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Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.
We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from
$z = 0.35$
to 3; and a deep, high-redshift HI IM survey over 100 deg2 from
$z = 3$
to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to
$z \sim 3$
with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to
$z = 6$
. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
The National Institute of Standards and Technology (NIST) certifies a suite of Standard Reference Materials (SRMs) to evaluate specific aspects of instrument performance of both X-ray and neutron powder diffractometers. This report describes SRM 660c, the fourth generation of this powder diffraction SRM, which is used primarily for calibrating powder diffractometers with respect to line position and line shape for the determination of the instrument profile function (IPF). It is certified with respect to lattice parameter and consists of approximately 6 g of lanthanum hexaboride (LaB6) powder. So that this SRM would be applicable for the neutron diffraction community, the powder was prepared from an isotopically enriched 11B precursor material. The microstructure of the LaB6 powder was engineered specifically to yield a crystallite size above that where size broadening is typically observed and to minimize the crystallographic defects that lead to strain broadening. A NIST-built diffractometer, incorporating many advanced design features, was used to certify the lattice parameter of the LaB6 powder. Both Type A, statistical, and Type B, systematic, uncertainties have been assigned to yield a certified value for the lattice parameter at 22.5 °C of a = 0.415 682 6 ± 0.000 008 nm (95% confidence).
Carers of people experiencing a first episode of psychosis are at an increased risk of developing their own physical and mental health problems. Psychoeducation has been found to improve carer wellbeing and reduce distress. However, few psychoeducation interventions have considered the resource constraints on mental health services and the impact that these can have on the implementation of any such interventions. The present service evaluation aimed to evaluate an abbreviated version (sole session) of a previously tested psychoeducation intervention (three sessions) that targets less adaptive illness beliefs (n = 17). Pre–post effect sizes reveal that all of the carers’ illness beliefs changed in the desired direction, with four out of the 10 illness beliefs associated with large to moderate improvements. When compared with the outcomes obtained in our evaluation of the more intensive, three-session version of the intervention, the between-group effects largely favoured the three-session version but were mostly small. Moderate to large effects in favour of the three-session version were found for two of the 10 illness beliefs. These findings support the further investigation of the sole session psychoeducation intervention as part of a randomised controlled trial.
Key learning aims
(1) To evaluate the impact of a sole-session psychoeducation intervention on illness beliefs.
(2) To compare the outcomes of the sole-session psychoeducation intervention to the previous, more intensive (three-session) version of the same intervention.
(3) To consider the value of research approaches to evaluating psychoeducation interventions for carers of people with psychosis.
Optimising short- and long-term outcomes for children and patients with CHD depends on continued scientific discovery and translation to clinical improvements in a coordinated effort by multiple stakeholders. Several challenges remain for clinicians, researchers, administrators, patients, and families seeking continuous scientific and clinical advancements in the field. We describe a new integrated research and improvement network – Cardiac Networks United – that seeks to build upon the experience and success achieved to-date to create a new infrastructure for research and quality improvement that will serve the needs of the paediatric and congenital heart community in the future. Existing gaps in data integration and barriers to improvement are described, along with the mission and vision, organisational structure, and early objectives of Cardiac Networks United. Finally, representatives of key stakeholder groups – heart centre executives, research leaders, learning health system experts, and parent advocates – offer their perspectives on the need for this new collaborative effort.
Design problems are often presented as structured briefs with detailed constraints and requirements, suggesting a fixed definition. However, past studies have identified the importance of exploring design problems for creative design outcomes. Previous protocol studies of designers has shown that problems can “co-evolve” with the development of solutions during the design process. But to date, little evidence has been provided about how designers systematically explore presented problems to create better solutions. In this study, we conducted a qualitative analysis of 252 design problems collected from publically available sources, including award-winning product designs and open-source design competitions. This database offers an independent sample of presented problems, designers’ alternative problem descriptions, and innovative solutions. We report the results of this large-scale qualitative analysis aimed at characterizing changes to problems during the design process. Inductive coding was used to identify content patterns in “discovered” problem descriptions, with qualitative codes reliably scored by two independent coders. A total of 32 distinct patterns of problem exploration were identified across designers and presented problems. Each pattern is described in the form of a generalized strategy to guide designers as they explore problem spaces. The exploration patterns identified in this study are the first empirical evidence of problem exploration in independent design problems. Further, the presence of exploration patterns in discovered problems is associated with the selection of the corresponding solution as a challenge finalist. These empirically identified strategies for problem exploration may be useful for computational tools supporting designers.
We examine supervisor-subordinate (dis)agreement regarding perceptions of the supervisor’s ethical leadership and its relationship to organizational deviance. We find that, on average, supervisors rate themselves more favorably on ethical leadership compared to how followers rate them. In addition, polynomial regression results reveal that unit-level organizational deviance is higher when there is agreement about lower levels of ethical leadership, and disagreement when supervisors rate themselves higher on ethical leadership than subordinates’ ratings of the supervisors. Finally, drawing on social influence theories, we look at antecedents of (dis)agreement and find that supervisors’ beliefs about themselves (that they were “better-than-average” ethical leaders) and others (their assumptions about whether the morality of their subordinates is malleable or not) are associated with self-other (dis)agreement on ethical leadership.
The aim of this study was to compare satisfaction with residence, wellbeing and physical health of continuing care retirement community (CCRC) residents with people who considered enrolling in the same CCRCs but elected not to move. A total of 101 participants were recruited from 13 CCRCs located in multiple cities in the United States of America. A phone interview was conducted with participants three months or less from enrolment and one year later. Compared with those who chose not to move, CCRC residents reported lower satisfaction at baseline, but higher satisfaction at one year. Wellbeing declined from baseline to follow-up for both groups, but was higher in CCRC residents both at baseline and at one year. CCRCs might consider giving new residents a longer cancellation period in order to allow sufficient time for the adjustment process. This, in turn, might both prevent an early departure and affect the decision of potential CCRC residents to move into the community.
We compared sepsis “time zero” and Centers for Medicare and Medicaid Services (CMS) SEP-1 pass rates among 3 abstractors in 3 hospitals. Abstractors agreed on time zero in 29 of 80 (36%) cases. Perceived pass rates ranged from 9 of 80 cases (11%) to 19 of 80 cases (23%). Variability in time zero and perceived pass rates limits the utility of SEP-1 for measuring quality.
The idea that the churches became agents of empire through their missionary activity is very popular, but it is too simple. Established Churches, such as those of England and Scotland, could certainly be used by government, usually willingly; so could the Roman Catholic Church in the empires of other countries. But the position of the smaller churches, usually with no settler community behind them, was different. This study examines the effects of the Chilembwe Rising of 1915 on the British Churches of Christ mission in Nyasaland (modern Malawi). What is empire? The Colonial Office and the local administration might view a situation in different ways. Their decisions could thus divide native Christians from the UK, and even cause division in the UK church itself, as well as strengthening divisions on the mission field between different churches. Thus, even in the churches, imperial actions could foster the African desire for independence of empire.
Children with CHD and acquired heart disease have unique, high-risk physiology. They may have a higher risk of adverse tracheal-intubation-associated events, as compared with children with non-cardiac disease.
Materials and methods
We sought to evaluate the occurrence of adverse tracheal-intubation-associated events in children with cardiac disease compared to children with non-cardiac disease. A retrospective analysis of tracheal intubations from 38 international paediatric ICUs was performed using the National Emergency Airway Registry for Children (NEAR4KIDS) quality improvement registry. The primary outcome was the occurrence of any tracheal-intubation-associated event. Secondary outcomes included the occurrence of severe tracheal-intubation-associated events, multiple intubation attempts, and oxygen desaturation.
A total of 8851 intubations were reported between July, 2012 and March, 2016. Cardiac patients were younger, more likely to have haemodynamic instability, and less likely to have respiratory failure as an indication. The overall frequency of tracheal-intubation-associated events was not different (cardiac: 17% versus non-cardiac: 16%, p=0.13), nor was the rate of severe tracheal-intubation-associated events (cardiac: 7% versus non-cardiac: 6%, p=0.11). Tracheal-intubation-associated cardiac arrest occurred more often in cardiac patients (2.80 versus 1.28%; p<0.001), even after adjusting for patient and provider differences (adjusted odds ratio 1.79; p=0.03). Multiple intubation attempts occurred less often in cardiac patients (p=0.04), and oxygen desaturations occurred more often, even after excluding patients with cyanotic heart disease.
The overall incidence of adverse tracheal-intubation-associated events in cardiac patients was not different from that in non-cardiac patients. However, the presence of a cardiac diagnosis was associated with a higher occurrence of both tracheal-intubation-associated cardiac arrest and oxygen desaturation.
The “Stop the Bleed” campaign advocates for non-medical personnel to be trained in basic hemorrhage control. However, it is not clear what type of education or the duration of instruction needed to meet that requirement. The objective of this study was to determine the impact of a brief hemorrhage control educational curriculum on the willingness of laypersons to respond during a traumatic emergency.
This “Stop the Bleed” education initiative was conducted by the University of Texas Health San Antonio Office of the Medical Director (San Antonio, Texas USA) between September 2016 and March 2017. Individuals with formal medical certification were excluded from this analysis. Trainers used a pre-event questionnaire to assess participants knowledge and attitudes about tourniquets and responding to traumatic emergencies. Each training course included an individual evaluation of tourniquet placement, 20 minutes of didactic instruction on hemorrhage control techniques, and hands-on instruction with tourniquet application on both adult and child mannequins. The primary outcome in this study was the willingness to use a tourniquet in response to a traumatic medical emergency.
Of 236 participants, 218 met the eligibility criteria. When initially asked if they would use a tourniquet in real life, 64.2% (140/218) responded “Yes.” Following training, 95.6% (194/203) of participants responded that they would use a tourniquet in real life. When participants were asked about their comfort level with using a tourniquet in real life, there was a statistically significant improvement between their initial response and their response post training (2.5 versus 4.0, based on 5-point Likert scale; P<.001).
In this hemorrhage control education study, it was found that a short educational intervention can improve laypersons’ self-efficacy and reported willingness to use a tourniquet in an emergency. Identified barriers to act should be addressed when designing future hemorrhage control public health education campaigns. Community education should continue to be a priority of the “Stop the Bleed” campaign.
RossEM, RedmanTT, MappJG, BrownDJ, TanakaK, CooleyCW, KharodCU, WamplerDA. Stop the Bleed: The Effect of Hemorrhage Control Education on Laypersons’ Willingness to Respond During a Traumatic Medical Emergency. Prehosp Disaster Med. 2018;33(2):127–132.
The Numeniini is a tribe of 13 wader species (Scolopacidae, Charadriiformes) of which seven are Near Threatened or globally threatened, including two Critically Endangered. To help inform conservation management and policy responses, we present the results of an expert assessment of the threats that members of this taxonomic group face across migratory flyways. Most threats are increasing in intensity, particularly in non-breeding areas, where habitat loss resulting from residential and commercial development, aquaculture, mining, transport, disturbance, problematic invasive species, pollution and climate change were regarded as having the greatest detrimental impact. Fewer threats (mining, disturbance, problematic native species and climate change) were identified as widely affecting breeding areas. Numeniini populations face the greatest number of non-breeding threats in the East Asian-Australasian Flyway, especially those associated with coastal reclamation; related threats were also identified across the Central and Atlantic Americas, and East Atlantic flyways. Threats on the breeding grounds were greatest in Central and Atlantic Americas, East Atlantic and West Asian flyways. Three priority actions were associated with monitoring and research: to monitor breeding population trends (which for species breeding in remote areas may best be achieved through surveys at key non-breeding sites), to deploy tracking technologies to identify migratory connectivity, and to monitor land-cover change across breeding and non-breeding areas. Two priority actions were focused on conservation and policy responses: to identify and effectively protect key non-breeding sites across all flyways (particularly in the East Asian- Australasian Flyway), and to implement successful conservation interventions at a sufficient scale across human-dominated landscapes for species’ recovery to be achieved. If implemented urgently, these measures in combination have the potential to alter the current population declines of many Numeniini species and provide a template for the conservation of other groups of threatened species.
Electroconvulsive therapy prescribers, practitioners and many patients will be aware of an emerging clinical evidence base for non-ECT brain stimulation treatments. Although the previous edition of The ECT Handbook made no mention of brain stimulation treatments, a review of the status of the three most studied therapies is now relevant. These therapies are:
• repetitive transcranial magnetic stimulation
• vagus nerve stimulation
• deep brain stimulation.
In this chapter, we consider the use of these therapies in the management of depression and how they might relate to the ECT treatment pathway.
Repetitive transcranial magnetic stimulation (rTMS)
Repetitive transcranial magnetic stimulation is a non-invasive technique causing modification of brain activity by focal stimulation of the superficial layers of the cerebral cortex using a train of magnetic pulses via an external wire coil. The impetus for studies of rTMS in psychiatry has arisen from the need for a viable alternative to ECT with a lower burden of adverse effects and greater patient acceptability. A substantial literature, including several systematic reviews and meta-analyses, now exists on the use of rTMS in the management of depression. In 2008 the US Food and Drug Administration approved a TMS system ‘for the treatment of Major Depressive Disorder in adult patients who have failed to achieve satisfactory improvement from one prior antidepressant medication at or above the minimal effective dose and duration in the current episode’.
However, NICE published a technology appraisal in 2007, restating the core recommendations in the 2010 depression guideline update, which is consistent with the absence of convincing evidence of superior efficacy for rTMS over sham treatment and with the paucity of efficacy data extending beyond 4–6 weeks of treatment. The status of the technique is summarised as follows:
‘Current evidence suggests that there are no major safety concerns associated with transcranial magnetic stimulation (TMS) for severe depression. There is uncertainty about the procedure's clinical efficacy, which may depend on higher intensity, greater frequency, bilateral application and/or longer treatment durations than have appeared in the evidence to date. TMS should therefore be performed only in research studies designed to investigate these factors.’ (National Institute for Health and Clinical Excellence, 2007)
In our opinion, on the basis of current evidence, rTMS remains an interesting but experimental therapy which should not be considered a viable alternative to treatment with ECT.
Surgical site infections (SSIs) are responsible for significant morbidity and mortality. Preadmission skin antisepsis, while controversial, has gained acceptance as a strategy for reducing the risk of SSI. In this study, we analyze the benefit of an electronic alert system for enhancing compliance to preadmission application of 2% chlorhexidine gluconate (CHG).
DESIGN, SETTING, AND PARTICIPANTS
Following informed consent, 100 healthy volunteers in an academic, tertiary care medical center were randomized to 5 chlorhexidine gluconate (CHG) skin application groups: 1, 2, 3, 4, or 5 consecutive applications. Participants were further randomized into 2 subgroups: with or without electronic alert. Skin surface concentrations of CHG (μg/mL) were analyzed using a colorimetric assay at 5 separate anatomic sites.
Preadmission application of chlorhexidine gluconate, 2%
Mean composite skin surface CHG concentrations in volunteer participants receiving EA following 1, 2, 3, 4, and 5 applications were 1,040.5, 1,334.4, 1,278.2, 1,643.9, and 1,803.1 µg/mL, respectively, while composite skin surface concentrations in the no-EA group were 913.8, 1,240.0, 1,249.8, 1,194.4, and 1,364.2 µg/mL, respectively (ANOVA, P<.001). Composite ratios (CHG concentration/minimum inhibitory concentration required to inhibit the growth of 90% of organisms [MIC90]) for 1, 2, 3, 4, or 5 applications using the 2% CHG cloth were 208.1, 266.8, 255.6, 328.8, and 360.6, respectively, representing CHG skin concentrations effective against staphylococcal surgical pathogens. The use of an electronic alert system resulted in significant increase in skin concentrations of CHG in the 4- and 5-application groups (P<.04 and P<.007, respectively).
The findings of this study suggest an evidence-based standardized process that includes use of an Internet-based electronic alert system to improve patient compliance while maximizing skin surface concentrations effective against MRSA and other staphylococcal surgical pathogens.
Infect. Control Hosp. Epidemiol. 2016;37(3):254–259
The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples (N = 2,126, obs = 12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR < 0.1) and six others met our ‘suggestive’ criterion (FDR <0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies.