To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Acute change in mental status (ACMS), defined by the Confusion Assessment Method, is used to identify infections in nursing home residents. A medical record review revealed that none of 15,276 residents had an ACMS documented. Using the revised McGeer criteria with a possible ACMS definition, we identified 296 residents and 21 additional infections. The use of a possible ACMS definition should be considered for retrospective nursing home infection surveillance.
Treatment resistant schizophrenia (TRS) is one of the most disabling of psychiatric disorders, affecting about 1/3 of patients. First-line treatments include both atypical and typical antipsychotics. The original atypical, clozapine, is a final option, and although it has been shown to be the only effective treatment for TRS, many patients do not respond well to clozapine. Clozapine use is related to adverse events, most notably agranulocytosis, a potentially fatal blood disorder which affects about 1% of those prescribed clozapine and requires regular blood monitoring. This as a barrier to prescription and there is a long delay in access for TRS patients, of five or more years, from first antipsychotic prescription. Better tools to predict treatment resistance and to identify risk of adverse events would allow faster and safer access to clozapine for patients who are likely to benefit from it. The CRESTAR project (www.crestar-project.eu) is a European Framework 7 collaborative project that aims to develop tools to predict i) treatment response, particularly patients who are less likely to respond to usual antipsychotics, indicating treatment with clozapine as early as possible, ii) patients who are at high or low risk of adverse events and side effects, iii) extreme TRS patients so that they can be stratified in clinical trials for novel treatments. CRESTAR has addressed these questions by examining genome-wide association data, genome sequence, epigenetic biomarkers and epidemiological data in European patient cohorts characterized for treatment response, and adverse drug reaction using data from clozapine therapeutic drug monitoring and linked National population medical and pharmacy databases, to identify predictive factors. In parallel CRESTAR will perform health economic research on potential benefits, and ethics and patient-centred research with stakeholders.
Measurement of body composition is increasingly important in research and clinical settings but is difficult in very young children. Bioelectrical impedance analysis (BIA) and air displacement plethysmography (ADP) are well-established but require specialist equipment so are not always feasible. Our aim was to determine if anthropometry and skinfold thickness measurements can be used as a substitute for BIA or ADP for assessing body composition in very young New Zealand children. We used three multi-ethnic cohorts: 217 children at a mean age of 24·2 months with skinfold and BIA measurements; seventy-nine infants at a mean age of 20·9 weeks and seventy-three infants at a mean age of 16·2 weeks, both with skinfold and ADP measurements. We used Bland–Altman plots to compare fat and fat-free mass calculated using all potentially relevant equations with measurements using BIA or ADP. We also calculated the proportion of children in the same tertile for measured fat or fat-free mass and tertiles (i) calculated using each equation, (ii) each absolute skinfold, and (iii) sum of skinfold thicknesses. We found that even for the best equation for each cohort, the 95 % limits of agreement with standard measures were wide (25–200 % of the mean) and the proportion of children whose standard measures fell in the same tertile as the skinfold estimates was ≤69 %. We conclude that none of the available published skinfold thickness equations provides good prediction of body composition in multi-ethnic cohorts of very young New Zealand children with different birth history and growth patterns.
To evaluate the National Health Safety Network (NHSN) hospital-onset Clostridioides difficile infection (HO-CDI) standardized infection ratio (SIR) risk adjustment for general acute-care hospitals with large numbers of intensive care unit (ICU), oncology unit, and hematopoietic cell transplant (HCT) patients.
Retrospective cohort study.
Eight tertiary-care referral general hospitals in California.
We used FY 2016 data and the published 2015 rebaseline NHSN HO-CDI SIR. We compared facility-wide inpatient HO-CDI events and SIRs, with and without ICU data, oncology and/or HCT unit data, and ICU bed adjustment.
For these hospitals, the median unmodified HO-CDI SIR was 1.24 (interquartile range [IQR], 1.15–1.34); 7 hospitals qualified for the highest ICU bed adjustment; 1 hospital received the second highest ICU bed adjustment; and all had oncology-HCT units with no additional adjustment per the NHSN. Removal of ICU data and the ICU bed adjustment decreased HO-CDI events (median, −25%; IQR, −20% to −29%) but increased the SIR at all hospitals (median, 104%; IQR, 90%–105%). Removal of oncology-HCT unit data decreased HO-CDI events (median, −15%; IQR, −14% to −21%) and decreased the SIR at all hospitals (median, −8%; IQR, −4% to −11%).
For tertiary-care referral hospitals with specialized ICUs and a large number of ICU beds, the ICU bed adjustor functions as a global adjustment in the SIR calculation, accounting for the increased complexity of patients in ICUs and non-ICUs at these facilities. However, the SIR decrease with removal of oncology and HCT unit data, even with the ICU bed adjustment, suggests that an additional adjustment should be considered for oncology and HCT units within general hospitals, perhaps similar to what is done for ICU beds in the current SIR.
A longstanding issue in the field of nutrition is the potential inaccuracy of methods traditionally used for dietary assessment (i.e. food diaries and food frequency questionnaires). It is possible to overcome the limitations and biases of these techniques by combining them with analytical measurements in human biofluids. Metabolomic technologies are gaining popularity as nutritional tools due to their capacity to measure metabolic responses to external stimuli, such as the ingestion of certain foods. This project performed both LC-MS and 1H-NMR metabolomic profiling on serum samples collected as part of the NICOLA study (Northern Irish Cohort for the Longitudinal Study of Aging) in order to discover novel dietary biomarkers. A dietary validation cohort (NIDAS) was incorporated within NICOLA, involving 45 males and 50 females, aged 50 years and over. Participants provided detailed dietary data (4-day food diary) and blood samples at two time-points, six months apart. Serum samples were processed on two analytical platforms. 1H-NMR spectra were acquired using a Bruker 600 MHz Ascent coupled to a TCI cryoprobe and processed using Bayesil (University of Alberta, Canada). A Waters TQ-S coupled with an Acquity I-class UPLC was used in combination with a targeted commercially available kit (AbsoluteIDQ p180 kit, Biocrates). Mass spectra obtained were processed with MetIDQ and verified using MassLynx (v4.1). Data were tested for normality, and metabolite concentrations were correlated with recorded dietary intake of each food type using SPSS. Additional tests (PCA, PLS-DA, ROC Curves) were performed on MetaboAnalyst 4.0 (University of Alberta, Canada). More than 50 statistically significant (P < 0.05) food-metabolite correlations were detected, 15 of which remained significant after eliminating potential confounding from sex, age and BMI. The strongest correlations were between fruit consumption and acetic acid, and between dairy consumption and certain glycerophospholipids (e.g. LysoPC aa C20:3). Stratifying the cohort by gender yielded further correlations, including PC ae C38:2 (dairy; males), PC aa C34:4 (dairy; females), PC aa C36:4 (dairy; females) and trans-4-Hydroxyproline (meat; males). A number of potential blood-based food biomarkers were detected, many of which are gender-specific, and some are corroborated by previously published studies. However, further validation work is required. For example, biological plausibility needs to be established, and the findings need to be reproduced in other cohorts to demonstrate their applicability in larger and more diverse populations. These results contribute greatly to the ongoing efforts to discover and validate reliable nutritional biomarkers as an objective and unbiased measurement of food intake.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
This paper reports on an ultra-wideband low-noise distributed amplifier (LNDA) in a transferred-substrate InP double heterojunction bipolar transistor (DHBT) technology which exhibits a uniform low-noise characteristic over a large frequency range. To obtain very high bandwidth, a distributed architecture has been chosen with cascode unit gain cells. Each unit cell consists of two cascode-connected transistors with 500 nm emitter length and ft/fmax of ~360/492 GHz, respectively. Due to optimum line-impedance matching, low common-base transistor capacitance, and low collector-current operation, the circuit exhibits a low-noise figure (NF) over a broad frequency range. A 3-dB bandwidth from 40 to 185 GHz is measured, with an NF of 8 dB within the frequency range between 75 and 105 GHz. Moreover, this circuit demonstrates the widest 3-dB bandwidth operation among all reported single-stage amplifiers with a cascode configuration. Additionally, this work has proposed that the noise sources of the InP DHBTs are largely uncorrelated. As a result, a reliable prediction can be done for the NF of ultra-wideband circuits beyond the frequency range of the measurement equipment.
Soil nutrient constraints coupled with erratic rainfall have led to poor crop yields and occasionally to crop failure in sole cropping in the Guinea savanna of West Africa. We explored different maize-grain legume diversification and intensification options that can contribute to mitigating risks of crop failure, increase crop productivity under different soil fertility levels, while improving soil fertility due to biological N2-fixation by the legume. There were four relay patterns with cowpea sown first and maize sown at least 2 weeks after sowing (WAS) cowpea; two relay patterns with maize sown first and cowpea sown at least 3 WAS maize in different spatial arrangements. These were compared with groundnut-maize, soybean–maize, fallow-maize and continuous maize rotations in fields high, medium and poor in fertility at a site each in the southern (SGS) and northern (NGS) Guinea savanna of northern Ghana. Legumes grown in the poorly fertile fields relied more on N2-fixation for growth leading to generally larger net N inputs to the soil. Crop yields declined with decreasing soil fertility and were larger in the SGS than in the NGS due to more favourable rainfall and soil fertility. Spatial arrangements of relay intercrops did not have any significant impact on maize and legume grain yields. Sowing maize first followed by a cowpea relay resulted in 0.18–0.26 t ha−1 reduction in cowpea grain yield relative to cowpea sown from the onset. Relaying maize into cowpea led to a 0.29–0.64 t ha−1 reduction in maize grain yield relative to maize sown from the onset in the SGS. In the NGS, a decline of 0.66 and 0.82 t ha−1 in maize grain yield relative to maize sown from the onset was observed due to less rainfall received by the relay maize. Groundnut and soybean induced 0.38–1.01 t ha−1 more grain yield of a subsequent maize relative to continuous maize, and 1.17–1.71 t ha−1 more yield relative to relay maize across both sites. Accumulated crop yields over both years suggest that sowing maize first followed by cowpea relay is a promising ecological intensification option besides the more common legume–maize rotation in the Guinea savanna, as it was comparable with soybean–maize rotation and more productive than the other treatments.
OBJECTIVES/SPECIFIC AIMS: The morbidity and mortality in adults with single ventricular hearts who have undergone Fontan palliation is poorly defined. These patients have a high burden of arrhythmia, heart failure, and re-operation. We hypothesized that age and type of Fontan predict occurrence of arrhythmia. METHODS/STUDY POPULATION: In total, 205 patients aged 18 years who had undergone a Fontan procedure were identified. Those with incomplete data were excluded. Demographic, anatomic, pharmacologic, imaging, hemodynamic, and electrophysiologic data were collected. The χ2 and Mann-Whitney U tests were used to test significance defined as p<0.05. RESULTS/ANTICIPATED RESULTS: Of the 205 patients identified, 59 had been lost to follow-up. Of the 146 patients (77, 53% female) actively followed 18 (12%) had died at a median (IQR) age of 27 (21–34.3); in patients alive as of 10/2016 the median age was 26 years (22–34). Fontan types were lateral tunnel (LT) (n=79, 54.1%), extracardiac (EC) (n=32, 22%), right atrial to pulmonary artery (RV-PA) (n=28, 19%), and Fontan with Bjork modification (n=4, 2.7%). Systemic left ventricle (n=96, 66%) was more common than systemic right ventricle (n=43, 30%). Of the 146 patients, 101 (69%) had significant morbidity or mortality: 86 (59%) were diagnosed with arrhythmia, 18 (12%) died, and 11 (8%) underwent heart transplants. Frequent procedures included: Fontan revisions/cryoablation in 28 (19%), electrophysiology studies with ablation in 73 (50%), and pacemakers in 53 (36%). Of the arrhythmia diagnoses, 57 (64%) were atrial tachyarrhythmias. RV-PA Fontan procedures were associated with significantly more atrial arrhythmia than all other Fontan types (70% vs. 30%; p<0.01). There was no statistical difference in occurrence of atrial arrhythmia in adults with LT Versus EC Fontans (p=0.3). While patients who had undergone RV-PA and Bjork Fontans were older with median age 34 years, there was no significant difference in age between LT and EC (median 24.0 and 24.5). DISCUSSION/SIGNIFICANCE OF IMPACT: Adult survivors of the Fontan procedure suffer from significant morbidity and mortality. The single most prevalent morbidity is atrial arrhythmia. We conclude that RV-PA Fontans, now obsolete, have the highest prevalence of arrhythmia and that there is no difference in arrhythmia burden between LT and EC Fontans. Given the high prevalence of morbidity and mortality in this population, it is imperative that they be followed by cardiologists with expertise in congenital heart disease.
Soybean yields on smallholder farmers’ fields in Malawi are constrained by poor soil fertility, limited application of external inputs and poor crop husbandry. We tested crop management practices through on-farm experimentation and participatory technology evaluation. Two agronomic soybean trials were established in 2009 and 2010 in three contrasting agro-ecologies resulting in 72 replications per trial. Treatments in the first trial included several combinations of inoculation with Bradyrhizobium japonicum, inorganic fertiliser application and compost manure. In the second trial, farmers tested an improved variety, optimal weeding regime, increased plant population and chemical pest and disease control. A combination of inoculation, inorganic fertiliser (10 N, 8 P, 20 K in kg ha−1), and 6 t ha−1 compost manure increased yields from 0.86 t ha−1 under farmers’ practice to 1.56 t ha−1 and resulted in average profits of US$222 ha−1. Increased plant populations and biocide spraying also resulted in substantial yield increases. Inoculation and increased plant population resulted in an average value to cost ratio (VCR) > 2. Low investment costs make inoculants, compost manure and increased plant populations interesting options, whereas adoption of inorganic fertiliser application in soybean may be limited due to high costs and low VCR. The farmers ranked eight technologies in descending order of preference as: (i) early planting, (ii) plant population, (iii) variety choice, (iv) compost manure, (v) weeding, (vi) inoculant, (vii) fertiliser and (viii) spraying. Our participatory research approach demonstrated that there is a wide range of technologies with different levels of human and financial investment costs that smallholder farmers can adopt to enhance their soybean yields and profits.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
The present study aimed to: (i) examine associations between food store patronage and diet and weight-related outcomes; and (ii) explore consumer motivations for visiting different types of food store.
A stratified probability sample of residents completed household and individual-level surveys in 2009/2010 on food purchasing patterns and motivations, dietary intake, waist circumference (WC), weight and height. Diet quality was calculated using the Healthy Eating Index for Canada from a subset of participants (n 1362). Generalized estimating equations were created in 2015 to examine how frequency of patronizing different types of food store was associated with diet quality, intake of fruits and vegetable, mean intake of energy (kcal) sodium and saturated fat, WC and BMI.
Three mid-sized urban municipalities in Ontario, Canada.
A representative sample of residents (n 4574).
Participants who shopped frequently at food co-ops had significantly better diet quality (β=5·3; 99 % CI 0·3, 10·2) than those who did not. BMI and WC were significantly lower among those who frequently shopped at specialty shops (BMI, β=−2·1; 99 % CI −3·0, −1·1; WC, β=−4·8; 99 % CI −7·0, −2·5) and farmers’ markets (BMI, β=−1·4; 99 % CI −2·3, −0·5; WC, β=−3·8; 99 % CI −6·0, −1·6) compared with those who did not. Relative importance of reasons for food outlet selection differed by large (price, food quality) v. small (proximity, convenient hours) shopping trip and by outlet type.
Findings contribute to our understanding of food store selection and have implications for potentially relevant retail food intervention settings.
Bipolar disorder is a highly heritable polygenic disorder. Recent
enrichment analyses suggest that there may be true risk variants for
bipolar disorder in the expression quantitative trait loci (eQTL) in the
We sought to assess the impact of eQTL variants on bipolar disorder risk
by combining data from both bipolar disorder genome-wide association
studies (GWAS) and brain eQTL.
To detect single nucleotide polymorphisms (SNPs) that influence
expression levels of genes associated with bipolar disorder, we jointly
analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls)
and a genome-wide brain (cortical) eQTL (193 healthy controls) using a
Bayesian statistical method, with independent follow-up replications. The
identified risk SNP was then further tested for association with
hippocampal volume (n = 5775) and cognitive performance
(n = 342) among healthy individuals.
Integrative analysis revealed a significant association between a brain
eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes
factor = 5.48; bipolar disorder P =
5.85×10–5). Follow-up studies across multiple independent
samples confirmed the association of the risk SNP (rs6088662) with gene
expression and bipolar disorder susceptibility (P =
3.54×10–8). Further exploratory analysis revealed that
rs6088662 is also associated with hippocampal volume and cognitive
performance in healthy individuals.
Our findings suggest that 20q11.22 is likely a risk region for bipolar
disorder; they also highlight the informative value of integrating
functional annotation of genetic variants for gene expression in
advancing our understanding of the biological basis underlying complex
disorders, such as bipolar disorder.