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Given that the extracellular matrix polymer hyaluronan (HA) has been implicated in longevity, we asked whether 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, impacts lifespan in mice. We designed a prospective study of long-term administration of 4-MU with conventional C57BL/6J mice. We find that 4-MU extends median survival from 122 weeks (control) to 154 weeks (4-MU), an increase of 32 weeks (p < 0.0001 by Log-rank Mantel Cox test). The maximum lifespan of 4-MU treated mice increased from 159 to 194 weeks. In tandem with these effects, 4-MU enhances insulin sensitivity, a metabolic parameter known to regulate lifespan, as measured by insulin tolerance testing (ITT) as well as frequent sampling intra venous glucose tolerance tests (FSIVGTTs). We further observed that 4-MU treated mice weigh less while consuming the same amount of food, indicating that 4-MU treatment alters energy expenditure. However, we do not observe changes in tissue HA content in this model. We conclude that 4-MU promotes insulin sensitivity and longevity but that the underlying mechanism, and the contribution of HA is unclear. 4-MU, already approved in various countries for hepatobiliary conditions, is currently under investigation and clinical development as a therapy for several chronic inflammatory conditions. These data suggest that the beneficial effects of 4-MU on tissue metabolism may include effects on longevity.

IntroductionSeptic shock is a severe form of sepsis that has a high mortality rate, and a substantial proportion of these patients will develop cardiac dysfunction, often termed septic cardiomyopathy (SCM). Some SCM patients may develop frank cardiac failure, termed sepsis-related cardiogenic shock (SeRCS). Little is known of SeRCS. This study describes baseline characteristics of patients with SCM and SeRCS compared to patients with septic shock without cardiac dysfunction. We compare clinical outcomes among SCM, SeRCS, and septic shock, and identify risk factors for the development of SCM and SeRCS.MethodsSeptic patients admitted to the ICU with an echocardiogram obtained within 72 hours were included. Left ventricular ejection fraction of ≤55% was used to define SCM, and cardiac index ≤2.1 L/min/m2 among patients with SCM defined SeRCS. Machine learning was used to identify risk factors for development of SCM and SeRCS. Logistic regression was used to compare mortality among groups.ResultsAmong 1229 patients, 977 patients had septic shock without cardiac dysfunction, 207 had SCM, and 45 had SeRCS. In patients with septic shock, the strongest predictor for developing SCM and SeRCs was a prior history of cardiac dysfunction. Mortality did not significantly differ among the three groups.ConclusionsSCM and SeRCS affect a minority of patients with septic shock, disproportionately affecting individuals with a history of cardiac disease. We did not identify a mortality difference associated with SCM or SeRCS. Additional work is needed to define further subtypes and treatment options for this patient population.

Abstract Autism was formally recognized by the medical community in the first half of the twentieth century. Almost 100 years later, a small but growing literature has reported sex differences in the behavioral expression of autism. Recent research has also begun to explore the internal experiences of individuals with autism, including social and emotional insight. The current study examines sex differences in language-based markers of social and emotional insight in girls and boys with autism and non-autistic peers during semi-structured clinical interviews. Sixty-four participants aged 5 to 17 years were individually matched on chronological age and full-scale IQ to form four groups: autistic girls, autistic boys, non-autistic girls, and non-autistic boys. Transcribed interviews were scored using four scales that index aspects of social and emotional insight. Results revealed the main effects of diagnosis, such that youth with autism exhibited lower insight than non-autistic youth on scales indexing social cognition and object relations, emotional investment, and social causality. With regards to sex differences, across diagnoses, girls were rated higher than boys on the social cognition and object relations, emotional investment, and social causality scales. Examined within each diagnosis separately, clear sex differences emerged: both autistic and non-autistic girls demonstrated better social cognition and understanding of social causality than boys in their respective diagnostic groups. No within-diagnosis sex differences were found on the emotional insight scales, however. These results suggest that relatively enhanced social cognition and understanding of social causality in girls may be a population-level sex difference that is preserved in autism, despite the core social challenges that characterize this condition. The current findings reveal critical new information about insight into social and emotional thinking and relationships in autistic girls versus boys that have important implications for improving identification and designing effective interventions.

While lethal sampling can be the most effective technique to collect critical reproductive data for elasmobranchs, non-lethal techniques need to be validated for future use. Concentrations of reproductive hormones in plasma and muscle have been found to correlate to sexual maturity and/or reproductive cycles in oviparous as well as yolk-sac, placental, and histotrophic viviparous elasmobranchs, offering a potentially non-lethal technique to study reproduction. However, reproductive hormone analysis is scant for oophagous sharks. This study utilized muscle tissues from porbeagles Lamna nasus that were dissected for other life history studies and were stored frozen for up to 37 years to quantify testosterone (T) and estradiol (E2) concentrations in relation to previously-known maturity and reproductive stage. A total of 207 samples (92 males, 115 females) from porbeagles ranging in size from 80 to 256.5 cm fork length were analyzed. Muscle T and E2 concentrations were related to maturity and reproductive stage in porbeagles, with the highest T concentrations found in mature males during the spermatogenic season (summer) and the highest E2 concentrations found in gravid females. These results suggest muscle hormone concentrations have the potential to serve as a non-lethal proxy of reproductive stage in oophagous sharks. This study also demonstrates the value of specimen sharing and the potential for continued use of stored vertebral muscle tissue for reproductive hormone analysis in order to optimize the amount of data gained from biological samples. Future use of these methods would be particularly valuable for threatened species for which lethal sampling is restricted.

Diabetic retinopathy (DR) is a late microvascular complication of Diabetes Mellitus (DM) that could lead to permanent blindness in patients, without early detection. Although adequate management of DM via regular eye examination can preserve vision in in 98% of the DR cases, DR screening and diagnoses based on clinical lesion features devised by expert clinicians; are costly, time-consuming and not sufficiently accurate. This raises the requirements for Artificial Intelligent (AI) systems which can accurately detect DR automatically and thus preventing DR before affecting vision. Hence, such systems can help clinician experts in certain cases and aid ophthalmologists in rapid diagnoses. To address such requirements, several approaches have been proposed in the literature that use Machine Learning (ML) and Deep Learning (DL) techniques to develop such systems. However, these approaches ignore the highly valuable clinical lesion features that could contribute significantly to the accurate detection of DR. Therefore, in this study we introduce a framework called DR-detector that employs the Extreme Gradient Boosting (XGBoost) ML model trained via the combination of the features extracted by the pretrained convolutional neural networks commonly known as transfer learning (TL) models and the clinical retinal lesion features for accurate detection of DR. The retinal lesion features are extracted via image segmentation technique using the UNET DL model and captures exudates (EXs), microaneurysms (MAs), and hemorrhages (HEMs) that are relevant lesions for DR detection. The feature combination approach implemented in DR-detector has been applied to two common TL models in the literature namely VGG-16 and ResNet-50. We trained the DR-detector model using a training dataset comprising of 1,840 color fundus images collected from e-ophtha, retinal lesions and APTOS 2019 Kaggle datasets of which 920 images are healthy. To validate the DR-detector model, we test the model on external dataset that consists of 81 healthy images collected from High-Resolution Fundus (HRF) dataset and MESSIDOR-2 datasets and 81 images with DR signs collected from Indian Diabetic Retinopathy Image Dataset (IDRID) dataset annotated for DR by expert. The experimental results show that the DR-detector model achieves a testing accuracy of 100% in detecting DR after training it with the combination of ResNet-50 and lesion features and 99.38% accuracy after training it with the combination of VGG-16 and lesion features. More importantly, the results also show a higher contribution of specific lesion features toward the performance of the DR-detector model. For instance, using only the hemorrhages feature to train the model, our model achieves an accuracy of 99.38 in detecting DR, which is higher than the accuracy when training the model with the combination of all lesion features (89%) and equal to the accuracy when training the model with the combination of all lesions and VGG-16 features together. This highlights the possibility of using only the clinical features, such as lesions that are clinically interpretable, to build the next generation of robust artificial intelligence (AI) systems with great clinical interpretability for DR detection. The code of the DR-detector framework is available on GitHub at https://github.com/Janga-Lab/DR-detector and can be readily employed for detecting DR from retinal image datasets.

Tactical occupations regularly encounter life-threatening situations while on duty. Although these occupations are often trained to utilize slow breathing (SB) during intense stress, there is no evidence supporting the effects on markers of stress in response to a virtual reality active shooter training drill (VR-ASD). The purpose of the study was to determine the impact of acute SB on biomarkers of stress in response to a VR-ASD. Seventy-nine (n = 79) subjects performed either slow breathing method 1 (SB1), slow breathing method 2 (SB2), or normal breathing (control) for five minutes, both pre- and post-VR-ASD. Saliva samples were analyzed for stress markers, including α-amylase (sAA) and secretory immunoglobulin-A (SIgA). Both methods of SB resulted in significantly lower sAA concentrations at 5 (p < 0.001) and 30 min post-VR-ASD (SB1: p = 0.008; SB2: p < 0.001) compared to the control. In the control condition, the sAA concentrations were significantly elevated 5 min post-VR-ASD (p < 0.001) but did not change across time in SB1 or SB2 (p > 0.05). Thus, both SB1 and SB2 reduced the sAA response and resulted in lower concentrations post-VR-ASD. This study was pre-registered as a clinical trial (“Impact of Breathing Interventions on Stress Markers”; NCT05825846).

Since independence, Myanmar has prioritised a non-aligned foreign policy to preserve autonomy in the international arena. Yet, it has done so in contrasting and sometimes opposite ways. Historically, Myanmar's great power diplomacy has resembled a pendulum swinging between two ideal types: ‘positive non-alignment’ and ‘negative neutralism’. The former represents a proactive blend of non-aligned behaviour that seeks to assert independence by achieving a diversified range of international partnerships, whereas the latter endeavours to accomplish the same goal through diplomatic disengagement and self-aloofness. This article analyses Myanmar's shifting recourse to opposite archetypes of alignment by examining its foreign policy between 2011 and 2021. Building upon a comprehensive theoretical classification of different forms of non-alignment, the analysis contends that Myanmar's evolving great power diplomacy is ultimately rooted in oscillating degrees of political legitimation held by its leaders, which pushed them to alternatively tilt towards positive non-alignment or negative neutralism.

If validated, in-shoe pressure measuring technology allows for the field-based quantification of running gait, including kinematic and kinetic measures. Different algorithmic methods have been proposed to determine foot contact events from in-shoe pressure insole systems, however, these methods have not been evaluated for accuracy, reliability against a gold standard using running data across different slopes, and speeds. Using data from a plantar pressure measurement system, seven different foot contact event detection algorithms based on pressure signals (pressure sum) were compared to vertical ground reaction force data collected from a force instrumented treadmill. Subjects ran on level ground at 2.6, 3.0, 3.4, and 3.8 m/s, six degrees (10.5%) inclined at 2.6, 2.8, and 3.0 m/s, and six degrees declined at 2.6, 2.8, 3.0, and 3.4 m/s. The best performing foot contact event detection algorithm showed maximal mean absolute errors of only 1.0 ms and 5.2 ms for foot contact and foot off, respectively, on level grade, when compared to a 40 N ascending and descending force threshold from the force treadmill data. Additionally, this algorithm was unaffected by grade and had similar levels of errors across all grades.

Globally, SARS-CoV-2 has moved from one tide to another with ebbs in between. Genomic surveillance has greatly aided the detection and tracking of the virus and the identification of the variants of concern (VOC). The knowledge and understanding from genomic surveillance is important for a populous country like India for public health and healthcare officials for advance planning. An integrative analysis of the publicly available datasets in GISAID from India reveals the differential distribution of clades, lineages, gender, and age over a year (Apr 2020–Mar 2021). The significant insights include the early evidence towards B.1.617 and B.1.1.7 lineages in the specific states of India. Pan-India longitudinal data highlighted that B.1.36* was the predominant clade in India until January–February 2021 after which it has gradually been replaced by the B.1.617.1 lineage, from December 2020 onward. Regional analysis of the spread of SARS-CoV-2 indicated that B.1.617.3 was first seen in India in the month of October in the state of Maharashtra, while the now most prevalent strain B.1.617.2 was first seen in Bihar and subsequently spread to the states of Maharashtra, Gujarat, and West Bengal. To enable a real time understanding of the transmission and evolution of the SARS-CoV-2 genomes, we built a transmission map available on https://covid19-indiana.soic.iupui.edu/India/EmergingLineages/April2020/to/March2021. Based on our analysis, the rate estimate for divergence in our dataset was 9.48 e-4 substitutions per site/year for SARS-CoV-2. This would enable pandemic preparedness with the addition of future sequencing data from India available in the public repositories for tracking and monitoring the VOCs and variants of interest (VOI). This would help aid decision making from the public health perspective.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid evolution has led to a global health crisis. Increasing mutations across the SARS-CoV-2 genome have severely impacted the development of effective therapeutics and vaccines to combat the virus. However, the new SARS-CoV-2 variants and their evolutionary characteristics are not fully understood. Host cellular components such as the ACE2 receptor, RNA-binding proteins (RBPs), microRNAs, small nuclear RNA (snRNA), 18s rRNA, and the 7SL RNA component of the signal recognition particle (SRP) interact with various structural and non-structural proteins of the SARS-CoV-2. Several of these viral proteins are currently being examined for designing antiviral therapeutics. In this review, we discuss current advances in our understanding of various host cellular components targeted by the virus during SARS-CoV-2 infection. We also summarize the mutations across the SARS-CoV-2 genome that directs the evolution of new viral strains. Considering coronaviruses are rapidly evolving in humans, this enables them to escape therapeutic therapies and vaccine-induced immunity. In order to understand the virus’s evolution, it is essential to study its mutational patterns and their impact on host cellular machinery. Finally, we present a comprehensive survey of currently available databases and tools to study viral–host interactions that stand as crucial resources for developing novel therapeutic strategies for combating SARS-CoV-2 infection.

Generalized arterial calcification of infancy (GACI) is a rare, life-threatening disorder caused by loss-of-function mutations in the gene encoding ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1), which normally hydrolyzes extracellular ATP into AMP and pyrophosphate (PPi). The disease is characterized by extensive arterial calcification and stenosis of large- and medium-sized vessels, leading to vascular-related complications of hypertension and heart failure. There is currently no effective treatment available, but bisphosphonates – nonhydrolyzable PPi analogs – are being used off-label to reduce arterial calcification, although this has no reported impact on the hypertension and cardiac dysfunction features of GACI. In this study, the efficacy of a recombinant human ENPP1 protein therapeutic (rhENPP1) was tested in Enpp1asj-2J homozygous mice (Asj-2J or Asj-2J hom), a model previously described to show extensive mineralization in the arterial vasculature, similar to GACI patients. In a disease prevention study, Asj-2J mice treated with rhENPP1 for 3 weeks showed >95% reduction in aorta calcification. Terminal hemodynamics and echocardiography imaging of Asj-2J mice also revealed that a 6-week rhENPP1 treatment normalized elevated arterial and left ventricular pressure, which translated into significant improvements in myocardial compliance, contractility, heart workload and global cardiovascular efficiency. This study suggests that ENPP1 enzyme replacement therapy could be a more effective GACI therapeutic than bisphosphonates, treating not just the vascular calcification, but also the hypertension that eventually leads to cardiac failure in GACI patients.

Metagenomic sequencing has produced significant amounts of data in recent years. For example, as of summer 2013, MG-RAST has been used to annotate over 110,000 data sets totaling over 43 Terabases. With metagenomic sequencing finding even wider adoption in the scientific community, the existing web-based analysis tools and infrastructure in MG-RAST provide limited capability for data retrieval and analysis, such as comparative analysis between multiple data sets. Moreover, although the system provides many analysis tools, it is not comprehensive. By opening MG-RAST up via a web services API (application programmers interface) we have greatly expanded access to MG-RAST data, as well as provided a mechanism for the use of third-party analysis tools with MG-RAST data. This RESTful API makes all data and data objects created by the MG-RAST pipeline accessible as JSON objects. As part of the DOE Systems Biology Knowledgebase project (KBase, http://kbase.us) we have implemented a web services API for MG-RAST. This API complements the existing MG-RAST web interface and constitutes the basis of KBase's microbial community capabilities. In addition, the API exposes a comprehensive collection of data to programmers. This API, which uses a RESTful (Representational State Transfer) implementation, is compatible with most programming environments and should be easy to use for end users and third parties. It provides comprehensive access to sequence data, quality control results, annotations, and many other data types. Where feasible, we have used standards to expose data and metadata. Code examples are provided in a number of languages both to show the versatility of the API and to provide a starting point for users. We present an API that exposes the data in MG-RAST for consumption by our users, greatly enhancing the utility of the MG-RAST service.

Abstract Background Recent findings indicate that several insect lineages receive protection against particular natural enemies through infection with heritable symbionts, but little is yet known about whether enemies are able to discriminate and respond to symbiont-based defense. The pea aphid, Acyrthosiphon pisum, receives protection against the parasitic wasp, Aphidius ervi, when infected with the bacterial symbiont Hamiltonella defensa and its associated bacteriophage APSE (Acyrthosiphon pisum secondary endosymbiont). Internally developing parasitoid wasps, such as A. ervi, use maternal and embryonic factors to create an environment suitable for developing wasps. If more than one parasitoid egg is deposited into a single aphid host (superparasitism), then additional complements of these factors may contribute to the successful development of the single parasitoid that emerges. Results We performed experiments to determine if superparasitism is a tactic allowing wasps to overcome symbiont-mediated defense. We found that the deposition of two eggs into symbiont-protected aphids significantly increased rates of successful parasitism relative to singly parasitized aphids. We then conducted behavioral assays to determine whether A. ervi selectively superparasitizes H. defensa-infected aphids. In choice tests, we found that A. ervi tends to deposit a single egg in uninfected aphids, but two or more eggs in H. defensa-infected aphids, indicating that oviposition choices may be largely determined by infection status. Finally, we identified differences in the quantity of the trans-β-farnesene, the major component of aphid alarm pheromone, between H. defensa-infected and uninfected aphids, which may form the basis for discrimination. Conclusions Here we show that the parasitic wasp A. ervi discriminates among symbiont-infected and uninfected aphids, and changes its oviposition behavior in a way that increases the likelihood of overcoming symbiont-based defense. More generally, our results indicate that natural enemies are not passive victims of defensive symbionts, and that an evolutionary arms race between A. pisum and the parasitoid A. ervi may be mediated by a bacterial symbiosis.

Abstract Background Type 2 diabetes is an increasingly prevalent chronic illness and an important cause of avoidable mortality. Patients are managed by the integrated activities of clinical and non-clinical members of primary care teams. This study aimed to: investigate theoretically-based organisational, team, and individual factors determining the multiple behaviours needed to manage diabetes; and identify multilevel determinants of different diabetes management behaviours and potential interventions to improve them. This paper describes the instrument development, study recruitment, characteristics of the study participating practices and their constituent healthcare professionals and administrative staff and reports descriptive analyses of the data collected. Methods The study was a predictive study over a 12-month period. Practices (N = 99) were recruited from within the UK Medical Research Council General Practice Research Framework. We identified six behaviours chosen to cover a range of clinical activities (prescribing, non-prescribing), reflect decisions that were not necessarily straightforward (controlling blood pressure that was above target despite other drug treatment), and reflect recommended best practice as described by national guidelines. Practice attributes and a wide range of individually reported measures were assessed at baseline; measures of clinical outcome were collected over the ensuing 12 months, and a number of proxy measures of behaviour were collected at baseline and at 12 months. Data were collected by telephone interview, postal questionnaire (organisational and clinical) to practice staff, postal questionnaire to patients, and by computer data extraction query. Results All 99 practices completed a telephone interview and responded to baseline questionnaires. The organisational questionnaire was completed by 931/1236 (75.3%) administrative staff, 423/529 (80.0%) primary care doctors, and 255/314 (81.2%) nurses. Clinical questionnaires were completed by 326/361 (90.3%) primary care doctors and 163/186 (87.6%) nurses. At a practice level, we achieved response rates of 100% from clinicians in 40 practices and > 80% from clinicians in 67 practices. All measures had satisfactory internal consistency (alpha coefficient range from 0.61 to 0.97; Pearson correlation coefficient (two item measures) 0.32 to 0.81); scores were generally consistent with good practice. Measures of behaviour showed relatively high rates of performance of the six behaviours, but with considerable variability within and across the behaviours and measures. Discussion We have assembled an unparalleled data set from clinicians reporting on their cognitions in relation to the performance of six clinical behaviours involved in the management of people with one chronic disease (diabetes mellitus), using a range of organisational and individual level measures as well as information on the structure of the practice teams and across a large number of UK primary care practices. We would welcome approaches from other researchers to collaborate on the analysis of this data.

Abstract Background Type 2 diabetes is an increasingly prevalent chronic illness and is an important cause of avoidable mortality. Patients are managed by the integrated activities of clinical and non-clinical members of the primary care team. Studies of the quality of care for patients with diabetes suggest less than optimum care in a number of areas. Aim The aim of this study is to improve the quality of care for patients with diabetes cared for in primary care in the UK by identifying individual, team, and organisational factors that predict the implementation of best practice. Design Participants will be clinical and non-clinical staff within 100 general practices sampled from practices who are members of the MRC General Practice Research Framework. Self-completion questionnaires will be developed to measure the attributes of individual health care professionals, primary care teams (including both clinical and non-clinical staff), and their organisation in primary care. Questionnaires will be administered using postal survey methods. A range of validated theories will be used as a framework for the questionnaire instruments. Data relating to a range of dimensions of the organisational structure of primary care will be collected via a telephone interview at each practice using a structured interview schedule. We will also collect data relating to the processes of care, markers of biochemical control, and relevant indicator scores from the quality and outcomes framework (QOF). Process data (as a proxy indicator of clinical behaviours) will be collected from practice databases and via a postal questionnaire survey of a random selection of patients from each practice. Levels of biochemical control will be extracted from practice databases. A series of analyses will be conducted to relate the individual, team, and organisational data to the process, control, and QOF data to identify configurations associated with high quality care. Study registration UKCRN ref:DRN120 (ICPD)

We examined short-term changes in younger and older adults' control beliefs. Participants completed measures of general and memory-specific competence and locus of control on 10 bi-monthly occasions. At each occasion, participants rated their control beliefs prior to and following completion of a battery of cognitive tasks. Exposure to the set of cognitively demanding tasks led to declines in older adults' ratings of both general and memory-specific competence compared to little change or increases in younger adults' ratings. Older adults were also more inconsistent in their reported locus of control beliefs across the 10 occasions. Analyses examining the relationship between control beliefs and actual cognitive performance revealed few significant effects, suggesting that short-term changes in perceived control are not driven by monitoring changes in actual performance. The results suggest the importance of assessing short-term as well as long-term changes in perceived control to obtain a complete picture of aging-related changes. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing active cancer therapy or with metastatic cancer are at increased risk for acute cholecystitis and often present to general surgeons for evaluation and management. There is a paucity of data regarding the treatment processes used in these patients and the clinical outcomes achieved. Optimal management of acute cholecystitis in patients with cancer requires understanding their unique risk profile and options for treatment., Methods: Emergency general surgery data were collected at 10 hospitals from July 1, 2019, to February 29, 2024. Patients presenting with acute cholecystitis were selected for analysis. Propensity score matching was used to create matched cohorts of patients by the presence or absence of an active malignancy. The primary outcome was 30-day mortality. Secondary outcomes included complications, length of stay, readmission, and discharge disposition. Processes investigated include treatment modality, time to operation, and surgical technique., Results: The analysis included 8,673 patients. Mean age was 53.2 ± 19 years, 61.4% were female, and 17.8% were non-White. In total, 3.3% of patients had an active malignancy. Risk-adjusted 30-day mortality was higher in the cancer cohort (odds ratio: 5.85, 95% confidence interval: 2.38-14.4, P < .001). Patients with cancer also had higher rates of infectious complications (odds ratio: 2.55, 95% confidence interval: 1.54-4.2, P < .001), including sepsis (odds ratio: 2.95, 95% confidence interval: 1.61-5.39, P < .001) and pneumonia (odds ratio: 6.67, 95% confidence interval: 1.75-25.3, P < .005). Patients with cancer were more likely to receive nonoperative management (odds ratio: 2.85, 95% confidence interval: 2.11-3.84, P < .001)., Conclusion: Patients with cancer presenting with acute cholecystitis experience worse clinical outcomes after controlling for other factors. Furthermore, there is variation in the treatment process with increased rates of nonoperative management. These results have implications for the management of this population, particularly in relation to the impact on concurrent oncologic treatment plans., Competing Interests: Conflict of Interest/Disclosure Patrick L. Johnson and Jonathan Williams receive funding from grant NIH T32-DK108740 from the National Institutes of Health. Sara L. Schaefer receives funding from grant T32-CA-236621 and personal fees from the Journal of American Medical Association Network for serving as a visual abstract editor. Laura Gerhardinger and Mark R. Hemmila receive grant funding from Blue Cross Blue Shield of Michigan and Blue Care Network (a nonprofit mutual company) and the Michigan Department of Health and Human Services for support of the Michigan Trauma Quality Improvement Program. Mark R. Hemmila receives grant funding from General Motors Corporation, Toyota North America, and the Insurance Institute for Highway Safety for support of the International Center for Automotive Medicine. Mark R. Hemmila receives grant funding from the Uniformed Services University of the Health Sciences and the H M Jackson Foundation for the Advancement of Military Medicine for support of an evidence-based assessment of combat wound infection management. The remaining authors have no conflicts to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

There is a lack of information on effective burn prevention strategies. The objective of this study was to examine a safe fireplace program, as a method of burn prevention, in a resource-limited setting. We conducted a qualitative, phenomenological study at a community health and development program for a rural population in Kenya. Semi-structured, in-depth interviews were conducted with a purposive sample of community health workers involved with the safe fireplace program. Data were reviewed iteratively and coded independently by two researchers using NVivo 12. The study included five participants. Reflections from participants fell into three main domains: (1) effective methods of education, (2) strategies to incorporate stakeholders, and (3) implementation challenges. The results of this study emphasize the importance of community engagement in implementing a successful burn injury prevention program in a resource-limited setting. The participants involved in this study reported that rather than focusing on resources outside the community, effective methods of education and strategies for incorporating stakeholders depended on involving peers and community leaders. The challenges to the program were similarly specific to community concerns about resources and maintenance. These findings provide information to guide future community health programs in creating successful models for burn prevention strategies in resource-limited areas., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Widely applicable, modified Green-Kubo expressions for the local diffusion coefficient ( D l ) are obtained using linear response theory. In contrast to past definitions in use, these expressions are statistical mechanical results. Molecular simulations of systems with anisotropic diffusion and an inhomogeneous density profile confirm the validity of the results. Diffusion coefficients determined from different expressions in terms of currents and velocity correlations agree in the limit of large systems. Furthermore, they apply to arbitrarily small local regions, making them readily applicable to nanoscale and inhomogeneous systems where knowledge of D l is important.

Background: Burn injury continues to cause significant morbidity and mortality in the US pediatric population. Many studies using inpatient samples have found a relationship between low socioeconomic status (SES) and burn injury. The purpose of our study was to evaluate the association between SES and the likelihood of admission for Emergency Department (ED) visits for pediatric burn injury., Study Design: A retrospective database review of pediatric ED visits for burn injury from a statewide hospital system, from January 1, 2005 to December 31, 2014. SES was assigned using an eight factor Neighborhood Risk Index (NRI) created from census block group data, with a higher score indicative of lower SES. The outcome measure was ED visits admitted to inpatient care., Results: We analyzed a sample of 1845 pediatric ED visits for burn injuries. Most visits were discharged from the ED (88.4%) while 10.5% were admitted to inpatient care and 1.0% were transferred to another hospital. In a multivariable logistic regression model, patients from high risk areas (>75th percentile NRI) had 1.58 higher odds of inpatient admission compared to patients from low risk areas (<75th percentile NRI; 95% CI: 1.08-2.30), after adjusting for age, gender, ethnicity, distance to the hospital, and previous ED visit for burn injury in the past 30 days. In addition, for every 1-mile increase in distance, a child's likelihood of admission increased by 6% (95% CI: 4-9%)., Conclusions: Children with a burn injury from the highest risk socioeconomic areas in Rhode Island had a higher likelihood of inpatient admission. Further research is needed to determine what factors associated with socioeconomic status impact this finding., (Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.)

Burn injury represents a substantial burden of disease in resource-limited settings. Kenya has no formal trauma system and referral practices for burn injuries are not well understood. The purpose of this study was to determine the factors associated with burn injury referrals in rural Kenya. A retrospective chart review was conducted for patients with burn injury from January 1, 2014 to December 31, 2017 at a 300-bed faith-based, teaching hospital in southwest Kenya. Bivariate analysis compared referred and non-referred patients. Multivariable logistic regression was used to assess the association between burn severity and odds of referral adjusting for age, sex, insurance, time from injury to arrival, and estimated travel time from home to hospital. The study included 171 patients with burn injury; 11 patients were excluded due to missing referral data. Of the 160 patients, 31.9% (n = 51) were referred. Referral patients had higher average total body surface area burn (23.1 ± 2.4% vs 11.1 ± 1.2%, P < .001), were more likely to have full-thickness burns (41.3% vs 25.5%, P = .05), and less likely to present to the referral hospital within 24 hours after injury (47.8% vs 73.0%, P = .005). Referral patients had longer travel time to hospital (90+ min: 52.9% vs 22.0%, P < .001). Odds of referral increased 1.62 times (95% confidence interval: 1.19-2.22) for every 10% increase in total body surface area burn. Without a coordinated trauma system, referrals represent a substantial portion of burn injury patients at a hospital in rural Kenya. Referred patients present with more severe burns and experience delays to presentation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We used the BinaxNOW COVID-19 Ag Card to screen 1,540 asymptomatic college students for severe acute respiratory syndrome coronavirus 2 in a low-prevalence setting. Compared with reverse transcription PCR, BinaxNOW showed 20% overall sensitivity; among participants with culturable virus, sensitivity was 60%. BinaxNOW provides point-of-care screening but misses many infections.

Background: Persistent post-traumatic symptoms (PPS) after traumatic brain injury (TBI) can lead to significant chronic functional impairment. Pseudocontinuous arterial spin labeling (pCASL) has been used in multiple studies to explore changes in cerebral blood flow (CBF) that may result in acute and chronic TBI, and is a promising neuroimaging modality for assessing response to therapies. Methods: Twenty-four subjects with chronic mild-moderate TBI (mmTBI) were enrolled in a pilot study of 10 days of computerized executive function training combined with active or sham anodal transcranial direct current stimulation (tDCS) for treatment of cognitive PPS. Behavioral surveys, neuropsychological testing, and magnetic resonance imaging (MRI) with pCASL sequences to assess global and regional CBF were obtained before and after the training protocol. Results: Robust improvements in depression, anxiety, complex attention, and executive function were seen in both active and sham groups between the baseline and post-treatment visits. Global CBF decreased over time, with differences in regional CBF noted in the right inferior frontal gyrus (IFG). Active stimulation was associated with static or increased CBF in the right IFG, whereas sham was associated with reduced CBF. Neuropsychological performance and behavioral symptoms were not associated with changes in CBF. Discussion: The current study suggests a complex picture between mmTBI, cerebral perfusion, and recovery. Changes in CBF may result from physiologic effect of the intervention, compensatory neural mechanisms, or confounding factors. Limitations include a small sample size and heterogenous injury sample, but these findings suggest promising directions for future studies of cognitive training paradigms in mmTBI., (Copyright © 2020 Quinn, Upston, Jones, Brandt, Story-Remer, Fratzke, Wilson, Rieger, Hunter, Gill, Richardson, Campbell, Clark, Yeo, Shuttleworth and Mayer.)

Multiple heteroatom-doped carbons with 3D ordered macro/meso-microporous structures have not been realized by simple carbonization of metal-organic frameworks (MOFs). Herein, ordered macroporous phosphorus- and nitrogen-doped carbon (M-PNC) is prepared successfully by carbonization of double-solvent-induced MOF/polystyrene sphere (PS) precursors accompanied with spontaneous removal of the PS template, followed by post-doping. M-PNC shows a high specific surface area of 837 m 2 g -1 , nitrogen doping of 3.17 at%, and phosphorus doping of 1.12 at%. Thanks to the hierarchical structure, high specific surface area, and multiple heteroatom-doping, M-PNC exhibits unusual catalytic activity as an electrocatalyst for the oxygen reduction reaction. Computational calculation reveals that the P[double bond, length as m-dash]O group helps stabilize the adsorption of intermediates, and the position of P[double bond, length as m-dash]O relative to graphitic N significantly improves the activity of the adjacent carbons for electrocatalysis., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Auditory encoding abnormalities, gray-matter loss, and cognitive deficits are all candidate schizophrenia (SZ) endophenotypes. This study evaluated associations between and heritability of auditory network attributes (function and structure) and attention in healthy controls (HC), SZ patients, and unaffected relatives (UR)., Methods: Whole-brain maps of M100 auditory activity from magnetoencephalography recordings, cortical thickness (CT), and a measure of attention were obtained from 70 HC, 69 SZ patients, and 35 UR. Heritability estimates (h2r) were obtained for M100, CT at each group-difference region, and the attention measure., Results: SZ patients had weaker bilateral superior temporal gyrus (STG) M100 responses than HC and a weaker right frontal M100 response than UR. Abnormally large M100 responses in left superior frontal gyrus were observed in UR and SZ patients. SZ patients showed smaller CT in bilateral STG and right frontal regions. Interrelatedness between 3 putative SZ endophenotypes was demonstrated, although in the left STG the M100 and CT function-structure associations observed in HC and UR were absent in SZ patients. Heritability analyses also showed that right frontal M100 and bilateral STG CT measures are significantly heritable., Conclusions: Present findings indicated that the 3 SZ endophenotypes examined are not isolated markers of pathology but instead are connected. The pattern of auditory encoding group differences and the pattern of brain function-structure associations differ as a function of brain region, indicating the need for regional specificity when studying these endophenotypes, and with the presence of left STG function-structure associations in HC and UR but not in SZ perhaps reflecting disease-associated damage to gray matter that disrupts function-structure relationships in SZ., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Metal heteroatoms dispersed in nitrogen-doped graphene display promising catalytic activity for fuel cell reactions such as the hydrogen evolution reaction (HER). Here we explore the effects of the dopant concentration on the synergistic catalytic behavior of a paired metal atom active site comprising Co and Pt atoms that have been shown to be particularly active catalysts in these materials. The metals are coordinated to six atoms in a vacancy of N-doped graphene. We find that the HER activity is enhanced with increasing N concentration, where the free energy of hydrogen atom adsorption ranges from 0.23 to -0.42 eV as the doping changes from a single N atom doped in the pore to fully doped coordination sites. The results indicate that the effect of N is to make the metal atoms more active toward H adsorption, presenting a means through which transition metals can be modified to make more effective and sustainable fuel cell catalysts.

The growth in the direct-to-consumer genetic testing industry poses a number of challenges for healthcare practice, among a number of other areas of concern. Several companies providing this service send their customers reports including information variously referred to as genetic ethnicity, genetic heritage, biogeographic ancestry, and genetic ancestry. In this article, we argue that such information should not be used in healthcare consultations or to assess health risks. Far from representing a move toward personalized medicine, use of this information poses risks both to patients as individuals and to racialized ethnic groups because of the way it misrepresents human genetic diversity.

Positive emotional perceptions and healthy emotional intelligence (EI) are important for social functioning. In this study, we investigated whether loving kindness meditation (LKM) combined with anodal transcranial direct current stimulation (tDCS) would facilitate improvements in EI and changes in affective experience of visual stimuli. LKM has been shown to increase positive emotional experiences and we hypothesized that tDCS could enhance these effects. Eighty-seven undergraduates were randomly assigned to 30 minutes of LKM or a relaxation control recording with anodal tDCS applied to the left dorsolateral prefrontal cortex (left dlPFC) or right temporoparietal junction (right TPJ) at 0.1 or 2.0 milliamps. The primary outcomes were self-reported affect ratings of images from the International Affective Picture System and EI as measured by the Mayer, Salovey and Caruso Emotional Intelligence Test. Results indicated no effects of training on EI, and no main effects of LKM, electrode placement, or tDCS current strength on affect ratings. There was a significant interaction of electrode placement by meditation condition ( p  = 0.001), such that those assigned to LKM and right TPJ tDCS, regardless of current strength, rated neutral and positive images more positively after training. Results suggest that LKM may enhance positive affective experience.

Magnetoencephalography (MEG) and EEG have identified poststimulus low frequency and 40 Hz steady-state auditory encoding abnormalities in schizophrenia (SZ). Negative findings have also appeared. To identify factors contributing to these inconsistencies, healthy control (HC) and SZ group differences were examined in MEG and EEG source space and EEG sensor space, with better group differentiation hypothesized for source than sensor measures given greater predictive utility for source measures. Fifty-five HC and 41 chronic SZ were presented 500 Hz sinusoidal stimuli modulated at 40 Hz during simultaneous whole-head MEG and EEG. MEG and EEG source models using left and right superior temporal gyrus (STG) dipoles estimated trial-to-trial phase similarity and percent change from prestimulus baseline. Group differences in poststimulus low-frequency activity and 40 Hz steady-state response were evaluated. Several EEG sensor analysis strategies were also examined. Poststimulus low-frequency group differences were observed across all methods. Given an age-related decrease in left STG 40 Hz steady-state activity in HC (HC > SZ), 40 Hz steady-state group differences were evident only in younger participants' source measures. Findings thus indicated that optimal data collection and analysis methods depend on the auditory encoding measure of interest. In addition, whereas results indicated that HC and SZ auditory encoding low-frequency group differences are generally comparable across modality and analysis strategy (and thus not dependent on obtaining construct-valid measures of left and right auditory cortex activity), 40 Hz steady-state group-difference findings are much more dependent on analysis strategy, with 40 Hz steady-state source-space findings providing the best group differentiation., (© 2018 Society for Psychophysiological Research.)

Mindfulness-based training (MBT) and transcranial electrical stimulation (TES) methods such as direct current stimulation (tDCS) have demonstrated promise for the augmentation of cognitive abilities. The current study investigated the potential compatibility of concurrent "electrical" MBT and tDCS (or eMBT) by testing its combined effects on behavioral and neurophysiological indices of working memory (WM) and attentional resource allocation. Thirty-four healthy participants were randomly assigned to either a MBT task with tDCS group (eMBT) or an active control training task with sham tDCS (Control) group. Training lasted 4-weeks, with up to twenty MBT sessions and with up to eight of those sessions that were eMBT sessions. Electroencephalography was acquired during varying WM load conditions using the n-back task (1-, 2-, 3-back), along with performance on complex WM span tasks (operation and symmetry span) and fluid intelligence measures (Ravens and Shipley) before and after training. Improved performance was observed only on the 3-back and spatial span tasks for eMBT but not the Control group. During 3-back performance in the eMBT group, an increase in P3 amplitude and theta power at electrode site Pz was also observed, along with a simultaneous decrease in frontal midline P3 amplitude and theta power compared to the Control group. These results are consistent with the neural efficiency hypothesis, where higher cognitive capacity was associated with more distributed brain activity (i.e., increase in parietal and decrease in frontal amplitudes). Future longitudinal studies are called upon to further examine the direct contributions of tDCS on MBT by assessing the differential effects of electrode montage, polarity, current strength and a direct contrast between the eMBT and MBT conditions on performance and neuroimaging outcome data. While preliminary, the current results provided evidence for the potential compatibility of using eMBT to modulate WM capacity through the allocation of attention and its neurophysiological correlates.

Individual differences across a variety of cognitive processes are functionally associated with individual differences in intrinsic networks such as the default mode network (DMN). The extent to which these networks correlate or anticorrelate has been associated with performance in a variety of circumstances. Despite the established role of the DMN in mind wandering processes, little research has investigated how large-scale brain networks at rest relate to mind wandering tendencies outside the laboratory. Here we examine the extent to which the DMN, along with the dorsal attention network (DAN) and frontoparietal control network (FPCN) correlate with the tendency to mind wander in daily life. Participants completed the Mind Wandering Questionnaire and a 5-min resting state fMRI scan. In addition, participants completed measures of executive function, fluid intelligence, and creativity. We observed significant positive correlations between trait mind wandering and 1) increased DMN connectivity at rest and 2) increased connectivity between the DMN and FPCN at rest. Lastly, we found significant positive correlations between trait mind wandering and fluid intelligence (Ravens) and creativity (Remote Associates Task). We interpret these findings within the context of current theories of mind wandering and executive function and discuss the possibility that certain instances of mind wandering may not be inherently harmful. Due to the controversial nature of global signal regression (GSReg) in functional connectivity analyses, we performed our analyses with and without GSReg and contrast the results from each set of analyses., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Although the 40 Hz auditory steady-state response (ASSR) is of clinical interest, the construct validity of EEG and MEG measures of 40 Hz ASSR cortical microcircuits is unclear. This study evaluated several MEG and EEG metrics by leveraging findings of (a) an association between the 40 Hz ASSR and age in the left but not right hemisphere, and (b) right- > left-hemisphere differences in the strength of the 40 Hz ASSR. The contention is that, if an analysis method does not demonstrate a left 40 Hz ASSR and age relationship or hemisphere differences, then the obtained measures likely have low validity. Fifty-three adults were presented 500 Hz stimuli modulated at 40 Hz while MEG and EEG were collected. ASSR activity was examined as a function of phase similarity (intertrial coherence) and percent change from baseline (total power). A variety of head models (spherical and realistic) and a variety of dipole source modeling strategies (dipole source localization and dipoles fixed to Heschl's gyri) were compared. Several sensor analysis strategies were also tested. EEG sensor measures failed to detect left 40 Hz ASSR and age associations or hemisphere differences. A comparison of MEG and EEG head-source models showed similarity in the 40 Hz ASSR measures and in estimating age and left 40 Hz ASSR associations, indicating good construct validity across models. Given a goal of measuring the 40 Hz ASSR cortical microcircuits, a source-modeling approach was shown to be superior in measuring this construct versus methods that rely on EEG sensor measures., (© 2017 Society for Psychophysiological Research.)

Although working memory (WM) training programs consistently result in improvement on the trained task, benefit is typically short-lived and extends only to tasks very similar to the trained task (i.e., near transfer). It is possible that pairing repeated performance of a WM task with brain stimulation encourages plasticity in brain networks involved in WM task performance, thereby improving the training benefit. In the current study, transcranial direct current stimulation (tDCS) was paired with performance of a WM task (n-back). In Experiment 1, participants performed a spatial location-monitoring n-back during stimulation, while Experiment 2 used a verbal identity-monitoring n-back. In each experiment, participants received either active (2.0mA) or sham (0.1mA) stimulation with the anode placed over either the right or the left dorsolateral prefrontal cortex (DLPFC) and the cathode placed extracephalically. In Experiment 1, only participants receiving active stimulation with the anode placed over the right DLPFC showed marginal improvement on the trained spatial n-back, which did not extend to a near transfer (verbal n-back) or far transfer task (a matrix-reasoning task designed to measure fluid intelligence). In Experiment 2, both left and right anode placements led to improvement, and right DLPFC stimulation resulted in numerical (though not sham-adjusted) improvement on the near transfer (spatial n-back) and far transfer (fluid intelligence) task. Results suggest that WM training paired with brain stimulation may result in cognitive enhancement that transfers to performance on other tasks, depending on the combination of training task and tDCS parameters used., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

There is a great deal of debate concerning the benefits of working memory (WM) training and whether that training can transfer to other tasks. Although a consistent finding is that WM training programs elicit a short-term near-transfer effect (i.e., improvement in WM skills), results are inconsistent when considering persistence of such improvement and far transfer effects. In this study, we compared three groups of participants: a group that received WM training, a group that received training on how to use a mental imagery memory strategy, and a control group that received no training. Although the WM training group improved on the trained task, their posttraining performance on nontrained WM tasks did not differ from that of the other two groups. In addition, although the imagery training group's performance on a recognition memory task increased after training, the WM training group's performance on the task decreased after training. Participants' descriptions of the strategies they used to remember the studied items indicated that WM training may lead people to adopt memory strategies that are less effective for other types of memory tasks. These results indicate that WM training may have unintended consequences for other types of memory performance.

To assess the accuracy of initial combined cytological accuracy and radiological staging of patients suspected of having thyroid malignancy with their final histopathology. Retrospective case series in a tertiary referral centre for head and neck malignancy. All patients with malignant thyroid cytology and cytology suspicious for malignancy, between the dates of June 2010 and July 2014, were included. The pre-operative staging was compared against the final histological staging. Demographics and outcomes for each patient were recorded. Sixty-five patients were recorded in this group. 20 (30.7 %) were male. The mean age at presentation was 51 years (SD 16.8 years). 39 (60 %) patients were aged over 45 years. Fine needle aspiration cytology (FNAC) was performed in all patients and was Thy 4 in 40 (62 %) and Thy 5 in 25 (38 %). Following surgery or subsequent biopsy, FNAC was found to be accurate in 38/40 (Thy 4) and 25/25 (Thy 5) cases in diagnosing malignancy, with Thy 4 yielding 95 % malignancy and Thy 5 % 100 %. Fifty-eight patients underwent a surgical procedure for thyroid cancer. Two further patients had a diagnostic hemi-thyroidectomy for later proven benign disease. Five patients due to medical co morbidities, inoperable disease or refusal of surgery were managed non-surgically. In the surgical group 16 patients underwent a diagnostic hemi-thyroidectomy and 11 of these required a completion thyroidectomy. Forty-six patients underwent total thyroidectomy. Forty-six patients underwent a neck dissection: 27 prophylactic central compartment neck dissections and 19 planned therapeutic neck dissections were performed. Radiological staging correctly predicted final pathological TNM staging in 25 (43 %) patients. 27 (47 %) patients had radiological staging which under staged their final histological staging and 6 (10 %) patients had scans that over staged their cancer. Of those that were under staged, 15 (56 %) had their nodal disease under staged (following prophylactic central neck dissection). Radiological staging comprised ultrasound (n = 58) and CT scanning (n = 45/58 pre-operatively). Pre-operative staging in thyroid cancer should include cytology, ultrasound and CT scanning. Unless low-risk papillary thyroid cancer is suspected pre-operatively, patients with Thy 4 cytology can be given the offer of a total thyroidectomy as surgical management.

Background: Increased temporal and frontal slow-wave delta (1-4 Hz) and theta (4-7 Hz) activities are the most consistent resting-state neural abnormalities reported in schizophrenia. The frontal lobe is associated with negative symptoms and cognitive abilities such as attention, with negative symptoms and impaired attention associated with poor functional capacity., Aims: To establish whether frontal dysfunction, as indexed by slowing, would be associated with functional impairments., Method: Eyes-closed magnetoencephalography data were collected in 41 participants with schizophrenia and 37 healthy controls, and frequency-domain source imaging localised delta and theta activity., Results: Elevated delta and theta activity in right frontal and right temporoparietal regions was observed in the schizophrenia v., Control Group: In schizophrenia, right-frontal delta activity was uniquely associated with negative but not positive symptoms. In the full sample, increased right-frontal delta activity predicted poorer attention and functional capacity., Conclusions: Our findings suggest that treatment-associated decreases in slow-wave activity could be accompanied by improved functional outcome and thus better prognosis., (© The Royal College of Psychiatrists 2016.)

Transcranial direct current stimulation (tDCS) modulates glutamatergic neurotransmission and can be utilized as a novel treatment intervention for a multitude of populations. However, the exact mechanism by which tDCS modulates the brain׳s neural architecture, from the micro to macro scales, have yet to be investigated. Using a within-subjects design, resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy ((1)H MRS) were performed immediately before and after the administration of anodal tDCS over right parietal cortex. Group independent component analysis (ICA) was used to decompose fMRI scans into 75 brain networks, from which 12 resting-state networks were identified that had significant voxel-wise functional connectivity to anatomical regions of interest. (1)H MRS was used to obtain estimates of combined glutamate and glutamine (Glx) concentrations from bilateral intraparietal sulcus. Paired sample t-tests showed significantly increased Glx under the anodal electrode, but not in homologous regions of the contralateral hemisphere. Increases of within-network connectivity were observed within the superior parietal, inferior parietal, left frontal-parietal, salience and cerebellar intrinsic networks, and decreases in connectivity were observed in the anterior cingulate and the basal ganglia (p<0.05, FDR-corrected). Individual differences in Glx concentrations predicted network connectivity in most of these networks. The observed relationships between glutamatergic neurotransmission and network connectivity may be used to guide future tDCS protocols that aim to target and alter neuroplastic mechanisms in healthy individuals as well as those with psychiatric and neurologic disorders., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: Although brain rhythms depend on brain structure (e.g., gray and white matter), to our knowledge associations between brain oscillations and structure have not been investigated in healthy controls (HC) or in individuals with schizophrenia (SZ). Observing function-structure relationships, for example establishing an association between brain oscillations (defined in terms of amplitude or phase) and cortical gray matter, might inform models on the origins of psychosis. Given evidence of functional and structural abnormalities in primary/secondary auditory regions in SZ, the present study examined how superior temporal gyrus (STG) structure relates to auditory STG low-frequency and 40 Hz steady-state activity. Given changes in brain activity as a function of age, age-related associations in STG oscillatory activity were also examined., Methods: Thirty-nine individuals with SZ and 29 HC were recruited. 40 Hz amplitude-modulated tones of 1 s duration were presented. MEG and T1-weighted sMRI data were obtained. Using the sources localizing 40 Hz evoked steady-state activity (300 to 950 ms), left and right STG total power and inter-trial coherence were computed. Time-frequency group differences and associations with STG structure and age were also examined., Results: Decreased total power and inter-trial coherence in SZ were observed in the left STG for initial post-stimulus low-frequency activity (~ 50 to 200 ms, ~ 4 to 16 Hz) as well as 40 Hz steady-state activity (~ 400 to 1000 ms). Left STG 40 Hz total power and inter-trial coherence were positively associated with left STG cortical thickness in HC, not in SZ. Left STG post-stimulus low-frequency and 40 Hz total power were positively associated with age, again only in controls., Discussion: Left STG low-frequency and steady-state gamma abnormalities distinguish SZ and HC. Disease-associated damage to STG gray matter in schizophrenia may disrupt the age-related left STG gamma-band function-structure relationships observed in controls.

Background: Although magnetoencephalography (MEG) studies show superior temporal gyrus (STG) auditory processing abnormalities in schizophrenia at 50 and 100 ms, EEG and corticography studies suggest involvement of additional brain areas (e.g., frontal areas) during this interval. Study goals were to identify 30 to 130 ms auditory encoding processes in schizophrenia (SZ) and healthy controls (HC) and group differences throughout the cortex., Methods: The standard paired-click task was administered to 19 SZ and 21 HC subjects during MEG recording. Vector-based Spatial-temporal Analysis using L1-minimum-norm (VESTAL) provided 4D maps of activity from 30 to 130 ms. Within-group t-tests compared post-stimulus 50 ms and 100 ms activity to baseline. Between-group t-tests examined 50 and 100 ms group differences., Results: Bilateral 50 and 100 ms STG activity was observed in both groups. HC had stronger bilateral 50 and 100 ms STG activity than SZ. In addition to the STG group difference, non-STG activity was also observed in both groups. For example, whereas HC had stronger left and right inferior frontal gyrus activity than SZ, SZ had stronger right superior frontal gyrus and left supramarginal gyrus activity than HC., Conclusions: Less STG activity was observed in SZ than HC, indicating encoding problems in SZ. Yet auditory encoding abnormalities are not specific to STG, as group differences were observed in frontal and SMG areas. Thus, present findings indicate that individuals with SZ show abnormalities in multiple nodes of a concurrently activated auditory network.

Summary: We performed high-resolution DIR-BBI of the cervical arteries at 3T in 19 subjects with cervical dissection. It offered excellent visualization of both the lumen and arterial wall, allowing detection of the primary and secondary features of dissection. We suggest that this is a highly useful technique for diagnosis of cervical dissection, either routinely or in equivocal cases of suspected dissection. It also offers further insight into the pathogenesis of this disorder.

Background: Although gray matter (GM) abnormalities are frequently observed in individuals with schizophrenia (SCZ), the functional consequences of these structural abnormalities are not yet understood. The present study sought to better understand GM abnormalities in SCZ by examining associations between GM and two putative functional SCZ biomarkers: weak 100 ms (M100) auditory responses and impairment on tests of attention., Methods: Data were available from 103 subjects (healthy controls=52, SCZ=51). GM cortical thickness measures were obtained for superior temporal gyrus (STG) and prefrontal cortex (PFC). Magnetoencephalography (MEG) provided measures of left and right STG M100 source strength. Subjects were administered the Trail Making Test A and the Connors' Continuous Performance Test to assess attention., Results: A strong trend indicated less GM cortical thickness in SCZ than controls in both regions and in both hemispheres (p=0.06). Individuals with SCZ had weaker M100 responses than controls bilaterally, and individuals with SCZ performed more poorly than controls on tests of attention. Across groups, left STG GM was positively associated with left M00 source strength. In SCZ only, less left and right STG and PFC GM predicted poorer performance on tests of attention. After removing variance in attention associated with age, associations between GM and attention remained significant only in left and right STG., Conclusions: Reduced GM cortical thickness may serve as a common substrate for multiple functional abnormalities in SCZ, with structural-functional abnormalities in STG GM especially prominent. As suggested by others, functional abnormalities in SCZ may be a consequence of elimination of the neuropil (dendritic arbors and associated synaptic infrastructure) between neuron bodies., (Copyright © 2012 Elsevier B.V. All rights reserved.)