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Networks contain complex patterns of dependency and require multiple levels of analysis to explain their formation, structure, and outcomes. In this Element, the authors develop the Multilevel Network Framework. The framework serves as (i) a conceptual tool to think more deeply about network dynamics, (ii) a research tool to assist in connecting data, theory, and empirical models, and (iii) a diagnostic tool to analyze and categorize bodies of research. The authors then systematically review the network literature in public administration, management, and policy. They apply the Multilevel Network Framework to categorize the literature; identify significant gaps; examine micro, macro and cross-level relations; and examine relevant mechanisms and theories. Overall this Element helps readers to (i) understand and classify network research, (ii) use appropriate theoretical frameworks to examine network-related problems, (iii) understand how networks emerge and produce effects at different levels of analysis, and (iv) select appropriate empirical models.
Although many previous studies reported structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy (ECT) in major depressive disorder (MDD), yet the exact roles of both areas for antidepressant effects are still controversial.
In the current study, segmentation of amygdala and hippocampal sub-regions was used to investigate the longitudinal changes of volume, the relationship between volume and antidepressant effects, and prediction performances for ECT in MDD patients before and after ECT using two independent datasets.
As a result, MDD patients showed selectively and consistently increased volume in the left lateral nucleus, right accessory basal nucleus, bilateral basal nucleus, bilateral corticoamygdaloid transition (CAT), bilateral paralaminar nucleus of the amygdala, and bilateral hippocampus-amygdala transition area (HATA) after ECT in both datasets, whereas marginally significant increase of volume in bilateral granule cell molecular layer of the head of dentate gyrus, the bilateral head of cornu ammonis (CA) 4, and left head of CA 3. Correlation analyses revealed that increased volume of left HATA was significantly associated with antidepressant effects after ECT. Moreover, volumes of HATA in the MDD patients before ECT could be served as potential biomarkers to predict ECT remission with the highest accuracy of 86.95% and 82.92% in two datasets (The predictive models were trained on Dataset 2 and the sensitivity, specificity and accuracy of Dataset 2 were obtained from leave-one-out-cross-validation. Thus, they were not independent and very likely to be inflated).
These results not only suggested that ECT could selectively induce structural plasticity of the amygdala and hippocampal sub-regions associated with antidepressant effects of ECT in MDD patients, but also provided potential biomarkers (especially HATA) for effectively and timely interventions for ECT in clinical applications.
The epidemic of drug-resistant tuberculosis (DR-TB) has become a major concern in global TB control. This study aimed to investigate the patterns and trend of DR-TB epidemic between different time periods in Chongqing.
A total of 985 and 835 culture positive TB patients with drug susceptibility testing (DST) results admitted to the hospital in 2016 and 2019, respectively, were included. Chi-square testing was used to compare the prevalence and trends of DR-TB in 2016 and 2019.
The proportion of previously treated TB cases with culture positivity was 45.7% in 2019, significantly higher than that in 2016 (39.1%, P = 0.004). The overall rate of drug resistance in 2019 was 43.1%, higher than that in 2016 (40.2%). The rates of multi-drug resistant TB (MDR-TB) and pre-extensively drug resistant TB (pre-XDR-TB) increased significantly from 2016 to 2019 among all TB cases (MDR: 25% vs 33.4%, P < 0.001 and pre-XDR: 7.1% vs 12.8%, P < 0.001, respectively) and previously treated TB cases (MDR: 46.5% vs 56%, P = 0.008 and pre-XDR: 13.2% vs 21.5%, P = 0.003, respectively).
Our findings indicated that the prevalence of DR-TB remains high in Chongqing. The trend of resistance to anti-TB drugs beccame worse between 2016 and 2019. Moreover, acquired MDR may play a major role in MDR-TB epidemic in Chongqing. Therefore, rapid diagnosis and effective treatment of TB patients will be important to reduce the burden of DR-TB in Chongqing.
The pandemic caused by severe acute respiratory syndrome coronavirus 2 is sweeping the world, threatening millions of lives and drastically altering our ways of living. According to current studies, failure to either activate or eliminate inflammatory responses timely and properly at certain stages could result in the progression of the disease. In other words, robust immune responses to coronavirus disease 2019 (COVID-19) are critical. However, they do not theoretically present in some special groups of people, including the young, the aged, patients with autoimmunity or cancer. Differences also do occur between men and women. Our immune system evolves to ensure delicate coordination at different stages of life. The innate immune cells mainly consisted of myeloid lineage cells, including neutrophils, basophils, eosinophils, dendritic cells and mast cells; they possess phagocytic capacity to different degrees at different stages of life. They are firstly recruited upon infection and may activate the adaptive immunity when needed. The adaptive immune cells, on the other way, are comprised mainly of lymphoid lineages. As one grows up, the adaptive immunity matures and expands its memory repertoire, accompanied by an adjustment in quantity and quality. In this review, we would summarise and analyse the immunological characteristics of these groups from the perspective of the immune system ‘evolution’ as well as ‘revolution’ that has been studied and speculated so far, which would aid the comprehensive understanding of COVID-19 and personalised-treatment strategy.
The mumps resurgence has frequently been reported around the world in recent years, especially in many counties mumps vaccines have been widely used. This study aimed to describe the spatial epidemiological characteristics of mumps in Jiangsu, and provide a scientific basis for the implementation and adjustment of strategies to prevent and control mumps. The epidemiological characteristics were described with ratio or proportion. Spatial autocorrelation, Tango's flexible spatial scan statistics, and Kulldorff's elliptic spatiotemporal scan statistics were applied to identify the spatial autocorrelation, detect hot and cold spots of mumps incidence, and aggregation areas. A total of 172 775 cases were reported from 2004 to 2020 in Jiangsu. The general trend of mumps incidence is declining with a bimodal seasonal distribution identified mainly in summer and winter, respectively. Children aged 5–10 years old are the main risk group. A migration trend of hot spots from southeast to northwest over time was found. Similar high-risk aggregations were detected in the northwestern parts through spatial-temporal analysis with the most likely cluster time frame around 2019. Local medical and health administrations should formulate and implement targeted health care policies and allocate health resources more appropriately corresponding to the epidemiological characteristics of mumps.
In centrifugal compressors, the identification of flow instability signals from experiments is a difficult problem owing to the nonlinear and non-stationary characteristics. Otherwise, the complicated asymmetric structure of the volute brings a huge challenge to the evolution and circumferential nonuniformity characteristics of the flow instabilities. This paper presents experimental and numerical investigations on internal flow field to understand the flow instability characteristics in a centrifugal compressor. Considering nonlinear and non-stationary signals, a method based on Fourier-transform and variational mode decomposition was introduced to analyse the flow instability characteristics. The Fourier spectrum results show that at 0.21kg/s of 80krpm, the pressure signal has a noticeable high-frequency fluctuation, which indicates that the compressor enters the flow instability state. The variational mode decomposition results show that before a surge, the compressor experiences different flow instability stages: the RI stage, the coexistence stage of RI and stall, and the stall stage. Moreover, obvious circumferential nonuniformity characteristics of flow instabilities were observed during the throttling process. RI first occurred at the 180° circumferential position and then the stall first appeared in the circumferential range of 60° to 240°. The simulation results that it is because that the asymmetric volute causes the adverse pressure gradient inside the impeller passage and a high-pressure region (120°–240°) at the upstream of the impeller inlet. Under this combined action of the two, the effect region of tip leakage vortex expands the upstream of the impeller inlet. Meanwhile, the tip leakage vortex core migrates to a lower span of blades. This study demonstrates the ability to analyse nonlinear and non-stationary signals from a centrifugal compressor via variational mode decomposition, and provides a useful guidance for the identification of flow instability signals.
To examine the association between adherence to plant-based diets and mortality.
Prospective study. We calculated a plant-based diet index (PDI) by assigning positive scores to plant foods and reverse scores to animal foods. We also created a healthful PDI (hPDI) and an unhealthful PDI (uPDI) by further separating the healthy plant foods from less-healthy plant foods.
The VA Million Veteran Program.
315 919 men and women aged 19–104 years who completed a FFQ at the baseline.
We documented 31 136 deaths during the follow-up. A higher PDI was significantly associated with lower total mortality (hazard ratio (HR) comparing extreme deciles = 0·75, 95 % CI: 0·71, 0·79, Ptrend < 0·001]. We observed an inverse association between hPDI and total mortality (HR comparing extreme deciles = 0·64, 95 % CI: 0·61, 0·68, Ptrend < 0·001), whereas uPDI was positively associated with total mortality (HR comparing extreme deciles = 1·41, 95 % CI: 1·33, 1·49, Ptrend < 0·001). Similar significant associations of PDI, hPDI and uPDI were also observed for CVD and cancer mortality. The associations between the PDI and total mortality were consistent among African and European American participants, and participants free from CVD and cancer and those who were diagnosed with major chronic disease at baseline.
A greater adherence to a plant-based diet was associated with substantially lower total mortality in this large population of veterans. These findings support recommending plant-rich dietary patterns for the prevention of major chronic diseases.
A multidecadal-resolved stalagmite δ18O record from two nearby caves, Lianhua and Dragon, in Shanxi Province, northern China, characterizes the detailed East Asian summer monsoon (EASM) intensity changes at 114.6–108.3 ka during Marine Oxygen Isotope Stage 5d. Our record shows an intensification of the EASM at 114.6–109.5 ka, followed by a rapid weakening at 109.5–108.4 ka. The millennial-scale strong monsoonal event appears to be correlated with the warm Greenland interstadial 25 (GI 25), whereas the weak monsoonal event is related to the cold Greenland stadial 25 within dating errors. The GI 25 monsoonal event registered in our record is also documented in various published time series from different regions of China. The lines of evidence indicate that this event occurred over the entirety of monsoonal China and was also broadly antiphase, similar to the corresponding event on a millennial time scale in the South American monsoon territory. In our record, one 700 yr weak monsoon event at 110.7+0.6−0.5 to 110.0+0.8−0.4 ka divides the GI 25 into three substages. These multicentennial to millennial–scale monsoon events correspond to two warm periods and an intervening cold interval for the intra-interstadial climate oscillations within GI 25, thus supporting a persistent coupling of the high- and low-latitude climate systems over the last glacial period.
The wheat aphid Sitobion miscanthi (CWA) is an important harmful pest in wheat fields. Insecticide application is the main method to effectively control wheat aphids. However, CWA has developed resistance to some insecticides due to its extensive application, and understanding resistance mechanisms is crucial for the management of CWA. In our study, a new P450 gene, CYP4CJ6, was identified from CWA and showed a positive response to imidacloprid and thiamethoxam. Transcription of CYP4CJ6 was significantly induced by both imidacloprid and thiamethoxam, and overexpression of CYP4CJ6 in the imidacloprid-resistant strain was also observed. The sensitivity of CWA to these two insecticides was increased after the knockdown of CYP4CJ6. These results indicated that CYP4CJ6 could be associated with CWA resistance to imidacloprid and thiamethoxam. Subsequently, the posttranscriptional regulatory mechanism was assessed, and miR-316 was confirmed to participate in the posttranscriptional regulation of CYP4CJ6. These results are crucial for clarifying the roles of P450 in the resistance of CWA to insecticides.
Neuroimaging studies on major depressive disorder (MDD) have identified an extensive range of brain structural abnormalities, but the exact neural mechanisms associated with MDD remain elusive. Most previous studies were performed with voxel- or surface-based morphometry which were univariate methods without considering spatial information across voxels/vertices.
Brain morphology was investigated using voxel-based morphometry (VBM) and source-based morphometry (SBM) in 1082 MDD patients and 990 healthy controls (HCs) from the REST-meta-MDD Consortium. We first examined group differences in regional grey matter (GM) volumes and structural covariance networks between patients and HCs. We then compared first-episode, drug-naïve (FEDN) patients, and recurrent patients. Additionally, we assessed the effects of symptom severity and illness duration on brain alterations.
VBM showed decreased GM volume in various regions in MDD patients including the superior temporal cortex, anterior and middle cingulate cortex, inferior frontal cortex, and precuneus. SBM returned differences only in the prefrontal network. Comparisons between FEDN and recurrent MDD patients showed no significant differences by VBM, but SBM showed greater decreases in prefrontal, basal ganglia, visual, and cerebellar networks in the recurrent group. Moreover, depression severity was associated with volumes in the inferior frontal gyrus and precuneus, as well as the prefrontal network.
Simultaneous application of VBM and SBM methods revealed brain alterations in MDD patients and specified differences between recurrent and FEDN patients, which tentatively provide an effective multivariate method to identify potential neurobiological markers for depression.
We examined whether physical activity (PA) explains the association between dietary inflammatory potential and osteoarthritis (OA) in the elderly. A total of 1249 elderly people (≥65 years) were eligible for this study from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. The semi-quantitative Food Frequency Questionnaire (FFQ) and Global PA Questionnaire (GPAQ) were used to evaluate the diet and PA of the elderly, respectively. The multivariable logistic regression model estimated the odds ratio (OR) and 95% confidence interval (CI) between Energy-adjusted Dietary Inflammatory Index (E-DII) and OA. The interaction of E-DII and PA on depressive events was tested, and the mediation analysis of PA was performed. The average E-DII in this study was +0.68 (SE 0.08), and the score ranges from -5.32 (most anti-inflammatory) to +4.26 (most pro-inflammatory). In comparison with the first quartile, the elderly from the second quartile (OR: 1.16 [95% CI: 1.06, 1.68]) to the fourth quartile (OR: 1.64 [95% CI: 1.13, 2.37]) had a higher risk of OA before adjustment for PA. An interaction was observed between E-DII and PA in terms of the risk of OA (PInteraction < 0.001). The whole related part was mediated by PA (20.08%). Our findings indicated that the higher pro-inflammatory potential of diet was associated with a higher risk of OA, and low PA was an important part of the mediating factor in the relationship between systemic low-grade dietary inflammation and the risk of OA.
Schizophrenia is a severely debilitating psychiatric disorder with high heritability and polygenic architecture. A higher polygenic risk score for schizophrenia (SzPRS) has been associated with smaller gray matter volume, lower activation, and decreased functional connectivity (FC). However, the effect of polygenic inheritance on the brain white matter microstructure has only been sparsely reported.
Eighty-four patients with first-episode schizophrenia (FES) patients and ninety-three healthy controls (HC) with genetics, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI) data were included in our study. We investigated impaired white matter integrity as measured by fractional anisotropy (FA) in the FES group, further examined the effect of SzPRS on white matter FA and FC in the regions connected by SzPRS-related white matter tracts.
Decreased FA was observed in FES in many commonly identified regions. Among these regions, we observed that in the FES group, but not the HC group, SzPRS was negatively associated with the mean FA in the genu and body of corpus callosum, right anterior corona radiata, and right superior corona radiata. Higher SzPRS was also associated with lower FCs between the left inferior frontal gyrus (IFG)–left inferior temporal gyrus (ITG), right IFG–left ITG, right IFG–left middle frontal gyrus (MFG), and right IFG–right MFG in the FES group.
Higher polygenic risks are linked with disrupted white matter integrity and FC in patients with schizophrenia. These correlations are strongly driven by the interhemispheric callosal fibers and the connections between frontotemporal regions.
This paper investigates the monolithic edge-cladding process for the elliptical disk of N31-type Nd-doped phosphate laser glass, which will be utilized under liquid cooling conditions for high-power laser systems. The thermal stress, interface bubbles and residual reflectivity, which are due to high-temperature casting and bonding during the monolithic edge-cladding process, are simulated and determined. The applied mould is optimized to a rectangular cavity mould, and the casting temperature is optimized to 1000°C. The resulting lower bubble density makes the mean residual reflectivity as low as 6.75 × 10−5, which is enough to suppress the amplified spontaneous emission generated in the Nd-glass disk, and the resulting maximum optical retardation is converged to 10.2–13.3 nm/cm, which is a favourable base for fine annealing to achieve the stress specification of less than or equal to 5 nm/cm. After fine annealing at the optimized 520°C, the maximum optical retardation is as low as 4.8 nm/cm, and the minimum transmitted wavefront peak-to-valley value is 0.222 wavelength (632.8 nm). An N31 elliptical disk with the size of 194 mm × 102 mm × 40 mm can be successfully cladded by the optimized monolithic edge-cladding process, whose edge-cladded disk with the size of 200 mm × 108 mm × 40 mm can achieve laser gain one-third higher than that of an N21-type disk of the same size.
The early identification and prediction of hand-foot-and-mouth disease (HFMD) play an important role in the disease prevention and control. However, suitable models are different in regions due to the differences in geography, social economy factors. We collected data associated with daily reported HFMD cases and weather factors of Zibo city in 2010~2019 and used the generalised additive model (GAM) to evaluate the effects of weather factors on HFMD cases. Then, GAM, support vectors regression (SVR) and random forest regression (RFR) models are used to compare predictive results. The annual average incidence was 129.72/100 000 from 2010 to 2019. Its distribution showed a unimodal trend, with incidence increasing from March, peaking from May to September. Our study revealed the nonlinear relationship between temperature, rainfall and relative humidity and HFMD cases and based on the predictive result, the performances of three models constructed ranked in descending order are: SVR > GAM> RFR, and SVR has the smallest prediction errors. These findings provide quantitative evidence for the prediction of HFMD for special high-risk regions and can help public health agencies implement prevention and control measures in advance.
Hyperinsulinaemia and insulin resistance have been proposed to be associated with mortality risk, and diet can modulate insulin response. However, whether dietary patterns with high insulinaemic potential are associated with mortality remains unknown. We prospectively examined the associations between hyperinsulinaemic diets and the risk of total and cause-specific mortality in a large nationally representative population. Dietary factors were assessed by 24-h recalls. Two empirical dietary indices for hyperinsulinaemia (EDIH) and insulin resistance (EDIR) were developed to identify food groups most predictive of biomarkers for hyperinsulinaemia (C-peptide and insulin) and insulin resistance (homoeostatic model assessment for insulin resistance), respectively. Deaths from date of the first dietary interview until 31 December 2015 were identified by the National Death Index. Multivariable hazard ratios (HR) and 95 % CI were calculated using Cox regression models. During a median follow-up of 7·8 years, 4904 deaths were documented among 40 074 participants. For EDIH, the multivariable-adjusted HR (comparing extreme quintiles) were 1·20 (95 % CI 1·09, 1·32, P-trend<0·001) for overall mortality and 1·41 (95 % CI 1·15, 1·74, P-trend = 0·002) for CVD mortality. Similar associations were observed for EDIR with HR of 1·18 (95 % CI 1·07, 1·29, P-trend < 0·001) for total and 1·35 (95 % CI 1·09, 1·67, P-trend = 0·005) for CVD mortality. After further adjustments for BMI and diabetes, these positive associations were somewhat attenuated. Our findings suggested that diets with higher insulinaemic potential are associated with increased risk of overall and CVD-specific mortality.
Previous studies have demonstrated structural and functional changes of the hippocampus in patients with major depressive disorder (MDD). However, no studies have analyzed the dynamic functional connectivity (dFC) of hippocampal subregions in melancholic MDD. We aimed to reveal the patterns for dFC variability in hippocampus subregions – including the bilateral rostral and caudal areas and its associations with cognitive impairment in melancholic MDD.
Forty-two treatment-naive MDD patients with melancholic features and 55 demographically matched healthy controls were included. The sliding-window analysis was used to evaluate whole-brain dFC for each hippocampal subregions seed. We assessed between-group differences in the dFC variability values of each hippocampal subregion in the whole brain and cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB). Finally, association analysis was conducted to investigate their relationships.
Patients with melancholic MDD showed decreased dFC variability between the left rostral hippocampus and left anterior lobe of cerebellum compared with healthy controls (voxel p < 0.005, cluster p < 0.0125, GRF corrected), and poorer cognitive scores in working memory, verbal learning, visual learning, and social cognition (all p < 0.05). Association analysis showed that working memory was positively correlated with the dFC variability values of the left rostral hippocampus-left anterior lobe of the cerebellum (r = 0.338, p = 0.029) in melancholic MDD.
These findings confirmed the distinct dynamic functional pathway of hippocampal subregions in patients with melancholic MDD, and suggested that the dysfunction of hippocampus-cerebellum connectivity may be underlying the neural substrate of working memory impairment in melancholic MDD.
Mars exploration motivates the search for extraterrestrial life, the development of space technologies, and the design of human missions and habitations. Here, we seek new insights and pose unresolved questions relating to the natural history of Mars, habitability, robotic and human exploration, planetary protection, and the impacts on human society. Key observations and findings include:
– high escape rates of early Mars' atmosphere, including loss of water, impact present-day habitability;
– putative fossils on Mars will likely be ambiguous biomarkers for life;
– microbial contamination resulting from human habitation is unavoidable; and
– based on Mars' current planetary protection category, robotic payload(s) should characterize the local martian environment for any life-forms prior to human habitation.
Some of the outstanding questions are:
– which interpretation of the hemispheric dichotomy of the planet is correct;
– to what degree did deep-penetrating faults transport subsurface liquids to Mars' surface;
– in what abundance are carbonates formed by atmospheric processes;
– what properties of martian meteorites could be used to constrain their source locations;
– the origin(s) of organic macromolecules;
– was/is Mars inhabited;
– how can missions designed to uncover microbial activity in the subsurface eliminate potential false positives caused by microbial contaminants from Earth;
– how can we ensure that humans and microbes form a stable and benign biosphere; and
– should humans relate to putative extraterrestrial life from a biocentric viewpoint (preservation of all biology), or anthropocentric viewpoint of expanding habitation of space?
Studies of Mars' evolution can shed light on the habitability of extrasolar planets. In addition, Mars exploration can drive future policy developments and confirm (or put into question) the feasibility and/or extent of human habitability of space.