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For patients with methicillin-resistant Staphylococcus aureus (MRSA) colonization, a traditional fist-bump greeting did not significantly reduce MRSA transfer in comparison to a handshake. However, transfer was reduced with a modified fist bump that minimized the surface area of contact and when hand hygiene was performed before the handshake.
The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial.
Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded to study arm until after week 8. Medications on the combinatorial PGx test report were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Patient outcomes were assessed by arm at week 8 using HAM-D6 and HAM-D17 rating scales, including symptom improvement (percent change in scale), response (≥50% decrease in scale), and remission (HAM-D6 ≤4 and HAM-D17 ≤7).
At week 8, the guided-care arm demonstrated statistically significant symptom improvement over TAU using HAM-D6 scale (Δ=4.4%, p=0.023), but not using the HAM-D17 scale (Δ=3.2%, p=0.069). The response rate increased significantly for guided-care compared with TAU using both HAM-D6 (Δ=7.0%, p=0.004) and HAM-D17 (Δ=6.3%, p=0.007). Remission rates were also significantly greater for guided-care versus TAU using both scales (HAM-D6 Δ=4.6%, p=0.031; HAM-D17 Δ=5.5%, p=0.005). Patients taking medication(s) predicted to have gene-drug interactions at baseline showed further increased benefit over TAU at week 8 using HAM-D6 for symptom improvement (Δ=7.3%, p=0.004) response (Δ=10.0%, p=0.001) and remission (Δ=7.9%, p=0.005). Comparatively, the magnitude of the differences in outcomes between arms at week 8 was lower using HAM-D17 (symptom improvement Δ=5.0%, p=0.029; response Δ=8.0%, p=0.008; remission Δ=7.5%, p=0.003).
Combinatorial PGx-guided care achieved significantly better patient outcomes compared with TAU when assessed using the HAM-D6 scale. These findings suggest that the HAM-D6 scale is better suited than is the HAM-D17 for evaluating change in randomized, controlled trials comparing active treatment arms.
Selective laser sintering methods are workhorses for additively manufacturing polymer-based components. The ease of rapid prototyping also means it is easy to produce illicit components. It is necessary to have a data-calibrated in-situ physical model of the build process in order to predict expected and defective microstructure characteristics that inform component provenance. Toward this end, sintering models are calibrated and characteristics such as component defects are explored. This is accomplished by assimilating multiple data streams, imaging analysis, and computational model predictions in an adaptive Bayesian parameter estimation algorithm. From these data sources, along with a phase-field model, bulk porosity distributions are inferred. Model parameters are constrained to physically-relevant search directions by sensitivity analysis, and then matched to predictions using adaptive sampling. Using this feedback loop, data-constrained estimates of sintering model parameters along with uncertainty bounds are obtained.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
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.
The search for life in the Universe is a fundamental problem of astrobiology and modern science. The current progress in the detection of terrestrial-type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favourable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of global (astrospheric), and local (atmospheric and surface) environments of exoplanets in the habitable zones (HZs) around G-K-M dwarf stars including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favourable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro)physical, chemical and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the HZ to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field in light of presentations and discussions during the NASA Nexus for Exoplanetary System Science funded workshop ‘Exoplanetary Space Weather, Climate and Habitability’ and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.
We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.
India has the second largest number of people with type 2 diabetes (T2D) globally. Epidemiological evidence indicates that consumption of white rice is positively associated with T2D risk, while intake of brown rice is inversely associated. Thus, we explored the effect of substituting brown rice for white rice on T2D risk factors among adults in urban South India. A total of 166 overweight (BMI ≥ 23 kg/m2) adults aged 25–65 years were enrolled in a randomised cross-over trial in Chennai, India. Interventions were a parboiled brown rice or white rice regimen providing two ad libitum meals/d, 6 d/week for 3 months with a 2-week washout period. Primary outcomes were blood glucose, insulin, glycosylated Hb (HbA1c), insulin resistance (homeostasis model assessment of insulin resistance) and lipids. High-sensitivity C-reactive protein (hs-CRP) was a secondary outcome. We did not observe significant between-group differences for primary outcomes among all participants. However, a significant reduction in HbA1c was observed in the brown rice group among participants with the metabolic syndrome (−0·18 (se 0·08) %) relative to those without the metabolic syndrome (0·05 (se 0·05) %) (P-for-heterogeneity = 0·02). Improvements in HbA1c, total and LDL-cholesterol were observed in the brown rice group among participants with a BMI ≥ 25 kg/m2 compared with those with a BMI < 25 kg/m2 (P-for-heterogeneity < 0·05). We observed a smaller increase in hs-CRP in the brown (0·03 (sd 2·12) mg/l) compared with white rice group (0·63 (sd 2·35) mg/l) (P = 0·04). In conclusion, substituting brown rice for white rice showed a potential benefit on HbA1c among participants with the metabolic syndrome and an elevated BMI. A small benefit on inflammation was also observed.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
Although application of organic fertilizers has become a recommended way for developing sustainable agriculture, it is still unclear whether above-ground and below-ground crops have similar responses to chemical fertilizers (CF) and organic manure (OM) under the same farming conditions. The current study investigated soil quality and crop yield response to fertilization of a double-cropping system with rapeseed (above-ground) and sweet potato (below-ground) in an infertile red soil for 2 years (2014–16). Three fertilizer treatments were compared, including CF, OM and organic manure plus chemical fertilizer (MCF). Organic fertilizers (OM and MCF) increased the yield of both above- and below-ground crops and improved soil biochemical properties significantly. The current study also found that soil-chemical properties were the most important and direct factors in increasing crop yields. Also, crop yield was affected indirectly by soil-biological properties, because no significant effects of soil-biological activities on yield were detected after controlling the positive effects of soil-chemical properties. Since organic fertilizers could not only increase crop yield, but also improve soil nutrients and microbial activities efficiently and continuously, OM application is a reliable agricultural practice for both above- and below-ground crops in the red soils of China.
Exposure to the endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with health abnormalities that persist in subsequent generations. However, transgenerational effects of BPA on metabolic health are not widely studied. In a maternal C57BL/6J mice (F0) exposure model using BPA doses that are relevant to human exposure levels (10 μg/kg/day, LowerB; 10 mg/kg/day, UpperB), we showed male- and dose-specific effects on pancreatic islets of the first (F1) and second generation (F2) offspring relative to controls (7% corn oil diet; control). In this study, we determined the transgenerational effects (F3) of BPA on metabolic health and pancreatic islets in our model. Adult F3 LowerB and UpperB male offspring had increased body weight relative to Controls, however glucose tolerance was similar in the three groups. F3 LowerB, but not UpperB, males had reduced β-cell mass and smaller islets which was associated with increased glucose-stimulated insulin secretion. Similar to F1 and F2 BPA male offspring, staining for markers of T-cells and macrophages (CD3 and F4/80) was increased in pancreas of F3 LowerB and UpperB male offspring, which was associated with changes in cytokine levels. In contrast to F3 BPA males, LowerB and UpperB female offspring had comparable body weight, glucose tolerance and insulin secretion as Controls. Thus, maternal BPA exposure resulted in fewer metabolic defects in F3 than F1 and F2 offspring, and these were sex- and dose-specific.
During a study of the ore minerals belonging to the recently discovered Shuangjianzishan Ag–Pb–Zn deposit in NE China, we have discovered exceptional selenium enrichment in canfieldite (up to 11.6 wt.% of Se). Incorporation of Se into canfieldite has been investigated by an integrated approach using field emission scanning electron microscopy, electron microprobe and single-crystal X-ray diffraction. Canfieldite has been identified as one of the dominant Ag-bearing ore minerals in the studied deposit, which occurs mostly in slate-hosted vein type Ag–Pb–Zn ore bodies. Selenium is either homogeneously or, remarkably, heterogeneously distributed in the different canfieldite fragments studied. Chemical variations of Se are mostly attributable to a series of retrograde reactions resulting in diverse decomposition and exsolution of primary phases during cooling, or alternatively, related to influxes of Se-rich fluids during the formation of canfieldite. To evaluate the effects of the Se-for-S substitution in the structure, a crystal of Se-rich canfieldite [Ag7.98Sn1.02(S4.19Se1.81)Σ6.00] was investigated. The unit-cell parameters are: a = 10.8145(8) Å and V = 1264.8(3) Å3. The structure was refined in the space group F
3m to R1 = 0.0315 for 194 independent reflections, with 20 parameters. The crystal structure of Se-rich canfieldite was found to be topologically identical to that of pure canfieldite. If the short Ag–Ag contacts are ignored (due to the disorder), the two Ag atoms in the structure can be considered as three-fold (Ag1) and four-fold (Ag2) coordinated. Tin adopts a regular tetrahedral coordination. As in the case of Te-rich canfieldite, the refinement of the site-occupancy factor indicates that Se is disordered over the three anion positions.
The measurement accuracy of low-frequency narrow-band antenna is heavily influenced by its environment, which is also difficult to remove the clutter with a time gating. This paper proposes a method to improve the measurement accuracy of low-frequency narrow-band antenna using signal processing technique. The method is to predict the unknown value out of received original signal with an auto-regressive model (AR model) based on modern spectral estimation theory, and the parameters in AR model are calculated by maximum entropy spectral estimation algorithm. Thus, a wideband signal compared with the original band is obtained, and then the time-domain resolution is enhanced. The time gating is more exactly to separate the antenna radiation signal from multipath signals. The simulation and experimental results show that about 50% extended data for each ends of original band can be obtained after spectral extrapolation, and the time-domain resolution after extrapolation is twice than the original narrow-band signal, and the influence of measurement environment can be eliminated effectively. The method can be used to improve accuracy in actual antenna measurement.
Cultivated pastures in southern China are being used to improve forage productivity and animal performance, but studies on grazing behaviour of goats in these cultivated pastures are still rare. In the current study, the grazing behaviour of Yunling black goats under low (5 goats/ha) and high (15 goats/ha) stocking rates (SRs) was evaluated. Data showed that the proportion of time goats spent on activities was: eating (0.59–0.87), ruminating (0.05–0.35), walking (0.03–0.06) and resting (0.01–0.03). Compared with low SR, goats spent more time eating and walking, and less time ruminating and resting under high SR. Goats had similar diet preferences under both SR and preferred to eat grasses (ryegrass and cocksfoot) more than a legume (white clover). The distribution of eating time on each forage species was more uniform under high v. low SR. Bites/step, bite weight and daily intake were greater under low than high SR. Results suggest that the SR affects grazing behaviour of goats on cultivated pasture, and identifying an optimal SR is critical for increasing bite weight and intake.
Background: Acromegaly is associated with significant morbidity. The purpose of this study was to establish characteristics and outcomes of patients treated for acromegaly at The Ottawa Hospital, to compare our results with published reports from other centers and to identify opportunities to improve patient care. Methods: A retrospective chart review of patients surgically and medically treated for acromegaly between January 1, 2007 and December 31, 2016 was completed. Demographic information, biochemical data, presenting features, disease comorbidities, treatment interventions, and were collected. Results: Fifty-one patients were identified using CCI/ICD-10 codes and IGF-1 levels. Similar to other centers, the majority of patients had a macroadenoma (78.4% vs 11.8%) with a high percentage invading the cavernous sinus (57.5%). While surgical intervention was performed in 90% of patients, only 23.3% of patient achieved surgical cure (IGF-1 normalization within reference range). Approximately 30% of patients were controlled with adjuvant medical therapy while more than 40 % had elevated IGF-1 levels at last follow-up. Radiotherapy was less commonly used. Conclusions: Despite a multi-modal treatment approach for acromegaly, outcomes are variable. This study highlights the need for further research to better understand factors associated with surgical cure, response to medical therapy and the role of radiotherapy.
Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.
In May 2016 a Norovirus (NoV) gastroenteritis outbreak involved a high school class visiting a seaside resort near Taormina (Mascali, Sicily). Twenty-four students and a teacher were affected and 17 of them showed symptoms on the second day of the journey, while the others got ill within the following 2 days. Symptoms included vomiting, diarrhoea and fever, and 12 students required hospitalisation. Stool samples tested positive for NoV genome by Real-Time polymerase chain reaction assay in all 25 symptomatic subjects. The GII.P2/GII.2 NoV genotype was linked to the outbreak by ORF1/ORF2 sequence analysis. The epidemiological features of the outbreak were consistent with food/waterborne followed by person-to-person and/or vomit transmission. Food consumed at a shared lunch on the first day of the trip was associated to illness and drinking un-bottled tap water was also considered as a risk factor. The analysis of water samples revealed the presence of bacterial indicators of faecal contamination in the water used in the resort as well as in other areas of the municipal water network, linking the NoV gastroenteritis outbreak to tap water pollution from sewage leakage. From a single water sample, an amplicon whose sequence corresponded to the capsid genotype recovered from patients could be obtained.