No Detectable Fertility Benefit from a Single Additional Mating in Wild Stalk-Eyed Flies

Background: Multiple mating by female insects is widespread, and the explanation(s) for repeated mating by females has been the subject of much discussion. Females may profit from mating multiply through direct material benefits that increase their own reproductive output, or indirect genetic benefits that increase offspring fitness. One particular direct benefit that has attracted significant attention is that of fertility assurance, as females often need to mate multiply to achieve high fertility. This hypothesis has never been tested in a wild insect population.Methodology/Principal Findings: Female Malaysian stalk-eyed flies (Teleopsis dalmanni) mate repeatedly during their lifetime, and have been shown to be sperm limited under both laboratory and field conditions. Here we ask whether receiving an additional mating alleviates sperm limitation in wild females. In our experiment one group of females received a single additional mating, while a control group received an interrupted, and therefore unsuccessful, mating. Females that received an additional mating did not lay more fertilised eggs in total, nor did they lay proportionately more fertilised eggs. Female fertility declined significantly through time, demonstrating that females were sperm limited. However, receipt of an additional mating did not significantly alter the rate of this decline.Conclusions/Significance: Our data suggest that the fertility consequences of a single additional mating were small. We discuss this effect (or lack thereof), and suggest that it is likely to be attributed to small ejaculate size, a high proportion of failed copulations, and the presence of X-linked meiotic drive in this species

Prediction of Neonatal Respiratory Distress Biomarker Concentration by Application of Machine Learning to Mid-Infrared Spectra

The authors of this study developed the use of attenuated total reflectance Fourier transform infrared spectroscopy (ATR–FTIR) combined with machine learning as a point-of-care (POC) diagnostic platform, considering neonatal respiratory distress syndrome (nRDS), for which no POC currently exists, as an example. nRDS can be diagnosed by a ratio of less than 2.2 of two nRDS biomarkers, lecithin and sphingomyelin (L/S ratio), and in this study, ATR–FTIR spectra were recorded from L/S ratios of between 1.0 and 3.4, which were generated using purified reagents. The calibration of principal component (PCR) and partial least squares (PLSR) regression models was performed using 155 raw baselined and second derivative spectra prior to predicting the concentration of a further 104 spectra. A three-factor PLSR model of second derivative spectra best predicted L/S ratios across the full range (R2: 0.967; MSE: 0.014). The L/S ratios from 1.0 to 3.4 were predicted with a prediction interval of +0.29, −0.37 when using a second derivative spectra PLSR model and had a mean prediction interval of +0.26, −0.34 around the L/S 2.2 region. These results support the validity of combining ATR–FTIR with machine learning to develop a point-of-care device for detecting and quantifying any biomarker with an interpretable mid-infrared spectrum

“I don’t want to live too long!”: Successful ageing and the failure of longevity in Japan

This chapter examines ‘successful aging’ through its impacts on formal care workers in Japan. It is based on one year of fieldwork conducted in urban Japan and examines the affective, ethical, and cultural forces that result at times in resilience, compassion, and intimacy between carers and elderly clients, and at other times, in violence, abuse, and abandonment. I argue that locating the source of this divergence in individuals (i.e., adverse coping strategy) reproduces the same neoliberal model of success for care workers as it does for the elderly. Instead, care and abuse in formal care settings can be seen as symptoms of broader political and economic transformations that have been occurring in Japan since the 1990s

Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial

BACKGROUND: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has previously been shown to extend progression-free survival versus placebo when given to patients with relapsed high-grade serous or endometrioid ovarian cancer who were platinum sensitive and who had a BRCA1 or BRCA2 (BRCA1/2) mutation, as part of the SOLO2/ENGOT-Ov21 trial. The aim of this final analysis is to investigate the effect of olaparib on overall survival. METHODS: This double-blind, randomised, placebo-controlled, phase 3 trial was done across 123 medical centres in 16 countries. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status at baseline of 0-1, had histologically confirmed, relapsed, high-grade serous or high-grade endometrioid ovarian cancer, including primary peritoneal or fallopian tube cancer, and had received two or more previous platinum regimens. Patients were randomly assigned (2:1) to receive olaparib tablets (300 mg in two 150 mg tablets twice daily) or matching placebo tablets using an interactive web or voice-response system. Stratification was by response to previous chemotherapy and length of platinum-free interval. Treatment assignment was masked to patients, treatment providers, and data assessors. The primary endpoint of progression-free survival has been reported previously. Overall survival was a key secondary endpoint and was analysed in all patients as randomly allocated. Safety was assessed in all patients who received at least one treatment dose. This trial is registered with ClinicalTrials.gov, NCT01874353, and is no longer recruiting patients. FINDINGS: Between Sept 3, 2013 and Nov 21, 2014, 295 patients were enrolled. Patients were randomly assigned to receive either olaparib (n=196 [66%]) or placebo (n=99 [34%]). One patient, randomised in error, did not receive olaparib. Median follow-up was 65·7 months (IQR 63·6-69·3) with olaparib and 64·5 months (63·4-68·7) with placebo. Median overall survival was 51·7 months (95% CI 41·5-59·1) with olaparib and 38·8 months (31·4-48·6) with placebo (hazard ratio 0·74 [95% CI 0·54-1·00]; p=0·054), unadjusted for the 38% of patients in the placebo group who received subsequent PARP inhibitor therapy. The most common grade 3 or worse treatment-emergent adverse event was anaemia (which occurred in 41 [21%] of 195 patients in the olaparib group and two [2%] of 99 patients in the placebo group). Serious treatment-emergent adverse events were reported in 50 (26%) of 195 patients receiving olaparib and eight (8%) of 99 patients receiving placebo. Treatment-emergent adverse events with a fatal outcome occurred in eight (4%) of the 195 patients receiving olaparib, six of which were judged to be treatment-related (attributed to myelodysplastic syndrome [n=3] and acute myeloid leukaemia [n=3]). INTERPRETATION: Olaparib provided a median overall survival benefit of 12·9 months compared with placebo in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Although statistical significance was not reached, these findings are arguably clinically meaningful and support the use of maintenance olaparib in these patients. FUNDING: AstraZeneca and Merck

Do Meio- and Macrobenthic Nematodes Differ in Community Composition and Body Weight Trends with Depth?

Nematodes occur regularly in macrobenthic samples but are rarely identified from them and are thus considered exclusively a part of the meiobenthos. Our study compares the generic composition of nematode communities and their individual body weight trends with water depth in macrobenthic (>250/300 µm) samples from the deep Arctic (Canada Basin), Gulf of Mexico (GOM) and the Bermuda slope with meiobenthic samples (<45 µm) from GOM. The dry weight per individual (µg) of all macrobenthic nematodes combined showed an increasing trend with increasing water depth, while the dry weight per individual of the meiobenthic GOM nematodes showed a trend to decrease with increasing depth. Multivariate analyses showed that the macrobenthic nematode community in the GOM was more similar to the macrobenthic nematodes of the Canada Basin than to the GOM meiobenthic nematodes. In particular, the genera Enoploides, Crenopharynx, Micoletzkyia, Phanodermella were dominant in the macrobenthos and accounted for most of the difference. Relative abundance of non-selective deposit feeders (1B) significantly decreased with depth in macrobenthos but remained dominant in the meiobenthic community. The occurrence of a distinct assemblage of bigger nematodes of high dry weight per individual in the macrobenthos suggests the need to include nematodes in macrobenthic studies

The locus of sexual selection: moving sexual selection studies into the post-genomics era

Sexual selection drives fundamental evolutionary processes such as trait elaboration and speciation. Despite this importance, there are surprisingly few examples of genes unequivocally responsible for variation in sexually selected phenotypes. This lack of information inhibits our ability to predict phenotypic change due to universal behaviors, such as fighting over mates and mate choice. Here, we discuss reasons for this apparent gap and provide recommendations for how it can be overcome by adopting contemporary genomic methods, exploiting underutilized taxa that may be ideal for detecting the effects of sexual selection, and adopting appropriate experimental paradigms. Identifying genes that determine variation in sexually selected traits has the potential to improve theoretical models and reveal whether the genetic changes underlying phenotypic novelty utilize common or unique molecular mechanisms. Such a genomic approach to sexual selection will help answer questions in the evolution of sexually selected phenotypes that were first asked by Darwin and can furthermore serve as a model for the application of genomics in all areas of evolutionary biology. This article is protected by copyright. All rights reserved

Atomoxetine Enhances Connectivity of Prefrontal Networks in Parkinson's Disease.

Cognitive impairment is common in Parkinson's disease (PD), but often not improved by dopaminergic treatment. New treatment strategies targeting other neurotransmitter deficits are therefore of growing interest. Imaging the brain at rest ('task-free') provides the opportunity to examine the impact of a candidate drug on many of the brain networks that underpin cognition, while minimizing task-related performance confounds. We test this approach using atomoxetine, a selective noradrenaline reuptake inhibitor that modulates the prefrontal cortical activity and can facilitate some executive functions and response inhibition. Thirty-three patients with idiopathic PD underwent task-free fMRI. Patients were scanned twice in a double-blind, placebo-controlled crossover design, following either placebo or 40-mg oral atomoxetine. Seventy-six controls were scanned once without medication to provide normative data. Seed-based correlation analyses were used to measure changes in functional connectivity, with the right inferior frontal gyrus (IFG) a critical region for executive function. Patients on placebo had reduced connectivity relative to controls from right IFG to dorsal anterior cingulate cortex and to left IFG and dorsolateral prefrontal cortex. Atomoxetine increased connectivity from the right IFG to the dorsal anterior cingulate. In addition, the atomoxetine-induced change in connectivity from right IFG to dorsolateral prefrontal cortex was proportional to the change in verbal fluency, a simple index of executive function. The results support the hypothesis that atomoxetine may restore prefrontal networks related to executive functions. We suggest that task-free imaging can support translational pharmacological studies of new drug therapies and provide evidence for engagement of the relevant neurocognitive systems.This work was funded by the Wellcome trust (103838), Parkinson’s UK, National Institute for Health Research’s Cambridge Biomedical Research Centre and the Medical Research Council (MC_US_A060_0016 and RG62761) and the James F McDonnell Foundation (21st century science initiative on Understanding Human Cognition). The BCNI is supported by a joint award from the Wellcome Trust and Medical Research Council.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/npp.2016.1

The effects of smoking on obesity: Evidence from Indonesian panel data

Background: It has been known that smoking is negatively related to weight-related outcomes. However, it has been difficult to determine whether the relationship is causal, and if so, how strong it is. We attempted to estimate the approximately causal effects of smoking on weight, body mass index (BMI), and obesity. Methods: The Indonesian Family Life Survey provided a sample of over 9000 men aged 15-55 years - each of them was observed in 1993, 1997, 2000 and 2007. The preferred method was a fixed effects model; that is, we related changes in smoking status or smoking intensity to changes in weight-related outcomes, while controlling for time-varying covariates. We also compared these results to those estimated by ordinary least squares and assessed the importance of controlling for time invariant individual heterogeneity. Results: Although the effects of smoking were precisely estimated in a statistical sense, their size was minuscule: a quitter would gain weight by at most 1 kg, or a smoker would lose weight by the same amount. The results were similar for BMI and obesity. When we did not control for time invariant individual heterogeneity, the size of the relationship was overestimated at least three times. Conclusions: Smoking exerted little influence on weight, and it was important to control for bias stemming from time invariant individual heterogeneity

Using lithium as a neuroprotective agent in patients with cancer

Neurocognitive impairment is being increasingly recognized as an important issue in patients with cancer who develop cognitive difficulties either as part of direct or indirect involvement of the nervous system or as a consequence of either chemotherapy-related or radiotherapy-related complications. Brain radiotherapy in particular can lead to significant cognitive defects. Neurocognitive decline adversely affects quality of life, meaningful employment, and even simple daily activities. Neuroprotection may be a viable and realistic goal in preventing neurocognitive sequelae in these patients, especially in the setting of cranial irradiation. Lithium is an agent that has been in use for psychiatric disorders for decades, but recently there has been emerging evidence that it can have a neuroprotective effect.This review discusses neurocognitive impairment in patients with cancer and the potential for investigating the use of lithium as a neuroprotectant in such patients.<br /

Using lithium as a neuroprotective agent in patients with cancer

Neurocognitive impairment is being increasingly recognized as an important issue in patients with cancer who develop cognitive difficulties either as part of direct or indirect involvement of the nervous system or as a consequence of either chemotherapy-related or radiotherapy-related complications. Brain radiotherapy in particular can lead to significant cognitive defects. Neurocognitive decline adversely affects quality of life, meaningful employment, and even simple daily activities. Neuroprotection may be a viable and realistic goal in preventing neurocognitive sequelae in these patients, especially in the setting of cranial irradiation. Lithium is an agent that has been in use for psychiatric disorders for decades, but recently there has been emerging evidence that it can have a neuroprotective effect.This review discusses neurocognitive impairment in patients with cancer and the potential for investigating the use of lithium as a neuroprotectant in such patients.<br /