Background: Vitamin D promotes bone and muscle growth in non-athletes, suggesting supplementation may be ergogenic in athletes. Our primary aim was to determine if modest Vitamin D supplementation augments favorable body composition changes (increased bone and lean mass and decreased fat mass) and performance in collegiate basketball players following 12 weeks of standardized training. Methods: Members of a men's and women's NCAA D1 Basketball team were recruited. Volunteers were randomized to receive either a weekly 4000 IU Vitamin D3 supplement (D3) or placebo (P) over 12 weeks of standardized pre-season strength training. Pre- and post-measurements included 1) serum 25-hydroxy vitamin D (25(OH)D); 2) body composition variables (total body lean, fat, and bone mass) using dual-energy X-ray absorptiometry (DXA) scans and 3) vertical jump test to assess peak power output. Dietary intake was assessed using Food Frequency questionnaires. Main outcome measures included changes (∆: post-intervention minus pre-intervention) in 25(OH)D, body composition, and performance. Results: Eighteen of the 23 players completed the trial (8 females/10 males). Eight received the placebo (20 ± 1 years; 3 females) while ten received Vitamin D3 (20 ± 2 years; 5 females). Weekly Vitamin D3 supplementation induced non-significant increases (∆) in 25(OH)D (2.6 ± 7.2 vs. -3.5 ± 5.3 ng/mL; p = 0.06), total body bone mineral content (BMC) (73.1 ± 62.5 vs. 84.1 ± 46.5 g; p = 0.68), and total body lean mass (2803.9 ± 1655.4 vs. 4474.5 ± 11,389.8 g; p = 0.03), plus a non-significant change in body fat (-0.5 ± 0.8 vs. -1.1 ± 1.2%; p = 0.19) (Vitamin D3 vs. placebo supplementation groups, respectively). Pre 25(OH)D correlated with both Δ total fat mass (g) (r = 0.65; p = 0.003) and Δ total body fat% (r = 0.56; p = 0.02). No differences were noted in peak power output ∆ between the D3 vs. P group (-127.4 ± 335.4 vs. 50.9 ± 9 W; NS). Participants in the D3 group ingested significantly fewer total calories (-526.2 ± 583.9 vs. -10.0 ± 400 kcals; p = 0.02) than participants in the P group. Conclusions: Modest (~517 IU/day) Vitamin D3 supplementation did not enhance favorable changes in total body composition or performance, over 3 months of training, in collegiate basketball players. Weight training provides a robust training stimulus for bone and lean mass accrual, which likely predominates over isolated supplement use with adequate caloric intakes.
Background: Inhibition is a critical executive control process and an established neurobiological phenotype of PTSD, yet to our knowledge, no prospective studies have examined this using a contextual cue task that enables measurement of behavioural response and neural activation patterns across proactive and reactive inhibition. Objective: The current longitudinal study utilised functional magnetic resonance imaging (fMRI) to examine whether deficits in proactive and reactive inhibition predicted PTSD symptoms six months after trauma. Method: Twenty-three (65% males) medical patients receiving emergency medical care from a level 1 trauma centre were enrolled in the study and invited for an MRI scan 1-2-months post-trauma. PTSD symptoms were measured using self-report at scan and 6-months post-trauma. A stop-signal anticipation task (SSAT) during an fMRI scan was used to test whether impaired behavioural proactive and reactive inhibition, and reduced activation in right inferior frontal gyrus (rIFG), ventromedial prefrontal cortex (vmPFC), and bilateral hippocampus, were related to PTSD symptoms. We predicted that lower activation levels of vmPFC and rIFG during reactive inhibition and lower activation of hippocampus and rIFG during proactive inhibition would relate to higher 6-month PTSD symptoms. Results: No significant associations were found between behavioural measures and 6-month PTSD. Separate linear regression analyses showed that reduced rIFG activation (F1,21 = 9.97, R2 = .32, p = .005) and reduced vmPFC activation (F1,21 = 5.19, R2 = .20, p = .03) significantly predicted greater 6-month PTSD symptoms; this result held for rIFG activation controlling for demographic variables and baseline PTSD symptoms (β = -.45, p = .04) and Bonferroni correction. Conclusion: Our findings suggest that impaired rIFG and, to a lesser extent, vmPFC activation during response inhibition may predict the development of PTSD symptoms following acute trauma exposure. Given the small sample size, future replication studies are needed. Highlights: Impaired inhibition may be an important risk factor for the development of PTSD following trauma, with less right inferior frontal gyrus and ventromedial prefrontal cortex activation during response inhibition predicting PTSD development.
Immune checkpoint inhibitors (ICI) have improved outcomes for a variety of malignancies; however, many patients fail to benefit. While tumor-intrinsic mechanisms are likely involved in therapy resistance, it is unclear to what extent host genetic background influences response. To investigate this, we utilized the Diversity Outbred (DO) and Collaborative Cross (CC) mouse models. DO mice are an outbred stock generated by crossbreeding eight inbred founder strains, and CC mice are recombinant inbred mice generated from the same eight founders. We generated 207 DOB6F1 mice representing 48 DO dams and demonstrated that these mice reliably accept the C57BL/6-syngeneic B16F0 tumor and that host genetic background influences response to ICI. Genetic linkage analysis from 142 mice identified multiple regions including one within chromosome 13 that associated with therapeutic response. We utilized 6 CC strains bearing the positive (NZO) or negative (C57BL/6) driver genotype in this locus. We found that 2/3 of predicted responder CCB6F1 crosses show reproducible ICI response. The chromosome 13 locus contains the murine prolactin family, which is a known immunomodulating cytokine associated with various autoimmune disorders. To directly test whether prolactin influences ICI response rates, we implanted inbred C57BL/6 mice with subcutaneous slow-release prolactin pellets to induce mild hyperprolactinemia. Prolactin augmented ICI response against B16F0, with increased CD8 infiltration and 5/8 mice exhibiting slowed tumor growth relative to controls. This study highlights the role of host genetics in ICI response and supports the use of F1 crosses in the DO and CC mouse populations as powerful cancer immunotherapy models.
Background: Posttraumatic stress symptoms (PTSS) include a constellation of physical and emotional profiles that youth exposed to trauma may experience. An estimated 20% of youth are exposed to trauma, and in refugee populations, up to 54% experience posttraumatic stress. Given the physical and mental health consequences associated with trauma exposure and subsequent psychopathology, identifying biomarkers of symptom severity is a top research priority. Objective: Previous research in adults found that skin conductance responses to trauma interview predicted current and future PTSS. We extended this method to refugee youth exposed to civilian war trauma and forced migration, to examine associations between PTSS and skin conductance in this uniquely vulnerable child and adolescent population. Methods: 86 refugee youth ages 7-17 years completed a trauma interview and assessment of self-reported PTSS. The mobile eSense app on a iPad was used to obtain continuous recordings of skin conductance level (SCL) during a trauma interview (trauma SCL). Skin conductance response (SCR) was calculated by subtracting the baseline SCL from the maximum amplitude of the trauma SCL. Results: SCL during trauma was significantly greater than baseline SCL, Trauma exposure was significantly associated with SCR to trauma interview, R2 = .084, p = .042. SCR to trauma interview was positively correlated with reexperiencing (R2 = .127, p = .028), and hyperarousal symptoms (R 2 = .123, p = .048). Conclusions: The present study provides evidence for feasibility of SCR to trauma interview as a candidate biomarker of PTSS in youth. This is the first study to look at SCR to trauma interview in youth resettled as refugees and is part of the limited but growing body of research to look at biomarkers in refugee cohorts more broadly. As the number of forcibly displaced persons surges, early detection and prevention of trauma-related psychology is becoming more important than ever. Highlights: Using the mobile eSense app, we demonstrate that skin conductance is measurable in a variety of research settings and that skin conductance response may be a biological indicator of trauma and related psychopathology - namely re-experiencing symptoms - in youth resettled as refugees.
Russian invasion of Ukraine has led to one of the largest refugee crises in recent history. Many internally displaced Ukrainians and refugees will need care for PTSD, anxiety, and depression. Here I will suggest practical steps to reduce long-term impact of trauma and stress on refugees' mental and physical health, and functioning. These include mental health first aid in acute phase of arrival, education of mental health and navigating healthcare system in the host countries. As well, training of manualized trauma-focused therapy and intervention methods in the host countries, focused education for physicians on psychopharmacological interventions for common mental health issues among refugees (PTSD, depression, anxiety), and utilization of videoconferencing for treatment, and consultation and supervision for providers. Highlights: Many internally displaced Ukrainians and refugees will need care for PTSD, anxiety, and depression to prevent long-term disability and health consequences.There are challenges in receiving the needed care including stigma, lack of awareness by patients and providers, lack of resources, and lack of skills in trauma-focused treatments.In this article, suggestions are made on how to overcome these obstacles, that include mental health first aid upon arrival, education for refugees and those serving them, training providers at different layers, and remote treatment and counselling/supervision services.
Sarcoidosis is a systemic granulomatous disease of unknown etiology. Hypergammaglobulinemia and the presence of autoantibodies in sarcoidosis suggest active humoral immunity to unknown antigen(s). We developed a complex cDNA library derived from tissues of sarcoidosis patients. Using a high throughput method, we constructed a microarray platform from this cDNA library containing large numbers of sarcoidosis clones. After selective biopanning, 1070 sarcoidosis-specifc clones were arrayed and immunoscreend with 152 sera from patients with sarcoidosis and other pulmonary diseases. To identify the sarcoidosis classifiers two statistical approaches were conducted: First, we identified significant biomarkers between sarcoidosis and healthy controls, and second identified markers comparing sarcoidosis to all other groups. At the threshold of an False Discovery Rate (FDR) < 0.01, we identified 14 clones in the first approach and 12 clones in the second approach discriminating sarcoidosis from other groups. We used the classifiers to build a naïve Bayes model on the training-set and validated it on an independent test-set. The first approach yielded an AUC of 0.947 using 14 significant clones with a sensitivity of 0.93 and specificity of 0.88, whereas the AUC of the second option was 0.92 with a sensitivity of 0.96 and specificity of 0.83. These results suggest robust classifier performance. Furthermore, we characterized the informative phage clones by sequencing and homology searches. Large numbers of classifier-clones were peptides involved in cellular trafficking and cytoskeletons. These results show that sarcoidosis is associated with a specific pattern of immunoreactivity that can discriminate it from other diseases.
The p-center location problem in an area is an important yet very difficult problem in location science. The objective is to determine the location of p hubs within a service area so that the distance from any point in the area to its nearest hub is as small as possible. While effective heuristic methods exist for finding good feasible solutions, research work that probes the lower bound of the problem’s objective value is still limited. This paper presents an iterative solution framework along with two optimization-based heuristics for computing and improving the lower bound, which is at the core of the problem’s difficulty. One method obtains the lower bound via solving the discrete version of the Euclidean p-center problem, and the other via solving a relatively easier clustering problem. Both methods have been validated in various test cases, and their performances can serve as a benchmark for future methodological improvements.
Recent social protests and gatherings in the USA have prompted law enforcement agencies to increase their use of less lethal impact munitions (LLIMs) for crowd control. Media reports and firsthand accounts have indicated that many of the LLIMs are impacting individuals in the head and neck regions. There is very little data available on the risk of injury (ROI) from LLIM impacts to these body regions. The Facial and Ocular CountermeasUre for Safety (FOCUS) surrogate headform was used to assess the ROI (fracture) from LLIM impacts. LLIMs were fired at the FOCUS headform to determine the ROI to the frontal and maxilla bones. Sixteen different LLIMs were assessed which included 12-gauge, 37-mm, and 40-mm caliber projectiles from five manufacturers. The LLIMs included bean bag style, rubber, and foam/sponge projectiles. Each LLIM was tested multiple times to determine the average ROI. The average peak resultant frontal bone force ranged from 2.0 to 7.6 kN which represented ROIs from ~ 30% up to 95%. The average peak resultant maxilla bone force ranged from 1.0 to 4.4 kN which represented ROIs from ~ 30% up to 99%. In general, 12-gauge LLIMs had a lower ROI than the larger caliber LLIMs and the rubber projectiles had a lower ROI than the bean bag style projectiles. Due to the relative thickness, the maxilla has a much lower fracture force than the frontal bone, and this was borne out in the ROIs from the maxilla impacts. Impacts to both bones showed a positive correlation between normalized energy and resultant force (p < 0.01). The slope of the plotted resultant force against the normalized energy for the 12-gauge munitions was significantly smaller compared to larger calibers for both impact sites, frontal (p = 0.031), and maxilla (p < 0.001).
Injury patterns of various less-lethal impact munitions (LLIMs) including 40-mm sponge rounds and a 12-gauge drag-stabilized, bean bag round were collected. Relating real-world injury to forces measured by a biomechanical surrogate, the Facial and Ocular CountermeasUre for Safety (FOCUS) headform is investigated for its utility for future injury evaluation of LLIMs. An online search for cases of LLIM impacts to the head from May 15 to July 15, 2020, was conducted. A total of 107 cases were identified, and potential study subjects were sent a questionnaire with demographical, incidental, and experiential data collected. Ten (10) responses were obtained, leading to six (6) recreations using the FOCUS headform. Facial load cells measured forces ranging from 534 to 4364 N from which the risk of injury (ROI) was calculated. The abbreviated injury scale (AIS), maximum AIS (MAIS), and Injury Severity Scale (ISS) values were determined along with the head injury criterion (HIC) for all cases. For cases with eye injury, the Duma Eye Score (DES) was determined, and the probability of globe rupture was calculated. There is a high probability that an impact to the face from a LLIM can lead to soft tissue injuries, fractures, and even more severe injuries. As a preliminary study, there were a limited number of cases to study and high variability. Therefore, further testing including increased sample size and additional munitions is needed to better determine the sensitivity and specificity of the FOCUS headform to measure the risk of injuries from LLIMs.
Stauffer syndrome, first described by Herbert Stauffer in 1961, is a hepatic paraneoplastic syndrome characterized by multiple extrahepatic malignancies, most commonly renal cell carcinoma. The syndrome manifests a wide range of symptoms caused by various pathophysiological mechanisms and presents with abnormalities in liver function tests in either cholestatic or non-cholestatic patterns. Stauffer’s syndrome is classified into two types: classical and jaundice variants. Some crossovers continue to occur, complicating the diagnosis of such a rare and frequently missed syndrome, which can be the only diagnostic clue for the retrograde detection of a hidden malignancy. To bridge the gap regarding such an important, but still unrecognized, syndrome, not only did we thoroughly cover what had previously been proposed in the literature, but we also proposed a diagnostic protocol based on multicenter experience with such a rare disease.
Background Drug overdose and firearm injury are two of the United States (US) most unrelenting public health crises, both of which have been compounded by the COVID-19 pandemic. Programs and policies typically focus on each epidemic, alone, which may produce less efficient interventions if overlap does exist. The objective is to examine whether drug overdose correlates with and is associated with firearm injury at the census tract level while controlling for neighborhood characteristics. Methods An ecological study of census tracts in Indianapolis, Indiana from 2018 to 2020. Population rates per 100,000 and census tracts with the highest overlap of overdose and firearm injury were identified based on spatial clusters. Bivariate association between census tract characteristic and drug overdose and firearm violence rate within spatial clusters. Zero-inflated negative binominal regression was used to estimate if the drug overdose activity is associated with higher future firearm injury. Results In high overdose—high firearm injury census tracts, rates of firearm injury and drug overdose are two times higher compared to city wide rates. Indicators of structural disadvantage and structural racism are higher in high overdose—high firearm injury census tracts compared to city-wide averages. Drug overdoses are associated with higher rates of firearm injury in the following year (IRR: 1.004, 95% CI 1.001, 1.007, p < 0.05), adjusting for census tract characteristics and spatial dependence. Conclusions Drug overdose and firearm injury co-spatially concentrate within census tracts. Moreover, drug overdoses are associated with future firearm injury. Interventions to reduce firearm injuries and drug overdoses should be a co-response in high drug overdose—high firearm injury communities.
Disassembly sequence planning is the foundation for disassembly process planning. Furthermore, integrating efficient geometrical disassembly feasibility of non-destructive operations can contribute to designing robotic disassembly and remanufacturing systems. Non-destructive operations increase the chance of repurposing parts with less cost but require collision-free trajectories between components. Thus, generating geometrically feasible disassembly sequences is critical for determining the optimal disassembly sequencing and disassembly trajectories. In this work, geometric collision data has generated to develop the disassembly precedence matrix that provides fundamental information for disassembly planning methods. Current methods often require significant manual resources to locate geometrically feasible sequences for disassembly of products. This paper describes the results of utilizing disassembly collision tests to automatically extract interference data from STEP CAD assembly files to determine feasible disassembly operations. A method to determine a precedence matrix that describes all geometrically feasible disassembly operations for disassembly of a selected part or a whole assembly to its components has been developed and tested. Extracted data from STEP files is used to characterize the spatial properties of a component in an assembly and is the basis for the collision test to determine the geometrically feasible disassembly operations. The precedence matrix also identifies the feasible disassembly directions for each component based on the outcomes of the collision tests.
Background: Though methadone has been shown to effectively treat opioid use disorder, many barriers prevent individuals from accessing and maintaining treatment. Barriers are prevalent in less populated areas where treatment options are limited. This study examines barriers to retention in methadone treatment in a small Midwest community and identifies factors associated with greater endorsement of barriers. Methods: Patients at an opioid treatment program (N = 267) were recruited to complete a computer-based survey onsite. Surveys assessed demographics, opioid misuse, depression and anxiety symptoms, trauma history and symptoms, social support, and barriers to retention in treatment (e.g., childcare, work, housing, transportation, legal obligations, cost, health). Descriptive statistics were used to examine individual barriers and multiple regression was calculated to identify demographic and psychosocial factors associated with greater cumulative barriers. Results: Most participants reported at least one barrier to retention in treatment and more than half reported multiple barriers. Travel hardships and work conflicts were the most highly endorsed barriers. Past year return to use (B = 2.31, p = 0.004) and more severe mental health symptomology (B = 0.20, p = 0.038) were associated with greater cumulative barriers. Greater levels of social support were associated with fewer barriers (B = - 0.23, p < 0.001). Conclusion: This study adds to the limited research on barriers to retention in methadone treatment among patients in rural and small urban communities. Findings suggest flexible regulations for dispensing methadone, co-location or care coordination, and family or peer support programs may further reduce opioid use and related harms in small communities. Individuals with past year return to use reported a greater number of barriers, highlighting the time following return to use as critical for wraparound services and support. Those with co-occurring mental health issues may be vulnerable to poor treatment outcomes, as evidenced by greater endorsement of barriers. As social support emerged as a protective factor, efforts to strengthen informal support networks should be explored as adjunctive services to methadone treatment.
Background: Septic cardiomyopathy was recognized more than 30 years ago, but the early phase remains uncharacterized as no existing studies captured patients at the time of Emergency Department (ED) presentation, prior to resuscitation. Therapeutic interventions alter cardiac function, thereby distorting the relationship with disease severity and outcomes. The goal of this study was to assess the impact of illness severity on cardiac function during the first 24 h of sepsis admission. Methods: This was a pre-planned secondary analysis of a prospective observational study of adults presenting to the ED with suspected sepsis (treatment for infection plus either lactate > 2 mmol/liter or systolic blood pressure < 90 mm/Hg) who received < 1L IV fluid before enrollment. Patients had 3 echocardiograms performed (presentation, 3, and 24 h). The primary outcome was the effect of increasing sepsis illness severity, defined by ED Sequential Organ Failure Assessment (SOFA) score, on parameters of cardiac function, assessed using linear mixed-effects models. The secondary goal was to determine whether cardiac function differed between survivors and non-survivors, also using mixed-effects models. Results: We enrolled 73 patients with a mean age of 60 (SD 16.1) years and in-hospital mortality of 23%. For the primary analysis, we found that increasing ED SOFA score was associated with worse cardiac function over the first 24 h across all assessed parameters of left-ventricular systolic and diastolic function as well as right-ventricular systolic function. While baseline strain and E/e' were better in survivors, in the mixed models analysis, the trajectory of Global Longitudinal Strain and septal E/e' over the first 24 h of illness differed between survivors and non-survivors, with improved function at 24 h in non-survivors. Conclusions: In the first study to capture patients prior to the initiation of resuscitation, we found a direct relationship between sepsis severity and global myocardial dysfunction. Future studies are needed to confirm these results, to identify myocardial depressants, and to investigate the link with adverse outcomes so that therapeutic interventions can be developed.
This paper proposes an architectural solution to enhance the resilience of distributed decision-making and control in microgrids and smart grids with respect to communication delays. The paper develops a resource allocation framework to optimally place the multiple-input multiple-output (MIMO) communication technology on critical channels to reduce the communication bottle neck and expedite the convergence speed of distributed online optimization algorithms, which require convergence in the cyber network before the solution can be implemented on the physical grid. The paper shows that optimal placement of the MIMO technology can decrease communication transmission delays, which in turn improves the reliability of power system operational protocols, such as distributed frequency regulation. Illustrative case studies using data from real-world power systems show that only upgrading the critical communication channels is sufficient to achieve system-wide performance improvement.
Parental emotion regulation plays a major role in parent‐child interactions, and in turn, neural plasticity in children, particularly during sensitive developmental periods. However, little is known about how parental emotion dysregulation is associated with variation in children's brain structure, which was the goal of this study. Forty‐five Black American mother–child dyads were recruited from an intergenerational trauma study; emotion regulation in mothers and their children (age 8–13 years) was assessed. Diffusion‐weighted images were collected in children; deterministic tractography was used to reconstruct pathways of relevance to emotion regulation. Metrics of white matter connectivity [fractional anisotropy (FA), mean diffusivity (MD)] were extracted for pathways. Socio‐economic variables were also included in statistical models. Maternal emotion dysregulation was the strongest predictor of child fornix MD (r = .35, p = .001), indicating that more severe emotion dysregulation in mothers corresponded with lower fornix connectivity in children. Maternal impulsivity was a strong predictor of child fornix MD (r = .51, p < .001). Maternal emotion dysregulation may adversely influence connectivity of the child.s fornix, a hippocampal‐striatal pathway implicated in reward processes; these associations remained even after accounting for other socio‐environmental factors. Dysregulated maternal emotions may uniquely impact children's adaptation to trauma/stress by affecting networks that support appetitive processing.
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