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B vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- and angiogenesis-related chronic diseases, such as colorectal cancer (CRC). Yet, the role of one-carbon metabolism in inflammation and angiogenesis among CRC patients remains unclear. The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed CRC patients (n 238) in the prospective ColoCare Study, Heidelberg. We cross-sectionally analysed associations between twelve B vitamins and one-carbon metabolites and ten inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesised that pyridoxal-5’-phosphate (PLP) is inversely associated with inflammatory biomarkers. We observed that PLP was inversely associated with C-reactive protein (CRP) (r –0·33, Plinear < 0·0001), serum amyloid A (SAA) (r –0·23, Plinear = 0·003), IL-6 (r –0·39, Plinear < 0·0001), IL-8 (r –0·20, Plinear = 0·02) and TNFα (r –0·12, Plinear = 0·045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r –0·14), SAA (r –0·14) and TNFα (r –0·15) among CRC patients. Folate catabolite acetyl-para-aminobenzoylglutamic acid (pABG) was positively correlated with IL-6 (r 0·27, Plinear < 0·0001), and pABG was positively correlated with IL-8 (r 0·21, Plinear < 0·0001), indicating higher folate utilisation during inflammation. Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among CRC patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for CRC patients.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
We compared systematic and random survey techniques to estimate breeding population sizes of burrow-nesting petrel species on Marion Island. White-chinned (Procellaria aequinoctialis) and blue (Halobaena caerulea) petrel population sizes were estimated in systematic surveys (which attempt to count every colony) in 2009 and 2012, respectively. In 2015, we counted burrows of white-chinned, blue and great-winged (Pterodroma macroptera) petrels within 52 randomized strip transects (25 m wide, total 144 km). Burrow densities were extrapolated by Geographic Information System-derived habitat attributes (geology, vegetation, slope, elevation, aspect) to generate island-wide burrow estimates. Great-winged petrel burrows were found singly or in small groups at low densities (2 burrows ha−1); white-chinned petrel burrows were in loose clusters at moderate densities (3 burrows ha−1); and blue petrel burrows were in tight clusters at high densities (13 burrows ha−1). The random survey estimated 58% more white-chinned petrels but 42% fewer blue petrels than the systematic surveys. The results suggest that random transects are best suited for species that are widely distributed at low densities, but become increasingly poor for estimating population sizes of species with clustered distributions. Repeated fixed transects provide a robust way to monitor changes in colony density and area, but might fail to detect the formation/disappearance of new colonies.
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
Williams syndrome is a rare genetic disease that affects elastin production, leading to medium and large vessel stenoses and other abnormalities. Cardiac manifestations of Williams syndrome are the most life-threatening, occurring in 80% of children. Children with Williams syndrome are known to be at risk for sudden cardiac death. These tragic events are often precipitated by diagnostic or therapeutic procedures requiring anaesthesia or sedation, such as cardiac catheterisation. We present the case of a 3-month-old infant with Williams syndrome who suffered sudden cardiac arrest during cardiac catheterisation and subsequent arrest approximately 48 hours after the procedure. We also review the current literature focused on children with Williams syndrome who have suffered sudden cardiac arrest during or after cardiac catheterisation procedures.
Patients suffering from an out-of-hospital cardiac arrest (OHCA) associated with an initial shockable rhythm have a better prognosis than their counterparts. The implications of recurrent or refractory malignant arrhythmia in such context remain unclear. The objective of this study is to evaluate the association between the number of prehospital shocks delivered and survival to hospital discharge among patients in OHCA.
This cohort study included adult patients with an initial shockable rhythm over a 5-year period from a registry of OHCA in Montreal, Canada. The relationship between the number of prehospital shocks delivered and survival to discharge was described using dynamic probabilities. The association between the number of prehospital shocks delivered and survival to discharge was assessed using multivariable logistic regression.
A total of 1,788 patients (78% male with a mean age of 64 years) were included in this analysis, of whom 536 (30%) received treatments from an advanced care paramedic. A third of the cohort (583 patients, 33%) survived to hospital discharge. The probability of survival was highest with the first shock (33% [95% confidence interval 30%-35%]), but decreased to 8% (95% confidence interval 4%-13%) following nine shocks. A higher number of prehospital shocks was independently associated with lower odds of survival (adjusted odds ratio=0.88 [95% confidence interval 0.85-0.92], p < 0.001).
Survival remains possible even after a high number of shocks for patients suffering from an OHCA with an initial shockable rhythm. However, requiring more shocks is independently associated with worse survival.
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.
We report the breeding success of four species of burrow-nesting petrels at sub-Antarctic Marion Island where house mice Mus musculus are the sole introduced mammal. Feral cats Felis catus were present on Marion for four decades from 1949, killing millions of seabirds and greatly reducing petrel populations. Cats were eradicated by 1991, but petrel populations have shown only marginal recoveries. We hypothesize that mice are suppressing their recovery through depredation of petrel eggs and chicks. Breeding success for winter breeders (grey petrels Procellaria cinerea (34±21%) and great-winged petrels Pterodroma macroptera (52±7%)) were lower than for summer breeders (blue petrels Halobaena caerulea (61±6%) and white-chinned petrels Procellaria aequinoctialis (59±6%)) and among winter breeders most chick fatalities were of small chicks up to 14 days old. We assessed the extent of mouse predation by monitoring the inside of 55 burrow chambers with video surveillance cameras (4024 film days from 2012–16) and recorded fatal attacks on grey (3/18 nests filmed, 17%) and great-winged petrel chicks (1/19, 5%). Our results show that burrow-nesting petrels are at risk from mouse predation, providing further motivation for the eradication of mice from Marion Island.
Objectives: The present study examined differences in neurocognitive outcomes among non-Hispanic Black and White stroke survivors using the NIH Toolbox-Cognition Battery (NIHTB-CB), and investigated the roles of healthcare variables in explaining racial differences in neurocognitive outcomes post-stroke. Methods: One-hundred seventy adults (91 Black; 79 White), who participated in a multisite study were included (age: M=56.4; SD=12.6; education: M=13.7; SD=2.5; 50% male; years post-stroke: 1–18; stroke type: 72% ischemic, 28% hemorrhagic). Neurocognitive function was assessed with the NIHTB-CB, using demographically corrected norms. Participants completed measures of socio-demographic characteristics, health literacy, and healthcare use and access. Stroke severity was assessed with the Modified Rankin Scale. Results: An independent samples t test indicated Blacks showed more neurocognitive impairment (NIHTB-CB Fluid Composite T-score: M=37.63; SD=11.67) than Whites (Fluid T-score: M=42.59, SD=11.54; p=.006). This difference remained significant after adjusting for reading level (NIHTB-CB Oral Reading), and when stratified by stroke severity. Blacks also scored lower on health literacy, reported differences in insurance type, and reported decreased confidence in the doctors treating them. Multivariable models adjusting for reading level and injury severity showed that health literacy and insurance type were statistically significant predictors of the Fluid cognitive composite (p<.001 and p=.02, respectively) and significantly mediated racial differences on neurocognitive impairment. Conclusions: We replicated prior work showing that Blacks are at increased risk for poorer neurocognitive outcomes post-stroke than Whites. Health literacy and insurance type might be important modifiable factors influencing these differences. (JINS, 2017, 23, 640–652)
It is unclear which of four popular contemporary diet patterns is best for weight maintenance among postmenopausal women. Four dietary patterns were characterised among postmenopausal women aged 49–81 years (mean 63·6 (sd 7·4) years) from the Women’s Health Initiative Observational Study: (1) a low-fat diet; (2) a reduced-carbohydrate diet; (3) a Mediterranean-style (Med) diet; and (4) a diet consistent with the US Department of Agriculture’s Dietary Guidelines for Americans (DGA). Discrete-time hazards models were used to compare the risk of weight gain (≥10 %) among high adherers of each diet pattern. In adjusted models, the reduced-carbohydrate diet was inversely related to weight gain (OR 0·71; 95 % CI 0·66, 0·76), whereas the low-fat (OR 1·43; 95 % CI 1·33, 1·54) and DGA (OR 1·24; 95 % CI 1·15, 1·33) diets were associated with increased risk of weight gain. By baseline weight status, the reduced-carbohydrate diet was inversely related to weight gain among women who were normal weight (OR 0·72; 95 % CI 0·63, 0·81), overweight (OR 0·67; 95 % CI 0·59, 0·76) or obese class I (OR 0·63; 95 % CI 0·53, 0·76) at baseline. The low-fat diet was associated with increased risk of weight gain in women who were normal weight (OR 1·28; 95 % CI 1·13, 1·46), overweight (OR 1·60; 95 % CI 1·40, 1·83), obese class I (OR 1·73; 95 % CI 1·43, 2·09) or obese class II (OR 1·44; 95 % CI 1·08, 1·92) at baseline. These findings suggest that a low-fat diet may promote weight gain, whereas a reduced-carbohydrate diet may decrease risk of postmenopausal weight gain.
Traditional solar power applications largely avoid using the infrared spectrum. Nevertheless, this region makes up about 45% of the solar power spectrum and therefore represents an untapped resource. Temperature control of buildings represents a significant cost for both businesses and private consumers. We are interested in developing thermochromic materials for building coatings to help moderate solar infrared absorption and thereby offset temperature control costs for buildings. Our initial effort in this study has been to characterize materials which might represent starting points for our research. We previously designed and 3D-printed an optical test platform to perform reflectance measurements with an ultraviolet-visible-near infrared spectrometer over a spectral range from 200-1000nm. The test platform temperature can be adjusted in real time using Peltier modules. In this study, a sample of microencapsulated 7-anilino-3-diethylamino-6-methyl fluoran was studied by diffuse reflectance spectroscopy from 15-40 degrees Celsius. Scanning electron microscopy was used to characterize the dye particles. Temperature and spectral data were monitored while the sample temperature was adjusted. The visible diffuse reflectance from the sample increased from around 15% below the transition to more than 40% above the transition. A modification of this fluoran which extends the switching behavior into the infrared may be viable for passive thermo-optical switching in building coatings.
Various medications and devices are available for facilitation of emergent endotracheal intubations (EETIs). The objective of this study was to survey which medications and devices are being utilized for intubation by Canadian physicians.
A clinical scenario-based survey was developed to determine which medications physicians would administer to facilitate EETI, their first choice of intubation device, and backup strategy should their first choice fail. The survey was distributed to Canadian emergency medicine (EM) and intensive care unit (ICU) physicians using web-based and postal methods. Physicians were asked questions based on three scenarios (trauma; pneumonia; heart failure) and responded using a 5-point scale ranging from “always” to “never” to capture usual practice.
The survey response rate was 50.2% (882/1,758). Most physicians indicated a Macintosh blade with direct laryngoscopy would “always/often” be their first choice of intubation device in the three scenarios (mean 85% [79%-89%]) followed by video laryngoscopy (mean 37% [30%-49%]). The most common backup device chosen was an extraglottic device (mean 59% [56%-60%]). The medications most physicians would “always/often” administer were fentanyl (mean 45% [42%-51%]) and etomidate (mean 38% [25%-50%]). EM physicians were more likely than ICU physicians to paralyze patients for EETI (adjusted odds ratio 3.40; 95% CI 2.90-4.00).
Most EM and ICU physicians utilize direct laryngoscopy with a Macintosh blade as a primary device for EETI and an extraglottic device as a backup strategy. This survey highlights variation in Canadian practice patterns for some aspects of intubation in critically ill patients.
An experiment applying controlled meteorological (CMET) balloons near the coast of Dronning Maud Land, Antarctica, in January 2013 is described. Two balloons were airborne for 60 and 106 hours with trajectory lengths of 885.8 km and 2367.4 km, respectively. The balloons carried out multiple controlled soundings on the atmospheric pressure, temperature and humidity up to 3.3 km. Wind speed and direction were derived from the balloon drift. Observations were compared with radiosonde sounding profiles from the Halley Research Station, and applied in evaluating simulations carried out with the weather research and forecasting (WRF) mesoscale atmospheric model. The most interesting feature detected by the CMET balloons was a mesoscale anticyclone over the Weddell Sea and the coastal zone, which was reproduced by the WRF model with reduced intensity. The modelled wind speed was up to 10 m s-1 slower and the relative humidity was 20–40% higher than the observed values. However, over the study period the WRF results generally agreed with the observations. The results suggest that CMET balloons could be an interesting supplement to Antarctic atmospheric observations, particularly in the free troposphere.
To assess whether diet quality before or during pregnancy predicts adverse pregnancy and birth outcomes in a sample of Australian women.
The Dietary Questionnaire for Epidemiological Studies was used to calculate diet quality using the Australian Recommended Food Score (ARFS) methodology modified for pregnancy.
A population-based cohort participating in the Australian Longitudinal Study on Women’s Health (ALSWH).
A national sample of Australian women, aged 20–25 and 31–36 years, who were classified as preconception or pregnant when completing Survey 3 or Survey 5 of the ALSWH, respectively. The 1907 women with biologically plausible energy intake estimates were included in regression analyses of associations between preconception and pregnancy ARFS and subsequent pregnancy outcomes.
Preconception and pregnancy groups were combined as no significant differences were detected for total and component ARFS. Women with gestational hypertension, compared with those without, had lower scores for total ARFS, vegetable, fruit, grain and nuts/bean/soya components. Women with gestational diabetes had a higher score for the vegetable component only, and women who had a low-birth-weight infant had lower scores for total ARFS and the grain component, compared with those who did not report these outcomes. Women with the highest ARFS had the lowest odds of developing gestational hypertension (OR=0·4; 95 % CI 0·2, 0·7) or delivering a child of low birth weight (OR=0·4; 95 % CI 0·2, 0·9), which remained significant for gestational hypertension after adjustment for potential confounders.
A high-quality diet before and during pregnancy may reduce the risk of gestational hypertension for the mother.
Flapping wings are important in many biological and bioinspired systems. Here, we investigate the fluid mechanics of flapping wings that possess a single flexible hinge allowing passive wing pitch rotation under load. We perform experiments on an insect-scale (
cm wing span) robotic flapper and compare the results with a quasi-steady dynamical model and a coupled fluid–structure computational fluid dynamics model. In experiments we measure the time varying kinematics, lift force and two-dimensional velocity fields of the induced flow from particle image velocimetry. We find that increasing hinge stiffness leads to advanced wing pitching, which is beneficial towards lift force production. The classical quasi-steady model gives an accurate prediction of passive wing pitching if the relative phase difference between the wing stroke and the pitch kinematics,
, is small. However, the quasi-steady model cannot account for the effect of
on leading edge vortex (LEV) growth and lift generation. We further explore the relationships between LEV, lift force, drag force and wing kinematics through experiments and numerical simulations. We show that the wing kinematics and flapping efficiency depend on the stiffness of a passive compliant hinge. Our dual approach of running at-scale experiments and numerical simulations gives useful guidelines for choosing wing hinge stiffnesses that lead to efficient flapping.
There is increasing evidence for the role of nutrition in the prevention of depression. This study aims to describe changes in diet quality over 12 years among participants in the Australian Longitudinal Study on Women’s Health in relation to changes in depressive symptoms. Women born between 1946 and 1951 were followed-up for 12 years (2001–2013). Dietary intake was assessed using the Dietary Questionnaire for Epidemiological Studies (version 2) in 2001, 2007 and every 2–3 years after that until 2013. Diet quality was summarised using the Australian Recommended Food Score (ARFS). Depressive symptoms were measured using the ten-item Centre for Epidemiologic Depression Scale at every 2–3-year intervals during 2001–2013. Linear mixed models were used to examine trends in diet quality and its sub-components. The same model including time-varying covariates was used to examine associations between diet quality and depressive symptoms adjusting for confounders. Sensitivity analyses were carried out using the Mediterranean dietary pattern (MDP) index to assess diet quality. Minimal changes in overall diet quality and its sub-components over 12 years were observed. There was a significant association between baseline diet quality and depression (β=−0·24, P=0·001), but this was lost when time-varying covariates were added (β=−0·04, P=0·10). Sensitivity analyses showed similar performance for both ARFS and MDP in predicting depressive symptoms. In conclusion, initial associations seen when using baseline measures of diet quality and depressive symptoms disappear when using methods that handle time-varying covariates, suggesting that previous studies indicating a relationship between diet and depression may have been affected by residual confounding.
Disorganized attachment is an important early risk factor for socioemotional problems throughout childhood and into adulthood. Prevailing models of the etiology of disorganized attachment emphasize the role of highly dysfunctional parenting, to the exclusion of complex models examining the interplay of child and parental factors. Decades of research have established that extreme child birth weight may have long-term effects on developmental processes. These effects are typically negative, but this is not always the case. Recent studies have also identified the dopamine D4 receptor (DRD4) as a moderator of childrearing effects on the development of disorganized attachment. However, there are inconsistent findings concerning which variant of the polymorphism (seven-repeat long-form allele or non–seven-repeat short-form allele) is most likely to interact with caregiving in predicting disorganized versus organized attachment. In this study, we examined possible two- and three-way interactions and child DRD4 polymorphisms and birth weight and maternal caregiving at age 6 months in longitudinally predicting attachment disorganization at 36 months. Our sample is from the Maternal Adversity, Vulnerability and Neurodevelopment project, a sample of 650 mother–child dyads. Birth weight was cross-referenced with normative data to calculate birth weight percentile. Infant DRD4 was obtained with buccal swabs and categorized according to the presence of the putative allele seven repeat. Macroanalytic and microanalytic measures of maternal behavior were extracted from a videotaped session of 20 min of nonfeeding interaction followed by a 10-min divided attention maternal task at 6 months. Attachment was assessed at 36 months using the Strange Situation procedure, and categorized into disorganized attachment and others. The results indicated that a main effect for DRD4 and a two-way interaction of birth weight and 6-month maternal attention (frequency of maternal looking away behavior) and sensitivity predicted disorganized attachment in robust logistic regression models adjusted for social demographic covariates. Specifically, children in the midrange of birth weight were more likely to develop a disorganized attachment when exposed to less attentive maternal care. However, the association reversed with extreme birth weight (low and high). The DRD4 seven-repeat allele was associated with less disorganized attachment (protective), while non–seven-repeat children were more likely to be classified as disorganized attachment. The implications for understanding inconsistencies in the literature about which DRD4 genotype is the risk direction are also considered. Suggestions for intervention with families with infants at different levels of biological risk and caregiving risk are also discussed.