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Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
This paper describes a computational investigation of multimode instability growth and multimaterial mixing induced by multiple shock waves in a high-energy-density (HED) environment, where pressures exceed 1 Mbar. The simulations are based on a series of experiments performed at the National Ignition Facility (NIF) and designed as an HED analogue of non-HED shock-tube studies of the Richtmyer–Meshkov instability and turbulent mixing. A three-dimensional computational modelling framework is presented. It treats many complications absent from canonical non-HED shock-tube flows, including distinct ion and free-electron internal energies, non-ideal equations of state, radiation transport and plasma-state mass diffusivities, viscosities and thermal conductivities. The simulations are tuned to the available NIF data, and traditional statistical quantities of turbulence are analysed. Integrated measures of turbulent kinetic energy and enstrophy both increase by over an order of magnitude due to reshock. Large contributions to enstrophy production during reshock are seen from both the baroclinic source and enstrophy–dilatation terms, highlighting the significance of fluid compressibility in the HED regime. Dimensional analysis reveals that Reynolds numbers and diffusive Péclet numbers in the HED flow are similar to those in a canonical non-HED analogue, but conductive Péclet numbers are much smaller in the HED flow due to efficient thermal conduction by free electrons. It is shown that the mechanism of electron thermal conduction significantly softens local spanwise gradients of both temperature and density, which causes a minor but non-negligible decrease in enstrophy production and small-scale mixing relative to a flow without this mechanism.
This study assesses the prevalence of childhood undernutrition from 2001 to 2016 and estimate projections of undernutrition for 2016–2030 in Nepal.
The study used data from four rounds of a cross-sectional survey of Nepal Demographic and Health Survey (NDHS) conducted in 2001, 2006, 2011 and 2016. Descriptive analyses were conducted to calculate prevalence, binary logistic regression was used to test the significance of trends over time and autoregressive integrated moving average model was used to forecast the prevalence of childhood undernutrition.
The children and household member datasets from four NDHS were merged to assess the trends of childhood undernutrition in Nepal.
A total of 16 613 children (8399 male and 8214 female) under 5 years of age were selected for anthropometric measurements using a stratified cluster random sampling method.
Overall results show a decline in prevalence of stunting from 57·2 % to 35·8 % (P < 0·001), underweight from 42·7 % to 27 % (P < 0·001) and wasting from 11·2 % to 9·7 % (P < 0·05) from 2001 to 2016. However, different population subgroups have a higher prevalence of undernutrition than national average. Further, the analyses show that the prevalence of stunting will decline to 14·3 % and wasting to 8·4 % by 2030.
A remarkable decrease in the prevalence of stunting and underweight has been observed over the last 15 years. Nepal is likely to achieve the nutritional targets for stunting but not for wasting by 2030. Given large subpopulation variations, further improvement in undernutrition require more specific, targeted and localised programmes.
One of the leading challenges in chemical sciences is the separation of complex mixtures. This is of vital importance for areas such as commodity chemical generation, where there is a need for the generation of high-purity chemical streams. Due to this, there has been a strong push toward the investigation of new materials capable of achieving chemoselective separation, with self-assembled materials having shown a great deal of promise for such separations. Many self-assembled materials are desirable candidates due to their low-cost synthesis, structural self-regulation, tunable properties, and an overall ease of composite material preparation. In this article, we aim to introduce examples of novel self-assembled materials and their practical usage in chemical separations. The specific approaches to fabricate these materials, as well as the strengths and shortcomings associated with their structures, will also be described. The strategies presented here will emphasize the production and employment of nonconventional self-assembled materials that exhibit a high potential for the advancement of the science of chemical separations.
In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.
Introduction: Inhaled toxins from tobacco smoking, cannabis leaf smoking as well as vaping/e-cigarette products use are known causes of cardio-respiratory injury. While tobacco smoking has decreased among Canadian adults, there are now several other forms of legal inhalant products. While legal, the evidence of benefit and safety of vaping is limited. Of concern, cases of e-cigarette or vaping products use associated lung injury (EVALI) have been accumulating in the U.S. and now in Canada. Despite this, very little is known about the inhalation exposure of emergency department (ED) patients; this study was designed to explore lung health in the ED. Methods: We investigated the prevalence of exposure to vaping, tobacco and cannabis among patients presenting to a Canadian ED from July to November 2019. Ambulatory (CTAS 2 to 5), stable, adult (≥ 17 years) patients were prospectively identified and invited to complete a survey addressing factors related to lung health (previous diagnosis of respiratory conditions and respiratory symptoms at the ED presentation) and information on current exposure to vaping, tobacco and cannabis smoking. Categorical variables are reported as frequencies and percentages; continuous variables are reported as medians with interquartile range (IQR). The study was approved by the Health Research Ethics Board. Results: Overall, 1024 (71%) of 1433 eligible patients completed the survey. The median age was 43.5 (IQR: 29, 60), and 51% were female. A total of 351 (31%) participants reported having been previously diagnosed with ≥1 respiratory conditions, and 177 (17%) were visiting the ED as a result of ≥1 respiratory symptoms (e.g., cough, shortness of breath, wheezing). Daily tobacco smoking was reported by 190 (19%), and 83 (8%) reported using vaping/e-cigarette products. Cannabis use within 30 days was described by 80 (15%) respondents. Exposure to tobacco and vaping products was reported by 39 (4%) participants, 63 (6%) reported using tobacco in combination with cannabis smoking, and 3% reported combining vaping and cannabis use. Conclusion: Patients seeking care in the ED are exposed to a large quantity of inhaled toxins. Vaping products, considered the cause of the most recent epidemic of severe lung injury, are used in isolation and in combination with other smoking products in Canada. These exposures should be documented and may increase the risk of lung health injuries and exacerbations of chronic respiratory conditions.
Introduction: Despite being legal in Canada, the vaporized liquid of vaping systems contains several chemicals presenting unknown risks to lung health and little is known about their use in patients visiting the emergency department (ED). This study explores associations between exposure to inhaled products and respiratory presentations in the ED. Methods: A cross-sectional lung health survey among patients presenting to a Canadian ED was conducted, exploring the association between inhaled toxic exposures (e.g., vaping, cannabis and cigarette smoking) and visits related to respiratory symptoms. Eligible participants were ambulatory (CTAS 2 to 5), stable, adults (≥ 17 years) visiting the ED from July to November, 2019. Results are described as frequencies and percentages (categorical variables) and medians with interquartile range (IQR, continuous variables). Univariate and multivariate logistic regression models report associations as odds ratios (OR) with 95% confidence intervals (CIs). The Health Research Ethics Board approved the study. Results: From 1433 eligible patients, 1024 (71%) completed the survey. The median age was 43.5 (IQR: 29, 60), and 51% were female. Overall, 177 (17%) reported ≥1 respiratory symptoms and 83 (8%) reported using any vaping products. In a univariate regression analysis, exposure to vaping was positively associated with ED visits related to respiratory symptoms (OR 2.11, 95% CI: 1.26 to 3.54). In the multivariate model, vaping and a previous diagnosis of ≥1 respiratory conditions showed positive association with respiratory-related ED visits (OR 1.86, 95% CI: 1.03 to 3.33; and OR 2.13, 95% CI: 1.50 to 3.02, respectively). There was evidence of an additive effect of the combined exposure to cigarettes and vaping and respiratory-related ED visits (OR 3.22, 95% CI: 1.61 to 6.43). Smoking cannabis and cigarettes alone were not associated with increased risk of respiratory-related visits. Conclusion: Using vaping products increased the occurrence of respiratory-related ED visits, particularly in people with pre-existing lung conditions. A dose-response relationship exists where the risk is highest in patients inhaling a combination of toxins. Contrary to previous assumptions, the use of vaping products has a negative impact on lung health.
Earlier studies examining structural brain abnormalities associated with cognitively derived subgroups were mainly cross-sectional in design and had mixed findings. Thus, we obtained cross-sectional and longitudinal data to characterize the extent and trajectory of brain structure abnormalities underlying distinct cognitive subtypes (“preserved,” “deteriorated,” and “compromised”) seen in psychotic spectrum disorders.
Data from 364 subjects (225 patients with psychotic conditions and 139 healthy controls) were first used to determine the relationship of cognitive subtypes with cross-sectional measures of subcortical volume and cortical thickness. To probe neurodevelopmental abnormalities, brain structure laterality was examined. To examine whether neuroprogressive abnormalities persist, longitudinal brain structural changes over 5 years were examined within a subset of 101 subjects. Subsequent discriminant analysis using the identified brain measures was performed on an independent subject group.
Cross-sectional comparisons showed that cortical thinning and limbic volume reductions were most widespread in “deteriorated” cognitive subtype. Laterality comparisons showed more rightward amygdala lateralization in “compromised” than “preserved” subtype. Longitudinal comparisons revealed progressive hippocampal shrinkage in “deteriorated” compared with healthy controls and “preserved” subtype, which correlated with worse negative symptoms, cognitive and psychosocial functioning. Post-hoc discrimination analysis on an independent group of 52 subjects using the identified brain structures found an overall accuracy of 71% for classification of cognitive subtypes.
These findings point toward distinct extent and trajectory of corticolimbic abnormalities associated with cognitive subtypes in psychosis, which can allow further understanding of the biological course of cognitive functioning over illness course and with treatment.
Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.
Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.
The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.
Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.
The majority of neuroimaging studies reported smaller hippocampal volumes in patients with posttraumatic stress disorder (PTSD). Our previous study found that PTSD is associated with selective volume loss of the CA3/dentate gyrus subfields However, the causality of smaller hippocampal volumes and PTSD cannot be determined in these studies because of the cross-sectional nature of them. The purpose of this longitudinal study was to determine if PTSD caused hippocampal subfields volume loss following traffic accidents. Volumes of hippocampal subfields in thirty seven traffic accident survivors were measured using 3T MRI in one week after accident, and twenty five of them completed one year follow-up MRI scan. Fourteen participants met the PTSD diagnosis in one year follow-up while other eleven did not met PTSD diagnosis criteria. PTSD was significantly associated with volumes reduction of CA3/dentate gyrus subfield (β=0.244 p=0.017) while other subfields were spared. It also shown volume loses of Entorhinal Cortex (ERC) of both side in one year follow-up for the whole sample (mean volume reduction: right 19.25mm3, left 22.04 mm3). But no association has been found between PTSD and ERC volume alteration. The findings indicate for the first time in humans that selective volume loss of the CA3/dentate gyrus subfields is the results but not the risk factor of PTSD. It also suggested that ERC may also be a stress sensitive region.
In this study, we aimed to identify protein molecules in the hypothalamus in the female rats injected exogenous androgen before sexual differentiation.
Neonatal female SD rats were randomly divided into two groups: experimental group and control female group. Four neonatal male SD rats were control male group. All animals were subjected to intraperitoneal injection of testosterone propionate as experimental group or aseptic oil as control. The rats were sacrificed 90 days after the injection and the brains were collected. 2-DE were performed in order to establish profiles of proteome from rat hypothalamus and followed by MALDITOF- TOF mass spectrometry was used to identify proteins differentially expressed in rat hypothalamus from experimental group as compared to normal control group.
11 differential spots were cut off from the Silver stained gel, and 9 of the spots were identified, which were Dihydropyrimidinase-like 3 (DPYSL3), heterogeneous nuclear ribonucleoprotein K(hnRNP K), Profilin2, Triosephosphate isomerase 1(Tpi 1), Carbonic anhydrase II(CA II), Annexin A3, Protein disulfide isomerase associated 3 (PDIA3), Creatine kinase-B and Secernin 1.
The results of the present study indicate that the development of sexual differentiation may be associated with the alteration in the expression of a large number of cytosolic proteins in the hypothalamus.
The aim of this study was to develop and externally validate a simple-to-use nomogram for predicting the survival of hospitalised human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients (hospitalised person living with HIV/AIDS (PLWHAs)). Hospitalised PLWHAs (n = 3724) between January 2012 and December 2014 were enrolled in the training cohort. HIV-infected inpatients (n = 1987) admitted in 2015 were included as the external-validation cohort. The least absolute shrinkage and selection operator method was used to perform data dimension reduction and select the optimal predictors. The nomogram incorporated 11 independent predictors, including occupation, antiretroviral therapy, pneumonia, tuberculosis, Talaromyces marneffei, hypertension, septicemia, anaemia, respiratory failure, hypoproteinemia and electrolyte disturbances. The Likelihood χ2 statistic of the model was 516.30 (P = 0.000). Integrated Brier Score was 0.076 and Brier scores of the nomogram at the 10-day and 20-day time points were 0.046 and 0.071, respectively. The area under the curves for receiver operating characteristic were 0.819 and 0.828, and precision-recall curves were 0.242 and 0.378 at two time points. Calibration plots and decision curve analysis in the two sets showed good performance and a high net benefit of nomogram. In conclusion, the nomogram developed in the current study has relatively high calibration and is clinically useful. It provides a convenient and useful tool for timely clinical decision-making and the risk management of hospitalised PLWHAs.
We examine the scaling of the two-point correlation function for
, the energy dissipation rate, over a range of values of the separation
between the two points and the Taylor microscale Reynolds number
. The correlation function is estimated from hot-wire measurements in grid turbulence, along the axes of wakes and jets, and along the centreline of a fully developed channel flow. When
exceeds a value of approximately 300, a condition which is achieved for both plane and circular jets, the correlation function collapses over nearly all values of
when the normalization uses Kolmogorov scales. However, there is no collapse in either the power-law range or dissipative range when the normalization is on the integral (or external) length scale, which indicates that there is no self-similarity based on external scales. Although the maximum value of
is not much larger than
, the behaviour of the energy dissipation correlation function on the axes of plane and circular jets seems consistent with the first similarity hypothesis of Kolmogorov (Dokl. Akad. Nauk SSSR, vol. 30, 1941, pp. 299–303) but not with the revised phenomenology of Kolmogorov (J. Fluid Mech., vol. 13, 1962, pp. 82–85).
In this paper, a novel continuous fiber reinforced piezoelectric composite (CFRPC) actuator is proposed to improve the stability and reliability of piezoelectric actuators. A piezoelectric driving structure composed of a cantilever beam and the CFRPC actuator is utilized to research the actuation performance of the CFRPC actuator. The expression of the equivalent moment for the CFRPC actuator is obtained using the equivalent load method and electro-mechanical coupling theory. Based on Euler-Bernoulli beam theory, the analytical expression of the deflection for the cantilever beam is derived. The accuracy of the obtained analytical expressions is demonstrated by finite element simulation as well as published experimental results. The actuation performance of the CFRPC actuator is investigated through the analytical expressions of the equivalent moment and deflection. The results show that the key parameters such as driving voltage, fiber volume fraction, cantilever beam height, actuator height, actuator length and actuator position have great influence on the actuation performance of the CFRPC actuator. The CFRPC actuator has good mechanical and electrical properties, and has a wide application prospect in the field of structural shape control.
This paper focus on the mechanical and martensitic transformation behaviors of axially functionally graded shape memory alloy (AFG SMA) beams. It is taken into consideration that material properties, such as austenitic elastic modulus, martensitic elastic modulus, critical transformation stresses and maximum transformation strain vary continuously along the longitudinal direction. According to the simplified linear SMA constitutive equations and Bernoulli-Euler beam theory, the formulations of stress, strain, martensitic volume fraction and governing equations of the deflection, height and length of transformed layers are derived. Employing the Galerkin’s weighted residual method, the governing differential equation of the deflection is solved. As an example, the bending behaviors of an AFG SMA cantilever beam subjected to an end concentrated load are numerically analyzed using the developed model. Results show that the mechanical and martensitic transformation behaviors of the AFG SMA beam are complex after the martensitic transformation of SMA occurs. The influences of FG parameter on the mechanical behaviors and geometrical shape of transformed regions are obvious, and should be considered in the design and analysis of AFG SMA beams in the related regions.
Drug Safety Communications (DSCs) are used by the Food and Drug Administration (FDA) to inform health care providers, patients, caregivers, and the general public about safety issues related to FDA-approved drugs. To assess patient knowledge of the messaging contained in DSCs related to the sleep aids zolpidem and eszopiclone, we conducted a large, cross-sectional patient survey of 1,982 commercially insured patients selected by stratified random sampling from the Optum Research Database who had filled at least two prescriptions for either zolpidem or eszopiclone between July 1, 2012 and June 30, 2013. Among the 594 respondents (32.7% response rate), two-thirds reported hearing generally about drug safety information prior to starting a new drug, with the remaining one-third “rarely” or “never” hearing such information. Providers and pharmacists were primary sources of drug safety information. Two-thirds of zolpidem users and half of eszopiclone users reported having heard about the related DSC messages, ability to accurately identify the major factual messages was limited (overall median 2 correct out of 5, with men and those reporting higher educational level scoring higher [2/5 vs. 1/5, p=0.001]). Respondents reacted to new drug safety information about their sleep aids by reporting that they would want to learn about alternative ways to help them sleep (70%) and seek out more information about the safety of their specific sleeping pill (59-78%). Opportunities may exist for the FDA to work with providers and pharmacies to help ensure the DSC information is more widely received and is more fully understood by those taking the affected medications.
We recently reported Cambrowania ovata Tang and Xiao in Tang et al., 2019, from the early Cambrian Hetang Formation in South China and interpreted it as a problematic animal fossil, possibly related to either sponges or bivalved arthropods (Tang et al., 2019). Slater and Budd (2019) contested our taxonomic identification and phylogenetic interpretation; instead, they claimed that Cambrowania ovata is a large acritarch referable to morphotaxon Leiosphaeridia Eisenack, 1958, and thus is not an animal. Here we refute their criticisms, clarify the differences between Cambrowania and Leiosphaeridia and other acritarchs, and reiterate why an animal affinity for Cambrowania cannot be ruled out.