We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save 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 saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.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 saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved 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.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Rapid molecular diagnostics, such as the BIOFIRE® Blood Culture Identification 2 (BCID2) panel, have improved the time to pathogen identification in bloodstream infections. However, accurate interpretation and antimicrobial optimization require Infectious Disease (ID) expertise, which may not always be readily available. GPT-powered chatbots could support antimicrobial stewardship programs (ASPs) by assisting non-specialist providers in BCID2 result interpretation and treatment recommendations. This study evaluates the performance of a GPT-4 chatbot compared to ASP prospective audit and feedback interventions.
Methods:
This prospective observational study assessed 43 consecutive real-world cases of bacteremia at a 399-bed VA Medical Center from January to May 2024. The GPT-chatbot utilized “chain-of-thought” prompting and external knowledge integration to generate recommendations. Two independent ID physicians evaluated chatbot and ASP recommendations across four domains: BCID2 interpretation, source control, antibiotic therapy, and additional diagnostic workup. The primary endpoint was the combined rate of harmful or inadequate recommendations. Secondary endpoints assessed the rate of harmful or inadequate responses for each domain.
Results:
The chatbot had a significantly higher rate of harmful or inadequate recommendations (13%) compared to ASP (4%, p = 0.047). The most significant discrepancy was observed in the domain of antibiotic therapy, where harmful recommendations occurred in up to 10% (p <0.05) of chatbot evaluations. The chatbot performed well in BCID2 interpretation (100% accuracy) but provided more inadequate responses in source control consideration (10% vs. 2% for ASP, p = 0.022).
Conclusions:
GPT-powered chatbots show potential for supporting antimicrobial stewardship but should only complement, not replace, human expertise in infectious disease management.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
Research articles in the clinical and translational science literature commonly use quantitative data to inform evaluation of interventions, learn about the etiology of disease, or develop methods for diagnostic testing or risk prediction of future events. The peer review process must evaluate the methodology used therein, including use of quantitative statistical methods. In this manuscript, we provide guidance for peer reviewers tasked with assessing quantitative methodology, intended to complement guidelines and recommendations that exist for manuscript authors. We describe components of clinical and translational science research manuscripts that require assessment including study design and hypothesis evaluation, sampling and data acquisition, interventions (for studies that include an intervention), measurement of data, statistical analysis methods, presentation of the study results, and interpretation of the study results. For each component, we describe what reviewers should look for and assess; how reviewers should provide helpful comments for fixable errors or omissions; and how reviewers should communicate uncorrectable and irreparable errors. We then discuss the critical concepts of transparency and acceptance/revision guidelines when communicating with responsible journal editors.
Edited by
Jong Chul Ye, Korea Advanced Institute of Science and Technology (KAIST),Yonina C. Eldar, Weizmann Institute of Science, Israel,Michael Unser, École Polytechnique Fédérale de Lausanne
With the present demand for high-quality image reconstruction and signal extraction from less (e.g., unfocused or parallel) transmissions that facilitate fast imaging, and the push towards compact probes, modern ultrasound imaging leans heavily on innovations in powerful digital receive channel processing. Beamforming, the process of mapping received ultrasound echoes to the spatial image domain, naturally lies at the heart of the ultrasound image formation chain. In this chapter, we discuss why and when deep learning methods can play a compelling role in the digital beamforming pipeline, and then show how these data-driven systems can be leveraged for improved ultrasound image reconstruction.
We develop a sheaf cohomology theory of algebraic varieties over an algebraically closed nontrivially valued nonarchimedean field K based on Hrushovski-Loeser’s stable completion. In parallel, we develop a sheaf cohomology of definable subsets in o-minimal expansions of the tropical semi-group $\Gamma _{\infty }$, where $\Gamma $ denotes the value group of K. For quasi-projective varieties, both cohomologies are strongly related by a deformation retraction of the stable completion homeomorphic to a definable subset of $\Gamma _{\infty }$. In both contexts, we show that the corresponding cohomology theory satisfies the Eilenberg-Steenrod axioms, finiteness and invariance, and we provide natural bounds of cohomological dimension in each case. As an application, we show that there are finitely many isomorphism types of cohomology groups in definable families. Moreover, due to the strong relation between the stable completion of an algebraic variety and its analytification in the sense of V. Berkovich, we recover and extend results on the singular cohomology of the analytification of algebraic varieties concerning finiteness and invariance.
To determine risk factors for mechanical (noninfectious) complications in peripherally inserted central catheters (PICCs) in children.
Design:
Retrospective cohort study.
Setting:
Pediatric tertiary-care center in Nova Scotia, Canada.
Patients:
Pediatric patients with a first PICC insertion.
Methods:
All PICCs inserted between January 2001 until 2016 were included. Age-stratified (neonates vs non-neonates) Fine–Grey competing risk proportional hazard models were used to model the association between each putative risk factor and the time to mechanical complication or removal of the PICC for reasons not related to a mechanical complication. Models were adjusted for confounding variables identified through directed acyclic graphs.
Results:
Of 3,205 patients with PICCs, 706 had mechanical complications (22% or 14 events/1000 device days). For both neonates and older children, disease group, lumen count, and prior leak were all associated with mechanical complications in the adjusted proportional hazards model. Access vein and prior infection were also associated with mechanical complications for neonates, and age group was associated with mechanical complications among non-neonates.
Conclusions:
We have identified several risk factors for mechanical complications in patients with PICCs that will help improve best practices for PICC insertion and care.
Sleep disturbance is an important factor in the pathophysiology and progression of psychiatric disorders, but whether it is a cause, or a downstream effect is still not clear.
Methods
To investigate causal relationships between three sleep-associated traits and seven psychiatric diseases, we used genetic variants related to insomnia, chronotype and sleep duration to perform a two-sample bidirectional Mendelian randomisation analysis. Summary-level data on psychiatric disorders were extracted from the Psychiatric Genomics Consortium. Effect estimates were obtained by using the inverse-variance-weighted (IVW), weights modified IVW, weighted-median methods, MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO) test and Robust Adjusted Profile Score (RAPS).
Results
The causal odds ratio (OR) estimate of genetically determined insomnia was 1.33 (95% confidence interval (CI) 1.22–1.45; p = 5.03 × 10−11) for attention-deficit/hyperactivity disorder (ADHD), 1.31 (95% CI 1.25–1.37; p = 6.88 × 10−31) for major depressive disorder (MDD) and 1.32 (95% CI 1.23–1.40; p = 1.42 × 10−16) for post-traumatic stress disorder (PTSD). There were suggestive inverse associations of morningness chronotype with risk of MDD and schizophrenia (SCZ). Genetically predicted sleep duration was also nominally associated with the risk of bipolar disorder (BD). Conversely, PTSD and MDD were associated with an increased risk of insomnia (OR = 1.06, 95% CI 1.03–1.10, p = 7.85 × 10−4 for PTSD; OR = 1.37, 95% CI 1.14–1.64; p = 0.001 for MDD). A suggestive inverse association of ADHD and MDD with sleep duration was also observed.
Conclusions
Our findings provide evidence of potential causal relationships between sleep disturbance and psychiatric disorders. This suggests that abnormal sleep patterns may serve as markers for psychiatric disorders and offer opportunities for prevention and management in psychiatric disorders.
We study the effect of negatively charged dust on the magnetic-field-aligned polarisation electrostatic field ($\boldsymbol {E}_{\parallel }$) using Cassini's RPWS/LP in situ measurements during the ‘ring-grazing’ orbits. We derive a general expression for $\boldsymbol {E}_{\parallel }$ and estimate for the first time in situ$\lVert \boldsymbol {E}_{\parallel } \rVert$ (approximately $10^{-5} \, \text {V}\, \text {m}^{-1}$) near the Janus and Epimetheus rings. We further demonstrate that the presence of the negatively charged dust close to the ring plane ($\vert \text {Z} \vert \lesssim 0.11 \, \text {R}_{s}$) amplifies $\lVert \boldsymbol {E}_{\parallel } \rVert$ by at least one order of magnitude and reverses its direction due to the effect of the charged dust gravitational and inertial forces. Such reversal confines the electrons at the magnetic equator within the dusty region, around $0.047 \, \text {R}_{s}$ above the ring plane. Furthermore, we discuss the role of the collision terms, in particular the ion–dust drag force, in amplifying $\boldsymbol {E}_{\parallel }$. These results imply that the charged dust, as small as nanometres in size, can have a significant influence on the plasma transport, in particular ambipolar diffusion along the magnetic field lines, and so their presence must be taken into account when studying such dynamical processes.
We observed an overall increase in the use of third- and fourth-generation cephalosporins after fluoroquinolone preauthorization was implemented. We examined the change in specific third- and fourth-generation cephalosporin use, and we sought to determine whether there was a consequent change in non-susceptibility of select Gram-negative bacterial isolates to these antibiotics.
Design:
Retrospective quasi-experimental study.
Setting:
Academic hospital.
Intervention:
Fluoroquinolone preauthorization was implemented in the hospital in October 2005. We used interrupted time series (ITS) Poisson regression models to examine trends in monthly rates of ceftriaxone, ceftazidime, and cefepime use and trends in yearly rates of nonsusceptible isolates (NSIs) of select Gram-negative bacteria before (1998–2004) and after (2006–2016) fluoroquinolone preauthorization was implemented.
Results:
Rates of use of ceftriaxone and cefepime increased after fluoroquinolone preauthorization was implemented (ceftriaxone RR, 1.002; 95% CI, 1.002–1.003; P < .0001; cefepime RR, 1.003; 95% CI, 1.001–1.004; P = .0006), but ceftazidime use continued to decline (RR, 0.991, 95% CI, 0.990–0.992; P < .0001). Rates of ceftazidime and cefepime NSIs of Pseudomonas aeruginosa (ceftazidime RR, 0.937; 95% CI, 0.910–0.965, P < .0001; cefepime RR, 0.937; 95% CI, 0.912–0.963; P < .0001) declined after fluoroquinolone preauthorization was implemented. Rates of ceftazidime and cefepime NSIs of Enterobacter cloacae (ceftazidime RR, 1.116; 95% CI, 1.078–1.154; P < .0001; cefepime RR, 1.198; 95% CI, 1.112–1.291; P < .0001) and cefepime NSI of Acinetobacter baumannii (RR, 1.169; 95% CI, 1.081–1.263; P < .0001) were increasing before fluoroquinolone preauthorization was implemented but became stable thereafter: E. cloacae (ceftazidime RR, 0.987; 95% CI, 0.948–1.028; P = .531; cefepime RR, 0.990; 95% CI, 0.962–1.018; P = .461) and A. baumannii (cefepime RR, 0.972; 95% CI, 0.939–1.006; P = .100).
Conclusions:
Fluoroquinolone preauthorization may increase use of unrestricted third- and fourth-generation cephalosporins; however, we did not observe increased antimicrobial resistance to these agents, especially among clinically important Gram-negative bacteria known for hospital-acquired infections.
To understand how the different data collections methods of the Alberta Health Services Infection Prevention and Control Program (IPC) and the National Surgical Quality Improvement Program (NSQIP) are affecting reported rates of surgical site infections (SSIs) following total hip replacements (THRs) and total knee replacements (TKRs).
Design:
Retrospective cohort study.
Setting:
Four hospitals in Alberta, Canada.
Patients:
Those with THR or TKR surgeries between September 1, 2015, and March 31, 2018.
Methods:
Demographic information, complex SSIs reported by IPC and NSQIP were compared and then IPC and NSQIP data were matched with percent agreement and Cohen’s κ calculated. Statistical analysis was performed for age, gender and complex SSIs. A P value <.05 was considered significant.
Results:
In total, 7,549 IPC and 2,037 NSQIP patients were compared. The complex SSI rate for NSQIP was higher compared to IPC (THR: 1.19 vs 0.68 [P = .147]; TKR: 0.92 vs 0.80 [P = .682]). After matching, 7 SSIs were identified by both IPC and NSQIP; 3 were identified only by IPC, and 12 were identified only by NSQIP (positive agreement, 0.48; negative agreement, 1.0; κ = 0.48).
Conclusions:
Different approaches to monitor SSIs may lead to different results and trending patterns. NSQIP reports total SSI rates that are consistently higher than IPC. If systems are compared at any point in time, confidence on the data may be eroded. Stakeholders need to be aware of these variations and education provided to facilitate an understanding of differences and a consistent approach to SSI surveillance monitoring over time.
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.
In support of the ICRF experiments planned on the Wendelstein 7-X (W7-X) stellarator, i.e. fast ion generation, wall conditioning, target plasma production and heating, a first experimental study on plasma production has been made in the Uragan-2M (U-2M) stellarator using W7-X-like two-strap antenna. In all the experiments, antenna monopole phasing was used. The W7-X-like antenna operation with launched radiofrequency power of ~100 kW have been performed in helium (p = (4–14) × 10−2 Pa) with the vacuum vessel walls pre-loaded with hydrogen. Production of plasma with a density higher than 1012 cm−3 was observed near the first harmonic of the hydrogen cyclotron frequency. Operation at first hydrogen harmonic is feasible in W7-X future ICRF experiments.
An increasing number of studies have described the relationship between celiac disease and schizophrenia. Based on the reported correlations and the overlapping linkage regions on 19p13, the myosin IXB gene (MYO9B) can be considered a highly relevant positional and functional candidate gene for schizophrenia. The present work was undertaken to investigate the association of the MYO9B gene with schizophrenia in a Chinese population.
Methods
A total of 329 patients with schizophrenia and 350 healthy control subjects in a Chinese population were recruited. A PCR-based RFLP protocol was applied to genotype 7 single nucleotide polymorphisms (SNPs), including rs7249490, rs7256689, rs2279007, rs8113494, rs2305767, rs1545620 and rs2305764, in the MYO9B gene to investigate their association with schizophrenia.
Results
The X2 goodness-of-fit test showed that the genotypic distributions of all 7 SNPs were in Hardy-Weinberg equilibrium in both the patient group and the control group. Disease association was shown for rs8113494 (X2=12.77, P=0.0003, OR=1.89, 95% CI 1.33-2.68) and rs1545620 (X2=15.44, P=8.379e-5, OR=1.65, 95% CI 1.29-2.12), while rs2279007 was associated with schizophrenia in the female subjects (X2=4.637, P=0.031, OR=0.69, 95% CI 0.49-0.97) but not in the male subjects (X2=1.082, P=0.299, OR=0.85, 95% CI 0.63-1.15).
Conclusions
The present work shows that the polymorphisms of the MYO9B gene are likely to confer susceptibility to schizophrenia. Because the MYO9B gene has been found to be highly expressed in the tight junction gate, it could be considered as a meeting point for the interaction between environmental and genetic factors in the pathogenesis of schizophrenia.
An increasing number of studies have described the relationship between velo-cardio-facial syndrome (VCFS) and schizophrenia. in a family-based study, we found that rs10314, a single nucleotide polymorphism (SNP) present in the 3’-flanking region of the CLDN5 gene, was associated with schizophrenia among a Chinese population. High false positive rate is a common problem with the association study of human diseases. It is very important to replicate an initial finding with different samples and experimental designs.
Methods:
A total of 749 patients with schizophrenia and 383 age and sex matched healthy control subjects in Chinese population were recruited. PCR-based RFLP protocol was applied to genotype rs10314 to see its disease association.
Results:
The χ2 goodness-of-fit test showed that the genotypic distributions of rs10314 were in Hardy-Weinberg equilibrium in both the patient group (χ2=1.12, P=0.289) and the control group (χ2=0.22, P=0.639). rs10314 was associated with schizophrenia with an odds ratio (OR) of 1.32 in the male subjects (χ2=5.45, P=0.02, 95% CI 1.05-1.67) but not in the female subjects (χ2=0.64, P=0.425, OR=1.14, 95% CI 0.83-1.57). the χ2 test showed a genotypic association only for combined samples (χ2=7.80, df=2, P=0.02). SNP rs10314 is a G to C base change. Frequency of the genotypes containing the C allele was significantly higher in the patient group than in the control group.
Conclusions:
The present work shows that the CLDN5 gene polymorphism is more likely to be involved in schizophrenic men than women, suggesting that this gene may contribute to the gender differences in schizophrenia.
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.
Combining different swine populations in genomic prediction can be an important tool, leading to an increased accuracy of genomic prediction using single nucleotide polymorphism (SNP) chip data compared with within-population genomic. However, the expected higher accuracy of multi-population genomic prediction has not been realized. This may be due to an inconsistent linkage disequilibrium (LD) between SNPs and quantitative trait loci (QTL) across populations, and the weak genetic relationships across populations. In this study, we determined the impact of different genomic relationship matrices, SNP density and pre-selected variants on prediction accuracy using a combined Yorkshire pig population. Our objective was to provide useful strategies for improving the accuracy of genomic prediction within a combined population. Results showed that the accuracy of genomic best linear unbiased prediction (GBLUP) using imputed whole-genome sequencing (WGS) data in the combined population was always higher than that within populations. Furthermore, the use of imputed WGS data always resulted in a higher accuracy of GBLUP than the use of 80K chip data for the combined population. Additionally, the accuracy of GBLUP with a non-linear genomic relationship matrix was markedly increased (0.87% to 15.17% for 80K chip data, and 0.43% to 4.01% for imputed WGS data) compared with that obtained with a linear genomic relationship matrix, except for the prediction of XD population in the combined population using imputed WGS data. More importantly, the application of pre-selected variants based on fixation index (Fst) scores improved the accuracy of multi-population genomic prediction, especially for 80K chip data. For BLUP|GA (BLUP approach given the genetic architecture), the use of a linear method with an appropriate weight to build a weight-relatedness matrix led to a higher prediction accuracy compared with the use of only pre-selected SNPs for genomic evaluations, especially for the total number of piglets born. However, for the non-linear method, BLUP|GA showed only a small increase or even a decrease in prediction accuracy compared with the use of only pre-selected SNPs. Overall, the best genomic evaluation strategy for reproduction-related traits for a combined population was found to be GBLUP performed with a non-linear genomic relationship matrix using variants pre-selected from the 80K chip data based on Fst scores.