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We studied the association between chlorhexidine gluconate (CHG) concentration on skin and resistant bacterial bioburden. CHG was almost always detected on the skin, and detection of methicillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, and vancomycin-resistant Enterococcus on skin sites was infrequent. However, we found no correlation between CHG concentration and bacterial bioburden.
Iron deficiency is common in pregnant and lactating women and is associated with reduced cognitive development of the offspring. Since iron affects lipid metabolism, the availability of fatty acids, particularly the polyunsaturated fatty acids required for early neural development, was investigated in the offspring of female rats fed iron-deficient diets during gestation and lactation. Subsequent to the dams giving birth, one group of iron-deficient dams was recuperated by feeding an iron-replete diet. Dams and neonates were killed on postnatal days 1, 3 and 10, and the fatty acid composition of brain and stomach contents was assessed by gas chromatography. Changes in the fatty acid profile on day 3 became more pronounced on day 10 with a decrease in the proportion of saturated fatty acids and a compensatory increase in monounsaturated fatty acids. Long-chain polyunsaturated fatty acids in the n-6 family were reduced, but there was no change in the n-3 family. The fatty acid profiles of neonatal brain and stomach contents were similar, suggesting that the change in milk composition may be related to the changes in the neonatal brain. When the dams were fed an iron-sufficient diet at birth, the effects of iron deficiency on the fatty acid composition of lipids in both dam’s milk and neonates’ brains were reduced. This study showed an interaction between maternal iron status and fatty acid composition of the offspring’s brain and suggests that these effects can be reduced by iron repletion of the dam’s diet at birth.
Individuals experiencing different medical conditions, as well as healthy volunteers, may often be interested in trial participation, and researchers similarly need to find participants to advance medical knowledge. The ResearchMatch (RM) Trials Today clinical trial searching tool leverages clinicaltrials.gov data to enable potential participants to look for trial opportunities relevant to their situation. To facilitate expanded use of this tool, we undertook a national digital public awareness campaign to increase awareness of Trials Today among members of the general public.
The awareness campaign promoted Trials Today using Facebook and digital banner messages in 2017, encompassing nine cities across the USA. The digital strategy was complemented by print media in several outlets. We employed descriptive statistics to summarize campaign metrics and site usage data during the campaign.
The campaign was successful in increasing visits to Trials Today, with 142,303 sessions logged during its run, as compared to pre-campaign data indicating 104,688 total sessions during the entire 2-year period since the site’s inception. The city-specific click-through rate for all digital impressions, combining Facebook and banner messaging, ranged from 0.50% to 1.09%, resulting in a cost-per-click range of $0.69–$1.15. In addition, visitors conducted 29,697 searches and viewed individual trial records 173,512 times.
The public awareness campaign was successful in increasing use of the RM Trials Today clinical trial searching tool. Our findings support the value of digital media messaging as a cost-effective vehicle for promoting clinical trial awareness, especially for chronic ailments.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.
The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.
There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.
Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.
We used a survey to characterize contemporary infection prevention and antibiotic stewardship program practices across 64 healthcare facilities, and we compared these findings to those of a similar 2013 survey. Notable findings include decreased frequency of active surveillance for methicillin-resistant Staphylococcus aureus, frequent active surveillance for carbapenem-resistant Enterobacteriaceae, and increased support for antibiotic stewardship programs.
To ascertain opinions regarding etiology and preventability of hospital-onset bacteremia and fungemia (HOB) and perspectives on HOB as a potential outcome measure reflecting quality of infection prevention and hospital care.
Hospital epidemiologists and infection preventionist members of the Society for Healthcare Epidemiology of America (SHEA) Research Network.
A web-based, multiple-choice survey was administered via the SHEA Research Network to 133 hospitals.
A total of 89 surveys were completed (67% response rate). Overall, 60% of respondents defined HOB as a positive blood culture on or after hospital day 3. Central line-associated bloodstream infections and intra-abdominal infections were perceived as the most frequent etiologies. Moreover, 61% thought that most HOB events are preventable, and 54% viewed HOB as a measure reflecting a hospital’s quality of care. Also, 29% of respondents’ hospitals already collect HOB data for internal purposes. Given a choice to publicly report central-line–associated bloodstream infections (CLABSIs) and/or HOB, 57% favored reporting either HOB alone (22%) or in addition to CLABSI (35%) and 34% favored CLABSI alone.
Among the majority of SHEA Research Network respondents, HOB is perceived as preventable, reflective of quality of care, and potentially acceptable as a publicly reported quality metric. Further studies on HOB are needed, including validation as a quality measure, assessment of risk adjustment, and formation of evidence-based bundles and toolkits to facilitate measurement and improvement of HOB rates.
Englerophytum and Synsepalum are two closely related genera of trees and shrubs from the African tropics. Previous molecular studies have shown that these genera collectively form a clade within the subfamily Chrysophylloideae (Sapotaceae). However, little is known about the inter-relationships of the taxa within the Englerophytum–Synsepalum clade. In this study, nuclear ribosomal DNA and plastid trnH–psbA sequences were used to estimate the phylogeny within the clade. Results indicate that the clade consists of six major lineages, two composed solely of taxa from the genus Englerophytum and four composed of taxa from the genus Synsepalum. Each lineage can be distinguished by suites of vegetative and floral characters. Leaf venation patterns, calyx fusion, style length and staminodal structure were among the most useful characters for distinguishing clades. Some of the subclades within the Englerophytum–Synsepalum clade were also found to closely fit descriptions of former genera, most of which were described by Aubréville, that have since been placed in synonymy with Englerophytum and Synsepalum. The clade with the type species of Englerophytum also contains the type species of the genera Wildemaniodoxa and Zeyherella, which are confirmed as synonyms.
Rare copy number variants (CNVs) are associated with risk of neurodevelopmental disorders characterised by varying degrees of cognitive impairment, including schizophrenia, autism spectrum disorder and intellectual disability. However, the effects of many individual CNVs in carriers without neurodevelopmental disorders are not yet fully understood, and little is known about the effects of reciprocal copy number changes of known pathogenic loci.
We aimed to analyse the effect of CNV carrier status on cognitive performance and measures of occupational and social outcomes in unaffected individuals from the UK Biobank.
We called CNVs in the full UK Biobank sample and analysed data from 420 247 individuals who passed CNV quality control, reported White British or Irish ancestry and were not diagnosed with neurodevelopmental disorders. We analysed 33 pathogenic CNVs, including their reciprocal deletions/duplications, for association with seven cognitive tests and four general measures of functioning: academic qualifications, occupation, household income and Townsend Deprivation Index.
Most CNVs (24 out of 33) were associated with reduced performance on at least one cognitive test or measure of functioning. The changes on the cognitive tests were modest (average reduction of 0.13 s.d.) but varied markedly between CNVs. All 12 schizophrenia-associated CNVs were associated with significant impairments on measures of functioning.
CNVs implicated in neurodevelopmental disorders, including schizophrenia, are associated with cognitive deficits, even among unaffected individuals. These deficits may be subtle but CNV carriers have significant disadvantages in educational attainment and ability to earn income in adult life.
Cognitive behavioral therapy (CBT) is an effective treatment for many patients suffering from major depressive disorder (MDD), but predictors of treatment outcome are lacking, and little is known about its neural mechanisms. We recently identified longitudinal changes in neural correlates of conscious emotion regulation that scaled with clinical responses to CBT for MDD, using a negative autobiographical memory-based task.
We now examine the neural correlates of emotional reactivity and emotion regulation during viewing of emotionally salient images as predictors of treatment outcome with CBT for MDD, and the relationship between longitudinal change in functional magnetic resonance imaging (fMRI) responses and clinical outcomes. Thirty-two participants with current MDD underwent baseline MRI scanning followed by 14 sessions of CBT. The fMRI task measured emotional reactivity and emotion regulation on separate trials using standardized images from the International Affective Pictures System. Twenty-one participants completed post-treatment scanning. Last observation carried forward was used to estimate clinical outcome for non-completers.
Pre-treatment emotional reactivity Blood Oxygen Level-Dependent (BOLD) signal within hippocampus including CA1 predicted worse treatment outcome. In contrast, better treatment outcome was associated with increased down-regulation of BOLD activity during emotion regulation from time 1 to time 2 in precuneus, occipital cortex, and middle frontal gyrus.
CBT may modulate the neural circuitry of emotion regulation. The neural correlates of emotional reactivity may be more strongly predictive of CBT outcome. The finding that treatment outcome was predicted by BOLD signal in CA1 may suggest overgeneralized memory as a negative prognostic factor in CBT outcome.
To enhance enrollment into randomized clinical trials (RCTs), we proposed electronic health record-based clinical decision support for patient–clinician shared decision-making about care and RCT enrollment, based on “mathematical equipoise.”
As an example, we created the Knee Osteoarthritis Mathematical Equipoise Tool (KOMET) to determine the presence of patient-specific equipoise between treatments for the choice between total knee replacement (TKR) and nonsurgical treatment of advanced knee osteoarthritis.
With input from patients and clinicians about important pain and physical function treatment outcomes, we created a database from non-RCT sources of knee osteoarthritis outcomes. We then developed multivariable linear regression models that predict 1-year individual-patient knee pain and physical function outcomes for TKR and for nonsurgical treatment. These predictions allowed detecting mathematical equipoise between these two options for patients eligible for TKR. Decision support software was developed to graphically illustrate, for a given patient, the degree of overlap of pain and functional outcomes between the treatments and was pilot tested for usability, responsiveness, and as support for shared decision-making.
The KOMET predictive regression model for knee pain had four patient-specific variables, and an r2 value of 0.32, and the model for physical functioning included six patient-specific variables, and an r2 of 0.34. These models were incorporated into prototype KOMET decision support software and pilot tested in clinics, and were generally well received.
Use of predictive models and mathematical equipoise may help discern patient-specific equipoise to support shared decision-making for selecting between alternative treatments and considering enrollment into an RCT.
Ten new species of Trypetheliaceae are described: Astrothelium bullatothallinum from Venezuela, which is close to A. aeneum but differs by the bullate thallus with a thick cortex, intermixed in a mosaic with the prothallus; A. cayennense from French Guiana, which is similar to A. flavomegaspermum but with a yellow pigment in the pseudostroma near the ostioles; A. diaphanocorticatum from Papua New Guinea, which has a bullate thallus with a thick hyaline cortex and 3-septate ascospores of 25–28×10–12 μm; A. macroeustomum from French Guiana, with joint lateral ostioles, UV+ yellow ostiolar region and 5-septate ascospores of 50–55×12–17 μm; A. minicecidiogenum from Costa Rica, with muriform ascospores of 70–90×20–25 μm, without pseudostromata, with solitary ascomata, lateral ostioles and an inspersed hamathecium; A. palaeoexostemmatis from Thailand, which is similar to A. exostemmatis but with larger, I+ blue ascospores; A. quasimamillanum from Brazil, with muriform ascospores of 30–33×9·5–10·5 μm, without pseudostromata, with solitary ascomata, lateral ostioles and an inspersed hamathecium; A. studerae from Brazil, with astrothelioid ascomata, lichexanthone only in the pseudostromata, 3-septate ascospores of 21·5–23·0×6·5–7·5 μm; A. tanianum from Malaysia, with a bullate thallus, solitary ascomata, covered by the thallus, (9–)11(–15)-septate ascospores, 75–100×20–22 μm; and Pseudopyrenula miniflavida from Brazil, with a yellow-inspersed hamathecium, the inspersion dissolving in KOH without colour change, and 3-septate ascospores, 15–17×5·5–6·5 μm. The unusually thick, hyaline cortical layer of the thallus of Astrothelium diaphanocorticatum, through which the individual algal cells are clearly visible, is discussed. Furthermore, 30 species are reported from 34 countries in which they had previously been unrecorded; one (Astrothelium inspersaeneum) is from a new continent, Asia.
Household surveys are one of the most commonly used tools for generating insight into rural communities. Despite their prevalence, few studies comprehensively evaluate the quality of data derived from farm household surveys. We critically evaluated a series of standard reported values and indicators that are captured in multiple farm household surveys, and then quantified their credibility, consistency and, thus, their reliability. Surprisingly, even variables which might be considered ‘easy to estimate’ had instances of non-credible observations. In addition, measurements of maize yields and land owned were found to be less reliable than other stationary variables. This lack of reliability has implications for monitoring food security status, poverty status and the land productivity of households. Despite this rather bleak picture, our analysis also shows that if the same farm households are followed over time, the sample sizes needed to detect substantial changes are in the order of hundreds of surveys, and not in the thousands. Our research highlights the value of targeted and systematised household surveys and the importance of ongoing efforts to improve data quality. Improvements must be based on the foundations of robust survey design, transparency of experimental design and effective training. The quality and usability of such data can be further enhanced by improving coordination between agencies, incorporating mixed modes of data collection and continuing systematic validation programmes.
Internal gravity wave energy contributes significantly to the energy budget of the oceans, affecting mixing and the thermohaline circulation. Hence it is important to determine the internal wave energy flux
is the pressure perturbation field and
is the velocity perturbation field. However, the pressure perturbation field is not directly accessible in laboratory or field observations. Previously, a Green’s function based method was developed to calculate the instantaneous energy flux field from a measured density perturbation field
, given a constant buoyancy frequency
. Here we present methods for computing the instantaneous energy flux
for an internal wave field with vertically varying background
, as in the oceans where
typically decreases by two orders of magnitude from the pycnocline to the deep ocean. Analytic methods are presented for computing
from a density perturbation field for
varying linearly with
. To generalize this approach to arbitrary
, we present a computational method for obtaining
. The results for
for the different cases agree well with results from direct numerical simulations of the Navier–Stokes equations. Our computational method can be applied to any density perturbation data using the MATLAB graphical user interface ‘EnergyFlux’.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Planning mental health carer services requires information about the number of carers, their characteristics, service use and unmet support needs. Available Australian estimates vary widely due to different definitions of mental illness and the types of carers included. This study aimed to provide a detailed profile of Australian mental health carers using a nationally representative household survey.
The number of mental health carers, characteristics of carers and their care recipients, caring hours and tasks provided, service use and unmet service needs were derived from the national 2012 Survey of Disability, Ageing and Carers. Co-resident carers of adults with a mental illness were compared with those caring for people with physical health and other cognitive/behavioural conditions (e.g., autism, intellectual disability, dementia) on measures of service use, service needs and aspects of their caring role.
In 2012, there were 225 421 co-resident carers of adults with mental illness in Australia, representing 1.0% of the population, and an estimated further 103 813 mental health carers not living with their care recipient. The majority of co-resident carers supported one person with mental illness, usually their partner or adult child. Mental health carers were more likely than physical health carers to provide emotional support (68.1% v. 19.7% of carers) and less likely to assist with practical tasks (64.1% v. 86.6%) and activities of daily living (31.9% v. 48.9%). Of co-resident mental health carers, 22.5% or 50 828 people were confirmed primary carers – the person providing the most support to their care recipient. Many primary mental health carers (37.8%) provided more than 40 h of care per week. Only 23.8% of primary mental health carers received government income support for carers and only 34.4% received formal service assistance in their caring role, while 49.0% wanted more support. Significantly more primary mental health than primary physical health carers were dissatisfied with received services (20.0% v. 3.2%), and 35.0% did not know what services were available to them.
Results reveal a sizable number of mental health carers with unmet needs in the Australian community, particularly with respect to financial assistance and respite care, and that these carers are poorly informed about available supports. The prominence of emotional support and their greater dissatisfaction with services indicate a need to better tailor carer services. If implemented carefully, recent Australian reforms including the Carer Gateway and National Disability Insurance Scheme hold promise for improving mental health carer supports.
Potential participants seek information about clinical trials for many reasons, but the process can be challenging. We analyzed 101,249 searches in ResearchMatch Trials Today, a free interface to recruiting trials from ClinicalTrials.gov. Searches from March 2015 to November 2016 included a broad range of conditions and healthy volunteer concepts, including 12,649 unique topics. Trials Today data indicate that it is being used to identify trials on a variety of topics.