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Human papillomavirus (HPV) infection contributes to approximately 5% of the worldwide cancer burden. The three-dose HPV vaccine has demonstrated immunogenicity and efficacy. Humoral responses may be critical for preventing, controlling, and/or eliminating HPV infection. Using data from the HITCH cohort, we analysed humoral immune response to HPV vaccination among women in relation to the phylogenetic relatedness of HPV genotypes. We included 96 women aged 18–24 years attending college or university in Montreal, Canada. Participants provided blood samples at enrolment and five follow-up visits. Antibody response to bacterially expressed L1 and E6 glutathione S‐transferase fusion proteins of multiple Alphapapillomavirus types, and to virus-like particles (VLP-L1) of HPV16 and HPV18 were measured using multiplex serology. We assessed correlations between antibody seroreactivities using Pearson correlations (r). At enrolment, 87.7% of participants were unvaccinated, 2.4% had received one, 3.2% two, and 6.7% three doses of HPV vaccine. The corresponding L1 seropositivity to any HPV was 41.2%, 83.3%, 100%, and 97.0%. Between-type correlations for L1 seroreactivities increased with the number of vaccine doses, from one to three. Among the latter, the strongest correlations were observed for HPV58–HPV33 (Pearson correlation [r] = 0.96; α9-species); HPV11–HPV6 (r = 0.96; α10-species); HPV45–HPV18 (r = 0.95; α7-species), and HPV68–HPV59 (r = 0.95; α7-species). Correlations between HPV-specific antibody seroreactivities are affected by phylogenetic relatedness, with anti-L1 correlations becoming stronger with the number of vaccine doses received. [ABSTRACT FROM AUTHOR]

Stimuli formerly associated with monetary reward capture our attention, even if this attraction is contrary to current goals (so-called value-driven attentional capture [VDAC], see Anderson (Ann N Y Acad Sci 1369:24–39, 2016), for a review). Despite the growing literature to this topic, little is known about the boundary conditions for the occurrence of VDAC. In three experiments, we investigated the role of response conflicts and spatial uncertainty regarding the target location during the training and test phase for the emergence of value-driven effects. Thus, we varied the occurrence of a response conflict, search components, and the type of task in both phases. In the training, value-driven effects were rather observed if the location of the value-associated target was not predictable and a response conflict was present. Value-driven effects also only occurred, if participants have not learned to deal with a response conflict, yet. However, the introduction of a response conflict during learning of the color-value association seemed to prevent attention to be distracted by this feature in a subsequent test. The study provides new insights not only into the boundary conditions of the learning of value associations, but also into the learning of cognitive control. [ABSTRACT FROM AUTHOR]

Background Humoral immune responses may be critical for preventing, controlling, and/or eliminating human papillomavirus (HPV) infection. We analyzed humoral response to natural HPV infection considering phylogenetic relatedness among unvaccinated women. Methods We included 399 young women attending university/college in Montreal, Canada who were participants of the HITCH cohort. Participants provided blood samples at baseline and 5 follow-up visits. Antibody response to bacterially expressed L1 and E6 glutathione S-transferase (GST) fusion proteins, and virus-like particles (VLP-L1) of Alphapapillomavirus types were measured using multiplex serology. We assessed correlations and associations between HPV types at baseline using Pearson correlation coefficients (r) and univariable linear regressions. Results At baseline, > 40% were seropositive for GST-L1 antibodies of at least 1 HPV type. Strong correlations between GST-L1 were observed for α9 HPV types: 58–52 (r = 0.86), 58–33 (r = 0.75), 33–52 (r = 0.72), and between GST-E6: 52–11 (r = 0.84), 52–18 (r = 0.79), 58–33 (r = 0.78), 35–11 (r = 0.76). HPV16 VLP-L1 moderately explained variability in HPV16 GST-L1 (regression coefficient [b] = 0.38, R 2 = 43.1%), and HPV45 GST-L1 in HPV18 GST-L1 (b = 0.68, R 2 = 42.8%). GST-E6 antibodies accounted for a low to moderate proportion of variability in HPV16 and HPV18 GST-E6 (R 2 = 6.4%–62.2%). Conclusions Associations between naturally induced HPV-specific antibodies depend on phylogenetic relatedness. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is among the most common diseases affecting both axial and appendicular joints and the lead cause of disability worldwide. OA incidence is rising due to extended life expectancy and the increasing obesity epidemic. Several joint interventions are available to manage pain and joint function in patients with OA, most of these treatments being widely applied using intra-articular injections. In this chapter, we will describe the different joint interventions available for the management of pain in OA focusing on intra-articular injections, including discussion on the evidence regarding the efficacy of these treatments, based on the most recent systematic reviews and meta-analyses available. We also discuss the importance of imaging in guiding these treatments, including the different imaging modalities available for intra-articular injection guidance, their advantages, and disadvantages. Finally, we briefly discuss safety data and the consensus regarding the most used intra-articular treatments to manage pain in OA. [ABSTRACT FROM AUTHOR]

Background: Previous studies examining the association between male circumcision (MC) and human papillomavirus (HPV) infections have reported inconsistent results. We used data from the HPV Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) cohort study to examine the association between MC and HPV infections in males and their female sexual partners.Methods: We enrolled monogamous couples in a longitudinal study between 2005 and 2011 in Montreal, Canada. We used logistic and Poisson regression models with propensity score adjustment to estimate odds ratios (ORs) and rate ratios for the association between MC and the prevalence, transmission, and clearance of HPV infections.Results: Four hundred thirteen couples were included in our study. The prevalence OR for the association between MC and baseline infections was 0.81 (95% confidence interval [CI], .56-1.16) in males and 1.05 (95% CI, .75-1.46) in females. The incidence rate ratio for infection transmission was 0.59 (95% CI, .16-2.20) for male-to-female transmission and 0.77 (95% CI, .37-1.60) for female-to-male transmission. The clearance rate ratio for clearance of infections was 0.81 (95% CI, .52-1.24).Conclusions: We found little evidence of an association between MC and HPV infection prevalence, transmission, or clearance in males and females. Further longitudinal couple-based studies are required to investigate this association. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Fremanezumab in individuals with chronic migraine showing inadequate response to onabotulinumtoxin A and topiramate or valproic acid. Topics include Fremanezumab, a humanized monoclonal antibody (IgG2Δa) selectively target calcitonin gene-related peptide; and treatment-by-subgroup interactions being assessed using an analysis of covariance model for the efficacy outcomes.

Many different proteins self-aggregate into insoluble fibrils growing apically by reversible addition of elementary building blocks. But beyond this common principle, the modalities of fibril formation are very disparate, with various intermediate forms which can be reshuffled by minor modifications of physico-chemical conditions or amino-acid sequences. To bypass this complexity, the multifaceted phenomenon of fibril formation is reduced here to its most elementary principles defined for a linear prototype of fibril. Selected generic features, including nucleation, elongation, and conformational recruitment, are modeled using minimalist hypotheses and tools, by separating equilibrium from kinetic aspects and in vitro from in vivo conditions. These reductionist approaches allow to bring out known and new rudiments, including the kinetic and equilibrium effects of nucleation, the dual influence of elongation on nucleation, the kinetic limitations on nucleation and fibril numbers, and the accumulation of complexes in vivo by rescue from degradation. Overlooked aspects of these processes are also pointed: the exponential distribution of fibril lengths can be recovered using various models because it is attributable to randomness only. It is also suggested that the same term "critical concentration" is used for different things, involved in either nucleation or elongation. [ABSTRACT FROM AUTHOR]

Under time pressure, it is usually not possible to respond quickly and accurately at the same time. Therefore, people must trade speed for accuracy, depending on the current payoff conditions. Ideally, they should choose a speed-accuracy tradeoff (SAT) that optimizes their monetary reward. However, this is hardly the case. Rather, persons exhibit an accuracy bias, which is often disadvantageous. To further investigate the role of errors for optimizing reward, we conducted a flanker-task study with different payoff and framing conditions. Whereas the reward for correct responses always increased continuously with speed, the costs of errors varied. In three of four conditions, responding very fast, even with low accuracy, was favorable. Furthermore, in addition to the usual gain framing, half of our participants were instructed according to a loss frame. Whereas framing had little effect on performance, we found a substantial accuracy bias. Only in the most extreme condition some participants overcame their bias and responded very quickly. To examine how SAT strategies differed between participants, we modeled the performance with a sequential-sampling model. The results suggest that various mechanisms were involved in realizing specific SATs. However, they were hardly applied to optimize reward. Rather, participants seem to have optimized their well-being. [ABSTRACT FROM AUTHOR]

Objective: To compare the diagnostic performance of two different sets of magnetic resonance imaging (MRI) for the detection of subchondral erosions in the sacroiliac joints regarding the application of fat-water separation techniques when acquiring T1-weighted (T1w) images, using multi-detector computed tomography (MDCT) as the reference standard. Methods: We retrospectively included 31 consecutive patients having or being suspected for axial spondyloarthritis (SpA) assessed using both MRI and MDCT. Three sets of images were independently assessed for the presence of erosions by two musculoskeletal radiologists (R1, R2): (1) MRI with standard T1w without fat suppression, (2) MRI with both T1w with and without fat suppression, and (3) MDCT. The diagnostic performance of both sets of MRIs was assessed using MDCT as the referent. Results: The assessment of T1w images with fat suppression substantially increased sensitivity (76% vs. 63% R1; 70% vs. 60% R2), specificity (97% vs. 84% R1; 96% vs. 81% R2), positive predictive value (85% vs. 45% R1; 81% vs. 40% R2), and overall accuracy (94% vs. 80% R1; 92% vs. 77% R2) in the detection of erosions when compared to the assessment using T1w images without fat suppression. Conclusion: The assessment of T1w images with fat suppression substantially improves the diagnostic performance of MRI in the detection of erosions in the sacroiliac joints. Key Points: • The presence of erosions in the sacroiliac joints may influence the decision on the diagnosis of axial spondyloarthritis. • T1w fat-suppressed MR imaging relatively increases the contrast between the joint space (high signal) and the adjacent subchondral bone (low signal), potentially improving the detection of erosions in the sacroiliac joints. • T1w fat-suppressed images improve the diagnostic performance of MRI in the detection of erosions in the sacroiliac joints compared to T1w without fat suppression, using MDCT as the reference. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that medications used for patients with enlarged prostates, may improve the clinical outcome for bladder cancer patients. Using provincial databases in Quebec, Canada, we identified a group of 2822 men who had their bladder removed due to bladder cancer between 20 0 0 and 2015. Contradicting the published literature, patients in our large cohort who used these prostate medications had a similar to worse survival than patients who did not use these medications. Background: Existing literature suggests that bladder cancer (BC) outcome may be improved when patients use 5 a-reductase inhibitors and/or α1 -blockers, but such a conclusion may be subject to publication bias. We evaluated whether preoperative use of 5 α-reductase inhibitors or α1 -blockers was associated with improved clinical outcomes in a cohort of patients with BC undergoing radical cystectomy (RC). Patients and Methods: Using provincial health administrative databases, we retrospectively identified male BC patients undergoing RC in Quebec province between 2000 and 2015, and we collected data from 2 years before RC until December 2016 or death. Survival analyses were conducted using Kaplan-Meier curves, log-rank tests, propensity score matching, and uni- and multivariable Cox proportional hazards models. Covariates included age, Charlson's comorbidity index, region of residence, year of RC, distance to hospital, hospital type, annual RC volume of each hospital and surgeon, neoadjuvant chemotherapy use, and type of bladder diversion. Results: Of the 2822 patients included, 284 patients used 5 α-reductase inhibitors and 1001 patients used α1 -blockers prior to surgery. Median follow-up time was 7.7 years. Patients who used 5 α-reductase inhibitors or α1 -blockers were generally older, had more comorbidities, and were treated more recently in academic centers. Overall, bladder cancer-specific and recurrence-free survival did not differ significantly between those using 5 α-reductase inhibitors prior to surgery and controls who never used 5 α-reductase inhibitors. Adjusted hazard ratios were 1.03 (95% confidence interval [CI], 0.88-1.21) for overall survival, 1.12 (95% CI, 0.92-1.36) for bladder cancer-specific survival, and 1.19 (95% CI, 0.99-1.42) for recurrence-free survival. The aforementioned outcomes were significantly worse in patients who used α1-blockers prior to surgery compared to controls, with respective adjusted hazard ratios of 1.15 (95% CI, 1.04-1.27), 1.19 (95% CI, 1.05-1.35), and 1.18 (95% CI, 1.05-1.33). Conclusion: Preoperative use of 5 α-reductase inhibitors and α1 -blockers did not improve clinical outcome in our cohort of male patients undergoing radical cystectomy for bladder cancer. [ABSTRACT FROM AUTHOR]

Although the speed of global development has been impressive, not all countries have developed at the same pace. The World Bank Group (WBG) report that Fragile and Conflict-Affected States (FCAS) are those countries that have lower health and development outcomes, and risk not being able to achieve Sustainable Development Goals (SDGs) in the next few years. Health systems play an important role in building capacity and infrastructure that can lead towards fulfilling the SDGs. In this editorial, we set the context, and launch a call to action, for a BMC Health Service Research Collection titled "Health services and systems in fragile and conflict-affected regions". [ABSTRACT FROM AUTHOR]

Pharmaceutical companies are increasingly using strategies to speed up recruitment for clinical trials, including encouraging the public to participate, overbooking study sites and countries, and enrolling patients competitively. While this approach may accelerate access to new medications, the ethics and potential negative consequences for patients are being questioned. The authors of the article participated in phase III trials for migraine prevention and experienced the sudden termination of studies due to overbooking. They argue that patients should be warned in advance about the risk of exclusion and that study sites should be better prepared for the consequences of competitive enrollment. [Extracted from the article]

The August 2020 explosion in Lebanon resulted in casualties, injuries, and a great number of internally displaced persons. The blast occurred during an economically and politically complex time in the country. Given multiple and competing post-explosion reconstruction priorities, in ths editorial we briefly examine the requirements for a build back better scenario. [ABSTRACT FROM AUTHOR]

The August 2020 explosion in Lebanon resulted in casualties, injuries, and a great number of internally displaced persons. The blast occurred during an economically and politically complex time in the country. Given multiple and competing post-explosion reconstruction priorities, in ths editorial we briefly examine the requirements for a build back better scenario. [ABSTRACT FROM AUTHOR]

Introduction: The objective was to assess whether an early response to neoadjuvant chemotherapy in women with advanced ovarian cancer may predict short- and long-term clinical outcome.Material and Methods: This is a retrospective study of all women with stage III-IV tubo-ovarian cancer treated with neoadjuvant chemotherapy at a single center in Montreal between 2003 and 2014. Logistic regression models were used to evaluate the association between cancer antigen 125 (CA-125) levels during neoadjuvant chemotherapy and debulking success. Cox proportional hazard models were used to estimate hazard ratios and their respective 95% CI for death and recurrence. Harrell's concordance indices were calculated to evaluate which variables best predicted the chemotherapy-free interval and overall survival in our population.Results: In all, 105 women were included. Following the first, second, and third cycles of neoadjuvant chemotherapy, CA-125 levels had a median reduction of 43.2%, 85.4%, and 92.9%, respectively, compared with CA-125 levels at diagnosis. As early as the second cycle, CA-125 was associated with overall survival (hazard ratio 1.03, 95% CI 1.01-1.05, per 50 U/mL increment). By the third cycle, CA-125 did not only predict overall survival (hazard ratio 1.04, 95% CI 1.01-1.08), but it predicted overall survival better than the success of debulking surgery (Harrell's concordance index 0.646 vs 0.616). Both absolute CA-125 levels and relative reduction in CA-125 levels after 2 and 3 cycles predicted the chance to achieve complete debulking (P < .05).Conclusions: Reduction of CA-125 levels during neoadjuvant chemotherapy provides an early predictive tool that strongly correlates with successful cytoreductive surgery and long-term clinical outcome in women with advanced high-grade serous and endometrioid ovarian cancer. [ABSTRACT FROM AUTHOR]

Introduction: Despite its proven benefit, studies have reported poor use of perioperative chemotherapy (POC) in bladder cancer patients undergoing radical cystectomy (RC). We evaluated POC use in Quebec between January 2000 and September 2016. Methods: Using provincial health administrative databases, data were retrospectively collected from patients from two years before RC until December 2016 or death. Logistic regression was used to identify variables predicting POC use. Survival analyses were conducted using Cox regression. Analyzed covariates were age, sex, comorbidities, year of RC, residence and hospital region, distance to hospital, hospital type and size, and hospital's and surgeon's RC volume. Results: A total of 790/4656 patients (17.0%) received POC. Neoadjuvant chemotherapy (NAC) use increased in recent years: 3.5% (2009), 11.2% (2012), and 20.7% (2015). POC use was increased in patients with recent surgery, a younger age, less comorbidities, residing closer to the hospital of surgery, and a high surgeon's RC volume (p<0.05). For patients treated between 2013 and 2016, a younger age (odds ratio [OR] 0.71; 95% confidence interval [CI] 0.64-0.80 per five years), shorter distance to the hospital (OR 0.88; 95% CI 0.77-0.99 per 50 km), surgery in an academic hospital (OR 1.86; 95% CI 1.06-3.29), and recent surgery (OR 1.34; 95% CI 1.14-1.58 per year) independently predicted NAC use. These NAC users had a significantly higher overall survival rate than patients without POC (hazard ratio 0.73; 95% CI 0.55-0.97). Limitations include missing data on pathological staging. Conclusions: NAC/POC use increased in Quebec but was lower compared to most developed countries. Its use was lower in patients residing further from the hospital and in those treated in non-academic hospitals. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis if presence and amount of effusion in the tibiotalar and talocalcaneal joints are associated with an increased risk for severe structural injury in ankle sprains. Methods: A total of 261 athletes sustaining acute ankle sprains were assessed on MRI for the presence and the amount of joint effusion in the tibiotalar and talocalcaneal joints, as well as for ligamentous and osteochondral injury. Specific patterns of injury severity were defined based on lateral collateral ligament, syndesmotic, and talar osteochondral involvement. The presence and the amount effusion (grades 1 and 2) were considered as risk factors for severe injury, while physiological amount of fluid (grade 0) was considered as the referent. Conditional logistic regression was used to assess the risk for associated severe injuries (syndesmotic ligament rupture and talar osteochondral lesions) based on the presence and amount of tibiotalar and talocalcaneal effusions. Results: For ankles exhibiting large (grade 2) effusion in the tibiotalar joint (without concomitant grade 2 effusion in the talocalcaneal joint), the risk for partial or complete syndesmotic ligament rupture was increased more than eightfold (adjusted odds ratio 8.7 (95% confidence intervals 3.7–20.7); p < 0.001). The presence of any degree of effusion in any of the joints was associated with an increased risk for severe talar osteochondral involvement (several odds ratio values reported; p < 0.001), including large subchondral contusions and any acute osteochondral lesion. Conclusion: The presence of tibiotalar and talocalcaneal effusions is associated with an increased risk for severe concomitant structural injury in acute ankle sprains. Key Points: • For ankles exhibiting severe (grade 2) effusion in the tibiotalar joint after sprain, the risk for partial or complete syndesmotic ligament rupture increases more than eightfold. • The presence of effusion in both tibiotalar and talocalcaneal joints is associated with an increased risk for severe ligament injury such as complete ATFL rupture as well as partial or complete syndesmotic ligament rupture. • The presence of effusion in the tibiotalar or talocalcaneal joints after sprain is associated with an increased risk for severe talar osteochondral involvement. [ABSTRACT FROM AUTHOR]

Background: We studied the association between human papillomavirus (HPV) viral load (VL) and HPV concordance.Methods: The HITCH cohort study included young, heterosexual, recently formed, sexually active couples. Questionnaires and genital samples were collected at 0 and 4 months. Samples were tested for HPV DNA by polymerase chain reaction (PCR; Linear Array). VLs of HPV6/11/16/18/31/42/51 were quantified using type-specific real-time PCR. Correlations between VL and type-specific HPV prevalence and incidence were evaluated using multilevel, mixed-effects linear/logistic regression models.Results: We included 492 couples. VLs were higher in penile than vaginal samples. VL at subsequent visits correlated significantly within men (r, 0.373), within women (r, 0.193), and within couples (r range: 0.303-0.328). Men with high VL had more type-specific persistent HPV infections (odds ratio [OR], 4.6 [95% confidence interval {CI}, 2.0-10.5]). High VL in men was associated with prevalent (OR, 5.3 [95% CI, 2.5-11.2]) and incident (OR, 6.7 [95% CI, 1.5-30.7]) type-specific HPV infections in their partner. Women's VL was associated with type-specific HPV prevalence in their partner at the same (OR, 5.9) and subsequent (OR, 4.7) visit.Conclusions: Persistent HPV infections have limited VL fluctuations. VL between sex partners are correlated and seem predictive of transmission episodes. [ABSTRACT FROM AUTHOR]

Background: Antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor have shown efficacy in the prevention of migraine attacks. We investigated the efficacy and tolerability of fremanezumab, a fully humanised CGRP antibody, in patients with migraine who had previously not responded to two to four classes of migraine preventive medications.Methods: The randomised, double-blind, placebo-controlled, parallel-group, phase 3b FOCUS trial was done at 104 sites (including hospitals, medical centres, research institutes, and group practice clinics) across Belgium, the Czech Republic, Denmark, Finland, France, Germany, Italy, the Netherlands, Poland, Spain, Sweden, Switzerland, the UK, and the USA. We enrolled participants aged 18-70 years with episodic or chronic migraine who had documented failure to two to four classes of migraine preventive medications in the past 10 years. Failure was defined as no clinically meaningful improvement after at least 3 months of therapy at a stable dose, as per the treating physician's judgment; discontinuation because of adverse events that made treatment intolerable; or treatment contraindicated or unsuitable for the preventive treatment of migraine for the patient. Participants were randomly assigned (1:1:1) by electronic interactive response technology to subcutaneously administered quarterly fremanezumab (month 1, 675 mg; months 2 and 3: placebo), monthly fremanezumab (month 1: 225 mg in episodic migraine and 675 mg in chronic migraine; months 2 and 3: 225 mg in both migraine subgroups), or matched monthly placebo for 12 weeks. The primary outcome was mean change from baseline in the monthly average number of migraine days during the 12-week treatment period. This trial is registered with ClinicalTrials.gov, number NCT03308968, and is now completed.Findings: Between Nov 10, 2017, and July 6, 2018, 838 participants with episodic (329 [39%]) or chronic (509 [61%]) migraine were randomly assigned to placebo (n=279), quarterly fremanezumab (n=276), or monthly fremanezumab (n=283). Reductions from baseline in monthly average migraine days over 12 weeks were greater versus placebo (least-squares mean [LSM] change -0·6 [SE 0·3]) with quarterly fremanezumab (LSM change -3·7 [0·3]; LSM difference vs placebo -3·1 [95% CI -3·8 to -2·4]; p<0·0001) and with monthly fremanezumab (LSM change -4·1 [0·34]; LSM difference vs placebo -3·5 [-4·2 to -2·8]; p<0·0001). Adverse events were similar for placebo and fremanezumab. Serious adverse events were reported in four (1%) of 277 participants with placebo, two (<1%) of 276 with quarterly fremanezumab, and four (1%) of 285 with monthly fremanezumab.Interpretation: Fremanezumab was effective and well tolerated in patients with difficult-to-treat migraine who had previously not responded to up to four classes of migraine preventive medications.Funding: Teva Pharmaceuticals. [ABSTRACT FROM AUTHOR]

The burden of physical impairments and disabilities is growing across high-, middle-, and low-income countries, but populations across the globe continue to lack access to basic physical rehabilitation. Global shortages, uneven distributions, and insufficient skill mix of human resources for health and rehabilitation (HRH&R) contribute to such inequitable access. However, there are no international standards to classify HRH&R and to promote their global monitoring and development. In this article, we conceptually develop an international classification of HRH&R based on the concept of monitoring HRH&R through their stock of practices and competencies, and not simply counting rehabilitation professionals such as physical or occupational therapists. This concept accounts for the varying HRH&R configurations as well as the different training, competencies, or practice regulations across locations, even within the same profession. Our perspective specifically develops the concept of a proposed classification, its structure, and possible applications. Among the benefits, stakeholders using the classification would be able to: (1) collect locally valid and internationally comparable data on HRH&R; (2) account for the rehabilitation practices and competencies among nonspecialized rehabilitation workers (eg, in less resourced/specialized contexts); (3) track competency upgrades or practice extensions over time; (4) implement competency-based human resources management practices, such as linking remuneration to competency levels rather than to professional categories; and (5) inform the development of (inter-)professional education, practice regulation, or even task-shifting processes for the whole of HRH&R. The proposed classification standard, still in a concept-development stage, could help drive policies to achieve the "right" stock of HRH&R, in terms of practices and competencies. [ABSTRACT FROM AUTHOR]

Objective: The psychosocial impact of a prostate cancer diagnosis significantly affects a patient's quality of life. We studied patient communication at the time of diagnosis and its impact on psychosocial adjustment of patients.Methods: This is a cross-sectional data analysis from self-administered questionnaires in the PROCURE biobank study, consisting of a cohort of patients with localized prostate cancer undergoing radical prostatectomy in Québec (Canada), 2006 to 2013. Odds ratios (OR) and their respective 95% confidence intervals (95% CI) were calculated using binary or ordered logistic regression models.Results: Data from 1841 patients were analyzed. The median age of patients was 62 years (range 41-80 years), the majority was French-Canadian (68.3%) and married (79.6%). Most patients (90.1%) considered conversations with their treating physician a useful information source. Patients were dissatisfied on the communication when receiving their diagnosis by telephone (OR = 0.19, 95% CI, 0.11-0.33). Younger patients were also more dissatisfied. Most patients preferred to receive information on prostate cancer (89.5%) and radical prostatectomy (88.0%) at the time of diagnosis, while only 58.8% and 52.4% of patients received this information at this stage. Patients who were dissatisfied with the communication of the diagnosis had more negative responses, such as increased worries and fear (P < 0.05). The five most useful coping mechanisms were physical activity (62.3%), breathing exercises (44.5%), music (32.8%), faith (30.3%), and muscle relaxation (30.1%), but varied by demographics.Conclusions: This study highlights the importance of physicians communicating a prostate cancer diagnosis well to their patients. Patients may benefit from individually tailored interventions to facilitate their overall coping. [ABSTRACT FROM AUTHOR]

We collected 729 Hypanus guttatus from the northern coast of the state of Rio Grande do Norte (RN), of which 196 were used to estimate age and growth. Ninety‐five were male (12.7 to 57.0 cm disc width; WD) and 101 were female (13.0 to 88.5 cm WD); females were significantly larger than males. Cross sections of vertebrae showed band‐pairs ranging from 0 to > 14 in females and from 0 to 9 in males. New‐borns presented an opaque edge at birth in vertebrae without a birthmark. The average percentage of error (APE; %E) for the entire sample provided evidence that ages were repeatable. The mean monthly marginal increment (IM) indicates annual band‐pair formation from August to November. The annual cycle model for one band‐pair deposition provided the best fit to data based on the AIC, with peaks between August and October, similar to that found in the IM analysis, suggesting an annual formation pattern. A multi‐model approach that included four models based on the observed mean WD at age indicated a modified von Bertalanffy growth model as the best for describing the species growth: W0 (WD at birth) = 14.6 cm for both sexes; females W∞ = 98.61 cm (95% CI = 87.34–114.61 cm); k = 0.112 year−1 (CI = 0.086–0.148 year−1); males W∞ = 60.22 cm (CI = 55.66–65.35 cm); k = 0.219 year−1 (CI = 0.185–0.276 year−1). The age‐at‐maturity in males and females is 5 years and 7 years, respectively. The age composition shows that most (84%) specimens were aged 0 to 2 years. The information provided here is essential for analytical assessments of H. guttatus, which is subject to significant fishing pressure mainly on new‐borns and juveniles. [ABSTRACT FROM AUTHOR]

Examines the relaxation of the microlever of the atomic force microscope after the unsticking instability. Different oscillating behavior in the polymer chain; Use of a rheological model in describing the different features of the atomic force microscope; Description of a microlever coupled to a polymer network.

Abstract Immunomodulatory monoclonal antibodies (IM-mAbs) are a cornerstone of modern immunotherapy; however, when administered systemically (i.e. , via injection), these agents can generate a variety of negative side effects. For many diseases, systemic delivery of IM-mAbs is the most effective mode of treatment, but in instances where the cellular target occupies a limited, well-defined space (e.g. , solid tumors or cellularized implants) local, controlled release of IM-mAbs might be desirable. Antibodies are highly sensitive to a variety of environmental conditions, which limit the kinds of polymers suitable for antibody retention and controlled release. The present study evaluates the release of antibodies from biocompatible, 2-mm diameter alginate spheres coated with poly- l -lysine and a thin outer layer of alginate (APA spheres). In vitro , rates of antibody release (including IM-mAbs) could be incrementally decreased and made linear by incrementally increasing the quantity of poly- l -lysine deposited on the alginate, with linear release lasting in one scenario for at least 46 days. To evaluate the bioactivity in vivo of IM-mAbs, APA spheres loaded with either anti-CD3ε or anti-CD95 mAb were incorporated into scaffolded islet implant (SI) test-beds and the SIs implanted into a mouse model of autoimmune (type 1) diabetes. Release of mAbs within the implanted SIs resulted in reduced autoimmune responses to both transplanted and native islets. Notably, mice implanted with APA spheres loaded with quantities of anti-CD95 mAb that would be lethal if given systemically showed immunomodulation with no toxic side effects. Collectively, our results indicate that APA spheres are a relatively simple means to evaluate the effects of local, controlled release of IM-mAbs in a way that preserves mAb function and limits systemic toxicity. Highlights • Controlled release of immunomodulatory (IM)-mAbs may be therapeutically useful. • IM-mAbs are released from PLL-coated alginate spheres in a controlled manner. • Coating alginate with PLL reduces and linearizes release rates of mAb in vitro. • Controlled, local release of IM-mAbs reduces immune responses to islet implants. • Systemically lethal quantities of IM-mAbs are made safe by controlled release. [ABSTRACT FROM AUTHOR]

Abstract Background Infection is the major cause of treatment-related mortality in childhood acute leukemia, mainly due to bacterial translocation across the intestinal mucosa. Only a few studies have reported the impact of different antibacterial prophylaxis treatments on digestive tract flora and infection-related mortality. Procedures We performed a retrospective analysis of two different digestive tract decontamination modalities (selective or total digestive decontamination) in a large single-center series of 323 children during the induction treatment of acute leukemia between January 1995 and December 2014. We examined the impact of antibiotic prophylaxis and food regimen (sterile or selected) on the digestive tract flora during the period of antibacterial prophylaxis, on the frequency of bacteremia, and on antibiotic sensitivity. Results Only one Gram-negative (Klebsiella pneumonia) translocation occurred in the SDD group. No infection-related death occurred. Extended-spectrum beta-lactamase (ESBL) bacteria were observed in seven of 170 (4%) patients in the SDD group. The faecal-flora total suppression and faecal-flora Gram-negative bacilli suppression was 67 and 77%, respectively, in the TDD group with sterile food, 0 and 58%, respectively, in the SDD group with sterile food, and 6 and 63%, respectively, in the SDD group with selective food. Conclusions This study gives a rationale not to use antibacterial prophylaxis systematically in children who receive induction treatment for acute leukemia; additionally, antibiotics should only be used in case of stool contamination by highly pathogenic bacteria with a high potential of translocation. [ABSTRACT FROM AUTHOR]

Accurate and timely rainfall prediction enhances productivity and can aid proper planning in sectors such as agriculture, health, transport and water resources. However quantitative rainfall prediction is normally a challenge and for this reason, this study was conducted with an aim of improving rainfall prediction using ensemble methods. It first assessed the performance of six convective schemes (Kain-Fritsch (KF); Betts-Miller-Janji'c (BMJ); Grell-Fretas (GF); Grell 3D ensemble (G3); New-Tiedke (NT) and Grell-Devenyi (GD)) using the root mean square error (RMSE) and mean error (ME) focusing on the March-May 2013 rainfall period over Uganda. 18 ensemble members were then generated from the three best performing convective schemes (i.e., KF, GF and G3). The daily rainfall predicted by the three ensemble methods (i.e., ensemble mean (ENS); ensemble mean analogue (EMA) and multi-member analogue ensemble (MAEM)) was then compared with the observed daily rainfall and the RMSE and ME computed. The results shows that the ENS presented a smaller RMSE compared to individual schemes (ENS: 10.02; KF: 23.96; BMJ: 26.04; GF: 25.85; G3: 24.07; NT: 29.13 and GD: 26.27) and a better bias (ENS: -1.28; KF: -1.62; BMJ: -4.04; GF: -3.90; G3: -3.62; NT: -5.41 and GD: -4.07). The EMA and MAEM presented 13 out of 21 stations and 17 out of 21 stations respectively with smaller RMSE compared to ENS thus demonstrating additional improvement in predictive performance. This study proposed and described MAEM and found it producing comparatively better quantitative rainfall prediction performance compared to the other ensemble methods used. The MAEM method should be valid regardless the nature of the rainfall season. [ABSTRACT FROM AUTHOR]

Objective: To assess the differences in morphology and alignment of the knee between patients with proximal patellar tendinopathy (PPT) and a control group, using MRI and focusing on the patellofemoral joint.Methods: We retrospectively included 35 patients with clinically diagnosed and unequivocal findings of PPT on knee MRI, the case group. For the control group, we included 70 patients who underwent knee MRI for other reasons, with no clinical or MRI evidence of PPT. Patients and controls were matched for age and gender, with all subjects reporting frequent physical activity. MRIs were evaluated by two musculoskeletal radiologists, who assessed parameters of patellar morphology, trochlear morphology, patellofemoral alignment, and tibiofemoral alignment. The differences in parameters between cases and controls were assessed using Student's t test. Logistic regression was applied to assess the associations between the MRI parameters and the presence of PPT.Results: The patellar height Insall-Salvati ratio was different between cases and controls (1.37 ± 0.21 vs. 1.24 ± 0.19; p = 0.003). The subchondral Wiberg angle was higher in cases than controls (136.8 ± 7.4 vs. 131.7 ± 8.8; p = 0.004). After applying logistic regression, significant associations with PPT were found [odds ratios (95% CI)] for patellar morphology [1.1 (1.0, 1.2)] and patellar height [1.3 (1.0, 1.7)].Conclusions: Patellar height and the subchondral patellar Wiberg angle were greater in patients with PPT and significantly associated with PPT. [ABSTRACT FROM AUTHOR]

Background: In the past decades the incidence of pregnancy-associated breast cancer (PABC) increased. Possible explanations are the trend to postpone childbearing and the general increase in the incidence of breast cancer. Materials and methods: A sytematic review of the literature was performed with the aim to report on incidence, diagnosis, treatment and prognosis of breast cancer during pregnancy. We also cover the issue of pregnancy following a diagnosis of breast cancer including fertility preservation and prognosis. Results: Ultrasound is the imaging method of choice in pregnancy, but mammography can also be performed as the fetal irradiation dose is low. To avoid a delay in diagnosis every sonographic mass in pregnant women which does not clearly correspond to a cyst needs further investigation by biopsy. Treatment should follow as close as possible the guidelines for non-pregnant patients. Administration of chemotherapy is possible after the first trimester. There is a large body of evidence for the use of anthracyclines. In contrast radiotherapy, trastuzumab and antihormonal treatment by tamoxifen are contraindicated during pregnancy. Pregnancy does not seem to influence prognosis. Most adverse obstetric outcomes are related to preterm delivery, which should therefore, whenever possible, be avoided. Young patients with breast cancer and incomplete family planning should be referred for counseling about fertility preservation options before the initiation of adjuvant treatment. A pregnancy following breast cancer does not have a negative impact on prognosis. Conclusion: Multidisciplinary management of women with breast cancer in pregnancy is mandatory and data should be collected to allow further improvement in management. [ABSTRACT FROM AUTHOR]

Switching between mental sets has been extensively investigated in both experimental and individual differences research using a wide range of task-switch paradigms. However, it is yet unclear whether these different tasks measure a unitary shifting ability or reflect different facets thereof. In this study, 20 task pairs were administered to 119 young adults to assess 5 proposed components of mental set shifting: switching between judgments, stimulus dimensions, stimulus-response mappings, response sets, and stimulus sets. Modeling latent factors for each of the components revealed that a model with 5 separate yet mostly correlated factors fit the data best. In this model, the components most strongly related to the other latent factors were stimulus-response mapping shifting and, to a lesser degree, response set shifting. In addition, both factors were statistically indistinguishable from a second-order general shifting factor. In contrast, shifting between judgments as well as stimulus dimensions consistently required separate factors and could, hence, not fully be accounted for by the general shifting factor. Finally, shifting between stimulus sets was unrelated to any other shifting component but mapping shifting. We conclude that tasks assessing shifting between mappings are most adequate to assess general shifting ability. In contrast, shifting between stimulus sets (e.g., as in the Trail Making Test) probably reflects shifts in visual attention rather than executive shifting ability. [ABSTRACT FROM AUTHOR]

The effects of large-scale (with Legendre modes ≲10) asymmetries in OMEGA direct-drive implosions caused by laser illumination nonuniformities (beam-power imbalance and beam mispointing and mistiming), target offset, and variation in target-layer thickness were investigated using the low-noise, three-dimensional Eulerian hydrodynamic code ASTER. Simulations indicate that these asymmetries can significantly degrade the implosion performance. The most important sources of the asymmetries are the target offsets (~10 to 20 µm), beam-power imbalance (σrms ~ 10%), and variations (~5%) in target-layer thickness. Large-scale asymmetries distort implosion cores, resulting in a reduced hot-spot confinement and an increased residual kinetic energy of implosion targets. The ion temperature inferred from the width of simulated neutron spectra is influenced by bulk fuel motion in the distorted hot spot and can result in up to an ~1-keV increase in apparent temperature. Similar temperature variations along different lines of sight are observed. Demonstrating hydrodynamic equivalence to ignition designs on OMEGA requires a reduction in large-scale target and laser-imposed nonuniformities, minimizing target offset, and employing highly efficient mid-adiabat (α = 4) implosion designs, which mitigate cross-beam energy transfer and suppress short-wavelength Rayleigh-Taylor growth. [ABSTRACT FROM AUTHOR]

The article explores global public health issues concerning the outbreak of Zika virus (ZKV). Topics discussed include the way the World Health Organization (WHO) regarded ZKV as a public health emergency, the origin, transmission and outbreak of ZKV in countries such as Brazil and the U.S., and the implementation of rehabilitation strategies in communities to improve quality of life of individuals affected by ZKV.

Background: People with disabilities face challenges accessing basic rehabilitation health care. In 2006, the United Nations Convention on the Rights of Persons with Disabilities (CRPD) outlined the global necessity to meet the rehabilitation needs of people with disabilities, but this goal is often challenged by the undersupply and inequitable distribution of rehabilitation workers. While the aggregate study and monitoring of the physical rehabilitation workforce has been mostly ignored by researchers or policy-makers, this paper aims to present the 'challenges and opportunities' for guiding further long-term research and policies on developing the relatively neglected, highly heterogeneous physical rehabilitation workforce.Methods: The challenges were identified through a two-phased investigation. Phase 1: critical review of the rehabilitation workforce literature, organized by the availability, accessibility, acceptability and quality (AAAQ) framework. Phase 2: integrate reviewed data into a SWOT framework to identify the strengths and opportunities to be maximized and the weaknesses and threats to be overcome.Results: The critical review and SWOT analysis have identified the following global situation: (i) needs-based shortages and lack of access to rehabilitation workers, particularly in lower income countries and in rural/remote areas; (ii) deficiencies in the data sources and monitoring structures; and (iii) few exemplary innovations, of both national and international scope, that may help reduce supply-side shortages in underserved areas.Discussion: Based on the results, we have prioritized the following 'Six Rehab-Workforce Challenges': (1) monitoring supply requirements: accounting for rehabilitation needs and demand; (2) supply data sources: the need for structural improvements; (3) ensuring the study of a whole rehabilitation workforce (i.e. not focused on single professions), including across service levels; (4) staffing underserved locations: the rising of education, attractiveness and tele-service; (5) adapt policy options to different contexts (e.g. rural vs urban), even within a country; and (6) develop international solutions, within an interdependent world.Conclusions: Concrete examples of feasible local, global and research action toward meeting the Six Rehab-Workforce Challenges are provided. Altogether, these may help advance a policy and research agenda for ensuring that an adequate rehabilitation workforce can meet the current and future rehabilitation health needs. [ABSTRACT FROM AUTHOR]

The frequency of natural disasters appears to be mounting at an alarming rate, and the degree to which people are surviving such traumatic events also is increasing. Postdisaster survival often triggers increases in population and individual disability-related outcomes in the form of impairments, activity limitations, and participation restrictions, all of which have an important impact on the individual, his or her family, and their community. The increase in postdisaster disability-related outcomes has provided a rationale for the increased role of the disability and rehabilitation sector's involvement in emergency response, including physical therapists. A recent major earthquake that has drawn the world's attention occurred in the spring of 2015 in Nepal. The response of the local and international communities was large and significant, and although the collection of complex health and disability issues have yet to be fully resolved, there has been a series of important lessons learned from the 2015 Nepal earth-quake(s). This perspective article outlines lessons learned from Nepal that can be applied to future disasters to reduce overall disability-related outcomes and more fully integrate rehabilitation in preparation and planning. First, information is presented on disasters in general, and then information is presented that focuses on the earthquake(s) in Nepal. Next, field experience in Nepal before, during, and after the earthquake is described, and actions that can and should be adopted prior to disasters as part of disability preparedness planning are examined. Then, the emerging roles of rehabilitation providers such as physical therapists during the immediate and postdisaster recovery phases are discussed. Finally, approaches are suggested that can be adopted to "build back better" for, and with, people with disabilities in postdisaster settings such as Nepal. [ABSTRACT FROM AUTHOR]

As hydrodynamics codes develop to increase understanding of three-dimensional (3-D) effects in inertial confinement fusion implosions, diagnostics must adapt to evaluate their predictive accuracy. A 3-D radiation postprocessor was developed to investigate the use of soft x-ray self-emission images of an imploding target to measure the size of nonuniformities on the target surface. Synthetic self-emission images calculated from 3-D simulations showed a narrow ring of emission outside the ablation surface of the target. Nonuniformities growing in directions perpendicular to the diagnostic axis were measured through angular variations in the radius of the steepest intensity gradient on the inside of the ring and through changes in the peak x-ray intensity in the ring as a function of angle. The technique was applied to an implosion to measure large 3-D nonuniformities resulting from two dropped laser beam quads at the National Ignition Facility. [ABSTRACT FROM AUTHOR]

Understanding variations in rainfall in tropical regions is important due to its impacts on water resources, health and agriculture. This study assessed the dekadal rainfall patterns and rain days to determine intra-seasonal rainfall variability during the March-May season using the Mann-Kendall (MK) trend test and simple linear regression (SLR) over the period 2000-2015. Results showed an increasing trend of both dekadal rainfall amount and rain days (third and seventh dekads). The light rain days (SLR = 0.181; MK = 0.350) and wet days (SLR = 0.092; MK = 0.118) also depict an increasing trend. The rate of increase of light rain days and wet days during the third dekad (light rain days: SLR = 0.020; MK = 0.279 and wet days: SLR = 0.146; MK = 0.376) was slightly greater than during the seventh dekad (light rain days: SLR = 0.014; MK = 0.018 and wet days: SLR = 0.061; MK = 0.315) dekad. Seventy-four percent accounted for 2-4 consecutive dry days, but no significant trend was detected. The extreme rainfall was increasing over the third (MK = 0.363) and seventh (MK = 0.429) dekads. The rainfall amount and rain days were highly correlated (r: 0.43-0.72). [ABSTRACT FROM AUTHOR]

Understanding the effects of laser imprint on target performance is critical to the success of direct-drive inertial confinement fusion. Directly measuring the disruption caused by laser imprints to the imploding shell and hot-spot formation, in comparison with multidimensional radiation–hydrodynamic simulations, can provide a clear picture of how laser nonuniformities cause target performance to degrade. With the recently developed x-ray self-emission imaging technique and the state-of-the-art physics models recently implemented in the two-dimensional hydrocode DRACO, a systematic study of laser-imprint effects on warm target implosions on OMEGA has been performed using both experimental results and simulations. By varying the laser-picket intensity, the imploding shells were set at different adiabats (from α = 2 to α = 6). As the shell adiabats decreased, it was observed that (1) the measured shell thickness at the time the hot spot lit up became larger than the uniform one-dimensional (1-D) predictions; (2) the hot-spot core emitted earlier than the corresponding 1-D predictions; (3) the measured neutron yield first increased then decreased as the shell adiabat α was reduced; and (4) the hot-spot size reduced as α decreased for cases where SSD (smoothing by spectral dispersion) was on but became larger for low-α shots in cases where SSD was off. Most of these experimental observations are well reproduced by DRACO simulations with laser imprints including modes up to λmax = 200. These studies identify the importance of laser imprint as the major source of degrading target performance for OMEGA implosions of adiabat α ≤ 3. Mitigating laser imprints is required to improve low-α target performance. [ABSTRACT FROM AUTHOR]

Purpose: There has been an increase in the number of natural disasters in recent history, and the rate of disability is increasing among survivors. The most recent major natural disaster was the earthquake(s) that occurred in Nepal on 25 April 2015 and 12 May 2015. In total, more than 8500 people were killed and over 18 500 people were left injured. This article aims to demonstrate the role of rehabilitation professionals in post-disaster relief and beyond in Nepal.Method: This is an experiential account of physiotherapists present during the earthquake and participating in the post-disaster relief.Results: Rehabilitation professionals played an important role in the acute phase post-disaster by providing essential services and equipment. However, discharge planning emerged as an important role for rehabilitation providers in the early days of post-disaster and signaled a relatively new and innovative function that facilitated the heavy imbalance between little supply and tremendous demand for care. In the coming years, rehabilitation will need to support local initiatives that focus on minimizing the long-term effects among people with a newly acquired disability.Conclusions: Rehabilitation serves an important role across the continuum in post-disaster relief from the initial stages to the months and years following an event.Implications for RehabilitationDriven by medical advances in acute field medicine, the relative proportion of casualties following natural disasters is decreasing, while relative rates of disability are rising among survivors.In post-disaster settings, the growing number of people with newly acquired disabilities will be added to the existing proportion of the population who lived with disabilities, creating a significant growth in the total number of people with disabilities (PWDs) in communities that are often ill prepared to provide necessary services.Rehabilitation interventions in the initial stages of emergency humanitarian response can minimize the long-term effects among people with newly acquired disabilities through early activation and prevention of secondary effects.Rehabilitation providers thus appear to have an important mediating effect on outcomes of disabilities in the early stages, but must also be strong partners with PWDs to advocate for social and political change in the long term. [ABSTRACT FROM PUBLISHER]

Background. Health human resources continue to emerge as a critical health policy issue across the United States. Objective. The purpose of this study was to develop a strategy for modeling future workforce projections to serve as a basis for analyzing annual supply of and demand for physical therapists across the United States into 2020. Design. A traditional stock-and-flow methodology or model was developed and populated with publicly available data to produce estimates of supply and demand for physical therapists by 2020. Methods. Supply was determined by adding the estimated number of physical therapists and the approximation of new graduates to the number of physical therapists who immigrated, minus US graduates who never passed the licensure examination, and an estimated attrition rate in any given year. Demand was determined by using projected US population with health care insurance multiplied by a demand ratio in any given year. The difference between projected supply and demand represented a shortage or surplus of physical therapists. Results. Three separate projection models were developed based on best available data in the years 2011, 2012, and 2013, respectively. Based on these projections, demand for physical therapists in the United States outstrips supply under most assumptions. Limitations. Workforce projection methodology research is based on assumptions using imperfect data: therefore, the results must be interpreted in terms of overall trends rather than as precise actuarial data-generated absolute numbers from specified forecasting. Conclusions. Outcomes of this projection study provide a foundation for discussion and debate regarding the most effective and efficient ways to influence supply-side variables so as to position physical therapists to meet current and future population demand. Attrition rates or permanent exits out of the profession can have important supply-side effects and appear to have an effect on predicting future shortage or surplus of physical therapists. [ABSTRACT FROM AUTHOR]

In this paper, the product of two independent and nonidentically distributed (i.n.i.d.) \alpha \- \mu variates is considered. Exact reasonably simple closed-form expressions for the probability density function (pdf), the cumulative distribution function (cdf) , and the moments of the resulting random variable (RV) are derived. These results find a wide range of applications in a number of fields, such as radar communications, multihop systems, multiple-input–multiple-input links, and cascaded communications in general. In particular, they are used here to describe a novel \alpha \-\mu/\alpha \- \mu composite multipath–shadowing fading model. Because the \alpha \- \mu model alone comprises a substantial number of useful fading environments, its \alpha \-\mu/\alpha \- \mu composite version leads to a variety and an immense amount of composite fading distributions. The novel expressions for this rather flexible scenario compute instantaneously, constituting a powerful tool to characterize wireless fading channels. [ABSTRACT FROM PUBLISHER]

Measurements of the conduction-zone length (110 ± 20 μm at t = 2.8 ns), the averaged mass ablation rate of the deuterated plastic (7.95 ± 0.3 μg/ns), shell trajectory, and laser absorption are made in direct-drive cryogenic implosions and are used to quantify the electron thermal transport through the conduction zone. Hydrodynamic simulations that use nonlocal thermal transport and cross-beam energy transfer models reproduce these experimental observables. Hydrodynamic simulations that use a time-dependent flux-limited model reproduce the measured shell trajectory and the laser absorption but underestimate the mass ablation rate by ~10% and the length of the conduction zone by nearly a factor of 2. [ABSTRACT FROM AUTHOR]

Summary Migraine is a common, disabling, and undertreated episodic brain disorder that is more common in women than in men. Unbiased genome-wide association studies have identified 13 migraine-associated variants pointing at genes that cluster in pathways for glutamatergic neurotransmission, synaptic function, pain sensing, metalloproteinases, and the vasculature. The individual pathogenetic contribution of each gene variant is difficult to assess because of small effect sizes and complex interactions. Six genes with large effect sizes were identified in patients with rare monogenic migraine syndromes, in which hemiplegic migraine and non-hemiplegic migraine with or without aura are part of a wider clinical spectrum. Transgenic mouse models with human monogenic-migraine-syndrome gene mutations showed migraine-like features, increased glutamatergic neurotransmission, cerebral hyperexcitability, and enhanced susceptibility to cortical spreading depression, which is the electrophysiological correlate of aura and a putative trigger for migraine. Enhanced susceptibility to cortical spreading depression increased sensitivity to focal cerebral ischaemia, and blocking of cortical spreading depression improved stroke outcome in these mice. Changes in female hormone levels in these mice modulated cortical spreading depression susceptibility in much the same way that hormonal fluctuations affect migraine activity in patients. These findings confirm the multifactorial basis of migraine and might allow new prophylactic options to be developed, not only for migraine but potentially also for migraine-comorbid disorders such as epilepsy, depression, and stroke. [ABSTRACT FROM AUTHOR]

BACKGROUND US Food and Drug Administration (FDA) approval of new drugs depends on results from clinical trials that must be generalized to the US population. However, racial minorities are frequently under-represented in clinical studies. The enrollment of racial minorities was compared in key clinical studies submitted to the FDA in the last 10 years in support of potential marketing approval for prostate cancer (PCa) prevention or treatment. METHODS Patient demographic data were obtained from archival data sets of large registration trials submitted to the FDA to support proposed PCa indications. Six countries/regions were analyzed: the United States, Canada, Australia, Europe, the United Kingdom, and Eastern Europe. Background racial demographics were collected from national census data. RESULTS Seventeen key PCa clinical trials were analyzed. These trials were conducted in the past 20 years, comprising 39,574 patients with known racial information. Most patients were enrolled in the United States, but there appeared to be a trend toward increased non-US enrollment over time. In all countries, racial minorities were generally under-represented. There was no significant improvement in racial minority enrollment over time. The United States enrolled the largest nonwhite population (7.1%). CONCLUSIONS Over the past 20 years, racial minorities were consistently under-represented in key PCa trials. There is a need for effective measures that will improve enrollment of racial minorities. With increased global enrollment, drug developers should aim to recruit a patient population that resembles the racial demographics of the patient population to which drug use will be generalized upon approval. Cancer 2014;120:3025-3032. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

We investigate interference between declarative and procedural representations in working memory (WM). Declarative representations are objects of thought, whereas procedural representations provide the (cognitive) actions to work upon these objects. In eight dual-task experiments we varied the number of representations to be maintained in WM (memory load). In Experiments 1–4, we varied declarative and procedural load separately in the two tasks used. In Experiments 5–8, only declarative or procedural load was manipulated in both tasks employed. We measured how much performance in the currently relevant task was impaired by increasing the load in the currently irrelevant task. These cross-task load effects were larger for Experiment 5–8 compared to Experiment 1–4. Yet, in task-switch trials we also obtained cross-task load effects in Experiment 1–4. Our findings support the distinction of declarative and procedural WM as largely independent sub-systems or distinct representational spaces. [ABSTRACT FROM AUTHOR]

Histone deacetylase inhibitors ( HDACIs) are being tested in clinical trials for the treatment of solid tumors. While most studies have focused on the reexpression of silenced tumor suppressor genes, a number of genes/pathways are downregulated by HDACIs. This provides opportunities for combination therapy: agents that further disable these pathways through inhibition of residual gene function are speculated to enhance cell death in combination with HDACIs. A previous study from our group indicated that mitotic checkpoint kinases such as PLK1 and Aurora A are downregulated by HDACIs. We used in vitro and in vivo xenograft models of prostate cancer ( PCA) to test whether combination of HDACIs with the pan-aurora kinase inhibitor AMG 900 can synergistically or additively kill PCA cells. AMG 900 and HDACIs synergistically decreased cell proliferation activity and clonogenic survival in DU-145, LNCaP, and PC3 PCA cell lines compared to single-agent treatment. Cellular senescence, polyploidy, and apoptosis was significantly increased in all cell lines after combination treatment. In vivo xenograft studies indicated decreased tumor growth and decreased aurora B kinase activity in mice treated with low-dose AMG 900 and vorinostat compared to either agent alone. Pharmacodynamics was assessed by scoring for phosphorylated histone H3 through immunofluorescence. Our results indicate that combination treatment with low doses of AMG 900 and HDACIs could be a promising therapy for future clinical trials against PCA. [ABSTRACT FROM AUTHOR]

A new chromene, (S)-banchromene (1), together with seven known compounds, ergosterol, beauvericin (2), fusaproliferin (3), radicinin (4), poly(3-hydroxybutyric acid) (PHB, 5), N-methylpyrrolidone and an inseparable mixture of isochromene derivatives 6a, 6b, were isolated from a culture of Fusarium sp. strain CAMKT24b1, an endophytic fungus from the leaves and twigs of Piper guineense (Piperaceae). The structures of these metabolites were elucidated on the basis of their spectroscopic data; the absolute configuration of 1 was determined by ab initio-calculation of the optical rotation. In tests with the zoospores of the grapevine downy mildew pathogen Plasmopara viticola, compounds 1-4 showed moderate to high levels of motility-impairing activity at concentrations as low as 2.5μg/mL. Compound 2 was the most active, exhibiting both motility-halting and lytic activities. Furthermore, compounds 2 and 3 displayed significant cytotoxic activity against brine shrimp larvae (Artemia salina) at 10μg/mL. This is the first report on motility inhibitory and lytic activities of metabolites from an endophytic Fusarium species against the zoospores of the downy mildew pathogen P. viticola. [ABSTRACT FROM AUTHOR]

Objective To evaluate the relationship between medial meniscal pathology and cartilage matrix status using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) in medial tibiofemoral cartilage in a sample of middle-aged women. Methods A total of 148 women ages ≥40 years were included, and 3.0T MRI of the knee was performed at baseline and at 1 year. T2-weighted, fat-suppressed and 3-dimensional inversion recovery-prepared spoiled gradient-recalled echo sequences were acquired 90 minutes after gadolinium injection. Baseline medial meniscal pathology was scored on a scale of 0-3, where 0 = normal, 1 = intrasubstance meniscal signal change, 2 = single tears, and 3 = complex tears/maceration. The central medial femur, the medial tibial plateau, and the posterior medial femur were subjected to dGEMRIC at baseline and at 1 year. Analysis of covariance was used to examine whether baseline and 1-year dGEMRIC indices in the same regions were related to the severity of meniscal damage at baseline, using normal medial menisci (grade 0) as the reference. Results Medial compartments with grade 3 lesions showed significantly lower dGEMRIC indices (less proteoglycan content) at the central medial femur region compared with compartments with normal menisci. Mean ± SEM differences in dGEMRIC indices between grade 3 and grade 0 menisci at the central medial femur were −119.1 ± 34.2 msec at baseline ( P = 0.03) and −120.3 ± 35.2 msec at followup ( P = 0.04). Conclusion High-grade damage of the medial meniscus showed significant associations with lower dGEMRIC indices. The dGEMRIC technique may be a useful tool in detecting early degenerative changes of cartilage when meniscal function is lost. [ABSTRACT FROM AUTHOR]