Fixed Size Confidence Regions for the Parameters of the Mixed Effects Logistic Regression Model

We develop fixed size confidence regions for estimating the fixed and random effects parameters of the mixed effects logistic regression model. This model applies to, among others, the study of the effects of covariates on a dichotomous response variable when subjects are sampled in clusters. Two sequential procedures are developed to estimate with a prescribed accuracy (confidence level) and fixed precision the set of fixed and random effects parameters and linear transformations of these parameters, respectively. We show that the two procedures are asymptotically consistent (i.e., the coverage probability converges to the nominal confidence level) and asymptotically efficient (i.e., the ratio of the expected random sample size to the unknown best fixed sample size converges to 1) as the width of the confidence region converges to 0. Suggestions to improve the performance of the procedures are provided based on Monte Carlo simulation and illustrated through a longitudinal clinical trial data

Rôle de la protéine tyrosine kinase Fer dans le cancer de la prostate

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal

Study of domestic wastewater treatment bymacrophyte plant in Arid Region of South-east Algeria (case of el oued region)

Removal of wastewater pollution by natural treatment systems such as wetlands is achieved using filter media and macrophytes plants. The functioning of constructed wetlands relies on physical, chemical and biological processes. The aim of the present study is to evaluate the performance of the Phragmites australis for domestic wastewater  treatment under an arid climate. Experiments were conducted during three months (February, March and April). Results indicate that the variation of pH values of raw and treated wastewater is not significant. The electrical conductivity increases strongly during March and April. It was also found that dissolved oxygen in planted filter exceeds that of the unplanted one. Also, the higher performance in BOD and Ntot removal by the planted filter confirms the important role of this plant in the treatment process.Keywords: Pollution; wetlands; filter media; performance; Phragmites australis

Tribbles 2 pseudokinase confers enzalutamide resistance in prostate cancer by promoting lineage plasticity

Enzalutamide, a second-generation antiandrogen, is commonly prescribed for the therapy of advanced prostate cancer, but enzalutamide-resistant, lethal, or incurable disease invariably develops. To understand the molecular mechanism(s) behind enzalutamide resistance, here, we comprehensively analyzed a range of prostate tumors and clinically relevant models by gene expression array, immunohistochemistry, and Western blot, which revealed that enzalutamide-resistant prostate cancer cells and tumors overexpress the pseudokinase, Tribbles 2 (TRIB2). Inhibition of TRIB2 decreases the viability of enzalutamide-resistant prostate cancer cells, suggesting a critical role of TRIB2 in these cells. Moreover, the overexpression of TRIB2 confers resistance in prostate cancer cells to clinically relevant doses of enzalutamide, and this resistance is lost upon inhibition of TRIB2. Interestingly, we found that TRIB2 downregulates the luminal markers androgen receptor and cytokeratin 8 in prostate cancer cells but upregulates the neuronal transcription factor BRN2 (Brain-2) and the stemness factor SOX2 (SRY-box 2) to induce neuroendocrine characteristics. Finally, we show that inhibition of either TRIB2 or its downstream targets, BRN2 or SOX2, resensitizes resistant prostate cancer cells to enzalutamide. Thus, TRIB2 emerges as a potential new regulator of transdifferentiation that confers enzalutamide resistance in prostate cancer cells via a mechanism involving increased cellular plasticity and lineage switching

Central retinal vein occlusion revealing celiac disease

Introduction: Thrombosis has been widely reported in coeliac disease (CD) but central retinal vein occlusion (CRVO) is rarely described. Case presentation: A 27-year-old woman presented with acute visual loss and was diagnosed with CRVO. Her protein S and protein C levels were low and CD was diagnosed on the basis of endoscopic, immunological and histological results. A gluten-free diet resulted in favourable evolution. Conclusion: CD should be considered in young patients with thrombosis, especially if in an unusual location. Treatment is based on a gluten-free diet

Demographics and microbiological profile of Pneumonia in United Arab Emirates

Background. Pneumonia is a common respiratory disease, which has a mortality rate of approximately 14% worldwide. The management of pneumonia is based on the patient and microbiological profile existing in the community. There is a paucity of data regarding patient demographics and the microbiological profile for pneumonia in the United Arab Emirates (UAE). Methods. We conducted a retrospective analysis of inpatients with pneumonia in the UAE. Epidemiological, clinical and microbiological data was collected from patients over the age of 16 years admitted to a single university hospital with a diagnosis of pneumonia between the years 1997 and 2002. Patients were categorised as having community acquired (CAP) or hospital acquired pneumonia (HAP). Results. Among the 361 patients, 186 were females and 175 males. The mean age (±SEM) of the males was 59±1.6 years and of the females, 56.9±1.5 years. The annual hospital admission rate for pneumonia increased from 410 per million population in 1997 to 760 in 2002. The pneumonia was community acquired in 289 (80%) and hospital acquired in 72 (20%). Hospitalisation for CAP showed a significant seasonal variation with peak admission rates in March and April and the nadir in August and September. The overall mortality rate was 13%, and was significantly higher for HAP (24%) than for CAP (10%, p<0.01). The common microorganisms isolated from sputum culture in CAP were Haemophilus.influenzae (18.6%) and Streptococcus.pneumoniae (10%). The common pathogen in HAP was Pseudomonas.aeruginosa in (50%). 4 out of 17 (23%) H. influenzae isolates were resistant to amoxicillin and 2 of 9 S. pneumoniae isolates (22%) were resistant to penicillin. Conclusions. The hospitalisation rate for CAP has increased over the years and showed a clear seasonal trend in the UAE. H. influenzae was the most common organism among patients with CAP and P. aeruginosa in HAP. The mortality rate for HAP was significantly higher than for CAP. The drug resistance pattern was similar to reports from centres elsewhere in South East Asia

Epidemiological, clinical, and therapeutic characteristics of Behçet's disease: a monocentric study in Tunisia

Introduction:&nbsp;to describe the epidemiological, clinical, therapeutic and evolving characteristics of Behçet´s disease and identify prognostic factors. Methods:&nbsp;we have realized a retrospective, single-center study, conducted over a period of 26 years and including 130 patients presenting Behçet´s disease and hospitalized in an Internal Medicine Department. Results:&nbsp;the mean age of the Behçet´s disease at onset was 30.3 ±8.8 years and that at diagnosis was 34.6 ±9.4 years. The sex ratio (male/female) was 2.5. The mean delay of diagnosis was 53.5 months. Oral aphthosis was constant. The frequency of the manifestations was: genital aphtosis 71.5%, pseudofolliculitis 84.6%, erythema nodosum 11.5%, positive pathergy test 50%, ocular disease 36.9%, venous thrombosis 30%, arterial disease 4.6%, joint damage 30.8%, neurological disease 19.2% and digestive disease 0.8%. The male gender was significantly associated with ocular involvement (p =0.02), venous disease (p =0.01) and occurrence of relapses (p =0.01). The mean follow up was 68.5 ± 77.3 months. The poor survival prognostic factors were male gender, ocular involvement, venous disease, cardiovascular disease, a duration of follow up ≤12 months and a diagnostic delay ≤ 24 months. Conclusion:&nbsp;improving the prognosis of Behçet´s disease requires a shortening of the time to diagnosis, multidisciplinary collaboration, intensive treatment of functional threats, regular monitoring, and patient adherence

Constitutively-active androgen receptor variants function independently of the HSP90 chaperone but do not confer resistance to HSP90 inhibitors

The development of lethal, castration resistant prostate cancer is associated with adaptive changes to the androgen receptor (AR), including the emergence of mutant receptors and truncated, constitutively active AR variants. AR relies on the molecular chaperone HSP90 for its function in both normal and malignant prostate cells, but the requirement for HSP90 in environments with aberrant AR expression is largely unknown. Here, we investigated the efficacy of three HSP90 inhibitors, 17-AAG, HSP990 and AUY922, against clinically-relevant AR missense mutants and truncated variants. HSP90 inhibition effectively suppressed the signaling of wild-type AR and all AR missense mutants tested. By contrast, two truncated AR variants, AR-V7 and ARv567es, exhibited marked resistance to HSP90 inhibitors. Supporting this observation, nuclear localization of the truncated AR variants was not affected by HSP90 inhibition and AR variant:HSP90 complexes could not be detected in prostate cancer cells. Interestingly, HSP90 inhibition resulted in accumulation of AR-V7 and ARv567es in both cell lines and human tumor explants. Despite the apparent independence of AR variants from HSP90 and their treatment-associated induction, the growth of cell lines with endogenous or enforced expression of AR-V7 or ARv567es remained highly sensitive to AUY922. This study demonstrates that functional AR variant signaling does not confer resistance to HSP90 inhibition, yields insight into the interaction between AR and HSP90 and provides further impetus for the clinical application of HSP90 inhibitors in advanced prostate cancer.Joanna L. Gillis, Luke A. Selth, Margaret M. Centenera, Scott L. Townley, Shihua Sun, Stephen R. Plymate, Wayne D. Tilley and Lisa M. Butle

Kaposi’s Sarcoma Presenting As Lymphadenopathy In An Immunocompetent Patient

Introduction: Kaposi’s sarcoma (KS) is an angioproliferative disorder first described in 1872 by Moritz Kaposi. Four main clinical presentations of KS have been described: classic, endemic, iatrogenic and epidemic. KS involvement of the lymph nodes is extremely uncommon in the classical variant form, especially if it precedes the skin manifestations. We describe the case of an elderly HIV-negative patient presenting with lymphadenopathy who was found to have KS. Case Report: A 67-year-old patient was admitted for exploration of polyadenopathies in the context of a general decline in health. Physical examination revealed an erythematosus left lower limb rash associated with angiomatous nodules and multiple lymphadenopathies. The diagnosis of erysipelas in the left leg was retained and the patient was treated with good evolution of the rash but persistence of the angiomatous nodules and the polyadenopathies. Skin and lymph node biopsies led to a diagnosis of KS. The patient is proposed for polychemotherapy. Conclusion: KS must be suspected in lymphadenopathies despite the absence of typical cutaneous signs of the disease and in immunocompetent patients