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.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
During the COVID-19 pandemic, the antimicrobial stewardship module in our electronic medical record was reconfigured for the management of COVID-19 patients. This change allowed our subspecialist providers to review charts quickly to optimize potential therapy and management during the patient surge.
Introduction: For rhythm control of acute atrial flutter (AAFL) in the emergency department (ED), choices include initial drug therapy or initial electrical cardioversion (ECV). We compared the strategies of pharmacological cardioversion followed by ECV if necessary (Drug-Shock), and ECV alone (Shock Only). Methods: We conducted a randomized, blinded, placebo-controlled trial (1:1 allocation) comparing two rhythm control strategies at 11 academic EDs. We included stable adult patients with AAFL, where onset of symptoms was <48 hours. Patients underwent central web-based randomization stratified by site. The Drug-Shock group received an infusion of procainamide (15mg/kg over 30 minutes) followed 30 minutes later, if necessary, by ECV at 200 joules x 3 shocks. The Shock Only group received an infusion of saline followed, if necessary, by ECV x 3 shocks. The primary outcome was conversion to sinus rhythm for ≥30 minutes at any time following onset of infusion. Patients were followed for 14 days. The primary outcome was evaluated on an intention-to-treat basis. Statistical significance was assessed using chi-squared tests and multivariable logistic regression. Results: We randomized 76 patients, and none was lost to follow-up. The Drug-Shock (N = 33) and Shock Only (N = 43) groups were similar for all characteristics including mean age (66.3 vs 63.4 yrs), duration of AAFL (30.1 vs 24.5 hrs), previous AAFL (72.7% vs 69.8%), median CHADS2 score (1 vs 1), and mean initial heart rate (128.9 vs 126.0 bpm). The Drug-Shock and Shock only groups were similar for the primary outcome of conversion (100% vs 93%; absolute difference 7.0%, 95% CI -0.6;14.6; P = 0.25). The multivariable analyses confirmed the similarity of the two strategies (P = 0.19). In the Drug-Shock group 21.2% of patients converted with the infusion. There were no statistically significant differences for time to conversion (84.2 vs 97.6 minutes), total ED length of stay (9.4 vs 7.5 hours), disposition home (100% vs 95.3%), and stroke within 14 days (0 vs 0). Premature discontinuation of infusion (usually for transient hypotension) was more common in the Drug-Shock group (9.1% vs 0.0%) but there were no serious adverse events. Conclusion: Both the Drug-Shock and Shock Only strategies were highly effective and safe in allowing AAFL patients to go home in sinus rhythm. IV procainamide alone was effective in only one fifth of patients, much less than for acute AF.
Introduction: For rhythm control of acute atrial fibrillation (AAF) in the emergency department (ED), choices include initial drug therapy or initial electrical cardioversion (ECV). We compared the strategies of pharmacological cardioversion followed by ECV if necessary (Drug-Shock), and ECV alone (Shock Only). Methods: We conducted a randomized, blinded, placebo-controlled trial (1:1 allocation) comparing two rhythm control strategies at 11 academic EDs. We included stable adult patients with AAF, where onset of symptoms was <48 hours. Patients underwent central web-based randomization stratified by site. The Drug-Shock group received an infusion of procainamide (15mg/kg over 30 minutes) followed 30 minutes later, if necessary, by ECV at 200 joules x 3 shocks. The Shock Only group received an infusion of saline followed, if necessary, by ECV x 3 shocks. The primary outcome was conversion to sinus rhythm for ≥30 minutes at any time following onset of infusion. Patients were followed for 14 days. The primary outcome was evaluated on an apriori-specified modified intention-to-treat (MITT) basis excluding patients who never received the study infusion (e.g. spontaneous conversion). Data were analyzed using chi-squared tests and logistic regression. Our target sample size was 374 evaluable patients. Results: Of 395 randomized patients, 18 were excluded from the MITT analysis; none were lost to follow-up. The Drug-Shock (N = 198) and Shock Only (N = 180) groups (total = 378) were similar for all characteristics including mean age (60.0 vs 59.5 yrs), duration of AAF (10.1 vs 10.8 hrs), previous AF (67.2% vs 68.3%), median CHADS2 score (0 vs 0), and mean initial heart rate (119.9 vs 118.0 bpm). More patients converted to normal sinus rhythm in the Drug-Shock group (97.0% vs 92.2%; absolute difference 4.8%, 95% CI 0.2-9.9; P = 0.04). The multivariable analyses confirmed the Drug-Shock strategy superiority (P = 0.04). There were no statistically significant differences for time to conversion (91.4 vs 85.4 minutes), total ED length of stay (7.1 vs 7.7 hours), disposition home (97.0% vs 96.1%), and stroke within 14 days (0 vs 0). Premature discontinuation of infusion was more common in the Drug-Shock group (8.1% vs 0.6%) but there were no serious adverse events. Conclusion: Both the Drug-Shock and Shock Only strategies were highly effective and safe in allowing AAF patients to go home in sinus rhythm. A strategy of initial cardioversion with procainamide was superior to a strategy of immediate ECV.
With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (μ LIR > 1013 L⊙, where μ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICA’s far-infrared spectrometer SAFARI, which will probe a spectral range (35–230 μm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 − 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARI’s ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI.
The SPICA mid- and far-infrared telescope will address fundamental issues in our understanding of star formation and ISM physics in galaxies. A particular hallmark of SPICA is the outstanding sensitivity enabled by the cold telescope, optimised detectors, and wide instantaneous bandwidth throughout the mid- and far-infrared. The spectroscopic, imaging, and polarimetric observations that SPICA will be able to collect will help in clarifying the complex physical mechanisms which underlie the baryon cycle of galaxies. In particular, (i) the access to a large suite of atomic and ionic fine-structure lines for large samples of galaxies will shed light on the origin of the observed spread in star-formation rates within and between galaxies, (ii) observations of HD rotational lines (out to ~10 Mpc) and fine structure lines such as [C ii] 158 μm (out to ~100 Mpc) will clarify the main reservoirs of interstellar matter in galaxies, including phases where CO does not emit, (iii) far-infrared spectroscopy of dust and ice features will address uncertainties in the mass and composition of dust in galaxies, and the contributions of supernovae to the interstellar dust budget will be quantified by photometry and monitoring of supernova remnants in nearby galaxies, (iv) observations of far-infrared cooling lines such as [O i] 63 μm from star-forming molecular clouds in our Galaxy will evaluate the importance of shocks to dissipate turbulent energy. The paper concludes with requirements for the telescope and instruments, and recommendations for the observing strategy.
IR spectroscopy in the range 12–230 μm with the SPace IR telescope for Cosmology and Astrophysics (SPICA) will reveal the physical processes governing the formation and evolution of galaxies and black holes through cosmic time, bridging the gap between the James Webb Space Telescope and the upcoming Extremely Large Telescopes at shorter wavelengths and the Atacama Large Millimeter Array at longer wavelengths. The SPICA, with its 2.5-m telescope actively cooled to below 8 K, will obtain the first spectroscopic determination, in the mid-IR rest-frame, of both the star-formation rate and black hole accretion rate histories of galaxies, reaching lookback times of 12 Gyr, for large statistically significant samples. Densities, temperatures, radiation fields, and gas-phase metallicities will be measured in dust-obscured galaxies and active galactic nuclei, sampling a large range in mass and luminosity, from faint local dwarf galaxies to luminous quasars in the distant Universe. Active galactic nuclei and starburst feedback and feeding mechanisms in distant galaxies will be uncovered through detailed measurements of molecular and atomic line profiles. The SPICA’s large-area deep spectrophotometric surveys will provide mid-IR spectra and continuum fluxes for unbiased samples of tens of thousands of galaxies, out to redshifts of z ~ 6.
Glacier surface mass-balance measurements on Greenland started more than a century ago, but no compilation exists of the observations from the ablation area of the ice sheet and local glaciers. Such data could be used in the evaluation of modelled surface mass balance, or to document changes in glacier melt independently from model output. Here, we present a comprehensive database of Greenland glacier surface mass-balance observations from the ablation area of the ice sheet and local glaciers. The database spans the 123 a from 1892 to 2015, contains a total of ~3000 measurements from 46 sites, and is openly accessible through the PROMICE web portal (http://www.promice.dk). For each measurement we provide X, Y and Z coordinates, starting and ending dates as well as quality flags. We give sources for each entry and for all metadata. Two thirds of the data were collected from grey literature and unpublished archive documents. Roughly 60% of the measurements were performed by the Geological Survey of Denmark and Greenland (GEUS, previously GGU). The data cover all regions of Greenland except for the southernmost part of the east coast, but also emphasize the importance of long-term time series of which there are only two exceeding 20 a. We use the data to analyse uncertainties in point measurements of surface mass balance, as well as to estimate surface mass-balance profiles for most regions of Greenland.
Introduction: Acute upper gastrointestinal bleeding is a potentially life-threatening medical emergency that frequently requires red blood cell (RBC) transfusions. However, the optimal hemoglobin thresholds for transfusion is controversial. The objective of this study was to establish the most efficacious transfusion threshold. Methods: A systematic review of the published literature was completed. MEDLINE, Health technology assessment database, Cochrane central register, Cochrane database of systematic reviews, and EMBASE were searched from inception to May 2015 using search terms including “blood transfusions”, “hemoglobin”, and “red blood cell”. Studies were included if they: reported original data, were peer-reviewed, studied adult populations, were randomized controlled clinical trials and primarily focused on clinical efficacy or effectiveness of liberal and restrictive pre-transfusion hemoglobin level thresholds. Quality was assessed using the Cochrane Risk of Bias tool. Data were extracted and meta-analysis was conducted using a random effects model to determine the risk ratio for: all-cause mortality, further bleeding and any adverse events. All steps were completed independently by two reviewers. Results: The literature search identified 4037 unique abstracts. Of these, 156 abstracts proceeded to full text review. 154 articles were excluded during full-text review resulting in 2 articles for final analysis. The total number of participants included was 701. The hemoglobin threshold to transfuse RBC varied between 70-80g/L versus 90-100g/L in restrictive and liberal policies, respectively. Both studies were at low risk of bias. Meta-analysis resulted in a pooled decreased risk of all-cause mortality (RR 0.65, 95% CI 0.44-0.96), re-bleeding (RR 0.63, 95% CI 0.46-0.85) and adverse events (RR 0.83, 95% CI 0.73-0.95) in the restrictive blood transfusion group versus the liberal blood transfusion group. Conclusion: While the evidence is limited, the risk of death is lower and there is no significant harm for a restrictive strategy. In this context, there is a decreased risk of transfusion associated adverse events among those receiving a restrictive strategy and should be considered for its impact on patient safety and health system resources.
Most research on interventions to counter stigma and discrimination has
focused on short-term outcomes and has been conducted in high-income
To synthesise what is known globally about effective interventions to
reduce mental illness-based stigma and discrimination, in relation first
to effectiveness in the medium and long term (minimum 4 weeks), and
second to interventions in low- and middle-income countries (LMICs).
We searched six databases from 1980 to 2013 and conducted a
multi-language Google search for quantitative studies addressing the
research questions. Effect sizes were calculated from eligible studies
where possible, and narrative syntheses conducted. Subgroup analysis
compared interventions with and without social contact.
Eighty studies (n = 422 653) were included in the
review. For studies with medium or long-term follow-up (72, of which 21
had calculable effect sizes) median standardised mean differences were
0.54 for knowledge and −0.26 for stigmatising attitudes. Those containing
social contact (direct or indirect) were not more effective than those
without. The 11 LMIC studies were all from middle-income countries.
Effect sizes were rarely calculable for behavioural outcomes or in LMIC
There is modest evidence for the effectiveness of anti-stigma
interventions beyond 4 weeks follow-up in terms of increasing knowledge
and reducing stigmatising attitudes. Evidence does not support the view
that social contact is the more effective type of intervention for
improving attitudes in the medium to long term. Methodologically strong
research is needed on which to base decisions on investment in
As a result of several judicial rulings, processing of horses for human consumption came to a halt in 2007. This article determines the change in horse prices resulting from elimination of horse-processing facilities. As expected, lower-valued horses were more affected by the ban than higher-valued horses. The analysis suggests the slaughter ban reduced horse prices, on average, by about 13% and resulted in a loss in producer surplus to sellers of approximately 14% at the sale we analyzed. We also show horse prices are affected by a myriad of factors including breed, gender, age, coat color, and sale catalog description.
The induced diffusion of tracers in a bacterial suspension is studied theoretically and experimentally at low bacterial concentrations. Considering the swimmer–tracer hydrodynamic interactions at low Reynolds number and using a kinetic theory approach, it is shown that the induced diffusion coefficient is proportional to the swimmer concentration, their mean velocity and a coefficient $\beta $, as observed experimentally. This paper shows that $\beta $ increases as a result of the interaction with solid surfaces. The coefficient $\beta $ scales as the tracer–swimmer cross-section times the mean square displacement produced by single scattering events, which depends on the swimmer propulsion forces. Considering simple swimmer models (acting on the fluid as two monopoles or as a force dipole), it is shown that $\beta $ increases for decreasing swimming efficiencies. Close to solid surfaces, the swimming efficiency degrades and, consequently, the induced diffusion increases. Experiments on wild-type Escherichia coli in a Hele-Shaw cell, under buoyant conditions, are performed to measure the induced diffusion on tracers near surfaces. The modification of the suspension pH varies the swimmers’ velocity over a wide range, allowing the $\beta $ coefficient to be extracted with precision. It is found that solid surfaces modify the induced diffusion: decreasing the confinement height of the cell, $\beta $ increases by a factor of 4. The theoretical model reproduces this increase, although there are quantitative differences, probably attributed to the simplicity of the swimmer models and to the estimates for the parameters that model E. coli.
Despite containing only 14% of the Greenland ice sheet by area, the southeastern sector has the highest accumulation rates, and hence receives ∼30% of the total snow accumulation. We present accumulation rates obtained during our 2010 Arctic Circle Traverse derived from three 50 m firn cores dated using geochemical analysis. We tracked continuous internal reflection horizons between the firn cores using a 400 MHz ground-penetrating radar (GPR). GPR data combined with depth-age scales from the firn cores provide accumulation rates along a 70 km transect. We followed an elevation gradient from ∼2350 to ∼1830m to understand how progressive surface melt may affect the ability to chemically date the firn cores and trace the internal layers with GPR. From the firn cores, we find a 52% (∼0.43 m w.e. a-1) increase in average snow accumulation and greater interannual variability at the lower site than the upper site. The GPR profiling reveals that accumulation rates are influenced by topographic undulations on the surface, with up to 23% variability over 7 km. These measurements confirm the presence of high accumulation rates in the southeast as predicted by the calibrated regional climate model Polar MM5.
Schistosomiasis remains one of the most prevalent parasitic diseases in developing countries. After malaria, schistosomiasis is the most important tropical disease in terms of human morbidity with significant economic and public health consequences. Although schistosomiasis has recently attracted increased focus and funding for control, it has been estimated that less than 20% of the funding needed to control the disease in Africa is currently available. In this article the following issues are discussed: the rationale, development and objectives of the Schistosomiasis Control Initiative (SCI)-supported programmes; the management approaches followed to achieve implementation by each country; mapping, monitoring and evaluation activities with quantifiable impact of control programmes; monitoring for any potential drug resistance; and finally exit strategies within each country. The results have demonstrated that morbidity due to schistosomiasis has been reduced by the control programmes. While challenges remain, the case for the control of schistosomiasis has been strengthened by research by SCI teams and the principle that a national programme using ‘preventive chemotherapy’ can be successfully implemented in sub-Saharan Africa, whenever the resources are available. SCI and partners are now actively striving to raise further funds to expand the coverage of integrated control of neglected tropical diseases (NTDs) in sub-Saharan Africa.
Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene–nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient–genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.
Abnormalities of growth and development are prevalent in children with cerebral palsy (CP). The purpose of this study was to assess skeletal maturation (‘bone age’) in this population and to identify those factors related to alterations in this aspect of development. The study group was a convenience sample of 80 participants (47 males, 33 females; age range 2y 6mo to 21y 1mo; mean age 10y 10mo, SD 4y 2mo). All had moderate to severe spastic or mixed spastic CP at Gross Motor Function Classification System level III (n=8, 10%); level IV (n=21, 26%); or level V (n=51, 64%). Skeletal maturation was assessed by the detailed Fels method of scoring hand–wrist radiographs. Each evaluation included clinical and anthropometric assessments, Tanner staging, bone density measurements, and the Children's Health Status Questionnaire. Follow-up evaluations were obtained for 41 participants, providing a total of 143 evaluations. Median interval between first and last evaluations was 24.7 months (range 11.9 to 45mo). For the study group as a whole there was no significant difference between a child's skeletal age and chronological age. However, there was a high prevalence of individual participants in whom skeletal age was advanced (7%) or delayed (10%), relative to chronological age, by more than 2 years. In multivariant analyses it was found that diminished linear growth (height), low lumbar-spine bone density, and low body fat as measured by triceps skinfolds were all independently associated with delays in skeletal maturation. Multiple aspects of skeletal growth and development, including skeletal maturation, are frequently altered in children with moderate to severe CP.