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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.
A Rank Forum was convened to discuss the evidence around food insecurity (FIS), its impact on health, and interventions which could make a difference both at individual and societal level, with a focus on the UK. This paper summarises the proceedings and recommendations. Speakers highlighted the growing issue of FIS due to current economic and social pressures. It was clear that the health implications of FIS varied geographically since food insecure women in higher income regions tend to be living with overweight or obesity, in contrast to those living in low-to-middle income countries. This paradox could be due to stress and/or metabolic or behavioural responses to an unpredictable food supply. The gut microbiota may play a role given the negative effects of low fibre diets on bacterial diversity, species balance and chronic disease risk. Solutions to FIS involve individual behavioural change, targeted services and societal/policy change. Obesity-related services are currently difficult to access. Whilst poverty is the root cause of FIS, it cannot be solved simply by making healthy food cheaper due to various ingrained beliefs, attitudes and behaviours in target groups. Person-centred models, such as Capability-Opportunity-Motivation Behavioural Change Techniques and Elicit-Provide-Elicit communication techniques are recommended. Societal change or improved resilience through psychological support may be more equitable ways to address FIS and can combine fiscal or food environment policies to shift purchasing towards healthier foods. However, policy implementation can be slow to enact due to the need for strong evidence, consultation and political will. Eradicating FIS must involve co-creation of interventions and policies to ensure that all stakeholders reach a consensus on solutions.
Background: The complement component C5 inhibitor, ravulizumab, is approved in Canada for the treatment of adults with AQP4-Ab+ NMOSD. Updated efficacy and safety results from the ongoing CHAMPION-NMOSD (NCT04201262) trial are reported. Methods: Participants received IV-administered, weight-based dosing of ravulizumab, with loading on day 1 and maintenance doses on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Outcome measures included safety, time to first adjudicated on-trial relapse (OTR), risk reduction, and disability scores. Results: 56/41 patients entered/completed the LTE as of June 14, 2024. Median follow-up was 170.3 weeks (186.6 patient-years). No patients experienced an OTR. 94.8% (55/58 patients) had stable or improved Hauser Ambulation Index scores. 89.7% (52/58 patients) had no clinically important worsening in Expanded Disability Status Scale scores. Treatment-emergent adverse events (98.4%) were predominantly mild and unrelated to ravulizumab. Serious adverse events occurred in 25.9% of patients. Two cases of meningococcal infection occurred during the PTP, and none in the LTE. One unrelated death (cardiovascular) occurred during the LTE. Conclusions: Ravulizumab demonstrated long-term clinical benefit in AQP4-Ab+ NMOSD relapse prevention while maintaining or improving disability measures, with no new safety concerns.
Flumioxazin and S-metolachlor are widely used in conventional sweetpotato production in North Carolina and other states; however, some growers have recently expressed concerns about potential effects of these herbicides on sweetpotato yield and quality. Previous research indicates that activated charcoal has the potential to reduce herbicide injury. Field studies were conducted in 2021 and 2022 to determine whether flumioxazin applied preplant and S-metolachlor applied before and after transplanting negatively affect sweetpotato yield and quality when activated charcoal is applied with transplant water. The studies evaluated five herbicide treatments and two activated charcoal treatments. Herbicide treatments included two flumioxazin rates, one S-metolachlor rate applied immediately before and immediately after transplanting, and no herbicide. Charcoal treatments consisted of activated charcoal applied at 9 kg ha−1, and no charcoal. No visual injury from herbicides or charcoal was observed. Likewise, no effect of herbicide or charcoal treatment on no. 1, marketable (sum of no. 1 and jumbo grades), or total yield (sum of canner, no. 1, and jumbo grades) was observed. Additionally, shape analysis conducted on calculated length-to-width ratio (LWR) for no. 1 sweetpotato roots found no effect from flumioxazin at either rate on sweetpotato root shape. However, both S-metolachlor treatments resulted in lower LWR of no. 1 sweetpotato roots in 2021. Results are consistent with prior research and indicate that flumioxazin and S-metolachlor are safe for continued use on sweetpotato at registered rates.
Background: CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in AQP4+ NMOSD. Methods: Adult patients received an intravenous, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Results: 58 patients completed the PTP; 56/2 entered/completed the LTE. As of June 16, 2023, median (range) follow-up was 138.4 (11.0-183.1) weeks for ravulizumab (n=58), with 153.9 patient-years. Across the PTP and LTE, no patients had an adjudicated on-trial relapse during ravulizumab treatment. 91.4% (53/58 patients) had stable or improved Hauser Ambulation Index score. 91.4% (53/58 patients) had no clinically important worsening in Expanded Disability Status Scale score. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events was 94.8% and 25.9%, respectively. Most TEAEs were mild to moderate in severity and unrelated to ravulizumab. TEAEs leading to withdrawal from ravulizumab occurred in 1 patient. Conclusions: Ravulizumab demonstrated long-term clinical benefit in the prevention of relapses in AQP4+ NMOSD with a safety profile consistent with prior analyses.
Indigenous people in the Americas disproportionately depend on wild meat. Many approaches have been applied to assess the impact of hunting on wildlife populations by determining whether or not it can be defined as “sustainable.” Proper understanding of sustainability requires specification of what is being sustained, the spatial extent under consideration, the duration over which the resource is being sustained, and how the impact of a particular use compares with realistic forms of alternative uses. The sustainability of hunting is species specific with harvest-sensitive species often succumbing to depletion, while others persist indefinitely. Prey profiles of Amazonian hunters rapidly shift from low-fecundity and harvest-sensitive to high-fecundity and harvest-insensitive species as local human population density increases. This is a consequence of the life history of each hunted species, which dictates age at first birth, fecundity, and survivorship, and its “catchability,” which is a measure of the effectiveness of hunting effort. Here we review density-dependent population growth in wildlife and the implementation of harvest models typical to human central-place foragers to project wildlife populations in space and time rather than a binary assessment of whether hunting is “sustainable.”
Understanding the dynamics of inter-group cooperation in human adaptation has been the subject of recent empirical and theoretical studies in evolutionary anthropology, beginning to fill gaps in our knowledge of how interactions across political, economic and social domains can – and often do – lead to stable, large-scale cooperation. Here we investigate dyadic intergroup cooperation in shotgun hunting in the Republic of the Congo. In the Congo Basin, inter-group cooperation between foragers and farmers is at the centre of an exchange system maintained by traditional norms and institutions such as fictive kinship. Here, we focused on what factors predict cooperative shotgun hunting exchanges between BaYaka and Yambe. We conducted structured interviews with 48 BaYaka hunters and 18 Yambe men who organise hunts in a village along the Motaba River. We used Bayesian multilevel regression models to investigate the influence of Yambe and BaYaka attributes on probability of dyadic cooperation. We found that BaYaka men's reputations as skilled hunters and their family size each predicted cooperation in shotgun hunting, whereas there was no effect of Yambe attributes (status, wealth, family size). We discuss the results in terms of evolutionary models of men as hunters and inter-group cooperation, as well as biodiversity conservation implications.
The effect of anions on clay dispersion and the hydraulic conductivity (HC) of clay-sand mixtures has received little attention. This study investigates the effect that adding small amounts of anions has on the dispersivity and HC of reference clays. Mixtures of 3 and 6 g 100 g−1 kaolinite, smectite, and illite with quartz sand were packed in columns. The columns were saturated with Ca and then leached with 1 molc m−3 of one of the following organic and inorganic Na salts: chloride, hydroxide, EDTA, silicate, citrate, formate, oxalate, hexametaphosphate, orthophosphate, tartrate, or humate. Changes in HC and clay concentration in the effluent were measured and clay dispersion was evaluated as a function of the various anions added. In the kaolinite clay-sand mixtures, a significant amount of clay was observed in the effluent for all anions tested, and the HC increased above its original value. The HC of smectite clay-sand mixtures decreased following the addition of the various anions. Dispersed clay appeared in the effluent only upon addition of citrate or hexametaphosphate. In the latter two cases, the HC started to increase once maximum clay concentration appeared in the effluent. Clay concentration in the effluent of smectite was one order of magnitude lower than that of kaolinite. Illite clay-sand mixtures showed dispersion behavior intermediate between smectite and kaolinite but behaved in the same way as kaolinite with respect to HC changes.
Radiocarbon (14C) dating of sediment deposition around Antarctica is often challenging due to heterogeneity in sources and ages of organic carbon in the sediment. Chemical and thermochemical techniques have been used to separate organic carbon when microfossils are not present. These techniques generally improve on bulk sediment dates, but they necessitate assumptions about the age spectra of specific molecules or compound classes and about the chemical heterogeneity of thermochemical separations. To address this, the Rafter Radiocarbon Laboratory has established parallel ramped pyrolysis oxidation (RPO) and ramped pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) systems to thermochemically separate distinct carbon fractions, diagnose the chemical composition of each fraction, and target suitable RPO fractions for radiocarbon dating. Three case studies of sediment taken from locations around Antarctica are presented to demonstrate the implementation of combined RPO-AMS and Py-GC-MS to provide more robust age determination in detrital sediment stratigraphy. These three depositional environments are good examples of analytical and interpretive challenges related to oceanographic conditions, carbon sources, and other factors. Using parallel RPO-AMS and Py-GC-MS analyses, we reduce the number of radiocarbon measurements required, minimize run times, provide context for unexpected 14C ages, and better support interpretations of radiocarbon measurements in the context of environmental reconstruction.
iLookOut, a web-based child abuse training for early childcare professionals (ECPs), has been shown to improve knowledge and attitudes related to correctly identifying and reporting suspected cases of child abuse. The overarching goal of the present study is to examine “what works for whom” for iLookOut in order to identify strategies for optimizing learner outcomes.
Methods:
This prospective study enrolled 12,705 ECPs who completed iLookOut (November 2014–December 2018). We used structural equation models to test whether learner demographic and professional characteristics were differentially associated with implementation outcomes (i.e., acceptability and appropriateness) and whether these mediated subsequent indicators of training effectiveness (i.e., gains in knowledge).
Results:
Consistent with previous research, individuals with lower baseline knowledge scores showed greater knowledge gains (β = −.57; p < .001). Greater knowledge gains were seen for learners who reported higher acceptability (β = .08; p < .001) or appropriateness (β = .14; p < .001). Implementation outcomes strongly associated with knowledge gains included acceptability for female learners and appropriateness for learners who had not completed high school or had >15 years of experience in childcare settings. Where mediation was found, for the majority of groups, appropriateness emerged as the driving mediator.
Conclusion:
Implementation outcomes emerged as important drivers of knowledge change for most groups. The iLookOut Core Training’s use of a multimedia learning environment, video-based storylines, and game-based techniques were endorsed by learners and correlated with increases in knowledge. Future work should explore why aspects of the iLookOut training are rated as less acceptable or appropriate by some groups and what changes would improve efficacy for low performing learners.
Academic medical centers (AMCs) rely on engaged and motivated faculty for their success. Significant burnout among clinical and research faculty has resulted in career disengagement and turnover. As such, AMCs must be vested in cultivating faculty engagement and well-being through novel initiatives that support faculty. The Well-Being Education Grants program was established by the Office for Well-Being within the Center for Faculty Development at Massachusetts General Hospital to provide the impetus many faculty needed to dedicate time to their well-being, demonstrating that investments in multi-component interventions around faculty well-being require resources and funding.
Adults with congenital heart disease (CHD) face a unique set of medical, psychological, and social challenges, and access to specialised adult congenital heart disease care has been associated with improved outcomes. Rural adults with CHD may represent a uniquely disadvantaged group given additional challenges when accessing specialised care. The aim of this study was to investigate the challenges faced by adults with CHD in accessing outpatient cardiac care, with a specific focus on understanding differences between urban- and rural-dwelling patients.
Methods:
This cross-sectional, survey-based study took place in the adult congenital heart disease clinic at an urban academic medical center. Additional medical information was abstracted in a retrospective manner from the electronic health record. In addition to descriptive statistics, t-tests and Chi-square tests were performed to investigate differences between urban and rural dwelling patients.
Results:
A total of 100 patients participated in the study (mean age 40 ± 13 years, 60% female, 18% rural dwelling). Across the total sample, the median driving distance to clinic was 20 miles (interquartile range 12–77); it was 15 miles for urban dwellers and 77 miles for rural dwelling patients (p < 0.001). The most commonly identified barriers to cardiac clinic visits were financial losses related to taking time off from work (39%), distance of clinic from home (33%), and weather (33%). Compared to urban dwelling patients, on average those who were rural dwelling had a lower level of education (p = 0.04), more difficulty paying insurance premiums (p < 0.001) and copays (p = 0.005), and were more likely to identify the distance from clinic (p = 0.05) and having to go into the city (p = 0.02) as barriers to clinic appointments.
Conclusions:
The financial impact and distance to clinic were the most commonly identified barriers to outpatient cardiac care in this cohort of adults with CHD. These barriers, along with difficulty paying insurance premiums, are more common in rural dwelling patients. Initiatives such as telemedicine visits or providing financial subsidies for travel and treatment could help to expand specialty adult congenital heart disease care and better serve this growing patient population.
The management of acquired coagulopathy in multiple clinical settings frequently involves fibrinogen supplementation. Cryoprecipitate, a multidonor product, is widely used for the treatment of acquired hypofibrinogenemia following massive bleeding, but it has been associated with adverse events. We aimed to review the latest evidence on cryoprecipitate for treatment of bleeding.
Methods
We conducted a narrative review of current literature on cryoprecipitate therapy, describing its history, formulations and preparation, and recommended dosing. We also reviewed guideline recommendations on the use of cryoprecipitate in bleeding situations and recent studies on its efficacy and safety.
Results
Cryoprecipitate has a relatively high fibrinogen content; however, as it is produced by pooling fresh frozen donor plasma, the fibrinogen content per unit can vary considerably. Current guidelines suggest that cryoprecipitate use should be limited to treating hypofibrinogenemia in patients with clinical bleeding. Until recently, cryoprecipitate was deemed unsuitable for pathogen reduction, and potential safety concerns and lack of standardized fibrinogen content have led to some professional bodies recommending that cryoprecipitate is only indicated for the treatment of bleeding and hypofibrinogenemia in perioperative settings where fibrinogen concentrate is not available. While cryoprecipitate is effective in increasing plasma fibrinogen levels, data on its clinical efficacy are limited.
Conclusions
There is a lack of robust evidence to support the use of cryoprecipitate in bleeding patients, with few prospective, randomized clinical trials performed to date. Clinical trials in bleeding settings are needed to investigate the safety and efficacy of cryoprecipitate and to determine its optimal use and administration.
Ménière's disease is a debilitating chronic peripheral vestibular disorder associated with psychiatric co-morbidities, notably depression.
Methods
Database searches were performed to identify studies that assessed depression in Ménière's disease. Metrics used to diagnose depression were extracted, along with the prevalence of depression in each study.
Results
Fifteen studies from 8 different countries reported on 6587 patients. The weighted average age was 55.3 years (range, 21–88 years). Depression was measured by eight different scales, with Zung's Self-Rating Depression Scale used most often. A weighted proportion of 45.9 per cent of patients (confidence interval = 28.9–63.3) were depressed. Weighted averages (± standard deviations) of Beck's Depression Inventory and the Illness Behavior Questionnaire – Dysphoria were 8.5 ± 7.9 and 2.4 ± 1.7, respectively.
Conclusion
The prevalence of depression in patients with Ménière's disease is nearly 50 per cent. Treating otolaryngologists should have a low threshold to screen and refer appropriately. Identifying and treating depression should allow for improvement of overall quality of life in patients with Ménière's disease.
Efforts to reduce Clostridioides difficile infection (CDI) have targeted transmission from patients with symptomatic C. difficile. However, many patients with the C. difficile organism are carriers without symptoms who may serve as reservoirs for spread of infection and may be at risk for progression to symptomatic C. difficile. To estimate the prevalence of C. difficile carriage and determine the risk and speed of progression to symptomatic C. difficile among carriers, we established a pilot screening program in a large urban hospital.
Design:
Prospective cohort study.
Setting:
An 800-bed, tertiary-care, academic medical center in the Bronx, New York.
Participants:
A sample of admitted adults without diarrhea, with oversampling of nursing facility patients.
Methods:
Perirectal swabs were tested by polymerase chain reaction for C. difficile within 24 hours of admission, and patients were followed for progression to symptomatic C. difficile. Development of symptomatic C. difficile was compared among C. difficile carriers and noncarriers using a Cox proportional hazards model.
Results:
Of the 220 subjects, 21 (9.6%) were C. difficile carriers, including 10.2% of the nursing facility residents and 7.7% of the community residents (P = .60). Among the 21 C. difficile carriers, 8 (38.1%) progressed to symptomatic C. difficile, but only 4 (2.0%) of the 199 noncarriers progressed to symptomatic C. difficile (hazard ratio, 23.9; 95% CI, 7.2–79.6; P < .0001).
Conclusions:
Asymptomatic carriage of C. difficile is prevalent among admitted patients and confers a significant risk of progression to symptomatic CDI. Screening for asymptomatic carriers may represent an opportunity to reduce CDI.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
Methods
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
Conclusions
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Trypanosoma cruzi is the causative agent of Chagas disease, a vector-borne disease. The parasite molecules involved in vector interaction have been little investigated. Metallopeptidases and gp63 molecules have been implicated in parasite adhesion of several trypanosomatids to the insect midgut. Although gp63 homologues are highly expanded in the T. cruzi genome, and are implicated in parasite–mammalian host interaction, its role in the insect vector has never been explored. Here, we showed that divalent metal chelators or anti-Tcgp63-I antibodies impaired T. cruzi adhesion to Rhodnius prolixus midgut. Parasites isolated after insect colonization presented a drastic enhancement in the expression of Tcgp63-I. These data highlight, for the first time, that Tcgp63-I and Zn-dependent enzymes contribute to the interaction of T. cruzi with the insect vector.