Correlations in parameter estimation of low-mass eccentric binaries: GW151226 & GW170608

The eccentricity of binary black hole mergers is predicted to be an indicator of the history of their formation. In particular, eccentricity is a strong signature of dynamical formation rather than formation by stellar evolution in isolated stellar systems. It has been shown that searches for eccentric signals with quasi-circular templates can lead to loss of SNR, and some signals could be missed by such a pipeline. We investigate the efficacy of the existing quasi-circular parameter estimation pipelines to determine the source parameters of such eccentric systems. We create a set of simulated signals with eccentricity up to 0.3 and find that as the eccentricity increases, the recovered mass parameters are consistent with those of a binary with up to a $\approx 10\%$ higher chirp mass and mass ratio closer to unity. We also employ a full inspiral-merger-ringdown waveform model to perform parameter estimation on two gravitational wave events, GW151226 and GW170608, to investigate this bias on real data. We find that the correlation between the masses and eccentricity persists in real data, but that there is also a correlation between the measured eccentricity and effective spin. In particular, using a non-spinning prior results in a spurious eccentricity measurement for GW151226. Performing parameter estimation with an aligned spin, eccentric model, we constrain the eccentricities of GW151226 and GW170608 to be $<0.15$ and $<0.12$ respectively

Dietary quality in a sample of adults with type 2 diabetes mellitus in Ireland; a cross-sectional case control study

BACKGROUND A number of dietary quality indices (DQIs) have been developed to assess the quality of dietary intake. Analysis of the intake of individual nutrients does not reflect the complexity of dietary behaviours and their association with health and disease. The aim of this study was to determine the dietary quality of individuals with type 2 diabetes mellitus (T2DM) using a variety of validated DQIs. METHODS In this cross-sectional analysis of 111 Caucasian adults, 65 cases with T2DM were recruited from the Diabetes Day Care Services of St. Columcille's and St. Vincent's Hospitals, Dublin, Ireland. Forty-six controls did not have T2DM and were recruited from the general population. Data from 3-day estimated diet diaries were used to calculate 4 DQIs. RESULTS Participants with T2DM had a significantly lower score for consumption of a Mediterranean dietary pattern compared to the control group, measured using the Mediterranean Diet Score (Range 0-9) and the Alternate Mediterranean Diet Score (Range 0-9) (mean ± SD) (3.4 ± 1.3 vs 4.8 ± 1.8, P < 0.001 and 3.3 ± 1.5 vs 4.2 ± 1.8, P = 0.02 respectively). Participants with T2DM also had lower dietary quality than the control population as assessed by the Healthy Diet Indicator (Range 0-9) (T2DM; 2.6 ± 2.3, control; 3.3 ± 1.1, P = 0.001). No differences between the two groups were found when dietary quality was assessed using the Alternate Healthy Eating Index. Micronutrient intake was assessed using the Micronutrient Adequacy Score (Range 0-8) and participants with T2DM had a significantly lower score than the control group (T2DM; 1.6 ± 1.4, control; 2.3 ± 1.4, P = 0.009). When individual nutrient intakes were assessed, no significant differences were observed in macronutrient intake. CONCLUSION Overall, these findings demonstrate that T2DM was associated with a lower score when dietary quality was assessed using a number of validated indices.This study was funded by Science Foundation Ireland (Grant number 08/RFP/BMT1342)

Palliative care interventions in advanced dementia (Review)

Background Dementia is a chronic, progressive and ultimately fatal neurodegenerative disease. Advanced dementia is characterised by profound cognitive impairment, inability to communicate verbally and complete functional dependence. Usual care of people with advanced dementia is not underpinned universally by a palliative approach. Palliative care has focused traditionally on care of people with cancer but for more than a decade, there have been increased calls worldwide to extend palliative care services to include all people with life-limiting illnesses in need of specialist care, including people with dementia. Objectives To assess the effect of palliative care interventions in advanced dementia and to report on the range of outcome measures used. Search methods We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 4 February 2016. ALOIS contains records of clinical trials identified from monthly searches of several major healthcare databases, trial registries and grey literature sources. We ran additional searches across MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCOhost), LILACS (BIREME), Web of Science Core Collection (ISI Web of Science), ClinicalTrials.gov and the World Health Organization ICTRP trial portal to ensure that the searches were as comprehensive and as up-to-date as possible. Selection criteria We searched for randomised (RCT) and non-randomised controlled trials (nRCT), controlled before-and-after studies (CBA) and interrupted time series studies evaluating the impact of palliative care interventions for adults with dementia of any type, staged as advanced dementia by a recognised and validated tool. Participants could be people with advanced dementia, their family members, clinicians or paid care staff. We included clinical interventions and non-clinical interventions. Comparators were usual care or another palliative care intervention. We did not exclude studies on the basis of outcomes measured and recorded all outcomes measured in included studies. Data collection and analysis Two review authors independently assessed for inclusion all the potential studies we identified as a result of the search strategy. We resolved any disagreement through discussion or, when required, consulted with the rest of the review team. We independently extracted data and conducted assessment of methodological quality, using standard Cochrane methods. Main results We identified two studies of palliative care interventions for people with advanced dementia. We did not pool data due to the heterogeneity between the two trials in terms of the interventions and the settings. The two studies measured 31 different outcomes, yet they did not measure the same outcome. There are six ongoing studies that we expect to include in future versions of this review. Both studies were at high risk of bias, in part because blinding was not possible. This and small sample sizes meant that the overall certainty of all the evidence was very low. One individually randomised RCT (99 participants) evaluated the effect of a palliative care team for people with advanced dementia hospitalised for an acute illness. While this trial reported that a palliative care plan was more likely to be developed for participants in the intervention group (risk ratio (RR) 5.84, 95% confidence interval (CI) 1.37 to 25.02), the plan was only adopted for two participants, both in the intervention group, while in hospital. The palliative care plan was more likely to be available on discharge in the intervention group (RR 4.50, 95% CI 1.03 to 19.75). We found no evidence that the intervention affected mortality in hospital (RR 1.06, 95% CI 0.53 to 2.13), decisions to forgo cardiopulmonary resuscitation in hospital or the clinical care provided during hospital admission, but for the latter, event rates were low and the results were associated with a lot of uncertainty. One cluster RCT (256 participants, each enrolled with a family carer) evaluated the effect of a decision aid on end-of-life feeding options on surrogate decision-makers of nursing home residents with advanced dementia. Data for 90 participants (35% of the original study) met the definition of advanced dementia for this review and were re-analysed for the purposes of the review. In this subset, intervention surrogates had lower scores for decisional conflict measured on the Decisional Conflict Scale (mean difference -0.30, 95% CI -0.61 to 0.01, reduction of 0.3 to 0.4 units considered meaningful) and were more likely than participants in the control group to discuss feeding options with a clinician (RR 1.57, 95% CI 0.93 to 2.64), but imprecision meant that there was significant uncertainty about both results. Authors' conclusions Very little high quality work has been completed exploring palliative care interventions in advanced dementia. There were only two included studies in this review, with variation in the interventions and in the settings that made it impossible to conduct a meta-analysis of data for any outcome. Thus, we conclude that there is insufficient evidence to assess the effect of palliative care interventions in advanced dementia. The fact that there are six ongoing studies at the time of this review indicates an increased interest in this area by researchers, which is welcome and needed. Plain language summary Palliative care for people with advanced dementia Review question In this research, we wanted to see if palliative care helps people with advanced dementia or helps their family or carers. We also wanted to describe how researchers tried to measure the effect of palliative care. Background People with advanced dementia have serious memory problems and have problems making simple decisions. They are usually no longer able to communicate by talking. They need a lot of help from their carers. People with advanced dementia can live for a long time. It is very hard to say exactly how long a person with advanced dementia will live. Palliative care (or end-of-life care) is a particular way of caring for people who have diseases that cannot be cured. The main aims of palliative care are to reduce pain and to maintain the best possible quality of life as death approaches. Palliative care is used a lot with people with cancer but is not used much for people with advanced dementia. Study characteristics We examined the research published up to January 2016. We found only two suitable studies (189 people), both from the US. We also found six studies that were underway but the results were not yet published. Key results One study found that having a small team of doctors and nurses trained in palliative care made little difference to how people with advanced dementia were treated while in hospital. But, having this special team meant that more people had a palliative care plan when they were discharged from hospital. The other study measured if giving written information to relatives explaining the different methods that can be used to feed people with advanced dementia helped either the relatives or the person. This study found that giving relatives this information made it a little easier for relatives to make decisions about what methods would be used to feed the person with dementia. Certainty of evidence We only found two studies and the two palliative care methods in these studies were very different. We cannot be very certain about how accurate either of these results reported here are, partly because only a small number of people took part in the studies. So from these studies, it is hard to be sure whether palliative care makes a difference to people with advanced dementia. Final thoughts Little research has been done about people with advanced dementia, often because of ethical concerns. However, although it is hard to do research with people with dementia, more well-designed studies are required to work out how palliative care can be used best in this special population

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Gravitational Waveform Modelling with Machine Learning and for Eccentric Binary Systems

154 pagesThe LIGO/Virgo collaboration has detected gravitational waves from dozens of binary black hole mergers. Accurate determination of the source parameters of these binaries is important for understanding the environments in which these objects can form and merge. Many techniques are employed to speed up the parameter estimation of events in LIGO/Virgo data. We demonstrate the success of the machine learning technique of normalizing flows for inferring the parameters of several LIGO events in a matter of milliseconds, and validate the novel machine learning pipeline against the widely used technique of parallel-tempered MCMC. Orbital eccentricity of a compact binary object is a signature of dynamical formation in dense stellar clusters. We employ two novel waveform models to investigate the effects of eccentricity on the detection and parameter estimation of the gravitational wave signal. We find that, for LIGO-type detectors, the signal-to-noise ratio (SNR) of eccentric signals is larger than that of quasi-circular mergers for e < 0.4. Furthermore, for future detectors such as Einstein telescope, the SNR of eccentric signals is similar to that of quasi-circular signals, and can still have appreciable SNR up to e < 0.6. We then investigate the effect of using quasi-circular waveforms for the parameter estimation of eccentric signals. We find that for eccentrities up to e_0 < 0.3, there is an up to 10% overestimation of the system's chirp mass, and the recovered mass ratio is determined to be closer to unity regardless of the true mass ratio. We also employ a full inspiral-merger-ringdown waveform to perform parameter estimation of two gravitational wave events, GW151226, and GW170608. We find that the chirp mass and eccentricity measurements are also correlated in real data, and furthermore that there is a correlation of the chirp mass and spin that can lead to spurious eccentricity measurements in the case of a signal with appreciable spin. We measure the eccentricities of these two events and constrain them to be < 0.15 and < 0.12 for GW151226 and GW170608 respectively

Hemodynamic responses during graded and constant-load plantar flexion exercise in middle-aged men and women with type 2 diabetes

We tested the hypotheses that type 2 diabetes (T2D) impairs the 1) leg hemodynamic responses to an incremental intermittent plantar-flexion exercise and 2) dynamic responses of leg vascular conductance (LVC) during low-intensity (30% maximal voluntary contraction, MVC) and high-intensity (70% MVC) constant-load plantar-flexion exercise in the supine posture. Forty-four middle-aged individuals with T2D (14 women), and 35 healthy nondiabetic (ND) individuals (18 women) were tested. Leg blood flow (LBF) was measured between each contraction using venous occlusion plethysmography. During the incremental test peak force (Fpeak) relative to MVC was significantly reduced (P < 0.05) in men and women with T2D compared with their respective nondiabetic counterparts. Peak LBF and the slope of LBF relative to percentage Fpeak were also reduced (P < 0.05) in women with T2D compared with healthy women (peak blood flow, 460.6 ± 126.8 vs. 628.3 ± 347.7 ml/min; slope, 3.78 ± 1.74 vs. 5.85 ± 3.14 ml·min−1·%Fpeak−1) and in men with T2D compared with nondiabetic men (peak blood flow, 621.7 ± 241.3 vs. 721.2 ± 359.7 ml/min; slope, 5.75 ± 2.66 vs. 6.33 ± 3.63 ml·min−1·%Fpeak−1). During constant-load contractions at 30% MVC T2D did not affect the dynamic responses of LVC (LBF/MAP). However, at 70% MVC [completed by a subgroup of participants (20 with T2D, 6 women; 13 ND, 6 women)] the time constant of the second growth phase of LVC was longer and the amplitude of the first growth phase was lower (P < 0.05 for both) in men and women with T2D. The results suggest that the T2D-induced impairments in performance of the leg muscles are related to reductions in blood flow in both men and women