (95% CI: 27.3, 32.6), and median DOR to 2L (n=863) was 31.9 months (95% CI: 27.5, 36.4). Generally, median TTNT and DOR decreased across LOT 2-4. Median TTNT from 3L (n=468) and 4L (n=201) initiation were 21.4 (95% CI: 18.2, 25.1) and 15.1 months (95% CI: 11.5, 20.2), respectively, and median DOR among 3L (n=333) and 4L (n=130) responders were 22.6 (95% CI: 18.3, 26.2) and 15.1 months (95% CI: 11.7, 22.9), respectively. More than three-quarters (78.3%) of 2L patients experienced a physician-documented CR or PR, and rwORR decreased over subsequent LOTs (71.2% in 3L and 64.7% in 4L). Median TTD varied by treatment type. Patients who received continuous therapy with Bruton's Tyrosine Kinase inhibitors (BTKis) experienced longer median TTD, while patients who received fixed-duration therapies experienced shorter median TTD. Median TTD among patients who received ibrutinib (n=391), acalabrutinib (n=54), or venetoclax + rituximab (n=48) in 2L was 24.8, 32.6, or 23.5 months, respectively, while median TTD among patients who received BR (n=194) or rituximab monotherapy (n=67) was 4.0 or 0.9 months, respectively. Finally, median rwPFS and rwOS decreased by LOT for patients who received 2L-4L. Median rwPFS for 2L, 3L, and 4L were 31.4 (95% CI: 28.6, 35.5), 22.8 (95% CI: 19.1, 26.4), and 16.5 (95% CI: 13.6, 22.6) months, respectively, and median rwOS were 79.0 (95% CI: 68.9, 85.3), 56.3 (95% CI: 51.6, 64.5), and 51.9 months (95% CI: 33.8, Not Reached), respectively. Conclusions: In this real-world, contemporary database analysis, median TTNT and DOR exceeded 2 years among 2L patients. Although the adoption of novel therapies has changed the CLL/SLL treatment paradigm and patients who received 2L BTKi therapy experienced numerically greater TTD relative to those who received other treatment types, patients with relapsed/refractory (R/R) disease continue to experience poor rwPFS and rwOS relative to patients in clinical trials. This study demonstrates the continued unmet need for this rw patient population and highlights the need for continued innovation, namely new therapeutic agents leveraging novel mechanisms of action, to improve rw outcomes for patients with R/R CLL/SLL.

Abstract Abstract 4610 Introduction Infections are a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). Up to 50% of CLL patients develop infectious complications, and 30–50% of all deaths in CLL patients are attributed to infections. Despite these data, the available research on infectious complications in CLL is primarily limited to patients participating in clinical trials of chemotherapy, obscuring the distinction between the risk of infection due to the disease’s natural history relative to the risk associated with therapy related immune suppression. METHODS: The Mayo Clinic Rochester (MCR), a tertiary referral center in rural southeastern Minnesota, is also the primary hematology center for southeastern Minnesota, northern Iowa, and western Wisconsin. There are no metropolitan areas or hematology specialty centers within a ∼50 mile radius. To explore the natural history of infection in a community-based cohort of CLL patients, we used the Mayo Clinic CLL database to identify all patients with newly diagnosed CLL who resided within 50 miles of MCR and diagnosed between January, 1999 and December, 2009. The comparison cohort consisted of 689 adult patients who also resided within 50 miles of MCR who were seen for a general medical examination between September, 2002 and December, 2009 and who were enrolled as controls in a case-control study of non-Hodgkin lymphoma. All hospitalizations at MCR among both cohorts were audited to document hospitalization with infection and cross-referenced with the Mayo Clinic infection database, which includes all culture results obtained from hospitalized MCR patients. Serologies and viral assays were also reviewed. Patients whose cultures were negative but who were given a clinical diagnosis of infection (e.g. pneumonia) and who were treated with a full course of antibiotic therapy were considered to have a culture negative infection. RESULTS: In May 2010, there were 2022 CLL patients in the Mayo Clinic CLL Database diagnosed between 1999 and 2009. Of these, 174 (9%) were local CLL patients residing within 50 miles of MCR. Median age at diagnosis for these non-referred CLL patients was 69 years (range 27–97). Most had early stage disease (60% stage 0; 32% stage I-II). On prognostic evaluation, 121 (75%) patients were CD38 negative, 66 (61%) ZAP-70 negative, 47 (50%) IGHV mutated, and 56 (62%) had either no abnormality or 13q14- as a sole abnormality on FISH analysis. 64 (37%) patients progressed to require treatment for CLL during follow-up. After median follow-up of 4.0 years (range 0–11), 32 (18.4%) CLL patients were hospitalized with infection at least once as compared to 20/689 (2.9%) individuals in the control cohort (odds ratio=7.5; p<0.0001) Figure 1A. Even prior to receiving treatment for CLL, the rate of hospitalization for infection remained higher than the control cohort (p=0.002; Figure 1B). The 32 CLL patients hospitalized with infection were admitted with infection a total of 89 times (median 1 hospitalization for infection per patient). A specific infectious organism was identified by cultures or serologies in 60 (63%) of the 89 infections in CLL cases and 10/27 (37%) infections among controls. Hospitalization for an opportunistic infection (e.g. cytomegalovirus, cryptococcus, filamentous fungi, mycobacteria, Pneumocystis) occurred in 5/174 (3%) CLL patients during follow-up compared to 0/689 controls (p<0.001). Finally, we performed a pooled multivariable analysis of all patients (n=863) to identify factors (age, sex, CLL diagnosis, CLL treatment) associated with infection risk. Most factors were independently associated with hospitalization for infection [Age (per year, OR=1.03, p=0.02), sex (male, OR=4.0, p<0.001), diagnosis of CLL (OR=2.1, p=0.09), and treatment for CLL (OR=5.9, p<0.001)]. In univariate analysis of CLL patients [sex (OR=4.2, p=0.01), higher Rai stage (p=0.046), unfavorable (del 17p13; del 11q23) FISH [OR=4.6, p=0.02] and unmutated IGHV [OR=2.8, p=0.07]) were associated with risk of infection. CONCLUSIONS: In this cohort study, patients with newly diagnosed CLL had a 7.5-fold risk of hospitalization for infection relative to the control cohort. After 4 year follow-up, ∼1 in 5 CLL patients required hospitalization for infection. Although CLL treatment was a substantial risk factor for infection, the risk of infection among untreated patients remained higher than controls. Disclosures: Kay: Biothera: Research Funding; Clegene: Research Funding; Cephalon: Research Funding; Genentech: Research Funding; Glaxo Smith Kline: Research Funding; Hospira: Research Funding; Novartis: Research Funding; Supergen: Research Funding; Calistoga: Membership on an entity’s Board of Directors or advisory committees; Celgene: Membership on an entity’s Board of Directors or advisory committees; Emergent Biosolutions (Formerly Trubion): Membership on an entity’s Board of Directors or advisory committees. Zent:GlaxoSmithKline: Research Funding; Genentech: Research Funding; Genzyme: Research Funding.

Nickel (Ni) laterites are regolith materials derived from ultramafic rocks and play an important role in the world's Ni production. Ni-laterite deposits are the supergene enrichment of Ni formed from the intense chemical and mechanical weathering of ultramafic parental rocks. In Vietnam, the weathering profile containing Ni laterite was first discovered in the Ha Tri massive (Cao Bang). This profile develops on the Ha Tri serpentinized peridotite rocks classified to the Cao Bang mafic-ultramafic complex (North Vietnam) and exhibits thick weathered zone (10 - 15m). This work carried out a detailed study of the weathering profile at the center of Ha Tri massive. Samples from different horizons of the profile were collected and analyzed in detail by XRF, XRD and SEM-EDX methods to establish the relationship between the Ni-rich supergene products and the parental peridotites (lherzolite) rocks in Ha Tri massive. The results show that the saprolite horizon is most Ni-rich in the weathering profile in Ha Tri. In this horizon, Ni-silicate minerals of garnierite group such as pimelite, nepouite and other Mg-Ni silicates have been found. The appearance of minerals of garnierite group is due to the exchange of Mg by Ni during weathering of peridotite minerals, especially olivine, which leads to the enrichment of the supergene Ni. The occurrence of Ni silicates suggests the existence of the supergene Ni ore in the weathering profile of the Ha Tri massive.References Bosio N.J., Hurst J.V., Smith R.L., 1975. Nickelliferousnontronite, a 15 Å garnierite, at Niquelandia, Goias Brazil. Clays Clay Miner., 23, 400-403. Brand N.W., Butt C.R.M., Elias M., 1998. Nickel Laterites: Classification and features. AGSO Journal of Australian Geology & Geophysics, 17(4), 81-88. Bricker O.P., Nesbitt H.W. and Gunter W.D., 1973. The stability of talc. American Mineralogist, 58, 64-72. Brindley G.W. and Hang P.T., 1973. 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Aim. To study the frequency of oral anticoagulants (ОАС) prescription for patients with atrial fibrillation (AF) after myocardial infarction (MI). Material and methods. The study includes 106 patients (60 men, 55.6%) with a previously established diagnosis of AF, who were on hospital treatment in the period 2016-2017 years in one of the university hospitals of the city and having at the time of discharge from the hospital the final diagnosis of МI. The median age was 70.0 (61.0;78.0) years. Patients with the first and only paroxysm of AF were excluded from the analysis and all further calculations were performed for 104 patients. In 64 (60.2%) of cases, AF was presented by paroxysmal form, while in 2 (1.9%) cases this paroxysm was the first and only, in 20 (18.9%) cases – persistent AF and in 20 (18.9%) – pernanent. Results. While assessing the risk of thromboembolic complications on the CHA2DS2-VASc scale, the median score for all patients was 5.0 (4.0;6.0) points. While assessing the risk of hemorrhagic complications on the HAS-BLED scale, the median score for all patients was 2.0 (2.0;3.0) points. HAS-BLED≤2 value had 71 (68.3%) patients, HAS-BLED≥3 – 33 (31.7%). Only one antiplatelet agent was prescribed to 4 (3.8%) patients. Aspirin was the only antiplatelet agent in 3 cases and clopidogrel – in one case. In 80 (76.9%) cases, patients were prescribed dual antiplatelet therapy, in 17 (16.3%) – ОАС therapy, among which 7 (6.7%) cases – a triple antithrombotic therapy (ATT), 9 (8.7%) cases – a double ATT (ОАС+ antiplatelet agent) and 1 (1.0%) case – a monotherapy. Among all cases of OAC prescription warfarin was prescribed in 11 (64.7%) cases and rivaroxaban – in 6 (35.3%). Conclusion. In real clinical practice, the prescription or refusal of ОАС occurs without taking into account the risk of thromboembolic and hemorrhagic complications according to appropriate scales.

Малые некодирующие белок РНК (микроРНК), включая микроРНК-21, в последние годы являются предметом изучения как потенциальные малоинвазивные ранние онкомаркеры. Цель. Оценить уровни экспрессии микроРНК-21 в слюне и плазме крови как метода диагностики колоректального рака (КРР), рака легкого (РЛ) и глиальных церебральных опухолей (ГЦО). Материалы и методы. Уровни экспрессии микроРНК-21 в плазме крови (ПМР-21) и слюне (СМР-21) пациентов с КРР (n = 65), РЛ (n = 14), ГЦО (n = 21) и 66 здоровых добровольцев (КГ) измерены методом полимеразной цепной реакции обратной транскрипции (ОТ-ПЦР) и выражены в условных единицах (УЕ). Для выявления предикторов КРР, РЛ, ГЦО применяли однофакторный анализ. Для формирования рисковых классов наличия онкологического процесса использовали логистическую регрессию. Результаты. СМР-21 (УЕ) при КРР (9,67 ± 18,52), ГЦО (2,51 ± 2,39), РЛ (12,27 ± 14,78) и КГ (1,30 ± 2,45) и ПМР-21 (УЕ) при КРР (3,71 ± 7,38), ГЦО (2,17 ± 2,05), РЛ (8,69 ± 6,76) и КГ (0,84 ± 0,64) статистически значимо (р < 0,001) отличались между собой. СМР-21, но не ПМР-21, при КРР с небольшой глубиной инвазии опухоли (T in situ, T2) был выше, чем при Т4 (р = 0,004; р = 0,042). Этого не наблюдалось у больных с РЛ (СМР-21: р = 0,36; ПМР-21: р = 0,6). Предикторами наличия КРР были возраст > 61 года, СМР-21 ≥ 2,0 УЕ или ПМР-21 ≥ 1,6 УЕ (чувствительность и специфичность — 52 % и 89 %, 61 % и 83 % соответственно). Предикторами для РЛ были: возраст ≥ 54 лет, ПМР-21 ≥ 3,5 УЕ или СМР-21 ≥ 2,5 УЕ (чувствительность и специфичность — 78 % и 64 %, 100 % и 86 % соответственно). У больных ГЦО предикторами были: ПМР-21 ≥ 1,5 УЕ или СМР-21 ≥ 1,6 УЕ (чувствительность и специфичность — 57 % и 71 %, 88 % и 77 % соответственно). Регрессионный анализ прогнозирования наличия онкологического процесса на основе СМР-21 хорошо показал себя при КРР (AuROC = 0,79), в отличии от РЛ (AuROC = 0,70) и ГЦО (AuROC = 0,55). Заключение. СМР-21 является перспективным для диагностики онкологических заболеваний и может быть применен как новый неинвазивный тест при КРР, включая ранние его стадии, и при солидных опухолях других локализаций.

The automotive design process and the materials in the automotive industry in recent years has caused great interest to the industrial and academic sector. In this study was to evaluate the effect of the amount of bentonite on the thermal and rheological properties of the compound bentonite / paraffin wax. Two bentonite ratios were used: paraffin wax (40:60 and 30:70). The paraffin was characterized by Fourier transform infrared spectroscopy (FTIR), the bentonite was characterized by means of x-ray diffraction (XRD), thermogravimetric analysis (TGA), X-ray fluorescence (XRF). The bentonite/paraffine wax composite was characterized by differential-scanning calorimetry (DSC) and rheology. The sample that contains a higher amount of bentonite shows a lower latent heat, and this could cause a greater heat transfer. Finally, the sample that has a lower amount of bentonite evidenced a lower viscosity, and it could be related to a lower interaction between the particles. 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The debate about diagnoses and treatment of attention deficit hyperactive disorder (ADHD) in children continue to range on between the developmental and biological perspectives. While there is increasing evidence that support the biological susceptibility of the disorder, a number of researches also emphasized the significant effect of environment on the syndrome. This study used developmental perspectives to evaluate and bring together various bio-psychosocial factors that impact on children diagnosed with ADHD. The study explored and integrated the existing and advancing study on ADHD to a more refined pattern that embraced developmental perspectives. The study also discussed how the linkage in childhood ADHD fits within the developmental psychopathology perspective. 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It is unclear how effectively jurors perform their task of assessing witness credibility. Drawing on evidence from a mock jury study involving 863 mock jurors deliberating across 64 juries, and building on existing research, this paper explores juries’ reliance on demeanour. While jurors make use of factors which the research literature suggests are often appropriate credibility markers, for example external consistency of accounts, there is cause for concern over the nuance with which jurors apply those assessments in high stakes contexts. The manner in which jurors look to manner of delivery as evidence of credibility is also problematic. The paper makes the case for a more circumspect approach towards jurors’ use of demeanour assessments. At a minimum, this requires that judicial directions no longer advocate their reliability, but remind jurors of the complexities associated with such assessments and the need to treat any conclusions grounded on presentational cues with caution.

Purpose . Whole-heart magnetic resonance coronary angiography (WH-MRCA) has been recently proposed for non-invasive coronary imaging. Early studies have suggested that WH-MRCA might have similarly high diagnostic accuracy for detection of coronary disease as multidetector CT (MDCT). Yet, no direct comparison between both techniques has been performed. The aim of the present study was therefore to perform a head-to-head comparison of both techniques for detection of significant coronary stenoses using invasive cardiac catheterization as reference standard. Methods. Seventy-seven consecutive patients (56 M, 61±14 years) prospectively underwent free-breathing 3-dimensional WH-MRCA and 40/64-slice MDCT before cardiac catheterization. WH-MRCA and MDCT images were visually graded by 2 blinded observers and the diagnostic accuracy of both methods for detecting >50% luminal diameter stenoses (DS) in segments and vessels >1.5 mm size was compared using quantitative angiography (QCA) as reference method. Results. MDCT was successfully completed in all 77 patients in < 5 minutes. By contrast, WH-MRCA failed in 9 patients (12%) because of poor navigator performance and lasted 20±4 minutes (p<.01 vs MDCT). According to QCA, out of 992 segments > 1.5 mm diameter, 49 presented >50% DS. If all segments including non interpretable segments were considered, WH-MRCA had lower sensibility (35/49 or 71% vs. 45/49 or 92%, p<0.001), lower specificity (644/943 or 68% vs. 863/943 or 92%, p<0.001) and accuracy (679/992 or 68% vs. 908/992 or 92%, p<0.001) for detection of coronary stenosis than MDCT. However if only interpretable segments were considered, the sensitivity (35/37 or 95% vs. 45/46 or 98%, p=0.58), specificity (644/689 or 93% vs. 863/917 or 94%, p=0.67) and diagnostic accuracy (679/726 or 94%, vs. 908/963 or 94%, p=0.58) of WH-MRCA and MDCT for detection of >50% DS was similar. This was also the case on per-vessel basis. Conclusion. In the present study, MDCT had higher success rate than WH-MRCA. Therefore on an intention to diagnose basis, MDCT was superior to WH-MRCA. However, the diagnostic accuracy of WH-MRCA on per-segment and per-vessel basis was not statistically different from MDCT if only interpretable segments were considered.

Strains USC-21046T and USC-21048T were isolated from foaming coastal marine waters on the Sunshine Coast, Queensland, Australia. Both strains displayed growth and morphological characteristics typical for members belonging to the genus Nocardia . The major polar lipids were diphosphatidylglycerol and phosphatidylethanolamine, and the major fatty acids were C16 : 0, C18 : 1 ω9c, C18 : 0 and C18 : 0 10-methyl. The mycolic acids of strains USC-21046T and USC-21048T consisted of chain lengths between 50–64 and 56–68, respectively. Moreover, both of those strains contained meso-diaminopimelic acid and ribose, arabinose, glucose and galactose as whole cell sugars. Based on the phylogenomic results, both strains belonged to the genus Nocardia with strain USC-21046T showing an 80.4 % genome similarity to N. vinacea NBRC 16497T and N. pseudovaccinii NBRC 100343T, whereas USC-21048T strain showed an 83.6 % genome similarity to N. aobensis NBRC 100429T. Both strains were delineated from their closely related relatives based on physiological (e.g. growth on sole carbon source) and chemotaxonomic (e.g. cellular fatty composition) differences. The digital DNA–DNA hybridization (dDDH) values between USC-21046T and USC-21048T and their closely related relatives were below the dDDH threshold value of ≤70 % used for the taxonomic classification of novel species status. The genome length of strains USC-21046T and USC-21048T were 6 878 863 and 7 066 978 bp, with G+C contents of 65.2 and 67.8 mol%, respectively. For the novel isolates, we propose the names Nocardia australiensis sp. nov. with the type strain USC-21046T (=DSM 111727T=NCCB 100867T) and Nocardia spumae sp. nov. with the type strain USC-21048T (=DSM 111726T=NCCB 100868T).

Background: In the Sesamum species complex, the lack of wild species genomic resources hinders the evolutionary comprehension of phylogenetic relationships.Results: In the present study, we generated complete chloroplast genomes of six wild relatives (Sesamum alatum, Sesamum angolense, Sesamum pedaloides, Ceratotheca sesamoides (syn. Sesamum sesamoides), Ceratotheca triloba (syn. Sesamum trilobum), and Sesamum radiatum) and a Korean cultivar, Sesamum indicum cv. Goenbaek. A typical quadripartite chloroplast structure, including two inverted repeats (IR), a large single copy (LSC), and a small single copy (SSC), was observed. A total of 114 unique genes encompassing 80 coding genes, four ribosomal RNAs, and 30 transfer RNAs were counted. The chloroplast genomes (152, 863–153, 338 bp) exhibited the IR contraction/expansion phenomenon and were quite conserved in both coding and non-coding regions. However, high values of the nucleotide diversity index were found in several genes, including ndhA, ndhE, ndhF, ycf1, and psaC–ndhD. Concordant tree topologies suggest ndhF as a useful marker for taxon discrimination. The phylogenetic inference and time divergence dating indicate that S. radiatum (2n = 64) occurred concomitantly with the sister species C. sesamoides (2n = 32) approximately 0.05 million years ago (Mya). In addition, S. alatum was clearly discriminated by forming a single clade, showing its long genetic distance and potential early speciation event in regards to the others.Conclusion: Altogether, we propose to rename C. sesamoides and C. triloba as S. sesamoides and S. trilobum, respectively, as suggested previously based on the morphological description. This study provides the first insight into the phylogenetic relationships among the cultivated and wild African native relatives. The chloroplast genome data lay a foundation for speciation genomics in the Sesamum species complex.

Background: Elevated pulmonary artery systolic pressure (PASP) is associated with a worse outcome in heart failure (HF), but the prognostic role of PASP in patients with coronary artery disease (CAD) remains unknown. Methods: 863 patients with known or suspected CAD (age: 64±13 years, 62% male) enrolled in the Emory Cardiovascular Biobank were followed for a median 455 days for all-cause death. Transthoracic echocardiographic parameters included measurement of left ventricular ejection fraction (LVEF, range: 5-80%) and diastolic function parameters. Youden’s index from the receiver operating curve analysis was used to determine the best discriminatory cutoff for PASP (cutoff=43 mmHg). Cox regression was performed to determine independent predictors of mortality. Results: 88 (10%) subjects died during follow-up. PASP correlated with left ventricular ejection fraction (LVEF, N=644, r=-0.20, p<0.0001), C-reactive protein (CRP, N=539, r=0.12, p=0.004), and mitral valve inflow E/A ratio (N=359, r=0.32, p<0.0001), mitral valve deceleration time (N=260, r=-0.16, p=0.007),and left atrial size (LAs, N=694, r=0.25, p<0.0001). High PASP predicted incident mortality in a model adjusted for age, gender, diabetes, hypertension, dyslipidemia, smoking, glomerular filtration rate, CRP, heart failure, Gensini angiographic severity score, as well as aspirin, statin, beta-blocker, and angiotensin converting enzyme-inhibitor use (HR: 3.3, p=0.000001). The association of PASP with death was independent of LVEF (HR=3.2, p=0.00002). Thus, high PASP also predicted mortality in subjects with LVEF>50% and no history of HF (HR: 4.7, p=0.004). In separate models, this association was also independent of LAs and E/A. Conclusion: High PASP >43 mmHg is an independent predictor of mortality in patients with CAD even in those with preserved LVEF without HF. Whether high PASP predicts future development of HF and hospitalization for HF exacerbation needs to be investigated.

ImportanceAnti–vascular endothelial growth factor (VEGF) intravitreal injections, a mainstay of treatment for many retinal diseases to optimize visual outcomes, have been included in prior authorization (PA) initiatives. However, if clinicians are extremely accurate in their use of anti-VEGF medications, such administrative burdens may need reconsideration.ObjectiveTo quantify PA for anti-VEGF medications (aflibercept, ranibizumab, and bevacizumab) that were approved and determine associated administrative burdens experienced by retina practices.Design, Setting, and ParticipantsProspective multicenter quality improvement study conducted from January 2022 through June 2022, and participants were 9 private retina practices across the US.Main Outcomes and MeasuresOverall rate of approval of PA requests, reasons for requesting PA, and overall rate of delay of care resulting from PA procedures.ResultsIn total, 2365 PA requests were recorded, 2225 of which met inclusion criteria. Overall, 2140 (96.2%) requests were approved. The most common reason for requesting PA, at 64% (1423 of 2225 requests), was reauthorization for a previously utilized medication. Of the 2140 approvals, 59.6% (1277) resulted in a delay in care greater than 24 hours, and 40% (863) were given on the date of service. In a granular analysis of a subset of delayed approvals, 23.9% (173 of 725) were approved within 1 day, 15.9% (115 of 725) were approved within 2 to 3 days, 21.5% (156 of 725) were approved within 4 to 7 days, 26.3% (191 of 725) were approved within 8 to 31 days, and 12.4% (90 of 725) were approved within more than 31 days. Overall, PA denial for step therapy was 2.9% (65 of 2225) of requests and uncovered diagnoses was 0.9% (20 of 2225) of requests. The median staff time spent to obtain a single PA was 100 (range, 0-200) minutes.Conclusions and RelevanceIn this study, PA requests were almost always approved but led to a delay in patient care in most patients. The current study suggests that the PA process may not be effective for retina specialists if these results can be generalized to other practices in the US and if less burdensome and less costly approaches could result in similar approval rates. Potential short-term solutions may include eliminating the PA process for bevacizumab and reauthorizations for established patients.

Abstract Background Lung ultrasound (LUS) detects pulmonary congestion as B-lines at rest. Methods After preliminary exclusion of 154 patients lost to follow-up, we analyzed transthoracic echocardiography (TTE) plus LUS (4-site simplified scan) data in 5165 subjects (age 64±11 years) referred to 19 certified centers of 9 countries for known or suspected coronary artery disease (n=3891, 75%), dyspnea (n=591, 12%), or screening in asymptomatic patients with risk factors (n=667, 13%). We analyzed the anterior and lateral hemi-thoraces, scanning from mid-axillary to mid-clavicular lines on the third intercostal space. B-lines score ranged from 0 (normal) to 40 (severely abnormal). By selection, follow-up information was available in all. All-cause death was the predetermined end-point. Results Feasibility of B-lines was 100% in all subjects. B-lines (median) were 0.1 [0–1]. Rest B-lines (≥2) were present in 863 patients (16.7%). Ejection fraction was 61±10%. After a median follow-up of 690 (Interquartile range 420–1065) days, 96 all-cause deaths occurred. Two-year mortality was 3.6% in patients with and 1.5% in patients without B-lines (p&lt;0.001) and increased progressively with the increasing number of B-lines, from 2.4% in mild (2–4, n=630), 5.0% in moderate (5–9, n=160) and 8.2% in patients with severe (≥10, n=73) B-lines (see figure). At multivariable analysis, rest B lines (HR 1.812, 95% CI: 1.165–2.916, p=0.008) and ejection fraction (HR 0.987, 95% CI: 0.976–0.998, p=0.020) were independent predictors of all-cause death, in addition to age (HR 1.045, 95% CI: 1.023–01.067, p&lt;0.001) and diabetes (HR 1.643, 95% CI: 1.079–2.503, p=0.021). Conclusion In all-comers referred for TTE, resting B-lines assessed by focused LUS with the simplified 4-site scan are detected in 1 out of 4 patients with symptos or coronary risk factors and are associated with worse survival. The severity of pulmonary congestion predicts the severity of outcomes. The prognostic value of resting B-lines is independent and additive over standard clinical and TTE predictors such as diabetes and ejection fraction. Focused LUS for pulmonary congestion can easily be incorporated in standard TTE examination. Funding Acknowledgement Type of funding sources: None.

Background: After the recent introduction of GnRH antagonists in ovarian stimulation, OCP has been used for cycle scheduling purposes. Cycle programming has become more difficult with the use of GnRH antagonists, as stimulation initiation is dependent on the occurrence of menstruation. To overcome this limitation in the GnRH antagonist protocol, patients can be offered the use of pretreatment with oral contraceptive pills (OCP). Objective: To evaluate the effect of oral contraceptive pills (OCP) pretreatment on pregnancy rate in GnRH antagonist cycles. Design: Observational cohort study. Setting: Observational study performed at Sri Ramachandra institute of higher education & research Chennai. Patients: Total 115 patients included in the study from January 2019 to December 2019. All patients divided into two groups, oral contraceptives pretreated group (n-64) and oral contraceptives non treated group (n-51). Results: All oral contraceptives pretreated patients required significantly higher dose of gonadotropins (4745±1476 versus 3659±1230;P <0.0005) and significantly longer days of stimulations (12.2±1.2 versus 10.5±0.8;P <0.0005) in comparison to non-oral contraceptives treated group. There were no difference in total oocytes retrieved and fertilization rate. There were no other differences in cycle characteristics between groups. Implantation and pregnancy rates were not affected by OCP pretreatment. Conclusions: OCP pretreatment use for synchronization of follicles and cycle scheduling in GnRH-antagonist protocol, though it may be associated with longer stimulation and higher gonadotropin consumption but similar pregnancy rates.

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Introduction I am a transmigrant who has moved back and forth between the West and the Rest. I was born and raised in a Muslim family in a predominantly Muslim country, Bangladesh, but I spent several years of my childhood in Pakistan. After my marriage, I lived in the United States for a year and a half, the Middle East for 5 years, Australia for three years, back to the Middle East for another 5 years, then, finally, in Australia for the last 12 years. I speak Bengali (my mother tongue), Urdu (which I learnt in Pakistan), a bit of Arabic (learnt in the Middle East); but English has always been my medium of instruction. So where is home? Is it my place of origin, the Muslim umma, or my land of settlement? Or is it my ‘root’ or my ‘route’ (Blunt and Dowling)? Blunt and Dowling (199) observe that the lives of transmigrants are often interpreted in terms of their ‘roots’ and ‘routes’, which are two frameworks for thinking about home, homeland and diaspora. Whereas ‘roots’ might imply an original homeland from which people have scattered, and to which they might seek to return, ‘routes’ focuses on mobile, multiple and transcultural geographies of home. However, both ‘roots’ and ‘routes’ are attached to emotion and identity, and both invoke a sense of place, belonging or alienation that is intrinsically tied to a sense of self (Blunt and Dowling 196-219). In this paper, I equate home with my root (place of birth) and route (transnational homing) within the context of the ‘diaspora and belonging’. First I define the diaspora and possible criteria of belonging. Next I describe my transnational homing within the framework of diaspora and belonging. Finally, I consider how Australia can be a ‘home’ for me and other Muslim Australians. The Diaspora and Belonging Blunt and Dowling (199) define diaspora as “scattering of people over space and transnational connections between people and the places”. Cohen emphasised the ethno-cultural aspects of the diaspora setting; that is, how migrants identify and position themselves in other nations in terms of their (different) ethnic and cultural orientation. Hall argues that the diasporic subjects form a cultural identity through transformation and difference. Speaking of the Hindu diaspora in the UK and Caribbean, Vertovec (21-23) contends that the migrants’ contact with their original ‘home’ or diaspora depends on four factors: migration processes and factors of settlement, cultural composition, structural and political power, and community development. With regard to the first factor, migration processes and factors of settlement, Vertovec explains that if the migrants are political or economic refugees, or on a temporary visa, they are likely to live in a ‘myth of return’. In the cultural composition context, Vertovec argues that religion, language, region of origin, caste, and degree of cultural homogenisation are factors in which migrants are bound to their homeland. Concerning the social structure and political power issue, Vertovec suggests that the extent and nature of racial and ethnic pluralism or social stigma, class composition, degree of institutionalised racism, involvement in party politics (or active citizenship) determine migrants’ connection to their new or old home. Finally, community development, including membership in organisations (political, union, religious, cultural, leisure), leadership qualities, and ethnic convergence or conflict (trends towards intra-communal or inter-ethnic/inter-religious co-operation) would also affect the migrants’ sense of belonging. Using these scholarly ideas as triggers, I will examine my home and belonging over the last few decades. My Home In an initial stage of my transmigrant history, my home was my root (place of birth, Dhaka, Bangladesh). Subsequently, my routes (settlement in different countries) reshaped my homes. In all respects, the ethno-cultural factors have played a big part in my definition of ‘home’. But on some occasions my ethnic identification has been overridden by my religious identification and vice versa. By ethnic identity, I mean my language (mother tongue) and my connection to my people (Bangladeshi). By my religious identity, I mean my Muslim religion, and my spiritual connection to the umma, a Muslim nation transcending all boundaries. Umma refers to the Muslim identity and unity within a larger Muslim group across national boundaries. The only thing the members of the umma have in common is their Islamic belief (Spencer and Wollman 169-170). In my childhood my father, a banker, was relocated to Karachi, Pakistan (then West Pakistan). Although I lived in Pakistan for much of my childhood, I have never considered it to be my home, even though it is predominantly a Muslim country. In this case, my home was my root (Bangladesh) where my grandparents and extended family lived. Every year I used to visit my grandparents who resided in a small town in Bangladesh (then East Pakistan). Thus my connection with my home was sustained through my extended family, ethnic traditions, language (Bengali/Bangla), and the occasional visits to the landscape of Bangladesh. Smith (9-11) notes that people build their connection or identity to their homeland through their historic land, common historical memories, myths, symbols and traditions. Though Pakistan and Bangladesh had common histories, their traditions of language, dress and ethnic culture were very different. For example, the celebration of the Bengali New Year (Pohela Baishakh), folk dance, folk music and folk tales, drama, poetry, lyrics of poets Rabindranath Tagore (Rabindra Sangeet) and Nazrul Islam (Nazrul Geeti) are distinct in the cultural heritage of Bangladesh. Special musical instruments such as the banshi (a bamboo flute), dhol (drums), ektara (a single-stringed instrument) and dotara (a four-stringed instrument) are unique to Bangladeshi culture. The Bangladeshi cuisine (rice and freshwater fish) is also different from Pakistan where people mainly eat flat round bread (roti) and meat (gosh). However, my bonding factor to Bangladesh was my relatives, particularly my grandparents as they made me feel one of ‘us’. Their affection for me was irreplaceable. The train journey from Dhaka (capital city) to their town, Noakhali, was captivating. The hustle and bustle at the train station and the lush green paddy fields along the train journey reminded me that this was my ‘home’. Though I spoke the official language (Urdu) in Pakistan and had a few Pakistani friends in Karachi, they could never replace my feelings for my friends, extended relatives and cousins who lived in Bangladesh. I could not relate to the landscape or dry weather of Pakistan. More importantly, some Pakistani women (our neighbours) were critical of my mother’s traditional dress (saree), and described it as revealing because it showed a bit of her back. They took pride in their traditional dress (shalwar, kameez, dopatta), which they considered to be more covered and ‘Islamic’. So, because of our traditional dress (saree) and perhaps other differences, we were regarded as the ‘Other’. In 1970 my father was relocated back to Dhaka, Bangladesh, and I was glad to go home. It should be noted that both Pakistan and Bangladesh were separated from India in 1947 – first as one nation; then, in 1971, Bangladesh became independent from Pakistan. The conflict between Bangladesh (then East Pakistan) and Pakistan (then West Pakistan) originated for economic and political reasons. At this time I was a high school student and witnessed acts of genocide committed by the Pakistani regime against the Bangladeshis (March-December 1971). My memories of these acts are vivid and still very painful. After my marriage, I moved from Bangladesh to the United States. In this instance, my new route (Austin, Texas, USA), as it happened, did not become my home. Here the ethno-cultural and Islamic cultural factors took precedence. I spoke the English language, made some American friends, and studied history at the University of Texas. I appreciated the warm friendship extended to me in the US, but experienced a degree of culture shock. I did not appreciate the pub life, alcohol consumption, and what I perceived to be the lack of family bonds (children moving out at the age of 18, families only meeting occasionally on birthdays and Christmas). Furthermore, I could not relate to de facto relationships and acceptance of sex before marriage. However, to me ‘home’ meant a family orientation and living in close contact with family. Besides the cultural divide, my husband and I were living in the US on student visas and, as Vertovec (21-23) noted, temporary visa status can deter people from their sense of belonging to the host country. In retrospect I can see that we lived in the ‘myth of return’. However, our next move for a better life was not to our root (Bangladesh), but another route to the Muslim world of Dhahran in Saudi Arabia. My husband moved to Dhahran not because it was a Muslim world but because it gave him better economic opportunities. However, I thought this new destination would become my home – the home that was coined by Anderson as the imagined nation, or my Muslim umma. Anderson argues that the imagined communities are “to be distinguished, not by their falsity/genuineness, but by the style in which they are imagined” (6; Wood 61). Hall (122) asserts: identity is actually formed through unconscious processes over time, rather than being innate in consciousness at birth. There is always something ‘imaginary’ or fantasized about its unity. It always remains incomplete, is always ‘in process’, always ‘being formed’. As discussed above, when I had returned home to Bangladesh from Pakistan – both Muslim countries – my primary connection to my home country was my ethnic identity, language and traditions. My ethnic identity overshadowed the religious identity. But when I moved to Saudi Arabia, where my ethnic identity differed from that of the mainstream Arabs and Bedouin/nomadic Arabs, my connection to this new land was through my Islamic cultural and religious identity. Admittedly, this connection to the umma was more psychological than physical, but I was now in close proximity to Mecca, and to my home of Dhaka, Bangladesh. Mecca is an important city in Saudi Arabia for Muslims because it is the holy city of Islam, the home to the Ka’aba (the religious centre of Islam), and the birthplace of Prophet Muhammad [Peace Be Upon Him]. It is also the destination of the Hajj, one of the five pillars of Islamic faith. Therefore, Mecca is home to significant events in Islamic history, as well as being an important present day centre for the Islamic faith. We lived in Dhahran, Saudi Arabia for 5 years. Though it was a 2.5 hours flight away, I treasured Mecca’s proximity and regarded Dhahran as my second and spiritual home. Saudi Arabia had a restricted lifestyle for women, but I liked it because it was a Muslim country that gave me the opportunity to perform umrah Hajj (pilgrimage). However, Saudi Arabia did not allow citizenship to expatriates. Saudi Arabia’s government was keen to protect the status quo and did not want to compromise its cultural values or standard of living by allowing foreigners to become a permanent part of society. In exceptional circumstances only, the King granted citizenship to a foreigner for outstanding service to the state over a number of years. Children of foreigners born in Saudi Arabia did not have rights of local citizenship; they automatically assumed the nationality of their parents. If it was available, Saudi citizenship would assure expatriates a secure and permanent living in Saudi Arabia; as it was, there was a fear among the non-Saudis that they would have to leave the country once their job contract expired. Under the circumstances, though my spiritual connection to Mecca was strong, my husband was convinced that Saudi Arabia did not provide any job security. So, in 1987 when Australia offered migration to highly skilled people, my husband decided to migrate to Australia for a better and more secure economic life. I agreed to his decision, but quite reluctantly because we were again moving to a non-Muslim part of the world, which would be culturally different and far away from my original homeland (Bangladesh). In Australia, we lived first in Brisbane, then Adelaide, and after three years we took our Australian citizenship. At that stage I loved the Barossa Valley and Victor Harbour in South Australia, and the Gold Coast and Sunshine Coast in Queensland, but did not feel at home in Australia. We bought a house in Adelaide and I was a full time home-maker but was always apprehensive that my children (two boys) would lose their culture in this non-Muslim world. In 1990 we once again moved back to the Muslim world, this time to Muscat, Sultanate of Oman. My connection to this route was again spiritual. I valued the fact that we would live in a Muslim country and our children would be brought up in a Muslim environment. But my husband’s move was purely financial as he got a lucrative job offer in Muscat. We had another son in Oman. We enjoyed the luxurious lifestyle provided by my husband’s workplace and the service provided by the housemaid. I loved the beaches and freedom to drive my car, and I appreciated the friendly Omani people. I also enjoyed our frequent trips (4 hours flight) to my root, Dhaka, Bangladesh. So our children were raised within our ethnic and Islamic culture, remained close to my root (family in Dhaka), though they attended a British school in Muscat. But by the time I started considering Oman to be my second home, we had to leave once again for a place that could provide us with a more secure future. Oman was like Saudi Arabia; it employed expatriates only on a contract basis, and did not give them citizenship (not even fellow Muslims). So after 5 years it was time to move back to Australia. It was with great reluctance that I moved with my husband to Brisbane in 1995 because once again we were to face a different cultural context. As mentioned earlier, we lived in Brisbane in the late 1980s; I liked the weather, the landscape, but did not consider it home for cultural reasons. Our boys started attending expensive private schools and we bought a house in a prestigious Western suburb in Brisbane. Soon after arriving I started my tertiary education at the University of Queensland, and finished an MA in Historical Studies in Indian History in 1998. Still Australia was not my home. I kept thinking that we would return to my previous routes or the ‘imagined’ homeland somewhere in the Middle East, in close proximity to my root (Bangladesh), where we could remain economically secure in a Muslim country. But gradually I began to feel that Australia was becoming my ‘home’. I had gradually become involved in professional and community activities (with university colleagues, the Bangladeshi community and Muslim women’s organisations), and in retrospect I could see that this was an early stage of my ‘self-actualisation’ (Maslow). Through my involvement with diverse people, I felt emotionally connected with the concerns, hopes and dreams of my Muslim-Australian friends. Subsequently, I also felt connected with my mainstream Australian friends whose emotions and fears (9/11 incident, Bali bombing and 7/7 tragedy) were similar to mine. In late 1998 I started my PhD studies on the immigration history of Australia, with a particular focus on the historical settlement of Muslims in Australia. This entailed retrieving archival files and interviewing people, mostly Muslims and some mainstream Australians, and enquiring into relevant migration issues. I also became more active in community issues, and was not constrained by my circumstances. By circumstances, I mean that even though I belonged to a patriarchally structured Muslim family, where my husband was the main breadwinner, main decision-maker, my independence and research activities (entailing frequent interstate trips for data collection, and public speaking) were not frowned upon or forbidden (Khan 14-15); fortunately, my husband appreciated my passion for research and gave me his trust and support. This, along with the Muslim community’s support (interviews), and the wider community’s recognition (for example, the publication of my letters in Australian newspapers, interviews on radio and television) enabled me to develop my self-esteem and built up my bicultural identity as a Muslim in a predominantly Christian country and as a Bangladeshi-Australian. In 2005, for the sake of a better job opportunity, my husband moved to the UK, but this time I asserted that I would not move again. I felt that here in Australia (now in Perth) I had a job, an identity and a home. This time my husband was able to secure a good job back in Australia and was only away for a year. I no longer dream of finding a home in the Middle East. Through my bicultural identity here in Australia I feel connected to the wider community and to the Muslim umma. However, my attachment to the umma has become ambivalent. I feel proud of my Australian-Muslim identity but I am concerned about the jihadi ideology of militant Muslims. By jihadi ideology, I mean the extremist ideology of the al-Qaeda terrorist group (Farrar 2007). The Muslim umma now incorporates both moderate and radical Muslims. The radical Muslims (though only a tiny minority of 1.4 billion Muslims worldwide) pose a threat to their moderate counterparts as well as to non-Muslims. In the UK, some second- and third-generation Muslims identify themselves with the umma rather than their parents’ homelands or their country of birth (Husain). It should not be a matter of concern if these young Muslims adopt a ‘pure’ Muslim identity, providing at the same time they are loyal to their country of residence. But when they resort to terrorism with their ‘pure’ Muslim identity (e.g., the 7/7 London bombers) they defame my religion Islam, and undermine my spiritual connection to the umma. As a 1st generation immigrant, the defining criteria of my ‘homeliness’ in Australia are my ethno-cultural and religious identity (which includes my family), my active citizenship, and my community development/contribution through my research work – all of which allow me a sense of efficacy in my life. My ethnic and religious identities generally co-exist equally, but when I see some Muslims kill my fellow Australians (such as the Bali bombings in 2002 and 2005) my Australian identity takes precedence. I feel for the victims and condemn the perpetrators. On the other hand, when I see politics play a role over the human rights issues (e.g., the Tampa incident), my religious identity begs me to comment on it (see Kabir, Muslims in Australia 295-305). Problematising ‘Home’ for Muslim Australians In the European context, Grillo (863) and Werbner (904), and in the Australian context, Kabir (Muslims in Australia) and Poynting and Mason, have identified the diversity within Islam (national, ethnic, religious etc). Werbner (904) notes that in spite of the “wishful talk of the emergence of a ‘British Islam’, even today there are Pakistani, Bangladeshi and Arab mosques, as well as Turkish and Shia’a mosques”; thus British Muslims retain their separate identities. Similarly, in Australia, the existence of separate mosques for the Bangladeshi, Pakistani, Arab and Shia’a peoples indicates that Australian Muslims have also kept their ethnic identities discrete (Saeed 64-77). However, in times of crisis, such as the Salman Rushdie affair in 1989, and the 1990-1991 Gulf crises, both British and Australian Muslims were quick to unite and express their Islamic identity by way of resistance (Kabir, Muslims in Australia 160-162; Poynting and Mason 68-70). In both British and Australian contexts, I argue that a peaceful rally or resistance is indicative of active citizenship of Muslims as it reveals their sense of belonging (also Werbner 905). So when a transmigrant Muslim wants to make a peaceful demonstration, the Western world should be encouraged, not threatened – as long as the transmigrant’s allegiances lie also with the host country. In the European context, Grillo (868) writes: when I asked Mehmet if he was planning to stay in Germany he answered without hesitation: ‘Yes, of course’. And then, after a little break, he added ‘as long as we can live here as Muslims’. In this context, I support Mehmet’s desire to live as a Muslim in a non-Muslim world as long as this is peaceful. Paradoxically, living a Muslim life through ijtihad can be either socially progressive or destructive. The Canadian Muslim feminist Irshad Manji relies on ijtihad, but so does Osama bin Laden! Manji emphasises that ijtihad can be, on the one hand, the adaptation of Islam using independent reasoning, hybridity and the contesting of ‘traditional’ family values (c.f. Doogue and Kirkwood 275-276, 314); and, on the other, ijtihad can take the form of conservative, patriarchal and militant Islamic values. The al-Qaeda terrorist Osama bin Laden espouses the jihadi ideology of Sayyid Qutb (1906-1966), an Egyptian who early in his career might have been described as a Muslim modernist who believed that Islam and Western secular ideals could be reconciled. But he discarded that idea after going to the US in 1948-50; there he was treated as ‘different’ and that treatment turned him against the West. He came back to Egypt and embraced a much more rigid and militaristic form of Islam (Esposito 136). Other scholars, such as Cesari, have identified a third orientation – a ‘secularised Islam’, which stresses general beliefs in the values of Islam and an Islamic identity, without too much concern for practices. Grillo (871) observed Islam in the West emphasised diversity. He stressed that, “some [Muslims were] more quietest, some more secular, some more clamorous, some more negotiatory”, while some were exclusively characterised by Islamic identity, such as wearing the burqa (elaborate veils), hijabs (headscarves), beards by men and total abstinence from drinking alcohol. So Mehmet, cited above, could be living a Muslim life within the spectrum of these possibilities, ranging from an integrating mode to a strict, militant Muslim manner. In the UK context, Zubaida (96) contends that marginalised, culturally-impoverished youth are the people for whom radical, militant Islamism may have an appeal, though it must be noted that the 7/7 bombers belonged to affluent families (O’Sullivan 14; Husain). In Australia, Muslim Australians are facing three challenges. First, the Muslim unemployment rate: it was three times higher than the national total in 1996 and 2001 (Kabir, Muslims in Australia 266-278; Kabir, “What Does It Mean” 63). Second, some spiritual leaders have used extreme rhetoric to appeal to marginalised youth; in January 2007, the Australian-born imam of Lebanese background, Sheikh Feiz Mohammad, was alleged to have employed a DVD format to urge children to kill the enemies of Islam and to have praised martyrs with a violent interpretation of jihad (Chulov 2). Third, the proposed citizenship test has the potential to make new migrants’ – particularly Muslims’ – settlement in Australia stressful (Kabir, “What Does It Mean” 62-79); in May 2007, fuelled by perceptions that some migrants – especially Muslims – were not integrating quickly enough, the Howard government introduced a citizenship test bill that proposes to test applicants on their English language skills and knowledge of Australian history and ‘values’. I contend that being able to demonstrate knowledge of history and having English language skills is no guarantee that a migrant will be a good citizen. Through my transmigrant history, I have learnt that developing a bond with a new place takes time, acceptance and a gradual change of identity, which are less likely to happen when facing assimilationist constraints. I spoke English and studied history in the United States, but I did not consider it my home. I did not speak the Arabic language, and did not study Middle Eastern history while I was in the Middle East, but I felt connected to it for cultural and religious reasons. Through my knowledge of history and English language proficiency I did not make Australia my home when I first migrated to Australia. Australia became my home when I started interacting with other Australians, which was made possible by having the time at my disposal and by fortunate circumstances, which included a fairly high level of efficacy and affluence. If I had been rejected because of my lack of knowledge of ‘Australian values’, or had encountered discrimination in the job market, I would have been much less willing to embrace my host country and call it home. I believe a stringent citizenship test is more likely to alienate would-be citizens than to induce their adoption of values and loyalty to their new home. Conclusion Blunt (5) observes that current studies of home often investigate mobile geographies of dwelling and how it shapes one’s identity and belonging. Such geographies of home negotiate from the domestic to the global context, thus mobilising the home beyond a fixed, bounded and confining location. Similarly, in this paper I have discussed how my mobile geography, from the domestic (root) to global (route), has shaped my identity. Though I received a degree of culture shock in the United States, loved the Middle East, and was at first quite resistant to the idea of making Australia my second home, the confidence I acquired in residing in these ‘several homes’ were cumulative and eventually enabled me to regard Australia as my ‘home’. I loved the Middle East, but I did not pursue an active involvement with the Arab community because I was a busy mother. Also I lacked the communication skill (fluency in Arabic) with the local residents who lived outside the expatriates’ campus. I am no longer a cultural freak. I am no longer the same Bangladeshi woman who saw her ethnic and Islamic culture as superior to all other cultures. I have learnt to appreciate Australian values, such as tolerance, ‘a fair go’ and multiculturalism (see Kabir, “What Does It Mean” 62-79). My bicultural identity is my strength. With my ethnic and religious identity, I can relate to the concerns of the Muslim community and other Australian ethnic and religious minorities. And with my Australian identity I have developed ‘a voice’ to pursue active citizenship. Thus my biculturalism has enabled me to retain and merge my former home with my present and permanent home of Australia. References Anderson, Benedict. Imagined Communities: Reflections on the Origin and Spread of Nationalism. London, New York: Verso, 1983. Australian Bureau of Statistics: Census of Housing and Population, 1996 and 2001. Blunt, Alison. Domicile and Diaspora: Anglo-Indian Women and the Spatial Politics of Home. 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Citation reference for this article MLA Style Kabir, Nahid. "Why I Call Australia ‘Home’?: A Transmigrant’s Perspective." M/C Journal 10.4 (2007). echo date('d M. Y'); ?> <http://journal.media-culture.org.au/0708/15-kabir.php>. APA Style Kabir, N. (Aug. 2007) "Why I Call Australia ‘Home’?: A Transmigrant’s Perspective," M/C Journal, 10(4). Retrieved echo date('d M. Y'); ?> from <http://journal.media-culture.org.au/0708/15-kabir.php>.