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A key step toward understanding psychiatric disorders that disproportionately impact female mental health is delineating the emergence of sex-specific patterns of brain organisation at the critical transition from childhood to adolescence. Prior work suggests that individual differences in the spatial organisation of functional brain networks across the cortex are associated with psychopathology and differ systematically by sex.
Aims
We aimed to evaluate the impact of sex on the spatial organisation of person-specific functional brain networks.
Method
We leveraged person-specific atlases of functional brain networks, defined using non-negative matrix factorisation, in a sample of n = 6437 youths from the Adolescent Brain Cognitive Development Study. Across independent discovery and replication samples, we used generalised additive models to uncover associations between sex and the spatial layout (topography) of personalised functional networks (PFNs). We also trained support vector machines to classify participants’ sex from multivariate patterns of PFN topography.
Results
Sex differences in PFN topography were greatest in association networks including the frontoparietal, ventral attention and default mode networks. Machine learning models trained on participants’ PFNs were able to classify participant sex with high accuracy.
Conclusions
Sex differences in PFN topography are robust, and replicate across large-scale samples of youth. These results suggest a potential contributor to the female-biased risk in depressive and anxiety disorders that emerge at the transition from childhood to adolescence.
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.
Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
Methods
Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
Results
Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
Conclusions
Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16–100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%–57%/25%–33%; <60: 32%–49%/18%–25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.
Hard cider is a sector of a maturing craft beverage industry that continues to experience growth in the United States. Cider is also experiencing challenges, however, such as competition from other alcohol markets, changing consumer preferences, the supply chain, and inflationary pressures. National policy changes may help promote more optimal outcomes for this sector, but public support is important to policy formation. This study uses survey data from a best-worst scaling experiment of consumers in four leading cider-producing states (Michigan, Washington, Wisconsin, and Vermont) to understand preferences toward ten broad cider policy initiatives. The results of multinomial logistic modeling reveal that consumers prefer policies mandating ingredients, nutrition facts, and allergen labeling across all ciders. The least preferred policy initiatives include allowing producers to use vintage on labeling and funding regional cider development. These results have important implications for stakeholders across the industry, including the benefits of labeling disclosures in marketing and the need to improve public awareness of barriers to cider industry development.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
We used a survey to characterize contemporary infection prevention and antibiotic stewardship program practices across 64 healthcare facilities, and we compared these findings to those of a similar 2013 survey. Notable findings include decreased frequency of active surveillance for methicillin-resistant Staphylococcus aureus, frequent active surveillance for carbapenem-resistant Enterobacteriaceae, and increased support for antibiotic stewardship programs.
Preparing and responding to the needs of children during public health emergencies continues to be challenging. The purpose of this study was to assess the usefulness of a tabletop exercise in initiating pediatric preparedness strategies and assessing the impact of the exercise on participants’ understanding of and confidence in their roles during pediatric public health emergencies.
Methods
A tabletop exercise was developed to simulate a public health emergency scenario involving smallpox in a child, with subsequent spread to multiple states. During the exercise, participants discussed and developed communication, collaboration, and medical countermeasure strategies to enhance pediatric public health preparedness. Exercise evaluation was designed to assess participants’ knowledge gained and level of confidence surrounding pediatric public health emergencies.
Results
In total, 22 participants identified over 100 communication and collaboration strategies to promote pediatric public health preparedness during the exercise and found that the most beneficial aspect during the exercise was the partnership between pediatricians and public health officials. Participants’ knowledge and level of confidence surrounding a pediatric public health emergency increased after the exercise.
Conclusion
The tabletop exercise was effective in identifying strategies to improve pediatric public health preparedness as well as enhancing participants’ knowledge and confidence surrounding a potential pediatric public health emergency. (Disaster Med Public Health Preparedness. 2018;12:582–586)
A total of ten experimental diets with protein concentrations ranging from 154 to 400 g/kg and two lipid levels (46 and 85 g/kg) with identical energy densities were offered to 240 male Ross 308 broilers from 7 to 28 d post-hatch. Growth performance was monitored and nutrient utilisation (apparent metabolisable energy (AME), N-corrected AME (AMEn), AME daily intake, AME:gross energy ratios, N retention) was determined. The weight gain response of broiler chickens to dietary protein concentrations in diets containing high and low lipid levels was diverse, with the relevant quadratic regressions being significantly different (P<0·05). With low lipid levels, the predicted maximum weight gain of 1809 g/bird equated to 342 g/kg dietary protein, whereas, for high lipid levels the predicted maximum weight gain of 1694 g/bird equated to 281 g/kg dietary protein. AME was linearly correlated with dietary protein concentration but regressions in diets with different lipid content were not significantly different (P>0·05). AMEn was also linearly (P<0·0001) increased with dietary protein concentrations but regressions in diets with low and high lipid content were significantly different (P<0·03). Carcass protein content increased linearly with dietary protein content in diets containing high lipid concentrations (r 0·933, P<0·0001); by contrast, this relationship was quadratic (R2=0·93, P<0·0001) in diets with low lipid levels. In conclusion, predictably, the effects of dietary protein concentrations on broiler performance were profound; however, the impact of dietary protein on performance in broiler chickens was modified by dietary lipid concentrations.
This article reports on a case study of a decade-long organizing forms response to the need for groundbreaking innovation while maintaining existing operational performance – the explore–exploit conundrum. Employing ‘grounded research,’ data were collected on the experiences of the Asia-Pacific arm of a multinational professional service firm’s key decision-makers, innovators and entrepreneurs. The findings reveal a three-tiered organizing forms response to the explore–exploit paradox, characterized by a novel combination of heavy exploitation-driven actions alongside deep exploration projects. This case suggests that one successful approach to delivering on both explore and exploit focuses on a productive tension that emerges by enacting innovative organizing forms with contextual awareness. This productive tension was sufficiently powerful to impel individuals to innovate, but also sufficiently contained to avoid interfering with commercial outcomes. An explore–exploit framework conceptualizes organizational changes incorporating complexity and contradiction, without the implicit emphasis on removing or denying the existing tension.
The right-angled triangle mixture experiment was designed to include fourteen diets with different concentrations of starch, protein and lipid. Experimental diets were offered to male Ross 308 broiler chickens from 10 to 23 d after hatching, and response curves and surfaces were generated to illustrate the influence of macronutrients on growth performance and nutrient utilisations. Despite the primary function of macronutrients, especially protein, may not be providing energy, macronutrients were expressed as energy derived from starch, protein and fat for statistical purposes in the mixture design. Energy derived from lipid had a greater impact on feed intake than energy derived from starch and protein. When we compared the influence of starch and protein on feed intake, ‘equal distance rule’ was observed, which means the animal consumes feed to the point on its respective nutritional rails where the shortage of starch exactly equals the surplus of consumed protein. Increasing the protein-derived energy intake increased weight gain in broiler chickens, whereas energy intake derived from starch and lipid had little impact on weight gain. Feed conversion ratio (FCR) may be reduced by either increasing protein energy intake or decreasing starch energy intake. As the slope of the contours was less than 1, the influence of starch energy intakes on FCR exceeded that of protein energy intakes. In conclusion, energy derived from protein is more important than non-protein energy in terms of weight gain, and a balance between protein and energy supplies is required for efficient muscle protein deposition.
Evolutionary stasis has often been explained by stabilizing selection, intrinsic constraints, or, more recently, by spatially patterned population dynamics. To distinguish which of these mechanisms explains a given case of stasis in the fossil record, stasis must first be rigorously documented in a high-resolution stratigraphic time series of fossil specimens. Furthermore, past studies of evolutionary mode in fossil mammalian lineages have often been limited to univariate traits (e.g., molar crown area). It is reasonable to assume that tooth shape, a multivariate trait, reflects important additional aspects of tooth form and function. Here we present the results of a geometric morphometric analysis of the lower dentition of the Paleocene-Eocene condylarth species Ectocion osbornianus collected from the Bighorn and Clarks Fork Basins of northwestern Wyoming. Tooth margin shape, cusp configuration, and shearing crest shape were digitized for the last lower premolar, p4, and for two lower molars, m1 and m3. Multivariate statistical tests of evolutionary mode were used to analyze the change in shape variance over time in addition to the magnitude and direction of shape change. Test results characterize the shape time series as consisting of counteracting changes with less change than expected under a random walk (i.e., stasis). The temporal structure of shape variance implies that the sampled E. osbornianus most likely represent a single population, which is not concordant with the population dynamic mechanism of stasis. Stabilizing selection and/or intrinsic constraints remain as the mechanisms that could explain stasis in the lower dental shape of E. osbornianus despite the variable environmental conditions of the Paleocene–Eocene.