The Quantitative-MFG Test: A linear mixed effect model to detect maternal-offspring gene interactions

Maternal-offspring gene interactions, aka maternal-fetal genotype (MFG) incompatibilities, are neglected in complex diseases and quantitative trait studies. They are implicated in birth to adult onset diseases but there are limited ways to investigate their influence on quantitative traits. We present the Quantitative-MFG (QMFG) test, a linear mixed model where maternal and offspring genotypes are fixed effects and residual correlations between family members are random effects. The QMFG handles families of any size, common or general scenarios of MFG incompatibility, and additional covariates. We develop likelihood ratio tests (LRTs) and rapid score tests and show they provide correct inference. In addition, the LRT’s alternative model provides unbiased parameter estimates. We show that testing the association of SNPs by fitting a standard model, which only considers the offspring genotypes, has very low power or can lead to incorrect conclusions. We also show that offspring genetic effects are missed if the MFG modeling assumptions are too restrictive. With GWAS data from the San Antonio Family Heart Study, we demonstrate that the QMFG score test is an effective and rapid screening tool. The QMFG test therefore has important potential to identify pathways of complex diseases for which the genetic etiology remains to be discovered

Guided graded exercise self-help plus specialist medical care versus specialist medical care alone for chronic fatigue syndrome (GETSET): a pragmatic randomised controlled trial

Background: Graded exercise therapy is an effective and safe treatment for chronic fatigue syndrome, but it is therapist intensive and availability is limited. We aimed to test the efficacy and safety of graded exercise delivered as guided self-help. Methods: In this pragmatic randomised controlled trial, we recruited adult patients (18 years and older) who met the UK National Institute for Health and Care Excellence criteria for chronic fatigue syndrome from two secondary-care clinics in the UK. Patients were randomly assigned to receive specialist medical care (SMC) alone (control group) or SMC with additional guided graded exercise self-help (GES). Block randomisation (randomly varying block sizes) was done at the level of the individual with a computer-generated sequence and was stratified by centre, depression score, and severity of physical disability. Patients and physiotherapists were necessarily unmasked from intervention assignment; the statistician was masked from intervention assignment. SMC was delivered by specialist doctors but was not standardised; GES consisted of a self-help booklet describing a six-step graded exercise programme that would take roughly 12 weeks to complete, and up to four guidance sessions with a physiotherapist over 8 weeks (maximum 90 min in total). Primary outcomes were fatigue (measured by the Chalder Fatigue Questionnaire) and physical function (assessed by the Short Form-36 physical function subscale); both were self-rated by patients at 12 weeks after randomisation and analysed in all randomised patients with outcome data at follow-up (ie, by modified intention to treat). We recorded adverse events, including serious adverse reactions to trial interventions. We used multiple linear regression analysis to compare SMC with GES, adjusting for baseline and stratification factors. This trial is registered at ISRCTN, number ISRCTN22975026. Findings: Between May 15, 2012, and Dec 24, 2014, we recruited 211 eligible patients, of whom 107 were assigned to the GES group and 104 to the control group. At 12 weeks, compared with the control group, mean fatigue score was 19·1 (SD 7·6) in the GES group and 22·9 (6·9) in the control group (adjusted difference −4·2 points, 95% CI −6·1 to −2·3, p<0·0001; effect size 0·53) and mean physical function score was 55·7 (23·3) in the GES group and 50·8 (25·3) in the control group (adjusted difference 6·3 points, 1·8 to 10·8, p=0·006; 0·20). No serious adverse reactions were recorded and other safety measures did not differ between the groups, after allowing for missing data. Interpretation: GES is a safe intervention that might reduce fatigue and, to a lesser extent, physical disability for patients with chronic fatigue syndrome. These findings need confirmation and extension to other health-care settings

Parent Perception of Their Child’s Asthma Control and Concurrent Complementary and Alternative Medicine Use

We conducted a cross-sectional survey of 1322 parents of children with asthma to measure the prevalence and factors associated with complementary and alternative medicine (CAM) use for pediatric asthma. Multivariate regression techniques were used to determine factors associated with CAM use. Eleven percent (141/1322) of children were given CAM. Parents of children on daily medications who were perceived to have poor asthma control were almost three times more likely to use CAM than parents of children on no daily medications who were perceived to have high asthma control (risk ratio: = 2.81; confidence interval: 1.72, 4.60); age, gender, race, income, and education level were not significant independent predictors. Parent perception of asthma control is significantly associated with CAM use. It is important for providers to elicit information regarding CAM use in the clinic, as this may imply that the asthma symptoms may not be well controlled.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63130/1/pai.2008.0503.pd

Closing the gap in Australian Aboriginal infant immunisation rates - the development and review of a pre-call strategy

Background: Improving timely immunisation is key to closing the inequitable gap in immunisation rates between Aboriginal children and non-Indigenous children. Aboriginal Immunisation Officers were employed in Hunter New England Local Health District (HNELHD), New South Wales (NSW), Australia, to telephone the families of all Aboriginal infants prior to the due date for their first scheduled vaccination. Methods: Aboriginal Immunisation Officers contacted the families of Aboriginal children born in the Hunter New England Local Health District (HNELHD) by telephone before their due immunisation date (pre-call) to provide the rationale for timely immunisation, and to facilitate contact with culturally safe local immunisation services if this was required. The impact of this strategy on immunisation coverage rates is reviewed. Results: For the period March 2010 to September 2014 there was a significant increase in immunisation coverage rate for Aboriginal children at 12 months of age in HNELHD (p < 0.0001). The coverage in the rest of NSW Aboriginal children also increased but not significantly (p = 0.218). Over the full study period there was a significant decrease in the immunisation coverage gap between Aboriginal children and non-Indigenous children in HNELHD (p < 0.0001) and the rest of NSW (p = 0.004). The immunisation coverage gap between Aboriginal and non-Indigenous infants decreased at a significantly faster rate in HNELHD than the rest of NSW (p = 0.0001). By the end of the study period in 2014, immunisation coverage in HNELHD Aboriginal infants had surpassed that of non-Indigenous infants by 0.8 %. Conclusions: The employment of Aboriginal immunisation officers may be associated with closing of the gap between Aboriginal and non-Indigenous infants' immunisation coverage in HNELHD and NSW. The pre-call telephone strategy provided accelerated benefit in closing this gap in HNELHD

Influence of Towing Force Magnitude on the Kinematics of Supramaximal Sprinting

The purpose of this study was to determine the influence of towing force magnitude on the kinematics of supramaximal sprinting. Ten high school and collegiate aged track and field athletes ran 60m maximal sprints under 5 different conditions: non-towed (NT), Tow A (2.0% body weight), Tow B (2.8%BW), Tow C (3.8%BW), and Tow D (4.7%BW). Three-dimensional kinematics of a 4-segment model of the right side of the body were collected starting at the 35m point of the trial. Significant differences were observed in stride length (SL) and horizontal velocity of the center of mass (VH) during Tow C and Tow D. For Tow D, a significant increase in the distance from the center of mass to the foot at touchdown (DH) was also observed. Contact time (CT) decreased significantly in all towing conditions, while stride rate (SR) increased slightly (\u3c 2.0%) under towed conditions. There were no significant changes in joint or segment angles at touchdown, with the exception of a significant decrease in the flexion/extension angle at the hip during the Tow D condition. We concluded that towing force magnitude does influence the kinematics of supramaximal running. Furthermore, we suggest that coaches and practitioners adjust towing force magnitude for each individual and avoid using towing forces in excess of 3.8%BW

Renal Peripheral Neuroectodermal Tumor Presenting at Age 78: Case Report

Primitive neuroectodermal tumor (PNET) of the kidney is a rare and aggressive tumor, often presenting in advanced stages and progressing rapidly. Renal PNET (rPNET) may affect a wide age spectrum, but the majority of cases are in young adults. We present a case of advanced rPNET in a 78-year-old woman. To our knowledge, this is the most advanced age of presentation of this neoplasm to date. We report on her presentation and management, and discuss the current clinical management of this tumor

Refined Neutron-Star Mass Determinations for Six Eclipsing X-Ray Pulsar Binaries

We present an improved method for determining the mass of neutron stars in eclipsing X-ray pulsar binaries and apply the method to six systems, namely Vela X-1, 4U 1538-52, SMC X-1, LMC X-4, Cen X-3, and Her X-1. In previous studies to determine neutron star mass, the X-ray eclipse duration has been approximated analytically by assuming the companion star is spherical with an effective Roche lobe radius. We use a numerical code based on Roche geometry with various optimizers to analyze the published data for these systems, which we supplement with new spectroscopic and photometric data for 4U 1538-52. This allows us to model the eclipse duration more accurately and thus calculate an improved value for the neutron star mass. The derived neutron star mass also depends on the assumed Roche lobe filling factor beta of the companion star, where beta = 1 indicates a completely filled Roche lobe. In previous work a range of beta between 0.9 and 1.0 was usually adopted. We use optical ellipsoidal lightcurve data to constrain beta. We find neutron star masses of 1.77 +/- 0.08 M_{sun} for Vela X-1, 0.87 +/- 0.07 M_{sun} for 4U 1538-52 (eccentric orbit), 1.00 +/- 0.10 M_{sun} for 4U 1538-52 (circular orbit), 1.04 +/- 0.09 M_{sun} for SMC X-1, 1.29 +/- 0.05 M_{sun} for LMC X-4, 1.49 +/- 0.08 M_{sun} for Cen X-3, and 1.07 +/- 0.36 M_{sun} for Her X-1. We discuss the limits of the approximations that were used to derive the earlier mass determinations, and we comment on the implications our new masses have for observationally refining the upper and lower bounds of the neutron star mass distribution.Comment: 10 figures, accepted for publication in The Astrophysical Journa

Causes of death among homeless people: a population-based cross-sectional study of linked hospitalisation and mortality data in England. [version 1; peer review: 2 approved]

Background: Homelessness has increased by 165% since 2010 in England, with evidence from many settings that those affected experience high levels of mortality. In this paper we examine the contribution of different causes of death to overall mortality in homeless people recently admitted to hospitals in England with specialist integrated homeless health and care (SIHHC) schemes.  Methods: We undertook an analysis of linked hospital admission records and mortality data for people attending any one of 17 SIHHC schemes between 1st November 2013 and 30th November 2016. Our primary outcome was death, which we analysed in subgroups of 10th version international classification of disease (ICD-10) specific deaths; and deaths from amenable causes. We compared our results to a sample of people living in areas of high social deprivation (IMD5 group). Results: We collected data on 3,882 individual homeless hospital admissions that were linked to 600 deaths. The median age of death was 51.6 years (interquartile range 42.7-60.2) for SIHHC and 71.5 for the IMD5 (60.67-79.0).  The top three underlying causes of death by ICD-10 chapter in the SIHHC group were external causes of death (21.7%; 130/600), cancer (19.0%; 114/600) and digestive disease (19.0%; 114/600).  The percentage of deaths due to an amenable cause after age and sex weighting was 30.2% in the homeless SIHHC group (181/600) compared to 23.0% in the IMD5 group (578/2,512). Conclusion: Nearly one in three homeless deaths were due to causes amenable to timely and effective health care. The high burden of amenable deaths highlights the extreme health harms of homelessness and the need for greater emphasis on prevention of homelessness and early healthcare interventions

Outcomes of specialist discharge coordination and intermediate care schemes for patients who are homeless: analysis protocol for a population-based historical cohort

Introduction People who are homeless often experience poor hospital discharge arrangements, reflecting ongoing care and housing needs. Specialist integrated homeless health and care provision (SIHHC) schemes have been developed and implemented to facilitate the safe and timely discharge of homeless patients from hospital. Our study aims to investigate the health outcomes of patients who were homeless and seen by a selection of SIHHC services. Methods and analysis Our study will employ a historical population-based cohort in England. We will examine health outcomes among three groups of adults: (1) homeless patients seen by specialist discharge schemes during their hospital admission; (2) homeless patients not seen by a specialist scheme and (3)admitted patients who live in deprived neighbourhoods and were not recorded as being homeless. Primary outcomes will be: time from discharge to next hospital inpatient admission; time from discharge to next accident and emergency attendance and 28-day emergency readmission. Outcome data will be generated through linkage to hospital admissions data (Hospital Episode Statistics) and mortality data for November 2013 to November 2016. Multivariable regression will be used to model the relationship between the study comparison groups and each of the outcomes. Ethics and dissemination Approval has been obtained from the National Health Service (NHS) Confidentiality Advisory Group (reference 16/CAG/0021) to undertake this work using unconsented identifiable data. Health Research Authority Research Ethics approval (REC 16/EE/0018) has been obtained in addition to local research and development approvals for data collection at NHS sites. We will feedback the results of our study to our advisory group of people who have lived experience of homelessness and seek their suggestions on ways to improve or take this work further for their benefit. We will disseminate our findings to SIHHC schemes through a series of regional workshops

“What if There's Something Wrong with Her?”‐How Biomedical Technologies Contribute to Epistemic Injustice in Healthcare

While there is a steadily growing literature on epistemic injustice in healthcare, there are few discussions of the role that biomedical technologies play in harming patients in their capacity as knowers. Through an analysis of newborn and pediatric genetic and genomic sequencing technologies (GSTs), I argue that biomedical technologies can lead to epistemic injustice through two primary pathways: epistemic capture and value partitioning. I close by discussing the larger ethical and political context of critical analyses of GSTs and their broader implications for just and equitable healthcare delivery