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Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.
We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.
We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.
Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.
X-ray laboratory diffraction contrast tomography (LabDCT) produces three-dimensional (3D) maps of crystallographic orientation. The non-destructive nature of the technique affords the key benefit of full 3D context of these, and other, in situ measurements. This study is the first to apply the technique to any material other than a metal or silicon. We report the first 3D measurements of the crystallographic orientation of olivine, which also makes this study the first to apply LabDCT to (1) a non-metallic, non-cubic system and (2) geological material. First, we scanned fragments of olivine set in resin alongside glass microbeads using LabDCT and absorption contrast tomography (ACT). Then we reconstructed these data assuming an orthorhombic crystal system. We show that: (1) the regions within the sample that index well according to the orthorhombic system correspond to olivine fragments in the ACT image; (2) crystalline regions not corresponding to olivine are not indexed assuming the same lattice parameters; and (3) the diffraction data discriminates crystalline from non-crystalline materials as expected. Finally, we demonstrate that the method resolves sub-degree orientation differences between distinct regions within individual olivine fragments. We conclude that DCT can be applied to the study of rocks and other crystalline materials, and offers advantages over conventional techniques. We also note that LabDCT may offer a solution to the crystallographic measurement of substances that would otherwise be difficult to measure due to challenges in obtaining a perfect sample polish. Future developments to accommodate larger experimental volumes and additional crystallographic systems within a sample promises to expand the applicability and impact of DCT.
To assess the effect of rural-to-urban migration on nutrition transition and overweight/obesity risk among women in Kenya.
Secondary analysis of data from nationally representative cross-sectional samples. Outcome variables were women’s BMI and nutrition transition. Nutrition transition was based on fifteen different household food groups and was adjusted for socio-economic and demographic characteristics. Stepwise backward multiple ordinal regression analysis was applied.
Kenya Demographic and Health Survey 2014.
Rural non-migrant, rural-to-urban migrant and urban non-migrant women aged 15–49 years (n 6171).
Crude data analysis showed rural-to-urban migration to be associated with overweight/obesity risk and nutrition transition. After adjustment for household wealth, no significant differences between rural non-migrants and rural-to-urban migrants for overweight/obesity risk and household consumption of several food groups characteristic of nutrition transition (animal-source, fats and sweets) were observed. Regardless of wealth, migrants were less likely to consume main staples and legumes, and more likely to consume fruits and vegetables. Identified predictive factors of overweight/obesity among migrant women were age, duration of residence in urban area, marital status and household wealth.
Our analysis showed that nutrition transition and overweight/obesity risk among rural-to-urban migrants is apparent with increasing wealth in urban areas. Several predictive factors were identified characterising migrant women being at risk for overweight/obesity. Future research is needed which investigates in depth the association between rural-to-urban migration and wealth to address inequalities in diet and overweight/obesity in Kenya.
The ventricular assist device is being increasingly used as a “bridge-to-transplant” option in children with heart failure who have failed medical management. Care for this medically complex population must be optimised, including through concomitant pharmacotherapy. Pharmacokinetic/pharmacodynamic alterations affecting pharmacotherapy are increasingly discovered in children supported with extracorporeal membrane oxygenation, another form of mechanical circulatory support. Similarities between extracorporeal membrane oxygenation and ventricular assist devices support the hypothesis that similar alterations may exist in ventricular assist device-supported patients. We conducted a literature review to assess the current data available on pharmacokinetics/pharmacodynamics in children with ventricular assist devices. We found two adult and no paediatric pharmacokinetic/pharmacodynamic studies in ventricular assist device-supported patients. While mechanisms may be partially extrapolated from children supported with extracorporeal membrane oxygenation, dedicated investigation of the paediatric ventricular assist device population is crucial given the inherent differences between the two forms of mechanical circulatory support, and pathophysiology that is unique to these patients. Commonly used drugs such as anticoagulants and antibiotics have narrow therapeutic windows with devastating consequences if under-dosed or over-dosed. Clinical studies are urgently needed to improve outcomes and maximise the potential of ventricular assist devices in this vulnerable population.
Emergency Medical Services (EMS) providers face many ethical issues while providing prehospital care to children and adults. Although provider judgment plays a large role in the resolution of conflicts at the scene, it is important to establish protocols and policies, when possible, to address these high-risk and complex situations. This article describes some of the common situations with ethical underpinnings encountered by EMS personnel and managers including denying or delaying transport of patients with non-emergency conditions, use of lights and sirens for patient transport, determination of medical futility in the field, termination of resuscitation, restriction of EMS provider duty hours to prevent fatigue, substance abuse by EMS providers, disaster triage and difficulty in switching from individual care to mass-casualty care, and the challenges of child maltreatment recognition and reporting. A series of ethical questions are proposed, followed by a review of the literature and, when possible, recommendations for management.
BeckerTK, Gausche-HillM, AsweganAL, BakerEF, BookmanKJ, BradleyRN, De LorenzoRA, SchoenwetterDJ for the American College of Emergency Physicians’ EMS Committee. Ethical Challenges in Emergency Medical Services: Controversies and Recommendations. Prehosp Disaster Med. 2013;28(5):1-10.
The primary objective of this study was to quantify the impact of a clinical practice intervention to promote the delivery of salbutamol by metered-dose inhaler (MDI) in a pediatric emergency department (PED). A secondary objective was to retrospectively document the components of the intervention.
PED inventory data for salbutamol inhalation solution (nebules), MDIs, and holding chambers were obtained from the pharmacy department. Patient data were obtained fromthe hospital's decision support unit. Interrupted time series analysis was used to evaluate trends in salbutamol inventory data, patient triage acuity, and hospital admissions from January 1, 2003, to May 31, 2010. Interviews and administrative documents were used to identify components of the intervention, which began in 2006.
There was a 1,215% increase in the proportion of salbutamol delivered as MDIs compared to total inhaled salbutamol (MDI plus nebulization solution) following the intervention (95% CI 1,032% to 1,396%, p < 0.001). Increases in salbutamol MDI use were associated with the implementation of an institution-specific asthma care map. A relative decrease of 32% in the hospital admission rate (absolute –7.25%: 95% CI –8.31 to –6.19, p < 0.001) was associated with the change in salbutamol MDI use and the use of the asthma care map.
A multifaceted intervention, designed and implemented by local PED clinical leaders, resulted in a pronounced change in salbutamol inhalation practice, with an associated decrease in admission rates. This intervention demonstrated many of the criteria for successful health system change. Findings from this research may be contextualized to inform change elsewhere.
A survey of the Milky Way disk and the Magellanic System at the wavelengths of the 21-cm atomic hydrogen (H i) line and three 18-cm lines of the OH molecule will be carried out with the Australian Square Kilometre Array Pathfinder telescope. The survey will study the distribution of H i emission and absorption with unprecedented angular and velocity resolution, as well as molecular line thermal emission, absorption, and maser lines. The area to be covered includes the Galactic plane (|b| < 10°) at all declinations south of δ = +40°, spanning longitudes 167° through 360°to 79° at b = 0°, plus the entire area of the Magellanic Stream and Clouds, a total of 13 020 deg2. The brightness temperature sensitivity will be very good, typically σT≃ 1 K at resolution 30 arcsec and 1 km s−1. The survey has a wide spectrum of scientific goals, from studies of galaxy evolution to star formation, with particular contributions to understanding stellar wind kinematics, the thermal phases of the interstellar medium, the interaction between gas in the disk and halo, and the dynamical and thermal states of gas at various positions along the Magellanic Stream.
The main aim of the present study was to identify food consumption in Sri Lankan adults based on serving characteristics.
Cross-sectional study. Fruits, vegetables, starch, meat, pulses, dairy products and added sugars in the diet were assessed with portion sizes estimated using standard methods.
Twelve randomly selected clusters from the Sri Lanka Diabetes and Cardiovascular Study.
Six hundred non-institutionalized adults.
The daily intake of fruit (0·43), vegetable (1·73) and dairy (0·39) portions were well below national recommendations. Only 3·5 % of adults consumed the recommended 5 portions of fruits and vegetables/d; over a third of the population consumed no dairy products and fewer than 1 % of adults consumed 2 portions/d. In contrast, Sri Lankan adults consumed over 14 portions of starch and 3·5 portions of added sugars daily. Almost 70 % of those studied exceeded the upper limit of the recommendations for starch intake. The total daily number of meat and pulse portions was 2·78.
Dietary guidelines emphasize the importance of a balanced and varied diet; however, a substantial proportion of the Sri Lankan population studied failed to achieve such a recommendation. Nutrition-related diseases in the country may be closely correlated with unhealthy eating habits.
This paper describes the results of two seasons of excavation and associated palaeoenvironmental analyses of a wetland site on Beccles Marshes, Beccles, Suffolk. The site has been identified as a triple post alignment of oak timbers (0.6–2.0 m long), over 100 m in length, and 3–4 m wide, running north-west to south-east towards the River Waveney. It was constructed in a single phase which has been dated dendrochronologically to 75 BC, although discrete brushwood features identified as possible short trackways have been dated by radiocarbon to both before and after the alignment was built. It is unclear if the posts ever supported a superstructure but notches (‘halving lap joints’) in some of the posts appear to have held timbers to support the posts and/or aid in their insertion. In addition, fragments of both Iron Age and Romano-British pottery were recovered. A substantial assemblage of worked wooden remains appears to reflect the construction of the post row itself and perhaps the on-site clearance of floodplain vegetation. This assemblage also contains waste material derived from the reduction splitting of timbers larger than the posts of the alignment, but which have not been recovered from the site. Environmental analyses indicate that the current landscape context of the site with respect to the River Waveney is probably similar to that which pertained in prehistory. The coleoptera (beetle) record illustrates a series of changes in the on-site vegetation in the period before, during and after the main phase of human activity which may be related to a range of factors including floodplain hydrology and anthropogenic utilisation of Beccles Marshes. The possible form and function of the site is discussed in relation to the later prehistoric period in Suffolk.
Bone-anchored hearing aid implantations have been performed in Manchester for over 20 years. This study examined a range of variables that can occur during the implantation process, and the effect they may have on successful outcome.
Retrospective study and literature review.
Tertiary referral centre in central Manchester.
Details of 602 bone-anchored hearing aid implantation procedures were retrieved from the departmental database. The overall complication rate was 23.9 per cent. The rate of revision surgery was 12.1 per cent.
This study involved a significantly larger number of patients than any previously reported, similar study. Possible reasons for differences in outcomes, and recommendations for best practice, are discussed.
The study of the host genetic component of infectious disease is potentially one of the most difficult areas of complex human genetic disease analysis for one major reason: the absolute requirement for a host–pathogen interaction to cause disease. Since the pathogen has its own genome, with all of its attendant potential for variability, there has been an ongoing “arms race” between man and microbe that has driven each to incorporate changes within their genomes that increase their survival chances should they encounter the other. However, this strong evolutionary pressure on the human genome has also inevitably produced associations between gene variants and disease. The field of genetic susceptibility to infectious disease has been around for over 50 years now and there is a substantial body of evidence for the role of genetics in infectious disease susceptibility.
Infectious disease is as old as humanity and remains a significant influence on polymorphism in the human genome. Major effects of infectious disease such as epidemics that have drastically reduced populations to a small percentage of individuals, so-called “bottlenecks,” such as the Black Death in Europe and the introduction of smallpox and other diseases to the Americas, have a strong selective effect. In addition, the slow continual onslaught of endemic diseases that are still with us today, such as malaria, tuberculosis and, more recently, AIDS, lead to a continual enrichment within the population for resistance alleles, even when these might be harmful and would be quickly lost in the absence of disease.