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The two pillars of modern physics are general relativity and quantum field theory, the former describes the large scale structure and dynamics of space-time, the latter, the microscopic constituents of matter. Combining the two yields quantum field theory in curved space-time, which is needed to understand quantum field processes in the early universe and black holes, such as the well-known Hawking effect. This book examines the effects of quantum field processes back-reacting on the background space-time which become important near the Planck time (10-43 sec). It explores the self-consistent description of both space-time and matter via the semiclassical Einstein equation of semiclassical gravity theory, exemplified by the inflationary cosmology, and fluctuations of quantum fields which underpin stochastic gravity, necessary for the description of metric fluctuations (space-time foams). Covering over four decades of thematic development, this book is a valuable resource for researchers interested in quantum field theory, gravitation and cosmology.
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.
Although parasites and microbial pathogens are both detrimental to insects, little information is currently available on the mechanism involved in how parasitized hosts balance their immune responses to defend against microbial infections. We addressed this in the present study by comparing the immune response between unparasitized and parasitized pupae of the chrysomelid beetle, Octodonta nipae (Maulik), to Escherichia coli invasion. In an in vivo survival assay, a markedly reduced number of E. coli colony-forming units per microliter was detected in parasitized pupae at 12 and 24 h post-parasitism, together with decreased phagocytosis and enhanced bactericidal activity at 12 h post-parasitism. The effects that parasitism had on the mRNA expression level of selected antimicrobial peptides (AMPs) of O. nipae pupae showed that nearly all transcripts of AMPs examined were highly upregulated during the early and late parasitism stages except defensin 2B, whose mRNA expression level was downregulated at 24 h post-parasitism. Further elucidation on the main maternal fluids responsible for alteration of the primary immune response against E. coli showed that ovarian fluid increased phagocytosis at 48 h post-injection. These results indicated that the enhanced degradation of E. coli in parasitized pupae resulted mainly from the elevated bactericidal activity without observing the increased transcripts of target AMPs. This study contributes to a better understanding of the mechanisms involved in the immune responses of a parasitized host to bacterial infections.
Sinonasal malignant melanoma is a relatively rare malignancy with poor prognosis, and effective treatments remain elusive. This analysis aimed to explore whether post-operative radiotherapy conferred any survival advantages in patients with this disease when compared with surgery alone.
Published studies were identified by searching four electronic databases. The endpoints evaluated were: rates of overall survival, disease-free survival and local control.
Twenty-eight studies including 1392 patients were identified. The results indicated that post-operative radiotherapy led to a significantly better three-year overall survival rate (p = 0.02), and suggested a borderline significant benefit for five-year overall survival (p = 0.05), when compared with surgery alone. However, no statistical advantage was found for disease-free survival, local control or one-year overall survival.
This meta-analysis indicated that adjuvant radiotherapy prolonged survival, but showed no benefit for disease-free survival or local control.
Dengue is the fastest spreading mosquito-transmitted disease in the world. In China, Guangzhou City is believed to be the most important epicenter of dengue outbreaks although the transmission patterns are still poorly understood. We developed an autoregressive integrated moving average model incorporating external regressors to examine the association between the monthly number of locally acquired dengue infections and imported cases, mosquito densities, temperature and precipitation in Guangzhou. In multivariate analysis, imported cases and minimum temperature (both at lag 0) were both associated with the number of locally acquired infections (P < 0.05). This multivariate model performed best, featuring the lowest fitting root mean squared error (RMSE) (0.7520), AIC (393.7854) and test RMSE (0.6445), as well as the best effect in model validation for testing outbreak with a sensitivity of 1.0000, a specificity of 0.7368 and a consistency rate of 0.7917. Our findings suggest that imported cases and minimum temperature are two key determinants of dengue local transmission in Guangzhou. The modelling method can be used to predict dengue transmission in non-endemic countries and to inform dengue prevention and control strategies.
Animal and cross-sectional epidemiological studies suggest that prenatal lead exposure is related to delayed menarche, but this has not been confirmed in longitudinal studies. We analyzed this association among 200 girls from Mexico City who were followed since the first trimester of gestation. Maternal blood lead levels were analyzed once during each trimester of pregnancy, and daughters were asked about their first menstrual cycle at a visit between the ages of 9.8 and 18.1 years. We estimated hazard ratios (HRs) and 95% confidence intervals (CI) for probability of menarche over the follow-up period using interval-censored Cox models, comparing those with prenatal blood lead level ⩾5 µg/dl to those with prenatal blood lead <5 µg/dl. We also estimated HRs and 95% CI with conventional Cox regression models, which utilized the self-reported age at menarche. In adjusted analyses, we accounted for maternal age, maternal parity, maternal education, and prenatal calcium treatment status. Across trimesters, 36−47% of mothers had blood lead levels ⩾5 µg/dl. Using interval-censored models, we found that during the second trimester only, girls with ⩾5 µg/dl prenatal blood lead had a later age at menarche compared with girls with prenatal blood lead levels <5 µg/dl (confounder-adjusted HR=0.59, 95% CI 0.28–0.90; P=0.05). Associations were in a similar direction, although not statistically significant, in the conventional Cox regression models, potentially indicating measurement error in the self-recalled age at menarche. In summary, higher prenatal lead exposure during the second trimester could be related to later onset of sexual maturation.
Few studies have evaluated the relationships between intake of sugar-sweetened beverages (SSB) and intermediate biomarkers of cardiometabolic risk. Associations between artificially sweetened beverages (ASB) and fruit juice with cardiometabolic biomarkers are also unclear. We investigated habitual SSB, ASB and fruit juice intake in relation to biomarkers of hepatic function, lipid metabolism, inflammation and glucose metabolism. We analysed cross-sectional data from 8492 participants in the Nurses’ Health Study who were free of diabetes and CVD. Multivariate linear regression was used to assess the associations of SSB, ASB and fruit juice intake with concentrations of fetuin-A, alanine transaminase, γ-glutamyl transferase, TAG, HDL-cholesterol, LDL-cholesterol, total cholesterol, C-reactive protein (CRP), intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1, adiponectin, insulin and HbA1c as well as total cholesterol:HDL-cholesterol ratio. More frequent intake of SSB was significantly associated with higher concentrations of fetuin-A, TAG, CRP, ICAM-1, adiponectin and insulin, a higher total cholesterol:HDL-cholesterol ratio, and a lower concentration of HDL-cholesterol (Ptrend ranges from <0·0001 to 0·04) after adjusting for demographic, medical, dietary and lifestyle variables. ASB intake was marginally associated with increased concentrations of CRP (Ptrend=0·04) and adiponectin (Ptrend=0·01). Fruit juice intake was associated with increased concentrations of TAG and HbA1c and a lower concentration of adiponectin (Ptrend ranges from <0·0001 to 0·01). In conclusion, habitual intake of SSB was associated with adverse levels of multiple cardiometabolic biomarkers. Associations between ASB and fruit juice with cardiometabolic risk markers warrant further exploration.
Monolithic large-aperture diffraction grating tiling is desired to increase the output capability of multi-kilojoule petawatt laser facilities. However, the wavefront errors of input pulse and gratings will degrade the focal spot quality and the compressibility of the output pulse. In this work, the effects of wavefront error of input pulse, deformation and wave aberration of the grating for the large-aperture tiled-grating compressor are investigated theoretically. A series of numerical simulations are presented to discuss the changing trends of focal spot energy caused by wavefront error of input pulse and obtain the error tolerance for specific goals. The influences of coating stress and the wave aberration of holographic exposure gratings on the diffraction wavefront are also discussed. Some advice is proposed for improving the performance of large-aperture tiled-grating. This work paves the way for the design of practical large-aperture tiled-grating compressor for ultrahigh intensity laser facilities in the future.
A substantial proportion of persons with mental disorders seek treatment from complementary and alternative medicine (CAM) professionals. However, data on how CAM contacts vary across countries, mental disorders and their severity, and health care settings is largely lacking. The aim was therefore to investigate the prevalence of contacts with CAM providers in a large cross-national sample of persons with 12-month mental disorders.
In the World Mental Health Surveys, the Composite International Diagnostic Interview was administered to determine the presence of past 12 month mental disorders in 138 801 participants aged 18–100 derived from representative general population samples. Participants were recruited between 2001 and 2012. Rates of self-reported CAM contacts for each of the 28 surveys across 25 countries and 12 mental disorder groups were calculated for all persons with past 12-month mental disorders. Mental disorders were grouped into mood disorders, anxiety disorders or behavioural disorders, and further divided by severity levels. Satisfaction with conventional care was also compared with CAM contact satisfaction.
An estimated 3.6% (standard error 0.2%) of persons with a past 12-month mental disorder reported a CAM contact, which was two times higher in high-income countries (4.6%; standard error 0.3%) than in low- and middle-income countries (2.3%; standard error 0.2%). CAM contacts were largely comparable for different disorder types, but particularly high in persons receiving conventional care (8.6–17.8%). CAM contacts increased with increasing mental disorder severity. Among persons receiving specialist mental health care, CAM contacts were reported by 14.0% for severe mood disorders, 16.2% for severe anxiety disorders and 22.5% for severe behavioural disorders. Satisfaction with care was comparable with respect to CAM contacts (78.3%) and conventional care (75.6%) in persons that received both.
CAM contacts are common in persons with severe mental disorders, in high-income countries, and in persons receiving conventional care. Our findings support the notion of CAM as largely complementary but are in contrast to suggestions that this concerns person with only mild, transient complaints. There was no indication that persons were less satisfied by CAM visits than by receiving conventional care. We encourage health care professionals in conventional settings to openly discuss the care patients are receiving, whether conventional or not, and their reasons for doing so.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
The treatment gap between the number of people with mental disorders and the number treated represents a major public health challenge. We examine this gap by socio-economic status (SES; indicated by family income and respondent education) and service sector in a cross-national analysis of community epidemiological survey data.
Data come from 16 753 respondents with 12-month DSM-IV disorders from community surveys in 25 countries in the WHO World Mental Health Survey Initiative. DSM-IV anxiety, mood, or substance disorders and treatment of these disorders were assessed with the WHO Composite International Diagnostic Interview (CIDI).
Only 13.7% of 12-month DSM-IV/CIDI cases in lower-middle-income countries, 22.0% in upper-middle-income countries, and 36.8% in high-income countries received treatment. Highest-SES respondents were somewhat more likely to receive treatment, but this was true mostly for specialty mental health treatment, where the association was positive with education (highest treatment among respondents with the highest education and a weak association of education with treatment among other respondents) but non-monotonic with income (somewhat lower treatment rates among middle-income respondents and equivalent among those with high and low incomes).
The modest, but nonetheless stronger, an association of education than income with treatment raises questions about a financial barriers interpretation of the inverse association of SES with treatment, although future within-country analyses that consider contextual factors might document other important specifications. While beyond the scope of this report, such an expanded analysis could have important implications for designing interventions aimed at increasing mental disorder treatment among socio-economically disadvantaged people.
Previous studies in sheep and cattle have demonstrated that the urinary excretion of purine derivatives (PD) provides an index of the intestinal flow of microbial protein (Chen et al. 1990). Yak is the most important ruminant species in Tibetan Plateau. It was of interest to establish whether the approach of PD excretion to estimate microbial protein supply is applicable in yaks. The objective of this work is to measure the effect of fasting and different levels of feeding on PD excretion in yaks.
The feeding experiments were carried out in Xi-ning, China at an altitude of 3100m and a latitude of 36.8° N. Six 5-year old female yaks were used and 3 experiments were completed.
Quantification of lean body mass and fat mass can provide important insight into epidemiological research. However, there is no consensus on generalisable anthropometric prediction equations to validly estimate body composition. We aimed to develop and validate practical anthropometric prediction equations for lean body mass, fat mass and percent fat in adults (men, n 7531; women, n 6534) from the National Health and Nutrition Examination Survey 1999–2006. Using a prediction sample, we predicted each of dual-energy X-ray absorptiometry (DXA)-measured lean body mass, fat mass and percent fat based on different combinations of anthropometric measures. The proposed equations were validated using a validation sample and obesity-related biomarkers. The practical equation including age, race, height, weight and waist circumference had high predictive ability for lean body mass (men: R2=0·91, standard error of estimate (SEE)=2·6 kg; women: R2=0·85, SEE=2·4 kg) and fat mass (men: R2=0·90, SEE=2·6 kg; women: R2=0·93, SEE=2·4 kg). Waist circumference was a strong predictor in men only. Addition of other circumference and skinfold measures slightly improved the prediction model. For percent fat, R2 were generally lower but the trend in variation explained was similar. Our validation tests showed robust and consistent results with no evidence of substantial bias. Additional validation using biomarkers demonstrated comparable abilities to predict obesity-related biomarkers between direct DXA measurements and predicted scores. Moreover, predicted fat mass and percent fat had significantly stronger associations with obesity-related biomarkers than BMI did. Our findings suggest the potential application of the proposed equations in various epidemiological settings.
A model of Twin-cell Composite Box Beam (TCCBB), which is composed of concrete plate and thin-walled steel box beam with twin-cell, is proposed in this paper. Combined with structural features, longitudinal interfacial slip mode (LISM) and related shear hysteresis functions (SHFS) of this TCCBB model are defined respectively; analytical formulation describing combination effect between interfacial slip and shear lag is launched for this TCCBB model under even load. Based on established governing differential equations and its relative boundary conditions (calculated with compatible mechanism of interfacial slip and shear lag effect), closed form solutions of normal stress and shear stress are derived for this TCCBB model, as well as effective shear-lag coefficient and effective coupled behavior coefficient. To obtain more accurate computational results of specific coupled mechanism of this TCCBB model, numerical example is carried out to analyze and predict coupled mechanism of interfacial slip and shear lag effect for this type of composite structures.
OBJECTIVES/SPECIFIC AIMS: To compare the accuracy and precision for estimating the diagnostic accuracies (sensitivities and specificities) between differential verification (DV) and partial verification (PV) methods. Comparisons were made under scenarios with different values of design parameters including disease prevalence, proportion of verification for positive results, proportion of verification for negative result, sensitivity and specificity of the brass standard (BS) test in DV method. Through comparing 2 different verification methods under different scenarios, we give suggestions that which verification method is optimal under different design settings. METHODS/STUDY POPULATION: For both PV and DV methods, simulation studies were performed using statistical package R, version 3.1.3. We were primarily interested in studying how the unbiasedness and precision for estimation of diagnostic accuracies (sensitivity and specificity) of an index test change with the following design parameters: disease prevalence, proportion of verification for positive test results, the proportion of verification for negative test results, and the sensitivity and specificity of a BS test. We chose different values for each of the above parameters. For each estimation, we allowed values in only 1 parameter to change by fixing the other 2 parameters, so that the effect of each design parameter on the unbiasedness and precision of both sensitivity and specificity can be determined. For the DV method, we also developed an analytical method to estimate the sensitivity and specificity of an index test using a quadratic equation with a unique solution of the specificity and sensitivity. RESULTS/ANTICIPATED RESULTS: For rare disease with prevalence less than 1%, the PV method resulted in a less biased and more precise estimate of sensitivities and specificities of the index test. If the disease prevalence was between 1% and 10%, the DV method using a BS test with moderate or high sensitivity and specificity (sensitivity and specificity >90%) resulted in a less biased and more precise estimate of diagnostic accuracies of the index test. When the disease prevalence was greater than 10%, the PV method was superior when the BS test had sensitivity and specificity <80%, and the DV method was superior when the BS test had both sensitivity and specificity >90%. When the proportion of verification of positive test results was <30% or >70%, the DV method yielded smaller bias for the estimated specificity than the PV method. However, the PV method generated a much smaller mean square error (MSE) for specificity than the DV method when the proportion of verification for positive test results was >50%. Although the disease prevalence was >10% and the proportion of verification of positive test results was <30%, the DV method resulted in a smaller MSE for specificity. DISCUSSION/SIGNIFICANCE OF IMPACT: Disease prevalence and proportions of verification for patients with positive and negative test results influence the accuracy of a new diagnostic test. If a new index test for a very rare disease is evaluated, the PV method should be used for assessing the performance of the index test. When a disease prevalence is >1%, the DV method will result in a less biased and more precise estimate of diagnostic accuracy of an index test, if the BS test itself used in the DV method has large specificity and specificity. One concern of using BS test for the DV method is the clinical cost. Depending on the disease type, the BS tests usually are imperfect, but may be less aggressive and/or less expensive than the gold standard test. Moreover, as all clinical examinations require professional personnel to perform, verification of the index test for relative large proportion of a large cohort of patients could become a burden on human resources. Thus, the future research of the optimal design method for a diagnostic accuracy study should be based on the comprehensive cost-effectiveness analysis.
Identifying the transmission sources and reservoirs of Streptococcus pneumoniae (SP) is a long-standing question for pneumococcal epidemiology, transmission dynamics, and vaccine policy. Here we use serotype to identify SP transmission and examine acquisitions (in the same household, local community, and county, or of unidentified origin) in a longitudinal cohort of children and adults from the Navajo Nation and the White Mountain Apache American Indian Tribes. We found that adults acquire SP relatively more in the household than other age groups, and children 2–8 years old typically acquire in their own or surrounding communities. Age-specific transmission probability matrices show that transmissions within household were mostly seen from older to younger siblings. Outside the household, children most often transmit to other children in the same age group, showing age-assortative mixing behavior. We find toddlers and older children to be most involved in SP transmission and acquisition, indicating their role as key drivers of SP epidemiology. Although infants have high carriage prevalence, they do not play a central role in transmission of SP compared with toddlers and older children. Our results are relevant to inform alternative pneumococcal conjugate vaccine dosing strategies and analytic efforts to inform optimization of vaccine programs, as well as assessing the transmission dynamics of pathogens transmitted by close contact in general.
We comment on the proposition “that lower temperatures and especially greater seasonal variation in temperature call for individuals and societies to adopt … a greater degree of self-control” (Van Lange et al., sect. 3, para. 4) for which we cannot find empirical support in a large data set with data-driven analyses. After providing greater nuance in our theoretical review, we suggest that Van Lange et al. revisit their model with an eye toward the social determinants of self-control.
Introduction: In Canada, family physicians (FPs) provide the majority of early pregnancy care. To receive a same day US, most patients will be sent to the emergency department (ED). FPs are starting to use point of care ultrasound (POCUS) for a variety of indications. The FaMOUS course was modeled after the Canadian Emergency Ultrasound Society (CEUS) ED Echo (EDE) curriculum and adapted with permission for FPs. The objective of this study was to assess the indications for POCUS use in early pregnancy and determine the diagnostic accuracy of POCUS performed by FPs following FaMOUS certification to detect intrauterine pregnancy (IUP) and fetal cardiac activity (FCA). Methods: This was a prospective, observational study conducted in 3 FP clinics from November 2015 to June 2016. Pregnant women <20 weeks gestational age who underwent a focused, transabdominal POCUS by a FaMOUS-certified FP using a handheld GE VScan were enrolled. FPs documented the presence or absence of IUP and FCA. The reference standard was radiologist-interpreted US performed after the FP POCUS. FPs were surveyed to assess provider confidence using POCUS and perceived impact on clinical decision-making. Results: Of 253 eligible patients, 56 (22.1%) underwent POCUS. Of these, 50 (89.3%) had a radiologist-interpreted US following the office-based FP visit. POCUS was used for the following indications: 11 (19.6%) had vaginal bleeding, 5 (8.9%) had abdominal pain, 7 (12.5%) had both vaginal bleeding and abdominal pain, and the indication for 33 (58.9%) patients was unclear. All patients had a documented IUP, resulting in a sensitivity of 94.0% (95% CI: 83.5%, 98.5%) and 100% positive predictive value. FCA resulted in sensitivity of 82.9% (95% CI: 69.2, 92.4%) and specificity of 100% (95% CI: 29.2%, 100.0%). When surveyed, 100% of FPs were confident performing POCUS and reported POCUS had an overall positive impact on clinical practice. 75% agreed the use of POCUS decreased the need for urgent radiologist-interpreted US. Conclusion: Following a certification process modeled after the CEUS EDE curriculum, FPs used POCUS for both CEUS-defined indications and indications that were unclear. FPs trained in early pregnancy POCUS demonstrated excellent diagnostic accuracy identifying IUP and FCA. Future study should assess the clinical impact of office-based POCUS, including whether its use results in decreased ED visits for this patient population.