Academic literature on the topic 'Tumor Size Growth Rate'

Object. This study was undertaken to analyze factors associated with the size of unilateral vestibular schwannomas (VSs). Methods. A retrospective analysis of an unselected and sequential series of 433 patients with unilateral VSs was conducted. Tumor size was defined by the largest dimension of the tumor in the cerebellopontine angle, and the size was tested for a relationship with patient age and sex. In a subgroup of 231 patients in whom data were available, tumor size was also tested for a relationship with tumor cysts or the absence of an internal auditory canal (IAC) component. Some patients underwent a period of surveillance with serial imaging studies to monitor for tumor growth. Data from these patients, excluding those with cystic tumors, were analyzed to see if tumor growth was related to patient age, sex, or tumor size. Conclusions. Larger tumors were found in younger patients, in females, in the subgroup of cystic tumors, and in patients in whom there was no tumor component in the IAC. The probable explanations for these larger tumors are a faster growth rate and/or a delay in symptom onset. When untreated tumors are managed with observation, measurable growth is more often seen in larger tumors, although smaller tumors have a faster relative growth rate than larger ones.

OBJECTIVEThe objective of this study was to elucidate the features and surgical outcomes of cervical schwannomas.METHODSThe authors retrospectively reviewed the records of 90 patients who underwent surgically treated cervical schwannomas from January 1995 to December 2017, with an emphasis on MRI findings such as tumor location, tumor size, extent of tumor resection, and growth of a residual tumor.RESULTSThis study included 51 men (56.7%) and 39 women (43.3%) with a mean age of 44.5 years (range 7–77 years). Dumbbell-shaped tumors comprised 62 (68.9%) of 90 cases and gross-total resection (GTR) was achieved in 59 (65.6%) of 90 cases. All nondumbbell tumors (n = 28) underwent GTR. Only 1 case of recurrence in the GTR group showed a gradual increase in size (by 8.9 mm) during the 150-month follow-up period. For the regrowth patients in the subtotal resection group, the mean percentage increase in tumor size was 47.5% ± 33.1% and the mean growth rate was 5.8 ± 4.6 mm/year during the 20.3-month follow-up period. However, the size of residual tumor spontaneously decreased by a mean of 8.3% ± 11.1% during the 48.4-month follow-up period in the nonregrowth group.CONCLUSIONSThese findings suggested that frequent MRI follow-up examinations are required for residual schwannomas in the cervical spine for at least 2 years, and continuous MRI follow-ups are also required thereafter.

In this study we investigated the relationship between thymidylate synthase (TS) protein expression, evaluated by Western blotting analysis and by immunohistochemistry (IHC), and growth rate in human colon xenograft tumors in nude mice. Human colon cancer cell lines were used to induce xenograft tumors and the tumor mass growth rate was calculated by measuring tumor size variations over time. TS 106 monoclonal antibody was used for both Western blotting and IHC TS detection. Tumor cell growth fraction was measured by Ki67/MIB1 immunolabeling and tumor cell growth rate by evaluating the mean nucleolar size in silver-stained sections. TS Western blotting values were related to tumor mass growth rate ( p<0.001) and cell growth rate ( p=0.002) but not to cell growth fraction ( p=0.676). The degree of the IHC staining showed only a trend to be associated with TS protein expression measured on Western blotting, and was not related either to tumor mass growth or cell proliferation rate. Tumor xenografts were also characterized for TS promoter tandem repeat and p53 status. No relationship was observed between these variables and TS expression evaluated by both Western blotting and IHC analysis. Our results demonstrate that TS expression evaluated by Western blotting analysis is directly related to the tumor mass growth rate and question the use of the IHC approach to obtain precise quantitative information on TS expression in tumor samples.

Abstract OBJECTIVE Little information about the natural history of incidental meningiomas exists in the literature. The aim of this study was to determine the natural history of asymptomatic meningiomas by comparing different methods of growth rate calculation to establish a strategy for dealing with these tumors. METHODS In 47 asymptomatic patients, hospital charts, follow-up records, and imaging studies were reviewed. Of these patients, 6 underwent surgery. Tumor growth rates were determined by calculating the absolute and relative growth rates and the tumor volume doubling times. RESULTS In 41 patients with conservative management, the average tumor size was 9 cm3, and the majority (66%) of growth rates were less than 1 cm3/yr. The absolute growth rate ranged from 0.03 to 2.62 cm3/yr (mean, 0.796 cm3/yr). Relative annual growth rates ranged from 0.48 to 72.8% (mean, 14.6%). The tumor doubling time ranged from 1.27 to 143.5 years (mean, 21.6 yr). A moderate correlation between the age and growth rates was found. In young patients, annual growth rates tended to be higher and tumor doubling times shorter. There was no clear correlation between the initial tumor size and tumor doubling time. The mean annual growth rate of meningiomas with calcification was lower than in tumors without calcification. Also, tumors with hypointense or isointense T2 signals on magnetic resonance imaging had a lower growth rate. In the group of six patients with surgical excision, tumor growth rates were higher and tumor doubling times shorter than in the nonsurgical group. CONCLUSION The majority of incidental meningiomas show minimal growth; thus, they may be observed without surgical intervention unless specific symptoms appear. Tumor growth is associated with patient age. The initial tumor size is not considered a predictive factor for tumor growth. Radiological features, such as calcification or T2 signal intensity, may provide useful information to predict the growth potential of meningiomas.

OBJECTIVEOver the last 30 years, stereotactic radiosurgery (SRS) has become an established noninvasive treatment alternative for small- to medium-sized vestibular schwannoma (VS). This study aims to further define long-term SRS tumor control in patients with documented pretreatment tumor growth for whom conservative observation failed.METHODSA prospective clinical database was queried, and patients with sporadic VS who elected initial observation and subsequently underwent SRS after documented tumor growth between 2004 and 2014 were identified. Posttreatment tumor growth or shrinkage was determined by a ≥ 2-mm increase or decrease in maximum linear dimension, respectively.RESULTSSixty-eight patients met study inclusion criteria. The median pre- and posttreatment observation periods were 16 and 43.5 months, respectively. The median dose to the tumor margin was 13 Gy (range 12–14 Gy), and the median maximum dose was 26 Gy (range 24–28 Gy). At the time of treatment, 59 tumors exhibited extracanalicular (EC) extension, and 9 were intracanalicular (IC). Of the 59 EC VSs, 50 (85%) remained stable or decreased in size following treatment, and 9 (15%) enlarged by > 2 mm. Among EC tumors, the median pretreatment tumor growth rate was 2.08 mm/year for tumors that decreased or were stable, compared with 3.26 mm/year for tumors that grew following SRS (p = 0.009). Patients who demonstrated a pretreatment growth rate of < 2.5 mm/year exhibited a 97% tumor control rate, compared with 69% for those demonstrating ≥ 2.5 mm/year of growth prior to SRS (p = 0.007). No other analyzed variables were found to predict tumor growth following SRS.CONCLUSIONSOverall, SRS administered using a marginal dose between 12–14 Gy is highly effective in treating VSs in which initial observation fails. Tumor control is achieved in 97% of VSs that exhibit slow (< 2.5 mm/year) pretreatment growth; however, SRS is less successful in treating tumors exhibiting rapid growth (≥ 2.5 mm/year).

Abstract Seventy of 178 patients with acoustic tumors initially were treated conservatively and have been followed up for an average of 26 ± 2 months. The tumor size was determined by the mean maximum anteroposterior and mediolateral diameters, using computed tomographic or magnetic resonance imaging scans obtained sequentially throughout the follow-up period. The average tumor growth was 1.6 ± 0.4 mm the 1st year, and 1.9 ± 1.0 mm the 2nd year (range, -2 to 17 mm/y): 4 tumors showed apparent regression, 28 (40%) had no detectable growth, and 37 (53%) exhibited growth (average, 3.8 ± 1.2 mm/y). Within individual patients, the tumor growth rate determined during the 1st year of follow-up was predictive of tumor growth rate during the following year. Rapid tumor growth or clinical deterioration in 9 of the 70 patients (13%) who initially were treated conservatively necessitated subsequent surgery an average of 14 ± 5 months after the patient was initially seen. This group had a larger initial tumor size (27.0 ± 3.4 mm vs. 21.3 ± 0.9 mm, P<0.05), and a faster 1-year growth rate (7.9 ± 2.3 mm/y vs. 1.3 ± 0.3 mm/y, P<0.05) than the 61 patients who did not require surgery. Two patients, however, experienced neurological deterioration that required surgery, even though there was no tumor growth. The high incidence of acoustic tumors with no detectable growth or apparent spontaneous regression must be taken into account when evaluating the indications for surgery and the efficacy of radiotherapy. Beacuse surgery carries some risk and acoustic tumors are generally slow growing, a trial of conservative treatment is possible in selected patients, provided serial radiological studies are obtained. Knowledge of the tumor growth rate established by these studies may be helpful in the treatment of individual patients.

Object The object of this study was to evaluate the natural history, pattern, and occurrence of tumor growth and its consequences for treatment of small-sized vestibular schwannomas (VSs). Methods From 1990 to 2005, 386 patients underwent conservative management for VS because of the following: age > 60 years, poor health/medical risks, risk of deterioration of good hearing, small tumor size, minimal or no incapacitating symptoms, and/or patient preference. Tumor size was measured by MR imaging according to the guidelines of the Committee on Hearing and Equilibrium. The first MR imaging study was performed 1 year after diagnosis, and subsequent imaging was performed yearly or every 2 years depending on the appearance of new symptoms, tumor growth, or both. Results Sixty-one patients were lost to follow-up the first year after presentation. Of the 325 patients for whom 1-year follow-up data were available, 39 showed tumor growth ≥ 3 mm. Conservative management was discontinued for these 39 patients. The patients who returned for follow-up were evaluated at 1- or 2-year intervals depending on tumor growth. The authors extrapolated to obtain data for 2-year intervals, yielding data for 160, 56, 21, and 8 patients at 3, 5, 7, and 9 years after initial presentation, respectively. The overall mean tumor growth rate (±standard deviation) was 1.15 ± 2.4 mm/year. This rate was estimated by pooling all values of tumor growth that had been determined for all patients and dividing by the total number of “events,” with each assessment constituting an event. In 58.6% of patients, the annual tumor growth rate was < 1 mm/year; in 29.2%, 1–3 mm/year; and in 12.2%, ≥ 3 mm/ year. The growth rates of intrameatal (1.02 ± 1.8 mm/year) and extrameatal (1.40 ± 3.1 mm/year) tumors did not differ significantly. No significant association was found between tumor growth rate and sex, age, initial hearing status, or initial tumor grade. Delay in diagnosis was the only significant factor associated with tumor growth rate. During follow-up, conservative management was discontinued for 77 (23.7%) of the 325 patients for whom at least 12-month follow-up data were available; surgery was performed in 60 (77.9%) and radiation therapy in 17 (22.1%). Conclusions The results of this study support the role of a conservative “wait-and-scan” policy of management for small-sized VSs because most have a slow growth rate. Long-term neuroimaging follow-up is needed even with non-growing tumors.

Human tumor xenograft studies are the primary means to evaluate the biological activity of anticancer agents in late-stage preclinical drug discovery. The variability in the growth rate of human tumors established in mice and the small sample sizes make rigorous statistical analysis critical. The most commonly used summary of antitumor activity for these studies is the T/C ratio. However, alternative methods based on growth rate modeling can be used. Here, we describe a summary metric called the rate-based T/C, derived by fitting each animal's tumor growth to a simple exponential model. The rate-based T/C uses all of the data, in contrast with the traditional T/C, which only uses a single measurement. We compare the rate-based T/C with the traditional T/C and assess their performance through a bootstrap analysis of 219 tumor xenograft studies. We find that the rate-based T/C requires fewer animals to achieve the same power as the traditional T/C. We also compare 14-day studies with 21-day studies and find that 14-day studies are more cost efficient. Finally, we perform a power analysis to determine an appropriate sample size.

✓ Little is known about the natural history and growth rate of asymptomatic meningiomas. To better delineate this problem, the authors reviewed the clinical records and imaging studies of the last 60 patients diagnosed with asymptomatic meningiomas at their institution. There were 45 women and 15 men, whose ages ranged from 38 to 84 years, with a mean age of 66 years. The most common tumor location was convexity (25 patients), but virtually all locations were represented. Three patients were lost to follow up. The average clinical follow-up review of the remaining 57 patients was 32 months (range 6 months to 15 years). None of the patients became symptomatic from an enlarging tumor during their follow-up period. Typically, once a meningioma was diagnosed, follow-up scans were obtained at 3 months, 9 months, and then yearly or every other year thereafter. Forty-five patients underwent follow-up scans, with comparison of tumor size to that found on the initial scan, over a period ranging from 3 months to 15 years. Thirty-five patients have shown no growth in their tumor size, with an average imaging follow up of 29 months (range 3–72 months). Ten patients have shown tumor growth calculated as an increase in the maximum diameter of the tumor. This growth ranged from 0.2 cm over 180 months to 1 cm over 12 months, with an average of 0.24 cm per year. Average imaging follow up for these patients was 47 months (range 6 months to 15 years). The authors conclude that patients with asymptomatic meningiomas need close clinical and radiological follow up to rule out other disease processes and to rule out rapidly enlarging tumors. Although the average follow-up time was short, the vast majority of these tumors appeared to show minimal or no growth over periods of time measured in years. With modern noninvasive imaging techniques, these tumors can be safely observed until they enlarge significantly or become symptomatic.

The growth rate of acoustic tumors varies widely. An immunohistochemical study with Ki-67 monoclonal antibody was performed on a random sample of 21 acoustic neuromas. The tumors belonged to 2 well-defined groups: 1 with a short duration of preoperative symptoms (<1 year) and 1 with a long duration of preoperative symptoms (>5 years). The tumors were of small to medium size (7 to 27 mm), and no large, cystic, or Recklinghausen tumors were included. The tumor proliferative fraction expressed by monoclonal antibody Ki-67 was determined. The results revealed a significant relation between the tumor proliferative fraction and symptom duration. Tumors with a high proliferative status had a short preoperative symptom duration, while tumors with a low proliferative status had a long symptom duration. The clinical implications of these results are discussed.

Glioblastoma multiforme (GBM) is a destructive brain cancer that results in death 12 to 15 months after diagnosis. The purpose of this retrospective study was to determine if variations in tumor size at diagnosis, treatment options, and survival rate occur in GBM patients living in urban and rural areas of the United States. Using the behavior model of health services as the theoretical framework, this study used secondary data sets of GBM cases reported from 1988 to 2011 from the Surveillance, Epidemiology, and End Results program. Tumor size was measured in millimeters; treatment was evaluated by ascertaining the number of GBM patients who had surgical resection of their tumors, radiation, and chemotherapy; and survival rate was evaluated using Cox Regression analysis. With a sample size of 33,202 cases, data were examined using descriptive and multivariable analyses with SPSS. Results showed statistically significant differences in tumor size at diagnosis in rural patients compared to urban patients (p = 0.0085; p = 0.018), more urban patients were treated with radiation compared to rural patients (p < 0.001), and rural patients had poorer survival rates than urban patients (p < 0.001). Finally, when controlling for region, race, age, gender, education, and income, longer survival time was associated with urban status, female cases, and higher family income (p < 0.0001), and greater age was associated with reduced survival time (p < 0.0001). Study results could promote positive social change by identifying predictive variables associated with health outcomes of GBM patients. It may also educate providers on the risk of rurality of patients diagnosed with GBM, and inform lawmakers responsible for the creation of healthcare policy and the equitable allocation of healthcare resources.

This thesis is about firm dynamics, and relates to the size and growth-rate distribution of firms. As such, it consists of an introductory and four separate chapters. The first chapter concerns the size distribution of firms, the two subsequent chapters deal more specically with high-growth firms (HGFs), and the last chapter covers a related topic in distributional estimation theory. The first three chapters are empirically oriented, whereas the fourth chapter develops a statistical concept.<br><p>QC 20130215</p>

[EN] The aim of this thesis was to evaluate the productive performance of a rabbit line (OR-LS) selected by ovulation rate during first 6 generations (period 1), and later by ovulation rate (OR) and litter size (LS) during 11 generations using independent culling levels (Period 2). Genetic parameters, direct response for OR and LS and the correlated response for embryo (ES), foetal (FS) and prenatal survival (PS) were estimated. Also, the correlated response on growth rates (GR), weaning (WW) and marketing weight (MW) were estimated. The objective of chapter 3 was to estimate the genetic parameters of the productive traits and the response to selection by OR and LS of OR-LS line. For traits analysis, Bayesian methods were used. Heritability values of litter size traits were low, 0.10, 0.07, 0.07 and 0.07 for litter size, number of born alive (NBA), number of kits at weaning (NW) and marketing (NM), respectively. Heritability for OR was moderate (0.25), while it was low (0.13 and 0.14) for number of implanted embryos (IE) and number of live foetuses at 12 days of gestation (LF12), respectively. Low heritability values for survival traits were found, 0.09 for embryo survival (ES), 0.16 for foetal survival (FS) and 0.14 for prenatal survival (PS). In the second period, after 11 generations of selection by OR and LS, a genetic response of 0.17 kits per generation for LS was achieved. This response was higher than the obtained in period 1 (0.07 kits per generation), in which just selection by OR was performed. The opposite effect was found for OR; the highest response for OR appeared in the first period (0.24 ova per generation) versus the second period (0.17 ova per generation). This reduction in OR response can be due to the decrease in selection differential during the second period of selection. Since high genetic correlations were obtained for LS and other litter size traits, a positive correlated response was observed for NBA, NW and NM (0.12, 0.12 and 0.11 kits per generation, respectively) in the second period. In the first period, no correlated response on ES was observed and a decrease in FS (-0.04) was found. Nevertheless, in the second period a correlated response on PS appeared due to an improvement in both ES (0.04) and FS (0.03). Summarizing, the improvement in litter size in the second period is due to an increase in ovulation rate as well as an increase in prenatal survival. The objective of chapter 4 was to study the correlated response on growth traits in the OR-LS line in both periods of selection, the selection by OR during six generations and the selection by independent levels by OR and LS during 11 generations. The heritability estimates were low for weaning weight (WW), marketing weight (MW) and growth rate (GR), 0.09, 0.13 and 0.14, respectively. The estimated genetic correlations of WW, GR and MW with LS were around zero and with OR were positive and from low (0.19) to moderate (0.38). The positive moderate genetic correlation estimated between OR and MW could explain the correlated response found in MW. Correlated response on WW could be explained by positive and high genetic correlation between MW and WW. The aim of chapter 5 was to investigate magnitude and timing of embryo and early foetal survival in females with high OR using hormonal treatment as a model for selection by OR. Two groups of females (treated and untreated) were used. Treated females were injected with 50 IU eCG 48 hours before mating. Females were slaughtered at day 18 of gestation. OR, IE, LF12 and LF18 were recorded. Besides, ES (IE/OR), FSLF18 (LF18/IE), FSLF18/LF12 (LF18/LF12) and PSLF18 (LF18/OR) were estimated. Treated females had a higher OR than untreated females. According to the previous results for OR and LF18, treated females showed a lower survival rate from ovulation to 18 d of gestation. Treated females also had lower embryo and foetal survival. Main difference in foetal survival appeared from day 12 to 18 of gestation.<br>[ES] El objetivo de esta tesis fue evaluar el tamaño de camada de una línea de conejo seleccionada por tasa de ovulación durante las primeras seis generaciones (periodo 1) y después por tasa de ovulación (OR) y tamaño de camada (LS) durante 11 generaciones mediante el método de niveles independientes (periodo 2). Se estimaron los parámetros genéticos, así como la respuesta en OR y LS y la respuesta correlacionada en los caracteres reproductivos (capítulo 3). Además, se evaluó la respuesta correlacionada en los caracteres de crecimiento (capítulo 4); peso al destete (WW), peso al sacrificio (MW) y ganancia de peso entre el destete y el sacrificio (GR). Para el análisis de los caracteres se utilizaron métodos bayesianos. El objetivo del capítulo 3 fue estimar los parámetros genéticos de los caracteres reproductivos y la respuesta a la selección. Los valores de heredabilidad de los caracteres del tamaño de camada fueron bajos (alrededor de 0.10). La heredabilidad estimada para OR fue moderada (0.25), mientras que fue baja para el número de embriones implantados (IE) y el número de fetos vivos a los 12 días de gestación (LF12). Se obtuvieron valores bajos de heredabilidad; 0.09 para la supervivencia embrionaria (ES), 0.16 para la supervivencia fetal (FS) y 0.14 para la supervivencia prenatal (PS). En el periodo 2, se obtuvo una respuesta genética de 0.17 gazapos por generación para LS. Esta respuesta fue mayor que la obtenida en el periodo 1. En el caso de la tasa de ovulación, la mayor respuesta en OR se obtuvo en el periodo 1 (0.24 óvulos por generación) versus (0.17 óvulos por generación) en el periodo 2. Esta reducción en la respuesta de OR se puede atribuir a la disminución del diferencial de selección durante el período 2 de selección. De acuerdo con la alta correlación genética entre LS y otros caracteres del tamaño de camada, también se observó una respuesta correlacionada positiva en el número de nacidos vivos (NBA), destetados (NW) y comercializados (NM); 0.12, 0.12 y 0.11 gazapos por generación, respectivamente, en el segundo periodo. En el primer periodo no se observa respuesta correlacionada en la SE y se produce una disminución de la SF (-0.04). Sin embargo, en el segundo periodo se produce una respuesta correlacionada positiva en la SP que se debe a una mejora de la SE (0.04) y SF (0.03). En resumen, la mejora del tamaño de camada en el segundo periodo se debe tanto a un aumento de la tasa de ovulación como a un aumento de la supervivencia prenatal. El objetivo del capítulo 4 fue estudiar la respuesta correlacionada en los caracteres de crecimiento en esta línea. Las estimas de heredabilidad fueron bajas para los caracteres WW (0.09), MW (0.13) y GR (0.14). Las correlaciones genéticas estimadas de LS con WW, MW y GR fueron cercanas a cero; con la tasa de ovulación, las correlaciones fueron positivas y variaban de bajas a moderadas (de 0.19 a 0.38). La correlación genética moderada entre OR y MW podría explicar la respuesta correlacionada observada en MW. La alta correlación entre MW y WW podría explicar la respuesta correlacionada obtenida para WW. Finalmente, el objetivo de capítulo 5 fue estudiar en hembras con alta tasa de ovulación en qué momento se producen las mayores pérdidas fetales y cómo se ve afectado el desarrollo fetal. Para ello, de un total de 51 hembras, 24 hembras fueron pinchadas con 50 UI de eCG 48 horas antes de la cubrición para aumentar la tasa de ovulación. Las hembras fueron sacrificadas a los 18 días de gestación. Se registró OR, IE y el número de fetos vivos a los 12 y 18 días de gestación (LF18). Las hembras tratadas tuvieron una tasa de ovulación mayor que las no tratadas. De acuerdo con los resultados obtenidos para OR y LF18, las hembras tratadas mostraron una supervivencia más baja desde la ovulación hasta los 18 días de gestación y tuvieron una menor supervivencia embrionaria y fetal. Las principales diferencias en l<br>[CAT] L'objectiu d'esta tesi va ser avaluar la millora de la grandària de ventrada d'una línia de conill seleccionada per tasa d'ovulació durant les primeres sis generacions (període 1) i després per tasa d'ovulació (OR) i la grandària de ventrada (LS) durant 11 generacions per mitjà del mètode de nivells independents (període 2). Es van estimar els paràmetres genètics, així com la resposta en OR i LS i la resposta correlacionada en caràcters reproductius (capítol 3). A més, es va estudiar la resposta correlacionada en els caràcters de creixement (capítol 4); pes al deslletament (WW), pes al sacrifici (MW) i guany de pes entre el deslletament y el sacrifici (GR). Per a l'anàlisi dels caràcters es van utilitzar mètodes bayesians. L'objectiu del capítol 3 va ser estimar els paràmetres genètics dels caràcters reproductius i la resposta a la selecció. Els valors d'heretabilitat dels caràcters de la grandària de ventrada van ser baixos (al voltant de 0.10). L'heretabilitat estimada per a OR va ser moderada (0.25), mentres que va ser baixa per al nombre d'embrions implantats (IE) i el nombre de fetus vius als 12 dies de gestació (LF12). Es van obtindre valors baixos d'heretabilitat; 0.09 per a ES, 0.16 per a FS i 0.14 per a PS. En el període 2, es va obtindre una resposta genètica de 0.17 llorigons per generació per a LS. Esta resposta va ser major que l'obtinguda en el període 1. En el cas de la tasa d'ovulació, la major resposta per a OR va ser en el primer període (0.24 òvuls per generació) versus (0.17 òvuls per generació) en el període 2. Esta reducció en la resposta d'OR es pot atribuir a la disminució del diferencial de selecció durant el període 2 de selecció. Donada l'alta correlació genètica entre LS i altres caràcters de la grandària de ventrada, també es va observar una resposta correlacionada positiva en el nombre de nascuts vius (NBA), deslletats (NW) i comercialitzats (NM); 0.12, 0.12 i 0.11 llorigons per generació, respectivament, en el segon període. En el primer període no s'observa resposta correlacionada en la SE i es produeix una disminució de la SF (-0.04). No obstant això, en el segon període es produeix una resposta correlacionada en la SP que es deu a una millora de la SE (0.04) i SF (0.03). En resum, la millora de la grandària de ventrada en el segon període es deu tant a un augment de la tasa d'ovulació com a un augment de la supervivència prenatal. L'objectiu del capítol 4 va ser estudiar la resposta correlacionada en els caràcters de creixement en aquesta línia. Les estimes d'heretabilitat van ser baixes per als caràcters WW (0.09), MW (0.13) i GR (0.14). Les correlacions genètiques estimades de LS amb WW, MW i GR van ser pròximes a zero; amb la tasa d'ovulació, les correlacions van ser positives i variaven de baixes a moderades (de 0.19 a 0.38). La correlació genètica moderada entre OR i MW podria explicar la resposta correlacionada trobada per a MW. D'altra banda, l'alta correlació entre MW i WW podria explicar la resposta correlacionada obtinguda per a WW. Finalment. l'objectiu del capítol 5 va ser estudiar en femelles amb alta tasa d'ovulació en quin moment es van produir les majors pèrdues fetals i com es veu afectat el desenvolupament fetal. Per a això, d'un total de 51 femelles, 24 femelles van ser punxades amb 50 UI d'eCG 48 hores abans del cobriment per a augmentar la tasa d'ovulació. Les femelles van ser sacrificades al 18 dies de gestació. Es va registrar OR, IE i el nombre de fetus vius al 12 i 18 dies de gestació (LF18). Les femelles tractades van tindre una tasa d'ovulació major que les no tractades. D¿acord als resultats obtinguts per OR i LF18, les femelles tractades van mostrar una supervivència més baixa des de l'ovulació fins als 18 dies de gestació i van tindre una menor supervivència embrionària i fetal. Les principals diferències en la supervivència fetal van aparèixer entre els dies 12 i 18 de gestaci<br>Yehia Badawy Elmoghazy, A. (2016). SELECTION FOR OVULATION RATE AND LITTER SIZE IN RABBITS [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/73265<br>TESIS

Morley, S. A. (1998). Environmental and parental influences on the size of herring larvae. Ph.D. thesis submitted to the University of Liverpool for the degree of Doctor of Philosophy Investigations were carried out into the effects of mean egg dry weight and incubation temperature on the size of larvae from four N.E. Atlantic herring stocks (Buchan, Manx, Clyde and Celtic Sea). Hatching characterisitics (length, weight and yolk volume) of Buchan, Manx and Clyde herring were investigated. The time of hatching was inversely related to incubation temperature, although there was some variation between experiments in the date of peak hatching. The total length of larvae increased through the hatching period. In all experiments mean egg dry weight per female was strongly related to the average length, weight and yolk volume of larvae at hatching. The same regression model could be applied to all stocks. There were, however, stock-specific responses of hatching characteristics to incubation temperature although a reduction in length at hatching at higher temperatures was the most consistent response. Development at low temperature resulted in a modification of the length-weight relationship; larvae of the same weight were longer at lower temperatures. Both the increase in length of larvae during the hatching period and the variation in the timing of peak hatching have implications for the comparison of larvae hatching at different temperatures. The otoliths of Manx herring larvae [from "large" (> 0.33mg mean dry weight) and "small" «0.2Smg mean dry weight) eggs] were marked with either alizarin complexone or calcein so that larvae from pairs of large and small egg batches could be reared under identical conditions (at both 10 and I3.S0C) and relative growth monitored. Within each rearing tank large eggs generally produced larger larvae at hatch (length and weight) with higher growth rates (both weight and length specific). There were significant differences both between eggs from different females and between rearing tanks that confounded the comparisons between rearing temperatures. Fultons Condition factor is not thought to be a good measure of nutritional condition of herring larvae smaller than ISmm total length but may be used as a relative measure of body reserves (ReF) and give an indication of ability to withstand periods of poor feeding. This is indicated by a period of high mortality of larvae hatched from small eggs at 10°C, which corresponded with the time period when these larvae had the lowest body reserves. Video recording of the foraging behaviour of laboratory reared herring larvae was used to investigate differences between the feeding strategies of groups of larvae of the same size but different ages, i.e. fast and slow growers. Slow growing larvae searched larger areas, thus expending more energy, than fast growing larvae, but there was no difference in food acquisition. The difference in behaviour tended to increase through development A simple energetics calculation suggested that approximately 50% of the difference in growth rate could be explained by the extra swimming costs of slower growing larvae. The size of Celtic Sea and Manx herring eggs were experimentally reduced in order to investigate if the volume of yolk in each egg determines the size of hatching larvae. Length at hatch was determined by the volume of yolk in each egg but body weight was not. The development and chemical composition of embryos and larvae needs to be investigated in a further series of experiments. All results are discussed in terms of the influence of larval size on survival.

We initiated bait station surveys for black bears in southwestern Virginia in 1999. Bait station surveys are intended to be used as an index to follow bear population trend over time. We compared the bait station visitation (black bear visitation) to black bear harvest and mast surveys 1999 = 2002. The mean bait station visitation rate during 1999 - 2002 was 15.3% (SE = 2.89, n = 4). The number of bears harvested in the 3 counties that also had bait station surveys was 48 (31 males, 17 females), 59 (44 males, 15 females), 45 (32 males, 13 females), and 43 (26 males, 17 females) in 1999, 2000, 2001, and 2002, respectively. Harvest of males and females differed (n = 2, F = 19.44, df = 1, P = 0.0045). Bait station visitation and female harvest had a strong functional relationship with a negative slope (n = 4, r = -0.78, P = 0.22). The strongest relationship was between male harvest and total harvest (n = 4, r = 0.97, P = 0.03). Mean index to mast production for 1999 - 2002 was 2.3 (range 1.5 - 3.1), 2.7 (range 1.8 - 3.4), 2.3 (range 1.6 - 3.6), and 1.6 (range 1.2 - 2.4), respectively. The overall summary for mast production for the same years was described as fair, good, fair, and poor to fair. Mast production was significantly different between years (n = 4, F = 3.44, df = 3, P = 0.0326), and soft and hard mast production appeared to be above average in 2000. This corresponded with the lowest visitation (10.2%) of the 4 years. There was no correlation between bait station visitation and mast production (n = 4, r = 0.11, P = 0.87). Since 1998, the annual bear harvest in Virginia has exceeded 900 individuals (with the exception of 824 in 2001), and peaked in 2000 when 1,000 bears were harvested. Though harvest rates were high, a reliable population estimate did not exist for black bears in Virginia. We estimated population size, growth rate, and minimum viable population size using data collected between 1995-2000. We used Jolly-Seber, direct recovery, and minimum population size methods to estimate population size. The Jolly-Seber method estimate of adult female density was 0.23-0.64 bears/km2, and 0.01 bears/km2 for adult males. We estimated a density of 0.09-0.23 bears/km2 for all sex and age classes using direct recovery data. Using minimum population size, we found adult female density was higher than any other sex or age class (n = 6, t = 2.02, df = 40, P < 0.0001) with an average density of 0.055 adult females/km2. We used mark-recapture data collected from 148 individual bears (96 males:52 females) captured 270 times in program MARK to estimate survival using recapture, dead recovery, and Burnham's combined models. Adult females had the highest survival rate of 0.84-0.86, while yearling males had the lowest with 0.35. Using direct recovery data, adult females again had the highest survival rate with 0.93 (0.83-1.0) and 3-year old males had the lowest with 0.59 (0.35-0.83). We estimated growth rate using population estimates from Jolly-Seber, direct recoveries, and minimum population size methods. The lowest growth rate estimated was for all females (ages lumped) using minimum population size data (λ=0.82). Direct recovery data for all bears (sex and age lumped) during 1995 - 2000 showed the highest positive annual growth rate (λ = 1.24). We developed a population model using Mathcad 8 Professional to determine population growth rate, MVP, and harvest effects for an exploited black bear population in southwestern Virginia. We used data collected during the CABS study (1995 - 2000) in the model including population estimates derived from direct recovery data, age and sex specific survival rates, and cub sex ratios. When we used actual population values in the model, the bear population in southwestern Virginia did not go extinct in 100 years (l = 1.03, r = 0.03). When we reduced adult female survival from 0.94 to 0.89, the probability of extinction in 100 years was 3.0% and l = 0.99 (r = -0.01; Table 3.2). When the survival was reduced by an additional 0.01 to 0.88, the probability of extinction increased to 13.0% (l = 0.99, r = -0.01). Growth rate and extinction probabilities were very sensitive to adult female survival rates. Two-year old and 3-year old females did not impact extinction probabilities and growth rates as much as adult females. Their survival could be decreased by 44.0%, and still be less than the 5.0% extinction probability.<br>Master of Science

Body size varies according to nutritional availability, which is of ecological and evolutionary relevance. The purpose of this study is to test the hypothesis that differences in adult body size are realized by increasing juvenile growth rate for white-tailed deer (Odocoileus virginianus). Harvest records are used to construct growth rate estimates by empirical nonlinear curve fitting. Results are compared to those of previous models that include additional parameters. The rate of growth increases during the study period. Models that estimate multiple parameters may not work with harvest data in which estimates of these parameters are prone to error, which renders estimates from complex models too variable to detect inter-annual changes in growth rate that this simpler model captures

Hypervariable, nuclear-encoded microsatellites were used to (i) estimate genetic effective size (Ne) of red drum spawning over a two-week period in nine brood tanks at a TPWD hatchery; (ii) estimate heritability of early-larval growth and of growth rate and cold tolerance of juveniles; and (iii) test Mendelian segregation and independent assortment of 31 nuclear-encoded microsatellites. Assuming all tanks contributed equally to an offspring population, the maximum (expected) and observed Ne over the nine brood tanks was 43.2 and 27.0, respectively. The estimate of Ne based on observed variation in family size was 19.4. Simulations indicated that over a limited time period the simplest approach to maximizing Ne for a release population would be to utilize equal numbers of progeny from each brood tank. A family (genetic) effect was found to contribute significantly to the variance in early larval growth, juvenile growth rate, and cold tolerance. Estimates of narrow-sense heritability for these three traits were 0.07 +- 0.03, 0.52 +- 0.21 and 0.20 +- 0.10 (two growth intervals measured), and 0.30 +- 0.11, respectively, under the genetic models employed. The relatively low estimate of heritability for early larval growth suggests that genetic improvement for this trait likely would be slow. The heritability estimates for juvenile growth rate and cold tolerance, alternatively, suggest that genetic selection for these traits could be effective. Segregation at all 31 microsatellites fit Mendelian expectations for autosomal loci; a null allele was inferred at two of the microsatellites. Results from pairwise tests of independent assortment demonstrated that 20 of the 31 microsatellites could be placed into seven linkage groups. Additional linkage groups inferred from a prior study increased the number of inferred linkage groups in red drum to nine, with a range of two - five (avg. = 2.78) microsatellites in each linkage group. The remaining 11 microsatellites tested in this study assorted independently from all other microsatellites, suggesting the possibility of 11 additional linkage groups.

Growth involves two flows of energy. The first is chemical potential energy in the monomers used to construct the proteins, lipids, polysaccharides and nucleic acids forming the new tissue. The second is the metabolic energy (ATP or GTP) used to construct the new tissue; this is the metabolic cost of growth and can be expressed as a dimensionless fraction of the energy retained in the new tissue. Its value is ~0.33. Typical temperature sensitivities for growth in the wild lie in the range Q10 1.5 – 3. Within species there may be evolutionary adjustments to growth rate to offset the effects of temperature, though these involve trade-offs with other physiological factors affecting fitness. Outside the tropics, many mammals and birds exhibit a cline in size, with larger species at higher latitudes (Bergmann’s rule). Carl Bergmann predicted such a cline from biophysical arguments based on endotherm thermoregulatory costs; Bergmann’s rule thus applies only to mammals and birds. Many ectotherms grow more slowly but attain a larger adult size when grown at lower temperatures (the temperature-size rule). The large size of some aquatic invertebrates at lower temperatures (notably in the polar regions and the deep sea) is associated with a higher oxygen content of the water.

This book examines the links between economic growth, changing employment conditions, and the reduction of poverty in Latin America in the 2000s. Its analysis answers the following broad questions: Has economic growth resulted in gains in standards of living and reductions in poverty via improved labour market conditions in Latin America in the 2000s, and have these improvements halted or been reversed since the international crisis of 2008? How do the rate and character of economic growth, changes in the various employment and earnings indicators, and changes in poverty and inequality indicators relate to each other? Our contribution is an in-depth study of the multi-pronged growth–employment–poverty nexus based on a large number of labour market indicators (twelve employment and earnings indicators and four poverty and inequality indicators) for a large number of Latin American countries (sixteen of them). The book presents a positive and hopeful set of findings for the period 2000 to 2012–13. Economic growth took place and brought about improvements in almost all labour market indicators and consequent reductions in poverty rates. But not all improvements were equal in size or caused by the same things. Some macroeconomic factors were associated with changes in labour market conditions, some of them always in the welfare-improving direction and others always in the welfare-reducing direction. Most countries in the region suffered a deterioration in at least some labour market indicators as a consequence of the international crisis of 2008, but the negative effects were reversed very quickly in most countries.

Physical activity in the general youth population and systematic training for sport among young athletes seems to have no effect on size attained and rate of growth in height, or on maturity status and timing. However, activity and training may influence body weight and composition. While both favourably influence bone mineral, variable effects are noted in some sports. Activity has a minimal effect on fatness in normal weight youth, but regular training generally has a positive influence on fatness in youth athletes. Data for fat-free/lean tissue mass are suggestive, but limited. Constitutional factors play a central role in the selection and retention of young athletes in a sport.

Intracranial aneurysms may be detected incidentally on imaging. Location and size of an intracranial aneurysm are helpful in stratifying risk of hemorrhage. Risk stratification is important for treatment decision-making. Modifiable risk factors associated with aneurysm growth and rupture (hypertension and tobacco use) should be addressed. Treatment needs to be individualized. Small aneurysms may be monitored. Surgery has been associated with neurological disability and cognitive impairment. Endovascular coiling may be associated with a higher rate of incomplete obliteration. There are no randomized trial data in patients with unruptured aneurysms.

Despite a relatively limited understanding of the factors associated with strength development, advances in equipment, and increased understanding of growth and maturation issues, have provided new insights into paediatric muscle strength development. Strength testing of children is performed routinely by researchers to monitor the determinants and development of strength throughout childhood, and also by physiotherapists to assess the degree of muscle disability and to diagnose the rate of recovery. It is important for strength test administrators to be equipped with knowledge of the normal age and sex-associated variations in strength and the factors attributable to that variation. Over time, the use of differing techniques to adjust for body size has changed our perspective of the historical concept of the age- and sex-associated differences in muscle strength. Likewise, the development of more sophisticated techniques to determine muscle size and body composition has allowed researchers to explore the factors associated with the development of strength during growth with a greater degree of validity.

Anaesthesia for children is tempered by changes that occur during both growth and development. Drug dose is affected by size and clearance maturation processes as well as the changing body composition that occurs with age. All organ systems undergo these maturation changes and most are complete within the first few years of life. Normal physiological variables in infancy and childhood are quite different from adults. The central nervous, cardiovascular, and respiratory systems are particularly important. Cerebral immaturity and plasticity impacts sensitivity to drugs, pain responses, and behaviour and increases potential harm from apoptosis with anaesthesia. The heart undergoes a transition from fetal to adult circulation during the first few weeks of life. Undiagnosed congenital defects are not uncommon. The neonate is very susceptible to conditions that trigger an increase in pulmonary vascular resistance, with reversion to fetal circulatory patterns. Respiratory anatomy and mechanics affect the propensity to apnoea, airway maintenance, artificial ventilation modalities, uptake of inhalational agents, and tracheal tube sizes. Metabolic rate and oxygen requirements increase with decreasing age. This physiology influences diverse aspects that include the rate of desaturation during apnoea, hypoglycaemia during starvation, cardiac output, drug metabolism, fluid requirements, and heat production or loss.

Introduction: Sertoli-Leydig cell tumor (SLCT) is a rare ovarian tumor, Constitute less than 0.5% of ovarian tumors. Most tumors are unilateral, confined to the ovaries. They are seen during the second and third decades of life. They are characterized by the presence of testicular structures that produce androgens. Patients have symptoms of virilization (depending on the quantity of androgen). Case Report: A 42-year-old woman presented Amenorrhea for 14 months. Change in her voice for 1 year and Excessive hair growth on her face, chest, and limbs for the last 2 months. She complained of vague abdominal discomfort. No history of anorexia, weight loss, increased libido. Her medical and family history was unremarkable. On examination - Hirsutism and clitoromegaly. Lump of size 10x8 cm palpable in left iliac fossa. Vaginal examination revealed a firm and mobile cystic mass in the right adnexa. An ultrasound examination of the pelvis showed a 17x 13x 9-cm heterogeneous solid cystic mass replacing the left ovary. The right ovary and the uterus were normal. CECT Scan Abdomen-Large heterogenous encapsulated solid soft tissue mass lesions containing areas of calcification arising from left ovary of size 17x13x10.6cm causing displacement of urinary bladder and surrounding bowel loops. Serum testosterone level -2 ng/mL (normal, 0.2–1.2 ng/mL); (DHEAS), CA 125, and alpha fetoprotein (AFP) -normal. On Laparotmy-Large mass of size 17 X 13 cm arising from left adnexa. Uterus and right ovary grossly normal. Total Abdominal hysterectomy, B/L Salpingo-opherectomy and infracolic omentectomy was done. Peritoneal washing were sent for cytologic examination for malignant cells. No liver metastasis. The post operative period was uneventful. Histopathology revealed- confirmed it be Sertoli Leydig cell tumor. 3month follow up – resolution of her virilization symptoms. No increase of her hirsutism. Repeat testosterone levels - within normal range. Conclusion: Only few cases of SLCT have been reported till date Prognosis depends on extent of disease, stage of disease, tumour differentiation, grade. The treatment should be individualized according to the location, state of spread and the patient’s condition.

Abstract Cancer is one of the most debilitating diseases in the world, affecting over 9.6 million people worldwide every year. Breast cancer remains the second largest cause of death in women. Despite major advances in treatment, over 40,920 women died of breast cancer in 2018 in the United States alone. Early detection of abnormal masses can be crucial for diagnosis and dramatically increase survival. Current screening techniques have varying accuracy and perform poorly when used on heterogeneously and extremely dense breast tissue. Infrared imaging has the potential to detect growing tumors within the breast based on thermal signatures on the breast surface by imaging temperature gradients induced by blood perfusion and tumor metabolic activity. Using clinical patient images, previous methods to estimate tumor properties involve an iterative algorithm to estimate the tumor position and diameter. The details from the MRI are used in estimating the volumetric heat generation rate. This is compared with the published values and the reasons for differences are investigated. The tumor pathology is used in estimating the expected growth rate and compared with the predicted values. The correlation between the tumor characteristics and heat generation rate is fundamental information that is needed in accurately predicting the tumor size and location.

Fibrin gel matrix organizes solid tumors into discrete cell nests and providesa provisional matrix for mature stroma generation. Fibrin deposits result fromlocal extravasation of plasma fibrinogen followed by extravascular coagulationand crosslinking. Unlike solid tumors, ascites tumor cells in body cavities grow in suspension, and are not envelopedin fibrin gel. The lack of fibrin gel in ascites tumors has several possible explanations: 1. Peritoneal wall blood vessels are impermeable to molecules as large as fibrinogen. 2. Fibrinogen leaks from peritoneal vessels, but is clotted to fibrin and never reaches the peritoneal cavity. 3. Fibrinogen leaks from vessels, reaches the peritoneal cavity, and is rapidly degraded. To distinguish among these possibilities we investigated the permselective properties of the peritoneal wall. We measured the influx of intravenously (iv) administered, fluorescein-labeled dextrans (FITC-D) of varying size into the peritonea of normal and tumor or inflammatory ascites-bearing mice and guinea pigs. FITC-D of MW 70-5,000 kD leaked from vessels and ∽ 10-fold more entered MOT or TA3/St tumor-associated or serotonin-induced inflammatory ascites than normal peritonea. In tumor bearing animals, 3-20% of injected FITC-D entered the peritoneum within 15-30 min., all of it intact by gel exclusion chromatography. We also investigated the influx of fluorescein-labeled fibrinogen (FITC-F). At 30-60 min after iv injection, FITC-F hadextravasated into the peritoneal wall as judged by fluorescence microscopy (tumor bearing ≫ normal animals). Moreover, monoclonal antibodies reactivewith fibrin, but not fibrinogen, stained such deposits by immunohistochemistry in guinea pigs bearing line 1 or line 10 ascites tumors. Following iv injection of 125l-fibrinogen, as much as 11% of injected radioactivity accumulated in tumor ascites fluid over1-3 hrs (versus ∽1% in normal controls). In both, only ∽half was clottableand 3040% was of low MW (≤.10 kD). In contrast, iv 125I-albumin also entered the peritoneal cavity at an enhanced rate but showed no evidence of degradation. We conclude that fibrinogen extravasates from peritoneal vessels,thatleakage is increased in ascites tumor-bearing animals, and that fibrinogen clots, at least in part, before it enters the peritoneal cavity. Also, fibrinogen undergoes selective degradation and much of the fibrinogen that does enter the peritoneum represents degradation products of fibrinogen/fibrin. The resulting lack of peritoneal fibrin gel matrixfavors the suspension pattern of ascites, as compared with solid tumor growth.

Magnetic nanofluids can be remotely heated by alternating magnetic field and have significant potential for cancer hyperthermia therapy. The heat generated by magnetic nanoparticles is typically quantified by the specific absorption rate (SAR), which represents the thermal power per unit mass of magnetic material generated in the presence of an alternating magnetic field. During hyperthermia treatment, heat dosage of tumor tissue correlates with slowing tumor growth. The therapeutic ratios of cancer can be increased with the use of biofunctionalized magnetic nanoparticles that have higher SAR for modest amplitudes of magnetic field[1]. Hence, understanding the factors that control the heat generation of magnetic nanoparticle suspensions is important to design fluids with optimized biocompatibility and functionality. In all biomedical applications, the nanoparticles must be coated on the surface to prevent their agglomeration [2], enhance biocompatibility and allow targeting to a specific area. Existing studies have shown that the SAR of nanoparticles may change in the presence of functional coating[3–5]. However, while these studies show that the coating may affect the heat generation rate, there is a limited understanding on the mechanisms that cause that changes of SAR. Hence, it is important to carry out a systematic investigation of nanoparticles similar in size but with different organic coating relevant to biomedical applications to obtain a more complete picture of the mechanisms contributing to changes in SAR. In this work, we present a review of our efforts in this area. Specifically, in our studies we are investigating the correlation between the magnetic and physical properties of commercially available nanoparticles systems and their heat generation rate. The susceptibility and SAR of suspensions of coated and uncoated iron oxide nanoparticles of similar particle size are measured. The coatings selected are highly relevant to biomedical applications and include amine and carboxyl functionalization as well as bioaffine ligands such as protein and biotin. The particle and cluster size was determined from transmission electron microscope (TEM), X-Ray diffraction (XRD) and Dynamic light scattering (DLS). TEM and DLS studies suggested that clusters exist in samples. A summary of all morphological properties together with pH of each suspension is shown in Table.1. The AC magnetic susceptibility of the suspensions was measured as a function of frequency with an in-house made apparatus. Finally SAR was determined by heating the suspension in a commercial induction system and measuring the temperature rise as function of time with a fiber optic sensor. Following these measurements, the SAR values were predicted in two ways: 1) based on measured AC susceptibility and 2) based on particle physical and magnetic properties, starting from Debye model for susceptibility. The normalized predicted and experimental SAR values for all samples are also shown in Table 1. From Table 1, it was found that pH may influence aggregation as described in Ref [6], which indicated that at pH about 2 nanoparticles are highly charged preventing their aggregation while in pH in 6–10 suspensions aggregations are more significant. Normalized SAR of nanoparticle system with aggregations seems to be not related to concentration, different from the well dispersed system[7]. The carboxyl coated sample has smallest diameter and show the lowest SAR, as reported in Ref[8]. The results of suspensions of uncoated iron oxide nanoparticles as well as particles coated with amine groups show that normalized experimental SAR (NSARE) agrees relatively well with calculated SAR using experimental susceptibility (NSARC_χ″E); poor agreement was found when experimental susceptibility was substituted with calculated one (NSART_χ″C) using Debye model, which is developed for non-interacting magnetic particles. These results suggest that the coating do not have a direct effect on SAR. On the other hand, agglomeration, which was present in both samples, may lead to dipolar interaction between nanoparticles and enhancement in magnetic properties and SAR. For carboxyl coated sample which has negligible clustering, showed no temperature increase and zero imaginary part of susceptibility. Therefore, good agreement between Debye-model based predictions of SAR and experimental results were obtained in this sample. However, unexpected results were obtained for bioaffine ligands coated sample, where the experimental SAR values are higher than the SAR values determined based on experimental susceptibility. Protein coated sample, which has the larger clusters among the two samples, has a heat generation rate is 6 times higher than the prediction. Meanwhile, the biotin coated sample which has relatively smaller clusters show only a small increase in heat generation rate. A possible explanation for these results is the loss of superparamagnetic character and an opening in hysteresis loop at test frequency for suspensions with large clusters, which may increase the dissipated power above that produced by the relaxation heat losses [9]. Above results show that coating had little effect on SAR. On the other hand, aggregations and clusters may significantly affect SAR, possibly due to dipolar interaction between nanoparticles in suspensions with relatively small clusters or loss of superparmagnetic characters when very large clusters are present.

Human foreskin fibroblasts secrete several different serine protease inhibitors which differ in size and protease specificities. These proteins, called protease nexins (PNs) all form SDS-resistant complexes with their protease targets. Fibroblast surface receptors recognize the protease-PN complexes and mediate their delivery to lysosomes. PNI is a 45 kilodalton glycoprotein that rapidly inhibits several arg or lys-specific proteases including trypsin, thrombin, and urokinase (k assoc.∼ 4×l06,∼ 6×105 and ∼ 2×105, m−1s−1 respectively). Like antithrombin III, PNI binds heparin and inhibits thrombin at a vastly accelerated rate in the presence of this glycoaminoglycan. Immunofluorescence studies show that in addition to secreting PNI foreskin fibroblasts carry this inhibitor on their surfaces. PNI cDNA has been cloned and sequenced. A mixed oligonucleotide probe derived from PNI N-terminal sequence was used to probe a foreskin fibroblast cDNA library constructed with λGT10. Identification of PNI cDNAs has been verified by sequencing and by expressing active PNI protein in mammalian cells. The full amino acid sequence of PNI, deduced from cDNA sequencing, is 392 residues long and has 30% homology to antithrombin III. An arg-ser pair 32 residues from the C-terminus of the inhibitor is proposed as the reactive center P1-P1 residues. In the hinge region a lys residue is present in a position occupied by a ginor glu residue in other serpins. PNI mRNA exists in 2 slightly different forms:One (αPNI) yields a thr-arg-ser sequence wherethe other βPNI) yields a thr-thr-gly-ser sequence. The presence of the appropriate splice acceptor sites in the genome indicates that these forms are generated from a single gene by alternative splicing. Expressed aPNI and 0PNI proteins both bind thrombin and urokinase. In foreskin fibroblaststhe α form of PNI mRNA predominates over the β form by about 2:1. In foreskin fibroblast cultures secreted PNI inhibits the mitogenic response to thrombin and regulate secreted urokinase. Purified PNI added to human fibrosarcoma (HT1080) cells inhibitsthe tumor cell-mediated destruction of extracellular matrix and transiently, but dramatically, inhibits tumor cell growth. PNI or PNI-like inhibitors may function at multiple physiological sites. The β form of PNI is virtually identical to a glia-derived neurite promoting factor, the cDNA for which has been recently cloned and sequenced by Gloor et al (1). The neurite outgrowth activity of PNI may result from inhibition of a thrombin-like protease that is associated with neurons, since a number of thrombin inhibitors stimulate neurite extension. Recent immunofluoresence experiments, carried out with D. Hantai (Inserm; Paris) demonstrate that anti-PNI antibody intensely stains neuromuscular synapses. In addition, a PNI-like inhibitor is associated with platelets. At low (0.5 nM &lt;) 125I-thrombin concentrations formation of 125I-thrombin-platelet PNI complexes accounts for most of the specific binding of 125I-thrombin to platelets (2). Although the platelet-associated form of PNI is electrophoretically and immunologically indistinguishable from fibroblast PNI, it does not bind urokinase, suggesting that it may be distinct.(1) Gloor, S., K. Odink, J. Guenther, H. Nick, and D. Monard. (1986) Cell 47:687-693.(2) Gronke, R.S., B.L. Bergman, and J.B. Baker. (1987) J. Biol. Chem. (in press)

This paper extends to different indicators of labor underutilization the Updated Okun Method (UOM) for estimation of potential output proposed in Fontanari et al (2020), which, from a demand-led growth perspective, regards potential output as an empirical approximation to full-employment output, as in A.M.Okun’s (1962) original method. Based on the apparent incapability of the official rate of unemployment to fully account for labor underutilization, in this paper we offer estimates of Okun’s law both with broad unemployment indicators and with an indicator of ‘standardized hours worked’ which we propose as a novel measure of the labor input. The paper reflects on the possible different empirical measures of full employment. The various measures of potential output that we extract from our analysis show greater output gaps than those produced by standard methods, thus highlighting a systematic tendency of the latter to underestimate potential output. Output gaps that underestimate the size of the output loss or that tend to close too soon during recovery, may produce a bias towards untimely restriction.

1.1 Macroeconomic summary Economic recovery has consistently outperformed the technical staff’s expectations following a steep decline in activity in the second quarter of 2020. At the same time, total and core inflation rates have fallen and remain at low levels, suggesting that a significant element of the reactivation of Colombia’s economy has been related to recovery in potential GDP. This would support the technical staff’s diagnosis of weak aggregate demand and ample excess capacity. The most recently available data on 2020 growth suggests a contraction in economic activity of 6.8%, lower than estimates from January’s Monetary Policy Report (-7.2%). High-frequency indicators suggest that economic performance was significantly more dynamic than expected in January, despite mobility restrictions and quarantine measures. This has also come amid declines in total and core inflation, the latter of which was below January projections if controlling for certain relative price changes. This suggests that the unexpected strength of recent growth contains elements of demand, and that excess capacity, while significant, could be lower than previously estimated. Nevertheless, uncertainty over the measurement of excess capacity continues to be unusually high and marked both by variations in the way different economic sectors and spending components have been affected by the pandemic, and by uneven price behavior. The size of excess capacity, and in particular the evolution of the pandemic in forthcoming quarters, constitute substantial risks to the macroeconomic forecast presented in this report. Despite the unexpected strength of the recovery, the technical staff continues to project ample excess capacity that is expected to remain on the forecast horizon, alongside core inflation that will likely remain below the target. Domestic demand remains below 2019 levels amid unusually significant uncertainty over the size of excess capacity in the economy. High national unemployment (14.6% for February 2021) reflects a loose labor market, while observed total and core inflation continue to be below 2%. Inflationary pressures from the exchange rate are expected to continue to be low, with relatively little pass-through on inflation. This would be compatible with a negative output gap. Excess productive capacity and the expectation of core inflation below the 3% target on the forecast horizon provide a basis for an expansive monetary policy posture. The technical staff’s assessment of certain shocks and their expected effects on the economy, as well as the presence of several sources of uncertainty and related assumptions about their potential macroeconomic impacts, remain a feature of this report. The coronavirus pandemic, in particular, continues to affect the public health environment, and the reopening of Colombia’s economy remains incomplete. The technical staff’s assessment is that the COVID-19 shock has affected both aggregate demand and supply, but that the impact on demand has been deeper and more persistent. Given this persistence, the central forecast accounts for a gradual tightening of the output gap in the absence of new waves of contagion, and as vaccination campaigns progress. The central forecast continues to include an expected increase of total and core inflation rates in the second quarter of 2021, alongside the lapse of the temporary price relief measures put in place in 2020. Additional COVID-19 outbreaks (of uncertain duration and intensity) represent a significant risk factor that could affect these projections. Additionally, the forecast continues to include an upward trend in sovereign risk premiums, reflected by higher levels of public debt that in the wake of the pandemic are likely to persist on the forecast horizon, even in the context of a fiscal adjustment. At the same time, the projection accounts for the shortterm effects on private domestic demand from a fiscal adjustment along the lines of the one currently being proposed by the national government. This would be compatible with a gradual recovery of private domestic demand in 2022. The size and characteristics of the fiscal adjustment that is ultimately implemented, as well as the corresponding market response, represent another source of forecast uncertainty. Newly available information offers evidence of the potential for significant changes to the macroeconomic scenario, though without altering the general diagnosis described above. The most recent data on inflation, growth, fiscal policy, and international financial conditions suggests a more dynamic economy than previously expected. However, a third wave of the pandemic has delayed the re-opening of Colombia’s economy and brought with it a deceleration in economic activity. Detailed descriptions of these considerations and subsequent changes to the macroeconomic forecast are presented below. The expected annual decline in GDP (-0.3%) in the first quarter of 2021 appears to have been less pronounced than projected in January (-4.8%). Partial closures in January to address a second wave of COVID-19 appear to have had a less significant negative impact on the economy than previously estimated. This is reflected in figures related to mobility, energy demand, industry and retail sales, foreign trade, commercial transactions from selected banks, and the national statistics agency’s (DANE) economic tracking indicator (ISE). Output is now expected to have declined annually in the first quarter by 0.3%. Private consumption likely continued to recover, registering levels somewhat above those from the previous year, while public consumption likely increased significantly. While a recovery in investment in both housing and in other buildings and structures is expected, overall investment levels in this case likely continued to be low, and gross fixed capital formation is expected to continue to show significant annual declines. Imports likely recovered to again outpace exports, though both are expected to register significant annual declines. Economic activity that outpaced projections, an increase in oil prices and other export products, and an expected increase in public spending this year account for the upward revision to the 2021 growth forecast (from 4.6% with a range between 2% and 6% in January, to 6.0% with a range between 3% and 7% in April). As a result, the output gap is expected to be smaller and to tighten more rapidly than projected in the previous report, though it is still expected to remain in negative territory on the forecast horizon. Wide forecast intervals reflect the fact that the future evolution of the COVID-19 pandemic remains a significant source of uncertainty on these projections. The delay in the recovery of economic activity as a result of the resurgence of COVID-19 in the first quarter appears to have been less significant than projected in the January report. The central forecast scenario expects this improved performance to continue in 2021 alongside increased consumer and business confidence. Low real interest rates and an active credit supply would also support this dynamic, and the overall conditions would be expected to spur a recovery in consumption and investment. Increased growth in public spending and public works based on the national government’s spending plan (Plan Financiero del Gobierno) are other factors to consider. Additionally, an expected recovery in global demand and higher projected prices for oil and coffee would further contribute to improved external revenues and would favor investment, in particular in the oil sector. Given the above, the technical staff’s 2021 growth forecast has been revised upward from 4.6% in January (range from 2% to 6%) to 6.0% in April (range from 3% to 7%). These projections account for the potential for the third wave of COVID-19 to have a larger and more persistent effect on the economy than the previous wave, while also supposing that there will not be any additional significant waves of the pandemic and that mobility restrictions will be relaxed as a result. Economic growth in 2022 is expected to be 3%, with a range between 1% and 5%. This figure would be lower than projected in the January report (3.6% with a range between 2% and 6%), due to a higher base of comparison given the upward revision to expected GDP in 2021. This forecast also takes into account the likely effects on private demand of a fiscal adjustment of the size currently being proposed by the national government, and which would come into effect in 2022. Excess in productive capacity is now expected to be lower than estimated in January but continues to be significant and affected by high levels of uncertainty, as reflected in the wide forecast intervals. The possibility of new waves of the virus (of uncertain intensity and duration) represents a significant downward risk to projected GDP growth, and is signaled by the lower limits of the ranges provided in this report. Inflation (1.51%) and inflation excluding food and regulated items (0.94%) declined in March compared to December, continuing below the 3% target. The decline in inflation in this period was below projections, explained in large part by unanticipated increases in the costs of certain foods (3.92%) and regulated items (1.52%). An increase in international food and shipping prices, increased foreign demand for beef, and specific upward pressures on perishable food supplies appear to explain a lower-than-expected deceleration in the consumer price index (CPI) for foods. An unexpected increase in regulated items prices came amid unanticipated increases in international fuel prices, on some utilities rates, and for regulated education prices. The decline in annual inflation excluding food and regulated items between December and March was in line with projections from January, though this included downward pressure from a significant reduction in telecommunications rates due to the imminent entry of a new operator. When controlling for the effects of this relative price change, inflation excluding food and regulated items exceeds levels forecast in the previous report. Within this indicator of core inflation, the CPI for goods (1.05%) accelerated due to a reversion of the effects of the VAT-free day in November, which was largely accounted for in February, and possibly by the transmission of a recent depreciation of the peso on domestic prices for certain items (electric and household appliances). For their part, services prices decelerated and showed the lowest rate of annual growth (0.89%) among the large consumer baskets in the CPI. Within the services basket, the annual change in rental prices continued to decline, while those services that continue to experience the most significant restrictions on returning to normal operations (tourism, cinemas, nightlife, etc.) continued to register significant price declines. As previously mentioned, telephone rates also fell significantly due to increased competition in the market. Total inflation is expected to continue to be affected by ample excesses in productive capacity for the remainder of 2021 and 2022, though less so than projected in January. As a result, convergence to the inflation target is now expected to be somewhat faster than estimated in the previous report, assuming the absence of significant additional outbreaks of COVID-19. The technical staff’s year-end inflation projections for 2021 and 2022 have increased, suggesting figures around 3% due largely to variation in food and regulated items prices. The projection for inflation excluding food and regulated items also increased, but remains below 3%. Price relief measures on indirect taxes implemented in 2020 are expected to lapse in the second quarter of 2021, generating a one-off effect on prices and temporarily affecting inflation excluding food and regulated items. However, indexation to low levels of past inflation, weak demand, and ample excess productive capacity are expected to keep core inflation below the target, near 2.3% at the end of 2021 (previously 2.1%). The reversion in 2021 of the effects of some price relief measures on utility rates from 2020 should lead to an increase in the CPI for regulated items in the second half of this year. Annual price changes are now expected to be higher than estimated in the January report due to an increased expected path for fuel prices and unanticipated increases in regulated education prices. The projection for the CPI for foods has increased compared to the previous report, taking into account certain factors that were not anticipated in January (a less favorable agricultural cycle, increased pressure from international prices, and transport costs). Given the above, year-end annual inflation for 2021 and 2022 is now expected to be 3% and 2.8%, respectively, which would be above projections from January (2.3% and 2,7%). For its part, expected inflation based on analyst surveys suggests year-end inflation in 2021 and 2022 of 2.8% and 3.1%, respectively. There remains significant uncertainty surrounding the inflation forecasts included in this report due to several factors: 1) the evolution of the pandemic; 2) the difficulty in evaluating the size and persistence of excess productive capacity; 3) the timing and manner in which price relief measures will lapse; and 4) the future behavior of food prices. Projected 2021 growth in foreign demand (4.4% to 5.2%) and the supposed average oil price (USD 53 to USD 61 per Brent benchmark barrel) were both revised upward. An increase in long-term international interest rates has been reflected in a depreciation of the peso and could result in relatively tighter external financial conditions for emerging market economies, including Colombia. Average growth among Colombia’s trade partners was greater than expected in the fourth quarter of 2020. This, together with a sizable fiscal stimulus approved in the United States and the onset of a massive global vaccination campaign, largely explains the projected increase in foreign demand growth in 2021. The resilience of the goods market in the face of global crisis and an expected normalization in international trade are additional factors. These considerations and the expected continuation of a gradual reduction of mobility restrictions abroad suggest that Colombia’s trade partners could grow on average by 5.2% in 2021 and around 3.4% in 2022. The improved prospects for global economic growth have led to an increase in current and expected oil prices. Production interruptions due to a heavy winter, reduced inventories, and increased supply restrictions instituted by producing countries have also contributed to the increase. Meanwhile, market forecasts and recent Federal Reserve pronouncements suggest that the benchmark interest rate in the U.S. will remain stable for the next two years. Nevertheless, a significant increase in public spending in the country has fostered expectations for greater growth and inflation, as well as increased uncertainty over the moment in which a normalization of monetary policy might begin. This has been reflected in an increase in long-term interest rates. In this context, emerging market economies in the region, including Colombia, have registered increases in sovereign risk premiums and long-term domestic interest rates, and a depreciation of local currencies against the dollar. Recent outbreaks of COVID-19 in several of these economies; limits on vaccine supply and the slow pace of immunization campaigns in some countries; a significant increase in public debt; and tensions between the United States and China, among other factors, all add to a high level of uncertainty surrounding interest rate spreads, external financing conditions, and the future performance of risk premiums. The impact that this environment could have on the exchange rate and on domestic financing conditions represent risks to the macroeconomic and monetary policy forecasts. Domestic financial conditions continue to favor recovery in economic activity. The transmission of reductions to the policy interest rate on credit rates has been significant. The banking portfolio continues to recover amid circumstances that have affected both the supply and demand for loans, and in which some credit risks have materialized. Preferential and ordinary commercial interest rates have fallen to a similar degree as the benchmark interest rate. As is generally the case, this transmission has come at a slower pace for consumer credit rates, and has been further delayed in the case of mortgage rates. Commercial credit levels stabilized above pre-pandemic levels in March, following an increase resulting from significant liquidity requirements for businesses in the second quarter of 2020. The consumer credit portfolio continued to recover and has now surpassed February 2020 levels, though overall growth in the portfolio remains low. At the same time, portfolio projections and default indicators have increased, and credit establishment earnings have come down. Despite this, credit disbursements continue to recover and solvency indicators remain well above regulatory minimums. 1.2 Monetary policy decision In its meetings in March and April the BDBR left the benchmark interest rate unchanged at 1.75%.