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Background: Focal cortical dysplasias (FCDs) are congenital structural abnormalities of the brain, and represent the most common cause of medication-resistant focal epilepsy in children and adults. Recent studies have shown that somatic mutations (i.e. mutations arising in the embryo) in mTOR pathway genes underlie some FCD cases. Specific therapies targeting the mTOR pathway are available. However, testing for somatic mTOR pathway mutations in FCD tissue is not performed on a clinical basis, and the contribution of such mutations to the pathogenesis of FCD remains unknown. Aim: To investigate the feasibility of screening for somatic mutations in resected FCD tissue and determine the proportion and spatial distribution of FCDs which are due to low-level somatic mTOR pathway mutations. Methods: We performed ultra-deep sequencing of 13 mTOR pathway genes using a custom HaloPlexHS target enrichment kit (Agilent Technologies) in 16 resected histologically-confirmed FCD specimens. Results: We identified causal variants in 62.5% (10/16) of patients at an alternate allele frequency of 0.75–33.7%. The spatial mutation frequency correlated with the FCD lesion’s size and severity. Conclusions: Screening FCD tissue using a custom panel results in a high yield, and should be considered clinically given the important potential implications regarding surgical resection, medical management and genetic counselling.
We assessed whether paternal demographic, anthropometric and clinical factors influence the risk of an infant being born large-for-gestational-age (LGA). We examined the data on 3659 fathers of term offspring (including 662 LGA infants) born to primiparous women from Screening for Pregnancy Endpoints (SCOPE). LGA was defined as birth weight >90th centile as per INTERGROWTH 21st standards, with reference group being infants ⩽90th centile. Associations between paternal factors and likelihood of an LGA infant were examined using univariable and multivariable models. Men who fathered LGA babies were 180 g heavier at birth (P<0.001) and were more likely to have been born macrosomic (P<0.001) than those whose infants were not LGA. Fathers of LGA infants were 2.1 cm taller (P<0.001), 2.8 kg heavier (P<0.001) and had similar body mass index (BMI). In multivariable models, increasing paternal birth weight and height were independently associated with greater odds of having an LGA infant, irrespective of maternal factors. One unit increase in paternal BMI was associated with 2.9% greater odds of having an LGA boy but not girl; however, this association disappeared after adjustment for maternal BMI. There were no associations between paternal demographic factors or clinical history and infant LGA. In conclusion, fathers who were heavier at birth and were taller were more likely to have an LGA infant, but maternal BMI had a dominant influence on LGA.
Hemorrhage remains the major cause of preventable death after trauma. Recent data suggest that earlier blood product administration may improve outcomes. The purpose of this study was to determine whether opportunities exist for blood product transfusion by ground Emergency Medical Services (EMS).
This was a single EMS agency retrospective study of ground and helicopter responses from January 1, 2011 through December 31, 2015 for adult trauma patients transported from the scene of injury who met predetermined hemodynamic (HD) parameters for potential transfusion (heart rate [HR]≥120 and/or systolic blood pressure [SBP]≤90).
A total of 7,900 scene trauma ground transports occurred during the study period. Of 420 patients meeting HD criteria for transfusion, 53 (12.6%) had a significant mechanism of injury (MOI). Outcome data were available for 51 patients; 17 received blood products during their emergency department (ED) resuscitation. The percentage of patients receiving blood products based upon HD criteria ranged from 1.0% (HR) to 5.9% (SBP) to 38.1% (HR+SBP). In all, 74 Helicopter EMS (HEMS) transports met HD criteria for blood transfusion, of which, 28 patients received prehospital blood transfusion. Statistically significant total patient care time differences were noted for both the HR and the SBP cohorts, with HEMS having longer time intervals; no statistically significant difference in mean total patient care time was noted in the HR+SBP cohort.
In this study population, HD parameters alone did not predict need for ED blood product administration. Despite longer transport times, only one-third of HEMS patients meeting HD criteria for blood administration received prehospital transfusion. While one-third of ground Advanced Life Support (ALS) transport patients manifesting HD compromise received blood products in the ED, this represented 0.2% of total trauma transports over the study period. Given complex logistical issues involved in prehospital blood product administration, opportunities for ground administration appear limited within the described system.
MixFM, ZielinskiMD, MyersLA, BernsKS, LukeA, StubbsJR, ZietlowSP, JenkinsDH, SztajnkrycerMD. Prehospital Blood Product Administration Opportunities in Ground Transport ALS EMS – A Descriptive Study. Prehosp Disaster Med. 2018;33(3):230–236.
The Joint Commission Centre for Transforming Healthcare's Web-based Targeted Solutions Tool (TST) for improving hand hygiene was implemented to elucidate contributing factors to low compliance rates of hand hygiene. Monitoring of compliance was done by trained unknown and known observers and rates of hospital-acquired infections were tracked and correlated against the changes in hand hygiene compliance. In total, 5669 of hand hygiene observations were recorded by the secret observers. The compliance rate increased from 75·4% at baseline (May–August 2014) to 88·6% during the intervention (13 months) and the control periods (P < 0·0001). Reductions in healthcare-associated infection rates were recorded for Clostridium difficle infections from 7·95 (CI 0·8937–28·72) to 1·84 (CI 0·02411–10·26) infections per 10 000 patient-days (P = 0·23), central line-associated blood-stream infections from 5·9 (CI 1·194–17·36) to 2·9 (0·7856–7·475) per 1000 device days (P = 0·37) and catheter-associated urinary tract infections from 5·941 (CI 1·194–17·36) to 0 per 1000 device days (P = 0·42). The top contributing factors for non-compliance were: improper use of gloves, hands full of supplies or medications and frequent entry or exit in isolation areas. We conclude that the application of TST allows healthcare organisations to improve hand hygiene compliance and to identify the factors contributing to non-compliance.
The government publishes 3 different public report surgical site infection (SSI) metrics, all called standardized infection ratios (SIRs), that impact perceived hospital quality. We conducted a non-random cross-sectional observational pilot study of 20 California hospitals that voluntarily submitted colon surgery and SSI data. Discordant SIR values, leading to contradictory conclusions, occurred in 35% of these hospitals.
There is limited evidence on the acceptability, feasibility and cost-effectiveness of task-sharing interventions to narrow the treatment gap for mental disorders in sub-Saharan Africa. The purpose of this article is to describe the rationale, aims and methods of the Africa Focus on Intervention Research for Mental health (AFFIRM) collaborative research hub. AFFIRM is investigating strategies for narrowing the treatment gap for mental disorders in sub-Saharan Africa in four areas. First, it is assessing the feasibility, acceptability and cost-effectiveness of task-sharing interventions by conducting randomised controlled trials in Ethiopia and South Africa. The AFFIRM Task-sharing for the Care of Severe mental disorders (TaSCS) trial in Ethiopia aims to determine the acceptability, affordability, effectiveness and sustainability of mental health care for people with severe mental disorder delivered by trained and supervised non-specialist, primary health care workers compared with an existing psychiatric nurse-led service. The AFFIRM trial in South Africa aims to determine the cost-effectiveness of a task-sharing counselling intervention for maternal depression, delivered by non-specialist community health workers, and to examine factors influencing the implementation of the intervention and future scale up. Second, AFFIRM is building individual and institutional capacity for intervention research in sub-Saharan Africa by providing fellowship and mentorship programmes for candidates in Ethiopia, Ghana, Malawi, Uganda and Zimbabwe. Each year five Fellowships are awarded (one to each country) to attend the MPhil in Public Mental Health, a joint postgraduate programme at the University of Cape Town and Stellenbosch University. AFFIRM also offers short courses in intervention research, and supports PhD students attached to the trials in Ethiopia and South Africa. Third, AFFIRM is collaborating with other regional National Institute of Mental Health funded hubs in Latin America, sub-Saharan Africa and south Asia, by designing and executing shared research projects related to task-sharing and narrowing the treatment gap. Finally, it is establishing a network of collaboration between researchers, non-governmental organisations and government agencies that facilitates the translation of research knowledge into policy and practice. This article describes the developmental process of this multi-site approach, and provides a narrative of challenges and opportunities that have arisen during the early phases. Crucial to the long-term sustainability of this work is the nurturing and sustaining of partnerships between African mental health researchers, policy makers, practitioners and international collaborators.
The source of variability in people's response to stressful life events is poorly understood.
We examine the genetic and environmental underpinning of resilience (i.e. the difference between the twins' internalising symptoms and their predicted symptoms based on cumulative stressful life events).
Stressful life event exposure and internalising symptoms were assessed at two time points in 7500 adult twins. Using the residual between actual and predicted internalising symptom total score, twin modelling was conducted for each wave separately and longitudinally.
Resilience was found to have a moderate genetic heritability at each wave (~31%). Qualitative gender effects were found. Incorporating error of measurement into the model increased the estimated heritability for the latent construct of resilience (~50%). When measurement error and occasion-specific effects were removed, environmental influences contributed roughly equally to level of resilience.
Both genes and environment influence level of psychiatric resilience, and are largely stable over time. Environmental influences can have an enduring effect on resilience.
Photoluminescence (PL) spectroscopy was carried out on a series of Si-doped bulk InGaN films in the low indium (In) composition regime. Room temperature PL showed a factor of 25 increase in integrated intensity as the In composition was increased from 0 to 0.07. Temperature dependent PL data was fit to an Arrhenius equation to reveal an increasing activation energy for thermal quenching of the PL intensity as the In composition is increased. Time resolved PL measurements revealed that only the sample with highest In (x=0.07) showed a strong spectral variation in decay time across the T=4K PL resonance, indicative of recombination from localized states at low temperatures. The decay times at room temperature were non-radiatively dominated for all films, and the room temperature (non-radiative) decay times increased with increasing In, from 50-230 psec for x=0-0.07. Our data demonstrate that non-radiative recombination is less effective with increasing In composition.
Hydrogen was ion-implanted into wurtzite-phase GaN, and its transport, bound states, and microstructural effects during annealing up to 980°C were investigated by nuclear-reaction profiling, ion-channeling analysis, transmission electron microscopy, and infrared (IR) vibrational spectroscopy. At implanted concentrations ∧1 at.%, faceted H2 bubbles formed, enabling identification of energetically preferred surfaces, examination of passivating N-H states on these surfaces, and determination of the diffusivity-solubility product of the H. Additionally, the formation and evolution of point and extended defects arising from implantation and bubble formation were characterized. At implanted H concentrations ∧0.1 at.%, bubble formation was not observed, and ion-channeling analysis indicated a defect-related H site located within the  channel.
The behavior of H in p-GaN(Mg) at temperatures >400°C is modeled by using energies and vibration frequencies from density-functional theory to parameterize transport and reaction equations. Predictions agree semiquantitatively with experiment for the solubility, uptake, and release of the H when account is taken of a surface barrier.
We have used ion channeling to examine the lattice configuration of deuterium in Mg doped GaN grown by MOCVD. The deuterium is introduced by exposure to gas phase or ECR plasmas. A density functional approach including lattice relaxation, was used to calculate total energies for various locations and charge states of hydrogen in the wurtzite Mg doped GaN lattice. Results of channeling measurements are compared with channeling simulations for hydrogen at lattice locations predicted by density functional theory.
Ion channeling and transmission electron microscopy were used to examine the microstructure of GaN implanted with deuterium (D) at high (>1 at. %) and low (< 0.1 at. %) D concentrations. At high concentrations, bubbles and basal-plane stacking faults were observed. Ion channeling showed the D was disordered relative to the GaN lattice, consistent with precipitation of D2 into bubbles. At low D concentrations, bubbles and stacking faults are absent and ion channeling shows that a large fraction of the D occupies sites near the center of the c-axis channel.
The Early Iron Age enclosures and associated sites on Sutton Common on the western edge of the Humberhead Levels contain an exceptional variety of archaeological data of importance not only to the region but for the study of later prehistory in the British Isles. Few other later prehistoric British sites outside the East Anglian fens and the Somerset Levels have thus far produced the quantity and quality of organically preserved archaeological materials that have been found, despite the small scale of the investigations to date. The excavations have provided an opportunity to integrate a variety of environmental analyses, of wood, pollen, beetles, waterlogged and carbonised plant remains, and of soil micromorphology, to address archaeological questions about the character, use, and environment of this Early Iron Age marsh fort. The site is comprised of a timber palisaded enclosure and a succeeding multivallate enclosure linked to a smaller enclosure by a timber alignment across a palaeochannel, with associated finds ranging in date from the Middle Bronze Age to the Roman and medieval periods. Among the four adjacent archaeological sites is an Early Mesolithic occupation site, also with organic preservation, and there is a Late Neolithic site beneath the large enclosure. Desiccation throughout the common is leading to the damage and loss of wooden and organic remains. It is hoped that the publication of these results, of investigations between 1987 and 1993, will lead to a fuller investigation taking place.