Phylogeny and historical biogeography of neotropical catfishes Trichomycterus (Siluriformes: Trichomycteridae) from eastern Brazil.

The catfish subfamily Trichomycterinae is widely distributed in South America inhabiting several habitats, but specially mountain streams. Trichomycterus is the most speciose trichomycterid genus and recently due to his paraphyletic condition has been restricted to a clade from eastern Brazil called Trichomycterus sensu stricto comprising around 80 valid species distributed in seven areas of endemism of eastern Brazil. This paper aims to analyse the biogeographical events responsible for the distribution of Trichomycterus s.s., by reconstructing the ancestral data based on a time-calibrated multigene phylogeny. A multi-gene phylogeny was generated using 61 species of Trichomycterus s.s. and 30 outgroups, with divergence events calculated based on the estimated origin of Trichomycteridae. Two event-based analyses were applied to investigate the biogeographical events responsible the present distribution of Trichomycterus s.s. and suggest that the modern distribution of the group is a result of different vicariance and dispersal events. The diversification of Trichomycterus s.s. subgenera occurred in the Miocene, except for Megacambeva, with different biogeographical events shaping its distribution in eastern Brazil. An initial vicariant event split up the Fluminense ecoregion from the Northeastern Mata Atlantica + Paraíba do Sul + Fluminense + Ribeira do Iguape + Upper Paraná ecoregions. Dispersal events occurred mainly between Paraíba do Sul and neighboring river basins, with additional dispersal events from Northeastern Mata Atlantica to Paraíba do Sul, from São Francisco to Northeastern Mata Atlântica, and from Upper Paraná to São Francisco.

Prostate cancer treatment and the relationship of androgen deprivation therapy to cognitive function.

Prostate cancer is the second most common form of cancer in men. For advanced, high risk prostate cancer, androgen deprivation therapy (ADT) is the preferred treatment and can induce remission, but resistance to ADT brings biochemical recurrence and progression of cancer. ADT brings adverse effects such as erectile dysfunction, decreased libido, and diminished physical strength. It is estimated that between 25 and 50% of men on ADT manifest some form of cognitive dysfunction that may be self-reported or reported by a family member. There is concern that impaired cognitive function with ADT is due to loss of testosterone support. Testosterone and its metabolites are known to possess neuroprotective properties. While a direct causal relationship between ADT and cognitive decline in prostate cancer patients has not been established, this review describes the controversy surrounding the possible connection between ADT and neurocognitive deterioration. The cellular and molecular mechanisms believed to underlie the protection of neuronal integrity by androgens are discussed. Results from animal models and human clinical studies are presented. Finally, we call attention to lifestyle modifications that may minimize cognitive issues in prostate cancer patients.

Four-year Prostate-specific Antigen Response Rate as a Predictive Measure in Intermediate-risk Prostate Cancer Treated With Ablative Therapies: The SPRAT Analysis.

AIMS: There is a lack of early predictive measures of outcome for patients with intermediate-risk prostate cancer (PCa) treated with stereotactic body radiotherapy (SBRT). The aim of the present study was to explore 4-year prostate-specific antigen response rate (4yPSARR) as an early predictive measure. MATERIALS AND METHODS: Individual patient data from six institutions for patients with intermediate-risk PCa treated with SBRT between 2006 and 2016 with a 4-year (42-54 months) PSA available were analysed. Cumulative incidences of biochemical failure and metastasis were calculated using Nelson-Aalen estimates and overall survival was calculated using the Kaplan-Meier method. Biochemical failure-free survival was analysed according to 4yPSARR, with groups dichotomised based on PSA <0.4 ng/ml or ≥0.4 ng/ml and compared using the Log-rank test. A multivariable competing risk analysis was carried out to predict for biochemical failure and the development of metastases. RESULTS: Six hundred and thirty-seven patients were included, including 424 (67%) with favourable and 213 (33%) with unfavourable intermediate-risk disease. The median follow-up was 6.2 years (interquartile range 4.9-7.9). The cumulative incidence of biochemical failure and metastasis was 7 and 0.6%, respectively; overall survival at 6 years was 97%. The cumulative incidence of biochemical failure at 6 years if 4yPSARR <0.4 ng/ml was 1.7% compared with 27% if 4yPSARR ≥0.4 ng/ml (P < 0.0001). On multivariable competing risk analysis, 4yPSARR was a statistically significant predictor of biochemical failure-free survival (subdistribution hazard ratio 15.3, 95% confidence interval 7.5-31.3, P < 0.001) and metastasis-free survival (subdistribution hazard ratio 31.2, 95% confidence interval 3.1-311.6, P = 0.003). CONCLUSION: 4yPSARR is an encouraging early predictor of outcome in patients with intermediate-risk PCa treated with SBRT. Validation in prospective trials is warranted.

Population Data Centre Profile: The Manitoba Centre for Health Policy.

OBJECTIVE: To profile the Manitoba Centre for Health Policy (MCHP), a population health data centre located at the University of Manitoba in Winnipeg, Canada. APPROACH: We describe how MCHP was established and funded, and how it continues to operate based on a foundation of trust and respect between researchers at the University of Manitoba and stakeholders in the Manitoba Government's Department of Health. MCHP's research priorities are jointly determined by its scientists' own research interests and by questions put forward from Manitoba government ministries. Data governance, data privacy, data linkage processes and data access are discussed in detail. We also provide three illustrative examples of the MCHP Data Repository in action, demonstrating how studies using a variety of Repository datasets have had an impact on health and social policies and programs in Manitoba. DISCUSSION: MCHP has experienced tremendous growth over the last three decades. We discuss emerging research directions as the capacity for innovation at MCHP continues to expand, including a focus on natural language processing and other applications of artificial intelligence techniques, a leadership role in the new SPOR Canadian Data Platform, and a foray into social policy evaluation and analysis. With these and other exciting opportunities on the horizon, the future at MCHP looks exceptionally bright.

Incidence and temporal trends of co-occurring personality disorder diagnoses in immune-mediated inflammatory diseases.

AIMS: Although immune-mediated inflammatory diseases (IMID) are associated with multiple mental health conditions, there is a paucity of literature assessing personality disorders (PDs) in these populations. We aimed to estimate and compare the incidence of any PD in IMID and matched cohorts over time, and identify sociodemographic characteristics associated with the incidence of PD. METHODS: We used population-based administrative data from Manitoba, Canada to identify persons with incident inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA) using validated case definitions. Unaffected controls were matched 5:1 on sex, age and region of residence. PDs were identified using hospitalisation or physician claims. We used unadjusted and covariate-adjusted negative binomial regression to compare the incidence of PDs between the IMID and matched cohorts. RESULTS: We identified 19 572 incident cases of IMID (IBD n = 6,119, MS n = 3,514, RA n = 10 206) and 97 727 matches overall. After covariate adjustment, the IMID cohort had an increased incidence of PDs (incidence rate ratio [IRR] 1.72; 95%CI: 1.47-2.01) as compared to the matched cohort, which remained consistent over time. The incidence of PDs was similarly elevated in IBD (IRR 2.19; 95%CI: 1.69-2.84), MS (IRR 1.79; 95%CI: 1.29-2.50) and RA (IRR 1.61; 95%CI: 1.29-1.99). Lower socioeconomic status and urban residence were associated with an increased incidence of PDs, whereas mid to older adulthood (age 45-64) was associated with overall decreased incidence. In a restricted sample with 5 years of data before and after IMID diagnosis, the incidence of PDs was also elevated before IMID diagnosis among all IMID groups relative to matched controls. CONCLUSIONS: IMID are associated with an increased incidence of PDs both before and after an IMID diagnosis. These results support the relevance of shared risk factors in the co-occurrence of PDs and IMID conditions.

Can Linked Electronic Medical Record and Administrative Data Help Us Identify Those Living with Frailty?

INTRODUCTION: Frailty is a complex condition that affects many aspects of patients' wellbeing and health outcomes. OBJECTIVES: We used available Electronic Medical Record (EMR) and administrative data to determine definitions of frailty. We also examined whether there were differences in demographics or health conditions among those identified as frail in either the EMR or administrative data. METHODS: EMR and administrative data were linked in British Columbia (BC) and Manitoba (MB) to identify those aged 65 years and older who were frail. The EMR data were obtained from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) and the administrative data (e.g. billing, hospitalizations) was obtained from Population Data BC and the Manitoba Population Research Data Repository. Sociodemographic characteristics, risk factors, prescribed medications, use and costs of healthcare are described for those identified as frail. RESULTS: Sociodemographic and utilization differences were found among those identified as frail from the EMR compared to those in the administrative data. Among those who were >65 years, who had a record in both EMR and administrative data, 5%-8% (n=191 of 3,553, BC; n=2,396 of 29,382, MB) were identified as frail. There was a higher likelihood of being frail with increasing age and being a woman. In BC and MB, those identified as frail in both data sources have approximately twice the number of contacts with primary care (n=20 vs. n=10) and more days in hospital (n=7.2 vs. n=1.9 in BC; n=9.8 vs. n=2.8 in MB) compared to those who are not frail; 27% (BC) and 14% (MB) of those identified as frail in 2014 died in 2015. CONCLUSIONS: Identifying frailty using EMR data is particularly challenging because many functional deficits are not routinely recorded in structured data fields. Our results suggest frailty can be captured along a continuum using both EMR and administrative data.

SGLT2 inhibition increases serum copeptin in young adults with type 1 diabetes.

AIMS: Copeptin, a surrogate of vasopressin, is elevated in type 1 diabetes (T1D) and predicts kidney disease and cardiovascular mortality. Given the cardiorenal protective effects of SGLT2 inhibition (SGLT2i), our aim was to examine: 1) the relationship between serum copeptin, metabolic, renal and systemic hemodynamic parameters in adults with T1D; and 2) serum copeptin after SGLT2i with empagliflozin. MATERIALS AND METHODS: In this post-hoc, exploratory analysis, serum copeptin, glomerular filtration rate (GFRInulin), effective renal plasma flow (ERPFPAH), plasma renin angiotensin aldosterone system markers, HbA1c, 24-hour urine volume and sodium excretion were measured in 40 participants with T1D (24.3±5.1 years) during eu- and hyperglycaemia before and after 8 weeks of 25mg of daily empagliflozin. RESULTS: Higher baseline copeptin correlated with higher HbA1c, lower 24-hour urine volume and sodium excretion, after correcting for age, sex, systolic blood pressure, and HbA1c. Copeptin concentrations increased in response to empagliflozin under euglycaemia (4.1±2.1 to 5.1±2.8pmol/L, P=0.0053) and hyperglycaemia (3.3±1.4 to 5.6±2.8pmol/L, P<0.0001). The rise in copeptin in response to empagliflozin correlated with change in 24-hour urine volume, but was independent of changes in fractional excretion of sodium and haematocrit. CONCLUSIONS: Elevated serum copeptin was associated with worse glycaemic control and lower diuresis and natriuresis. SGLT2i increased serum copeptin in adults with T1D, and the rise correlated with change in diuresis, but not natriuresis and hemo-concentration. Further work is required to evaluate the clinical implications of elevated copeptin with SGLT2i, including whether it is simply a marker of diuresis or may contribute to cardiorenal disease long-term.

Multigene assays in early breast cancer: Insights from recent phase 3 studies.

Multigene assays (MGAs) guide treatment in early-stage breast cancer (ESBC) enabling selective and effective use of adjuvant chemotherapy (CT). Support for all MGAs had previously been derived from retrospectively-analyzed, prospective studies. Only 2 ESBC MGAs, the 70-gene signature (MammaPrint®) and the 21-gene Recurrence Score (RS) assay (Oncotype DX®), are now supported by entirely prospective randomized phase 3 trials. These studies varied in their primary objectives, design, and eligibility. The MINDACT study provided the first level 1 evidence for the 70-gene signature, identifying a prognostic capability irrespective of lymph node (LN) or hormone receptor (HR) status. However, the study did not support predictive value for the assay regarding adjuvant CT utility. The second prospective study, WSG-PlanB, confirmed the prognostic value of the 21-gene RS assay in HR-positive tumors with RS ≤ 11. A 5-year disease free survival (DFS) of 94% was identified in this group when treated with endocrine therapy (ET) alone regardless of N0 or N1 nodal status. The final new prospective study, TAILORx, confirmed the prognostic value of the 21-gene assay in N0 HR-positive disease, demonstrating a lack of CT benefit in patients with midrange RS. The information from these phase 3 studies confirms that MGAs are not interchangeable and that each provides different information for differing patient populations. Prognosis-only is supported for the 70-gene signature while both prognosis and the predictive value of CT are provided by the 21-gene assay. This review assesses and contrasts these phase 3 studies in the context of target populations and clinical utility.

Training South African clinician-scientists: Lessons from the University of Cape Town's intercalated programme.

In 2011, the Faculty of Health Sciences at the University of Cape Town, South Africa (SA), established the Clinician-Scientist Training Programme (UCTCSTP), consisting of intercalated BMedSci Hons/MB ChB and integrated MB ChB/MSc/PhD tracks. We report and reflect on the programme's performance and challenges. The UCTCSTP has so far enrolled 71 students: 51 have received BMedSci Hons degrees and 4 have received Master's degrees, while there are 14 BMedSci Hons, 4 MSc and 4 PhD candidates. Graduates have produced significant research outputs, and many remain actively engaged in research. The UCTCSTP has been successful in encouraging a cohort of future clinician-scientists, but should aim to broaden and improve its appeal to address the need to transform and grow the SA clinical academic workforce. As graduates progress with their postgraduate clinical training, they require institutional support and guidance, which may necessitate policy reform.

Asthma prevalence disparities and differences in sociodemographic associations with asthma, between Native Hawaiian/Other Pacific Islander, Asian, and White adults in Hawaii - Behavioral Risk Factor Surveillance System (BRFSS), 2001-2010.

OBJECTIVES: Despite high asthma prevalence, relatively little is known about the epidemiology of asthma in Hawaii or among Native Hawaiian/Other Pacific Islanders (NHOPI). We sought to better characterize racial/ethnic differences in asthma prevalence and in sociodemographic factors associated with asthma among Hawaii adults. DESIGN: We conducted multivariable logistic regression using 2001-2010 Behavioral Risk Factor Surveillance System data from Hawaii, and computed adjusted prevalence and ratios. RESULTS: Asthma prevalence markedly varied between self-identified census categories of race in Hawaii, with NHOPI having the highest estimates of both lifetime (20.9%, 95% confidence interval [CI]: 19.5%-22.4%) and current (12.2%, CI: 11.2%-13.3%) asthma. Highest asthma prevalence among NHOPI persisted after controlling for potential confounders and within most sociodemographic categories. Among females Asians reported the lowest asthma prevalence, whereas among males point estimates of asthma prevalence were often lowest for Whites. Females often had greater asthma prevalence than males of the same race, but the degree to which gender modified asthma prevalence differed by both race and sociodemographic strata. Gender disparities in asthma prevalence were greatest and most frequent among Whites, and for current asthma among all races. Sociodemographic factors potentially predictive of adult asthma prevalence in Hawaii varied by race and gender. CONCLUSION: Asthma disproportionately affects or is recognized more often among women and NHOPI adults in Hawaii, and occurs less or is under-reported among Asian women. The sociodemographic characteristics included in this study's model did not explain asthma disparities between races and/or gender. This investigation provides a baseline with which to plan additionally needed prevention programs, epidemiological investigations, and surveillance for asthma in Hawaii.

Rising incidence of psychiatric disorders before diagnosis of immune-mediated inflammatory disease.

AIMS: After the diagnosis of immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA), the incidence of psychiatric comorbidity is increased relative to the general population. We aimed to determine whether the incidence of psychiatric disorders is increased in the 5 years before the diagnosis of IMID as compared with the general population. METHODS: Using population-based administrative health data from the Canadian province of Manitoba, we identified all persons with incident IBD, MS and RA between 1989 and 2012, and cohorts from the general population matched 5 : 1 on year of birth, sex and region to each disease cohort. We identified members of these groups with at least 5 years of residency before and after the IMID diagnosis date. We applied validated algorithms for depression, anxiety disorders, bipolar disorder, schizophrenia, and any psychiatric disorder to determine the annual incidence of these conditions in the 5-year periods before and after the diagnosis year. RESULTS: We identified 12 141 incident cases of IMID (3766 IBD, 2190 MS, 6350 RA) and 65 424 matched individuals. As early as 5 years before diagnosis, the incidence of depression [incidence rate ratio (IRR) 1.54; 95% CI 1.30-1.84) and anxiety disorders (IRR 1.30; 95% CI 1.12-1.51) were elevated in the IMID cohort as compared with the matched cohort. Similar results were obtained for each of the IBD, MS and RA cohorts. The incidence of bipolar disorder was elevated beginning 3 years before IMID diagnosis (IRR 1.63; 95% CI 1.10-2.40). CONCLUSION: The incidence of psychiatric comorbidity is elevated in the IMID population as compared with a matched population as early as 5 years before diagnosis. Future studies should elucidate whether this reflects shared risk factors for psychiatric disorders and IMID, a shared final common inflammatory pathway or other aetiology.

Resonantly pumped eye-safe Er3+:YAG SPS-HIP ceramic laser.

We report for the first time laser action in resonantly-pumped transparent polycrystalline Er3+:YAG ceramic developed through a 2-step approach combining spark plasma sintering and HIP post treatment. Microstructural and spectroscopic properties, as well as the laser performance of large scale 0.5at.% Er:YAG transparent polycrystalline ceramic are discussed. A maximum slope efficiency of ∼31% and optical-optical efficiency of 20% was measured.

Increased temperature accelerates glycogen synthesis and delays fatigue in isolated mouse muscle during repeated contractions.

AIM: Elevated glycogen content in muscle delays fatigue during exercise. We examined if increasing muscle temperature during recovery from exercise affects glycogen synthesis and muscle performance during a subsequent bout of exercise. METHODS: Isolated mouse extensor digitorum longus muscles were stimulated electrically to perform repeated tetanic contractions until force decreased to 40% of initial at 25°C. Thereafter, muscles recovered for 120 minutes at 25°C (control), 120 minutes at 35°C or 60 minutes at 35°C followed by 60 minutes at 25°C. After recovery, muscles were again stimulated to fatigue at 25°C. RESULTS: In the control group, the number of contractions in the second run was slightly less than during the first run (92 ± 5%). Following recovery for 120 minutes at 35°C, the number of contractions was similar to the first run (98 ± 6%). Allowing recovery for 120 minutes at 35°C in the presence of the antioxidant N-acetylcysteine also did not alter the number of contractions in the second run (98 ± 3%). However, recovery for 60 minutes at 35°C followed by 60 minutes at 25°C resulted in an increase in the number of contractions during the second run (110 ± 2%, P < .001). Incorporation of [14 C]glucose into glycogen (glycogen synthesis) during recovery was 1.7-fold higher at 35°C vs 25°C (1.44 ± 0.08 µmol (30 min)-1  (g wet muscle)-1 vs 0.84 ± 0.04; P < .001). CONCLUSION: These data demonstrate that, under the conditions studied, elevating muscle temperature for 60 minutes following a bout of repeated contractions delays muscle fatigue during a subsequent bout of repeated contractions and this is associated with enhanced glycogen synthesis in isolated muscle.

Patient-derived xenografts effectively capture responses to oncology therapy in a heterogeneous cohort of patients with solid tumors.

BACKGROUND: While patient-derived xenografts (PDXs) offer a powerful modality for translational cancer research, a precise evaluation of how accurately patient responses correlate with matching PDXs in a large, heterogeneous population is needed for assessing the utility of this platform for preclinical drug-testing and personalized patient cancer treatment. PATIENTS AND METHODS: Tumors obtained from surgical or biopsy procedures from 237 cancer patients with a variety of solid tumors were implanted into immunodeficient mice and whole-exome sequencing was carried out. For 92 patients, responses to anticancer therapies were compared with that of their corresponding PDX models. RESULTS: We compared whole-exome sequencing of 237 PDX models with equivalent information in The Cancer Genome Atlas database, demonstrating that tumorgrafts faithfully conserve genetic patterns of the primary tumors. We next screened PDXs established for 92 patients with various solid cancers against the same 129 treatments that were administered clinically and correlated patient outcomes with the responses in corresponding models. Our analysis demonstrates that PDXs accurately replicate patients' clinical outcomes, even as patients undergo several additional cycles of therapy over time, indicating the capacity of these models to correctly guide an oncologist to treatments that are most likely to be of clinical benefit. CONCLUSIONS: Integration of PDX models as a preclinical platform for assessment of drug efficacy may allow a higher success-rate in critical end points of clinical benefit.

Block copolymer templated self-assembly of disk-shaped molecules.

Stacking of disk-shaped organic molecules is a promising strategy to develop electronic and photovoltaic devices. Here, we investigate the capability of a soft block copolymer matrix that microphase separates into a cylindrical phase to direct the self-assembly of disk-shaped molecules by means of molecular simulations. We show that two disk molecules confined in the cylinder domain experience a depletion force, induced by the polymer chains, which results in the formation of stacks of disks. This entropic interaction and the soft confinement provided by the matrix are both responsible for the structures that can be self-assembled, which include slanted or columnar stacks. In addition, we evidence the transmission of stresses between the different minority domains of the microphase, which results in the establishment of a long-ranged interaction between disk molecules embedded in different domains; this interaction is of the order of the microphase periodicity and may be exploited to direct assembly of disks at larger scales.

Interventions to address sexual problems in people with cancer.

BACKGROUND: Sexual dysfunction in people with cancer is a significant problem. The present clinical practice guideline makes recommendations to improve sexual function in people with cancer. METHODS: This guideline was undertaken by the Interventions to Address Sexual Problems in People with Cancer Expert Panel, a group organized by the Program in Evidence-Based Care (pebc). Consistent with the pebc standardized approach, a systematic search was conducted for existing guidelines, and the literature in medline and embase for the years 2003-2015 was systematically searched for both systematic reviews and primary literature. Evidence found for men and for women was evaluated separately, and no restrictions were placed on cancer type or study design. Content and methodology experts performed an internal review of the resulting draft recommendations, which was followed by an external review by targeted experts and intended users. RESULTS: The search identified 4 existing guidelines, 13 systematic reviews, and 103 studies with relevance to the topic. The present guideline provides one overarching recommendation concerning the discussion of sexual health and dysfunction, which is aimed at all people with cancer. Eleven additional recommendations made separately for men and women deal with issues such as sexual response, body image, intimacy and relationships, overall sexual functioning and satisfaction, and vasomotor and genital symptoms. CONCLUSIONS: To our knowledge this clinical practice guideline is the first to comprehensively evaluate interventions for the improvement of sexual problems in people with cancer. The guideline will be a valuable resource to support practitioners and clinics in addressing sexuality in cancer survivors.

Psychiatric and behavioral side effects of anti-epileptic drugs in adolescents and children with epilepsy.

PURPOSE: The objective of the study was to compare the psychiatric and behavioral side effect (PBSE) profiles of both older and newer antiepileptic drugs (AEDs) in children and adolescent patients with epilepsy. METHOD: We used logistic regression analysis to test the correlation between 83 non-AED/patient related potential predictor variables and the rate of PBSE. We then compared for each AED the rate of PBSEs and the rate of PBSEs that led to intolerability (IPBSE) while controlling for non-AED predictors of PBSEs. RESULTS: 922 patients (≤18 years old) were included in our study. PBSEs and IPBSEs occurred in 13.8% and 11.2% of patients, respectively. Overall, a history of psychiatric condition, absence seizures, intractable epilepsy, and frontal lobe epilepsy were significantly associated with increased PBSE rates. Levetiracetam (LEV) had the greatest PBSE rate (16.2%). This was significantly higher compared to other AEDs. LEV was also significantly associated with a high rate of IPBSEs (13.4%) and dose-decrease rates due to IPBSE (6.7%). Zonisamide (ZNS) was associated with significantly higher cessation rate due to IPBSE (9.1%) compared to other AEDs. CONCLUSION: Patients with a history of psychiatric condition, absence seizures, intractable epilepsy, or frontal lobe epilepsy are more likely to develop PBSE. PBSEs appear to occur more frequently in adolescent and children patients taking LEV compared to other AEDs. LEV-attributed PBSEs are more likely to be associated with intolerability and subsequent decrease in dose. The rate of ZNS-attributed IPBSEs is more likely to be associated with complete cessation of AED.

Religiosity: Its Impact on Coping Styles Among Women Undergoing Fertility Treatment.

The Israeli worldview places great significance on childbearing. This could create emotional and ethical difficulties for women coping with fertility issues in addition to their treatments. This study examined the relations between coping strategies and level of religiosity in 159 women undergoing infertility treatment. Statistically significant relations were found between the problem-solving coping style and religious observance (p < 0.01) and religious beliefs (p < 0.05). An inverse correlation was found between the emotional coping style and religious beliefs (p < 0.001). Health professionals should recognize the patient's coping styles and understand the patient's religious belief system as part of an ongoing fertility treatment.

Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia.

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.

Elasticity-induced force reversal between active spinning particles in dense passive media.

The self-organization of active particles is governed by their dynamic effective interactions. Such interactions are controlled by the medium in which such active agents reside. Here we study the interactions between active agents in a dense non-active medium. Our system consists of actuated, spinning, active particles embedded in a dense monolayer of passive, or non-active, particles. We demonstrate that the presence of the passive monolayer alters markedly the properties of the system and results in a reversal of the forces between active spinning particles from repulsive to attractive. The origin of such reversal is due to the coupling between the active stresses and elasticity of the system. This discovery provides a mechanism for the interaction between active agents in complex and structured media, opening up opportunities to tune the interaction range and directionality via the mechanical properties of the medium.