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 firstname.lastname@example.org
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.
Major depressive disorder (MDD) is a common, debilitating, phenotypically heterogeneous disorder with heritability ranges from 30% to 50%. Compared to other psychiatric disorders, its high prevalence, moderate heritability, and strong polygenicity have posed major challenges for gene-mapping in MDD. Studies of common genetic variation in MDD, driven by large international collaborations such as the Psychiatric Genomics Consortium, have confirmed the highly polygenic nature of the disorder and implicated over 100 genetic risk loci to date. Rare copy number variants associated with MDD risk were also recently identified. The goal of this review is to present a broad picture of our current understanding of the epidemiology, genetic epidemiology, molecular genetics, and gene–environment interplay in MDD. Insights into the impact of genetic factors on the aetiology of this complex disorder hold great promise for improving clinical care.
This research communication addressed the hypothesis that late lactation cows offered an oat-grain-based supplement or a high level of α-TOC supplementation at pasture would have improved milk composition and processability. Over a grazing period of 49 d, 48 Holstein Friesian dairy cows were randomly assigned to one of four dietary treatments. The dietary treatments were: control, pasture only (CTRL), pasture + 2.65 kg DM barley-based concentrate + 350 IU α-TOC/kg (BARLO), pasture + 2.65 kg DM oat-based concentrate + 350 IU α-TOC/kg (OATLO) and pasture + 2.65 kg DM oat-based concentrate + 1050 IU α-TOC/kg (OATHI). Within this randomised complete block design experiment cows were blocked on days in milk (DIM) and balanced for parity, milk yield and composition. Rennet coagulation time (RCT) was reduced in milk from cows offered OATHI compared to CTRL cows and OATLO. Concentration of conjugated linoleic acid (CLA) was increased by OATHI compared to OATLO and in OATLO compared to CTRL. Supplementation with OATHI reduced individual saturated fatty acids (SFAs) in milk compared to OATLO. In conclusion, supplementing grazing dairy cows with an oat-based supplement improved total milk CLA concentration compared to pasture only. Offering a high level of α-TOC (2931 IU/d) to dairy cows reduced RCT, individual SFA and increased total CLA concentration of milk compared to a lower α-TOC level (738 IU α-TOC/d).
The coronavirus disease 2019 (COVID-19) pandemic represents an unprecedented threat to mental health. Herein, we assessed the impact of COVID-19 on subthreshold depressive symptoms and identified potential mitigating factors.
Participants were from Depression Cohort in China (ChiCTR registry number 1900022145). Adults (n = 1722) with subthreshold depressive symptoms were enrolled between March and October 2019 in a 6-month, community-based interventional study that aimed to prevent clinical depression using psychoeducation. A total of 1506 participants completed the study in Shenzhen, China: 726 participants, who completed the study between March 2019 and January 2020 (i.e. before COVID-19), comprised the ‘wave 1’ group; 780 participants, who were enrolled before COVID-19 and completed the 6-month endpoint assessment during COVID-19, comprised ‘wave 2’. Symptoms of depression, anxiety and insomnia were assessed at baseline and endpoint (i.e. 6-month follow-up) using the Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7) and Insomnia Severity Index (ISI), respectively. Measures of resilience and regular exercise were assessed at baseline. We compared the mental health outcomes between wave 1 and wave 2 groups. We additionally investigated how mental health outcomes changed across disparate stages of the COVID-19 pandemic in China, i.e. peak (7–13 February), post-peak (14–27 February), remission plateau (28 February−present).
COVID-19 increased the risk for three mental outcomes: (1) depression (odds ratio [OR] = 1.30, 95% confidence interval [CI]: 1.04–1.62); (2) anxiety (OR = 1.47, 95% CI: 1.16–1.88) and (3) insomnia (OR = 1.37, 95% CI: 1.07–1.77). The highest proportion of probable depression and anxiety was observed post-peak, with 52.9% and 41.4%, respectively. Greater baseline resilience scores had a protective effect on the three main outcomes (depression: OR = 0.26, 95% CI: 0.19–0.37; anxiety: OR = 1.22, 95% CI: 0.14–0.33 and insomnia: OR = 0.18, 95% CI: 0.11–0.28). Furthermore, regular physical activity mitigated the risk for depression (OR = 0.79, 95% CI: 0.79–0.99).
The COVID-19 pandemic exerted a highly significant and negative impact on symptoms of depression, anxiety and insomnia. Mental health outcomes fluctuated as a function of the duration of the pandemic and were alleviated to some extent with the observed decline in community-based transmission. Augmenting resiliency and regular exercise provide an opportunity to mitigate the risk for mental health symptoms during this severe public health crisis.
Imaging of cellular layers in a gut-on-a-chip system has been confined to two-dimensional (2D)-imaging through conventional light microscopy and confocal laser scanning microscopy (CLSM) yielding three-dimensional- and 2D-cross-sectional reconstructions. However, CLSM requires staining and is unsuitable for longitudinal visualization. Here, we compare merits of optical coherence tomography (OCT) with those of CLSM and light microscopy for visualization of intestinal epithelial layers during protection by a probiotic Bifidobacterium breve strain and a simultaneous pathogen challenge by an Escherichia coli strain. OCT cross-sectional images yielded film thicknesses that coincided with end-point thicknesses derived from cross-sectional CLSM images. Light microscopy on histological sections of epithelial layers at the end-point yielded smaller layer thicknesses than OCT and CLSM. Protective effects of B. breve adhering to an epithelial layer against an E. coli challenge included the preservation of layer thickness and membrane surface coverage by epithelial cells. OCT does not require staining or sectioning, making OCT suitable for longitudinal visualization of biological films, but as a drawback, OCT does not allow an epithelial layer to be distinguished from bacterial biofilms adhering to it. Thus, OCT is ideal to longitudinally evaluate epithelial layers under probiotic protection and pathogen challenges, but proper image interpretation requires the application of a second method at the end-point to distinguish bacterial and epithelial films.
Klebsiella pneumoniae is a common pathogen associated with nosocomial infections and is characterised serologically by capsular polysaccharide (K) and lipopolysaccharide O antigens. We surveyed a total of 348 non-duplicate K. pneumoniae clinical isolates collected over a 1-year period in a tertiary care hospital, and determined their O and K serotypes by sequencing of the wbb Y and wzi gene loci, respectively. Isolates were also screened for antimicrobial resistance and hypervirulent phenotypes; 94 (27.0%) were identified as carbapenem-resistant (CRKP) and 110 (31.6%) as hypervirulent (hvKP). isolates fell into 58 K, and six O types, with 92.0% and 94.2% typeability, respectively. The predominant K types were K14K64 (16.38%), K1 (14.66%), K2 (8.05%) and K57 (5.46%), while O1 (46%), O2a (27.9%) and O3 (11.8%) were the most common. CRKP and hvKP strains had different serotype distributions with O2a:K14K64 (41.0%) being the most frequent among CRKP, and O1:K1 (26.4%) and O1:K2 (17.3%) among hvKP strains. Serotyping by gene sequencing proved to be a useful tool to inform the clinical epidemiology of K. pneumoniae infections and provides valuable data relevant to vaccine design.
Glaciers in the eastern Pamir have reportedly been gaining mass during recent decades, even though glaciers in most other regions in High Mountain Asia have been in recession. Questions still remain about whether the trend is strengthening or weakening, and how far the positive balances extend into the eastern Pamir. To address these gaps, we use three different digital elevation models to reconstruct glacier surface elevation changes over two periods (2000–09 and 2000–15/16). We characterize the eastern Pamir as a zone of transition from positive to negative mass balance with the boundary lying at the northern end of Kongur Tagh, and find that glaciers situated at higher elevations are those with the most positive balances. Most (67% of 55) glaciers displayed a net mass gain since the 21st century. This led to an increasing regional geodetic glacier mass balance from −0.06 ± 0.16 m w.e. a−1 in 2000–09 to 0.06 ± 0.04 m w.e. a−1 in 2000–15/16. Surge-type glaciers, which are prevalent in the eastern Pamir, showed fluctuations in mass balance on an individual scale during and after surges, but no statistical difference compared to non-surge-type glaciers when aggregated across the region.
Fundamental materials properties are determined by electrons under the potential energy from the nuclei, the electron mass, and their mutual repulsion. The variable from material to material is the ion potential. The logical procedure of computing electronic properties is to go from the potential to the electron distribution. This enables practical computation of the material properties ranging from atoms and molecules to solids. This method has blossomed due to the effort of numerous people. The concept is analogous to changing prediction of human population distribution from the landscape of hills and dales to determination of the landscape from a population distribution. In atomic systems, quantum quirkiness allows this switch, but dictates that it is only one slice in the tomography of the quantum state. The author shares his experience in the development from this slice, but hews close to the powerful concept of switching the landscape with the population.
We propose two linearly implicit energy-preserving schemes for the complex modified Korteweg–de Vries equation, based on the invariant energy quadratization method. First, a new variable is introduced and a new Hamiltonian system is constructed for this equation. Then the Fourier pseudospectral method is used for the space discretization and the Crank–Nicolson leap-frog schemes for the time discretization. The proposed schemes are linearly implicit, which is only needed to solve a linear system at each time step. The fully discrete schemes can be shown to conserve both mass and energy in the discrete setting. Some numerical examples are also presented to validate the effectiveness of the proposed schemes.
In recent years, men who have sex with men (MSM) constitute a major group of HIV transmission in China. High primary drug-resistance (PDR) rate in MSM also represents a serious challenge for the Chinese antiretroviral therapy (ART) program. To assess the efficiency of ART in controlling HIV/AIDS infection among MSM, we developed a compartmental model for the annually reported HIV/AIDS MSM from 2007 to 2019 in the Zhejiang Province of China. R0 was 2.3946 (95% CI (2.2961–2.4881)). We predict that 90% of diagnosed HIV/AIDS individuals will have received treatment till 2020, while the proportion of the diagnosed remains as low as 40%. Even when the proportion of the diagnosed reaches 90%, R0 is still larger than the level of AIDS epidemic elimination. ART can effectively control the spread of HIV, even in the presence of drug resistance. The 90-90-90 strategy alone may not eliminate the HIV epidemic in Chinese MSM. Behavioural and biologic interventions are the most effective interventions to control the HIV/AIDS epidemic among MSM.
Fluid motion has two well-known fundamental processes: the vector transverse process characterized by vorticity, and the scalar longitudinal process consisting of a sound mode and an entropy mode, characterized by dilatation and thermodynamic variables. The existing theories for the sound mode involve the multi-variable issue and its associated difficulty of source identification. In this paper, we define the source of sound inside the fluid by the objective causality inherent in dynamic equations relevant to a longitudinal process, which naturally favours the material time-rate operator
rather than the local time-rate operator
, and describes the sound mode by inhomogeneous advective wave equations. The sources of sound physical production inside the fluid are then examined at two levels. For the conventional formulation in terms of thermodynamic variables at the first level, we show that the universal kinematic source can be condensed to a scalar invariant of the surface deformation tensor. Further, in the formulation in terms of dilatation at the second level, we find that the sound mode in viscous and heat-conducting flow has sources from rich nonlinear couplings of vorticity, entropy and surface deformation, which cannot be disclosed at the first level. Preliminary numerical demonstration of the theoretical findings is made for two typical compressible flows, i.e. the interaction of two corotating Gaussian vortices and the unsteady type IV shock/shock interaction. The results obtained in this study provide a new theoretical basis for, and physical insight into, understanding various nonlinear longitudinal processes and the interactions therein.
At present, analysis of diet and bladder cancer (BC) is mostly based on the intake of individual foods. The examination of food combinations provides a scope to deal with the complexity and unpredictability of the diet and aims to overcome the limitations of the study of nutrients and foods in isolation. This article aims to demonstrate the usability of supervised data mining methods to extract the food groups related to BC. In order to derive key food groups associated with BC risk, we applied the data mining technique C5.0 with 10-fold cross-validation in the BLadder cancer Epidemiology and Nutritional Determinants study, including data from eighteen case–control and one nested case–cohort study, compromising 8320 BC cases out of 31 551 participants. Dietary data, on the eleven main food groups of the Eurocode 2 Core classification codebook, and relevant non-diet data (i.e. sex, age and smoking status) were available. Primarily, five key food groups were extracted; in order of importance, beverages (non-milk); grains and grain products; vegetables and vegetable products; fats, oils and their products; meats and meat products were associated with BC risk. Since these food groups are corresponded with previously proposed BC-related dietary factors, data mining seems to be a promising technique in the field of nutritional epidemiology and deserves further examination.
The relative effect of the atypical antipsychotic drugs and conventional agents on neurocognition in patients with early-stage schizophrenia has not been comprehensively determined.
The present study aimed to assess the cognitive effects of atypical and conventional antipsychotic drugs on neurocognition under naturalistic treatment conditions.
In a 12 months open-label, multicenter study, 698 patients with early-stage schizophrenia (< 5 years) were monotherapy with chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine or aripiprazole. Wechsler Memory Scale--Revised Visual Reproduction Test, Wechsler Adult Intelligence Scale Revised Digit Symbol Test and Digit-span Task Test, Trail Making Tests Part A and Part B, and Wisconsin Card Sorting Test were administered at baseline and 12 months follow-up evaluation. The primary outcome was change in a cognitive composite score after 12 months of treatment.
Compared with scores at baseline, the composite cognitive test scores and individual test scores had significant improvement for all seven treatment groups at 12-month follow-up evaluation (all p-values ≤ 0.013). However, olanzapine and quetiapine provided greater improvement than that provided by chlorpromazine and sulpiride in the composite score, processing speed and executive function (all p-values ≤ 0.045).
Both conventional and atypical antipsychotic medication long-term maintenance treatment can benefit congitive function in patients with early-stage schizophrenia, but olanzapine and quetiapine may be superior to chlorpromazine and sulpiride in improving some areas of neurocognitive function.
There are strong links between circadian disturbance and some of the most characteristic symptoms of clinical major depressive disorder (MDD). However there are no published studies of changes in expression of clock genes or of other neuropeptides related to circadian-rhythm regulation, which may influence recurrent susceptibility after treatment with antidepressant in MDD.
Blood samples were collected from twelve healthy controls and twelve male major depressive patients pre- and post- treated with escitalopram for eight weeks at 4-hour intervals for 24 hours. Outcome measures were the relative expression of mRNA of clock genes (hPERIOD1, hPERIOD2, hPERIOD3, hCRY1, hBMAL1, hNPAS2 and hGSK-3beta) and the levels of serum melatonin, Vasoactive Intestinal Peptide (VIP), cortisol, Adrenocorticotropic Hormone (ACTH), Insulin-like Growth Factor-1(IGF-1) and growth hormone (GH) in twelve healthy controls and twelve pre- and post- treated MDD patients.
Compared with healthy controls, MDD patients showed disruptions in diurnal rhythms of expression of hPERIOD1, hPERIOD2, hCRY1, hBMAL1, hNPAS2 and hGSK-3beta, along with disruptions in diurnal rhythms of release of melatonin, VIP, cortisol, ACTH, IGF-1, and GH. Several of these disruptions (hPER1, hCRY1, melatonin, VIP, cortisol, ACTH, and IGF-1) persisted after eight weeks escitalopram treatment, as did elevation of 24-hour levels of VIP and decreases in 24-hour levels of cortisol and ACTH.
These persisted neurobiological changes may play a role in MDD symptoms that are thought to contribute to recurrence vulnerability and in maintenance therapy for a long term.
Finding the prediction factors for the risks of post-stroke depression (PSD) is important to stroke survivors. However, most existing studies focused only on general clinical data, which limited the predictive ability. To improve the predictive ability, this study proposed a comprehensive PSD risk prediction model with social psychological factors, neurological, cognitive functional factors and general clinical factors.
The study recruited 188 stroke patients. Patients were diagnosed by DSM-IV criteria. Predictors were collected within a week after stroke. Boosted regression trees (BRT) was used to classify these predictors, and then a predictive model was constructed based on the selected predictors. The receiver operating characteristic (ROC) curve was used to determine the performance of the predictive model .
The risk prediction model was constructed with 6 factors: Body Mass Index (BMI), cerebral infraction history (CI), Social Support Rating Scale (SSRS), Eysenck Personality Questionnaire-Neuroticism (EPQ-N), factor 1 of the 20 items Toronto Alexithymia Scale (TAS-F1) and Snaith-Hamilton-Pleasure Scale (SHARPS). In the contribution of risk prediction factors, social psychological factors was more than 0.60. ROC curve of prediction model was 0.826 (p<0.001; 95% CI) and the accuracy of prediction was 0.81 (p<0.001). Transforming the prediction model to a tree diagram, it was convenient to clinic operation.
A PSD risk prediction model with good prediction performance was constructed to achieve diagnose concisely and clearly. The social psychological factors play an important role for diagnosing PSD in the early period.
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 aimed to comprehensively examine the association of breast-feeding, types and initial timing of complementary foods with adolescent cognitive development in low- and middle-income countries. We conducted a prospective cohort study of 745 adolescents aged 10–12 years who were born to women who participated in a randomised trial of prenatal micronutrient supplementation in rural Western China. An infant feeding index was constructed based on the current WHO recommendations. Full-scale intelligence quotient (FSIQ) was assessed and derived by the fourth edition of the Wechsler Intelligence Scale for Children. The duration of exclusive or any breast-feeding was not significantly associated with adolescent cognitive development. Participants who regularly consumed Fe-rich or Fe-fortified foods during 6–23 months of age had higher FSIQ than those who did not (adjusted mean differences 4·25; 95 % CI 1·99, 6·51). For cows’/goats’ milk and high protein-based food, the highest FSIQ was found in participants who initially consumed at 10–12 and 7–9 months, respectively. A strong dose–response relationship of the composite infant feeding index was also identified, with participants in the highest tertile of overall feeding quality having 3·03 (95 % CI 1·37, 4·70) points higher FSIQ than those in the lowest tertile. These findings suggest that appropriate infant feeding practices (breast-feeding plus timely introduction of appropriate complementary foods) were associated with significantly improved early adolescent cognitive development scores in rural China. In addition, improvement in Fe-rich or Fe-fortified foods complementary feeding may produce better adolescent cognitive development outcomes.
We established a mastitis model using exogenous infection of the mammary gland of Chinese Holstein cows with Staphylococcus aureus and extracted total RNA from S. aureus-infected and healthy mammary quarters. Differential expression of genes due to mastitis was evaluated using Affymetrix technology and results revealed a total of 1230 differentially expressed mRNAs. A subset of affected genes was verified via Q-PCR and pathway analysis. In addition, Solexa high-throughput sequencing technology was used to analyze profiles of miRNA in infected and healthy quarters. These analyses revealed a total of 52 differentially expressed miRNAs. A subset of those results was verified via Q-PCR. Bioinformatics techniques were used to predict and analyze the correlations among differentially expressed miRNA and mRNA. Results revealed a total of 329 pairs of negatively associated miRNA/mRNA, with 31 upregulated pairs of mRNA and 298 downregulated pairs of mRNA. Differential expression of miR-15a and interleukin-1 receptor-associated kinase-like 2 (IRAK2), were evaluated by western blot and luciferase reporter assays. We conclude that miR-15a and miR-15a target genes (IRAK2) constitute potential miRNA–mRNA regulatory pairs for use as biomarkers to predict a mastitis response.
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.
Seasonal influenza virus epidemics have a major impact on healthcare systems. Data on population susceptibility to emerging influenza virus strains during the interepidemic period can guide planning for resource allocation of an upcoming influenza season. This study sought to assess the population susceptibility to representative emerging influenza virus strains collected during the interepidemic period. The microneutralisation antibody titers (MN titers) of a human serum panel against representative emerging influenza strains collected during the interepidemic period before the 2018/2019 winter influenza season (H1N1-inter and H3N2-inter) were compared with those against influenza strains representative of previous epidemics (H1N1-pre and H3N2-pre). A multifaceted approach, incorporating both genetic and antigenic data, was used in selecting these representative influenza virus strains for the MN assay. A significantly higher proportion of individuals had a ⩾four-fold reduction in MN titers between H1N1-inter and H1N1-pre than that between H3N2-inter and H3N2-pre (28.5% (127/445) vs. 4.9% (22/445), P < 0.001). The geometric mean titer (GMT) of H1N1-inter was significantly lower than that of H1N1-pre (381 (95% CI 339–428) vs. 713 (95% CI 641–792), P < 0.001), while there was no significant difference in the GMT between H3N2-inter and H3N2-pre. Since A(H1N1) predominated the 2018–2019 winter influenza epidemic, our results corroborated the epidemic subtype.