PFHydro: A New Watershed-Scale Model for Post-Fire Runoff Simulation

Runoff increases after wildfires that burn vegetation and create a condition of soil-water repellence (SWR). A new post-fire watershed hydrological model, PFHydro, was created to explicitly simulate vegetation interception and SWR effects for four burn severity categories: high, medium, low severity and unburned. The model was applied to simulate post-fire runoff from the Upper Cache Creek Watershed in California, USA. Nash–Sutcliffe modeling efficiency (NSE) was used to assess model performance. The NSE was 0.80 and 0.88 for pre-fire water years (WY) 2000 and 2015, respectively. NSE was 0.88 and 0.93 for WYs 2016 (first year post-fire) and 2017 respectively. The simulated percentage of surface runoff in total runoff of WY 2016 was about six times that of pre-fire WY 2000 and three times that of WY 2015. The modeling results suggest that SWR is an important factor for post-fire runoff generation. The model was successful at simulating SWR behavior

Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up.

BackgroundNovel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045.Patients and methodsAdult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab [200 mg every 3 weeks (Q3W)] or investigator's choice of paclitaxel (175 mg/m2 Q3W), docetaxel (75 mg/m2 Q3W), or vinflunine (320 mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR.ResultsA total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n = 272). Median follow-up as of 26 October 2017 was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4 months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy.ConclusionsLong-term results (>2 years' follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC.Trial registrationClinicalTrials.gov: NCT02256436

Seeing two faces together: preference formation in humans and rhesus macaques

Humans, great apes and old world monkeys show selective attention to faces depending on conspecificity, familiarity, and social status supporting the view that primates share similar face processing mechanisms. Although many studies have been done on face scanning strategy in monkeys and humans, the mechanisms influencing viewing preference have received little attention. To determine how face categories influence viewing preference in humans and rhesus macaques (Macaca mulatta), we performed two eye-tracking experiments using a visual preference task whereby pairs of faces from different species were presented simultaneously. The results indicated that viewing time was significantly influenced by the pairing of the face categories. Humans showed a strong bias towards an own-race face in an Asian–Caucasian condition. Rhesus macaques directed more attention towards non-human primate faces when they were paired with human faces, regardless of the species. When rhesus faces were paired with faces from Barbary macaques (Macaca sylvanus) or chimpanzees (Pan troglodytes), the novel species’ faces attracted more attention. These results indicate that monkeys’ viewing preferences, as assessed by a visual preference task, are modulated by several factors, species and dominance being the most influential

Big data and data repurposing – using existing data to answer new questions in vascular dementia research

Introduction: Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD. Methods: We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015). Results: We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach. Conclusions: There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use

Interleukin-15 Treatment Induces Weight Loss Independent of Lymphocytes

Obesity is a chronic inflammatory condition characterized by activation and infiltration of proinflammatory immune cells and a dysregulated production of proinflammatory cytokines. While known as a key regulator of immune natural killer (NK) cell function and development, we have recently demonstrated that reduced expression of the cytokine Interleukin-15 (IL-15) is closely linked with increased body weight and adiposity in mice and humans. Previously, we and others have shown that obese individuals have lower circulating levels of IL-15 and NK cells. Lean IL-15 overexpressing (IL-15 tg) mice had an accumulation in adipose NK cells compared to wildtype and NK cell deficient obese IL-15−/− mice. Since IL-15 induces weight loss in IL-15−/− and diet induced obese mice and has effects on various lymphocytes, the aim of this paper was to determine if lymphocytes, particularly NK cells, play a role in IL-15 mediated weight loss. Acute IL-15 treatment resulted in an increased accumulation of NK, NKT, and CD3+ T cells in adipose tissue of B6 mice. Mice depleted of NK and NKT cells had similar weight loss comparable to controls treated with IL-15. Finally, IL-15 treatment induces significant weight loss in lymphocyte deficient RAG2−/−γc−/− mice independent of food intake. Fat pad cross-sections show decreased pad size with cytokine treatment is due to adipocyte shrinkage. These results clearly suggest that IL-15 mediates weight loss independent of lymphocytes

More than Mere Numbers: The Impact of Lethal Control on the Social Stability of a Top-Order Predator

Population control of socially complex species may have profound ecological implications that remain largely invisible if only their abundance is considered. Here we discuss the effects of control on a socially complex top-order predator, the dingo (Canis lupus dingo). Since European occupation of Australia, dingoes have been controlled over much of the continent. Our aim was to investigate the effects of control on their abundance and social stability. We hypothesized that dingo abundance and social stability are not linearly related, and proposed a theoretical model in which dingo populations may fluctuate between three main states: (A) below carrying capacity and socially fractured, (B) above carrying capacity and socially fractured, or (C) at carrying capacity and socially stable. We predicted that lethal control would drive dingoes into the unstable states A or B, and that relaxation of control would allow recovery towards C. We tested our predictions by surveying relative abundance (track density) and indicators of social stability (scent-marking and howling) at seven sites in the arid zone subject to differing degrees of control. We also monitored changes in dingo abundance and social stability following relaxation and intensification of control. Sites where dingoes had been controlled within the previous two years were characterized by low scent-marking activity, but abundance was similar at sites with and without control. Signs of social stability steadily increased the longer an area was allowed to recover from control, but change in abundance did not follow a consistent path. Comparison of abundance and stability among all sites and years demonstrated that control severely fractures social groups, but that the effect of control on abundance was neither consistent nor predictable. Management decisions involving large social predators must therefore consider social stability to ensure their conservation and ecological functioning

Effects of shared medical appointments on quality of life and cost-effectiveness for patients with a chronic neuromuscular disease. Study protocol of a randomized controlled trial

Contains fulltext : 96862.pdf (publisher's version ) (Open Access)BACKGROUND: Shared medical appointments are a series of one-to-one doctor-patient contacts, in presence of a group of 6-10 fellow patients. This group visits substitute the annual control visits of patients with the neurologist. The same items attended to in a one-to-one appointment are addressed. The possible advantages of a shared medical appointment could be an added value to the present management of neuromuscular patients. The currently problem-focused one-to-one out-patient visits often leave little time for the patient's psychosocial needs, patient education, and patient empowerment. METHODS/DESIGN: A randomized, prospective controlled study (RCT) with a follow up of 6 months will be conducted to evaluate the clinical and cost-effectiveness of shared medical appointments compared to usual care for 300 neuromuscular patients and their partners at the Radboud University Nijmegen Medical Center. Every included patient will be randomly allocated to one of the two study arms. This study has been reviewed and approved by the medical ethics committee of the region Arnhem-Nijmegen, The Netherlands. The primary outcome measure is quality of life as measured by the EQ-5D, SF-36 and the Individualized neuromuscular Quality of Life Questionnaire. The primary analysis will be an intention-to-treat analysis on the area under the curve of the quality of life scores. A linear mixed model will be used with random factor group and fixed factors treatment, baseline score and type of neuromuscular disease. For the economic evaluation an incremental cost-effectiveness analysis will be conducted from a societal perspective, relating differences in costs to difference in health outcome. Results are expected in 2012. DISCUSSION: This study will be the first randomized controlled trial which evaluates the effect of shared medical appointments versus usual care for neuromuscular patients. This will enable to determine if there is additional value of shared medical appointments to the current therapeutical spectrum. When this study shows that group visits produce the alleged benefits, this may help to increase the acceptance of this innovative and creative way of using one of the most precious resources in health care more efficiently: time. TRIAL REGISTRATION: DutchTrial Register http://www.trialregister.nlNTR1412

Sperm from Hyh Mice Carrying a Point Mutation in αSNAP Have a Defect in Acrosome Reaction

Hydrocephalus with hop gait (hyh) is a recessive inheritable disease that arose spontaneously in a mouse strain. A missense mutation in the Napa gene that results in the substitution of a methionine for isoleucine at position 105 (M105I) of αSNAP has been detected in these animals. αSNAP is a ubiquitous protein that plays a key role in membrane fusion and exocytosis. In this study, we found that male hyh mice with a mild phenotype produced morphologically normal and motile sperm, but had a strongly reduced fertility. When stimulated with progesterone or A23187 (a calcium ionophore), sperm from these animals had a defective acrosome reaction. It has been reported that the M105I mutation affects the expression but not the function of the protein. Consistent with an hypomorphic phenotype, the testes and epididymides of hyh mice had low amounts of the mutated protein. In contrast, sperm had αSNAP levels indistinguishable from those found in wild type cells, suggesting that the mutated protein is not fully functional for acrosomal exocytosis. Corroborating this possibility, addition of recombinant wild type αSNAP rescued exocytosis in streptolysin O-permeabilized sperm, while the mutant protein was ineffective. Moreover, addition of recombinant αSNAP. M105I inhibited acrosomal exocytosis in permeabilized human and wild type mouse sperm. We conclude that the M105I mutation affects the expression and also the function of αSNAP, and that a fully functional αSNAP is necessary for acrosomal exocytosis, a key event in fertilization