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Introduction: In the past year, the use of large language models (LLMs) has generated significant interest and excitement because of their potential to revolutionise various fields, including medical education for aspiring physicians. Although medical students undergo a demanding educational process to become competent health care professionals, the emergence of LLMs presents a promising solution to challenges like information overload, time constraints and pressure on clinical educators. However, integrating LLMs into medical education raises critical concerns and challenges for educators, professionals and students. This systematic review aims to explore LLM applications in medical education, specifically their impact on medical students' learning experiences. Methods: A systematic search was performed in PubMed, Web of Science and Embase for articles discussing the applications of LLMs in medical education using selected keywords related to LLMs and medical education, from the time of ChatGPT's debut until February 2024. Only articles available in full text or English were reviewed. The credibility of each study was critically appraised by two independent reviewers. Results: The systematic review identified 166 studies, of which 40 were found by review to be relevant to the study. Among the 40 relevant studies, key themes included LLM capabilities, benefits such as personalised learning and challenges regarding content accuracy. Importantly, 42.5% of these studies specifically evaluated LLMs in a novel way, including ChatGPT, in contexts such as medical exams and clinical/biomedical information, highlighting their potential in replicating human‐level performance in medical knowledge. The remaining studies broadly discussed the prospective role of LLMs in medical education, reflecting a keen interest in their future potential despite current constraints. Conclusions: The responsible implementation of LLMs in medical education offers a promising opportunity to enhance learning experiences. However, ensuring information accuracy, emphasising skill‐building and maintaining ethical safeguards are crucial. Continuous critical evaluation and interdisciplinary collaboration are essential for the appropriate integration of LLMs in medical education. Addressing the hype around incorporating large language models and ChatGPT into medical education, Robinson et al. outline how to do it right and wrong. [ABSTRACT FROM AUTHOR]

Objective: To examine patterns of cognitive function among a clinical sample of patients seeking treatment for Post-Acute Sequelae of COVID-19 (PASC). Participants and Methods: One hundred nineteen patients each completed a baseline neuropsychological evaluation, including clinical diagnostic interview, cognitive assessments, and a comprehensive battery of self-report questionnaires. Patients had a mean age of 50 years (range:18 to 74, SD=10.1) and a mean of 15.5 years (SD=2.54) of formal education. Patients were primarily female (74%) and of White/Caucasian race (75%). Hierarchical agglomerative clustering was used to partition the data into groups based on cognitive performance. Euclidean distance was used as the similarity measure for the continuous variables and within-cluster variance was minimized using Ward's method. The optimal number of clusters was determined empirically by fitting models with 1 to 15 clusters, with the best number of clusters selected using the silhouette index. All analyses were conducted using the NbClust package, an R package for determining the relevant number of clusters in a data set. Results: Clustering yielded two distinct clusters of cognitive performance. Group 1 (n =57) performed worse than Group 2 (n =62) on most cognitive variables (including a brief cognitive screener and tests of attention/working memory, executive function, processing speed, learning and delayed recall). Of note, there were no significant differences between groups on an infection severity scale, hospitalizations/ICU admissions, initial or current COVID-19 symptoms, or prior comorbidities. Groups did not differ in age or gender, but Group 1 had a lower education level than Group 2 (M=14.7, SD=2.45 vs. M=16.2, SD=2.42; p=.001). Group 1 also had significantly more minorities than Group 2 (40% vs. 8%; p<.001). No other demographic differences (income, living arrangement, or marital status) were observed. In comparison to Group 2 patients, Group 1 patients self-reported significantly higher levels of anxiety and depression and functional impairment (Functional Activities Questionnaire: M=11.3, SD=8.33 vs. M=7.65, SD=7.97), perceived stress (Perceived Stress Scale: M=24.7, SD=7.90 vs. M=20.3, SD=7.89), insomnia (Insomnia Severity Index: M=16.0, SD=6.50 vs. M=13.1, SD=6.76), and subjective cognitive functioning (Cognitive Failures Questionnaire: M=58.8, SD=16.9 vs. M=50.3, SD=18.6; p's<.05). Conclusions: Findings indicate two predominant subtypes of patients seeking treatment for PASC, with one group presenting as more cognitively impaired and reporting greater levels of anxiety, depression, insomnia, perceived stress, functional limitations, and subjective cognitive impairment. Future directions include follow-up assessments with these patients to determine cognitive trajectories over time and tailoring treatment adjuncts to address mood symptoms, insomnia, functional ability, and lifestyle variables. Understanding mechanisms of differences in cognitive and affective symptoms is needed in future work. Limitations to the study were that patients were referred for evaluation based on the complaint of "brain fog" and the sample was a homogenous, highly educated, younger group of individuals who experienced generally mild COVID-19 course. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have discovered 27 loci associated with glioma risk. Whether these loci are causally implicated in glioma risk, and how risk differs across tissues, has yet to be systematically explored. We integrated multi-tissue expression quantitative trait loci (eQTLs) and glioma GWAS data using a combined Mendelian randomisation (MR) and colocalisation approach. We investigated how genetically predicted gene expression affects risk across tissue type (brain, estimated effective n = 1194 and whole blood, n = 31,684) and glioma subtype (all glioma (7400 cases, 8257 controls) glioblastoma (GBM, 3112 cases) and non-GBM gliomas (2411 cases)). We also leveraged tissue-specific eQTLs collected from 13 brain tissues (n = 114 to 209). The MR and colocalisation results suggested that genetically predicted increased gene expression of 12 genes were associated with glioma, GBM and/or non-GBM risk, three of which are novel glioma susceptibility genes (RETREG2/FAM134A, FAM178B and MVB12B/FAM125B). The effect of gene expression appears to be relatively consistent across glioma subtype diagnoses. Examining how risk differed across 13 brain tissues highlighted five candidate tissues (cerebellum, cortex, and the putamen, nucleus accumbens and caudate basal ganglia) and four previously implicated genes (JAK1, STMN3, PICK1 and EGFR). These analyses identified robust causal evidence for 12 genes and glioma risk, three of which are novel. The correlation of MR estimates in brain and blood are consistently low which suggested that tissue specificity needs to be carefully considered for glioma. Our results have implicated genes yet to be associated with glioma susceptibility and provided insight into putatively causal pathways for glioma risk. [ABSTRACT FROM AUTHOR]

Patient portals are consumer health applications that allow patients to view their health information. Portals facilitate the interactions between patients and their caregivers by offering secure messaging. Patients communicate different needs through portal messages. Medical needs contain requests for delivery of care (e.g. reporting new symptoms). Automating the classification of medical decision complexity in portal messages has not been investigated. We trained two multiclass classifiers, multinomial Naïve Bayes and random forest on 500 message threads, to quantify and label the complexity of decision-making into four classes: no decision, straightforward, low, and moderate. We compared the performance of the models to using only the number of medical terms without training a machine learning model. Our analysis demonstrated that machine learning models have better performance than the model that did not use machine learning. Moreover, machine learning models could quantify the complexity of decision-making that the messages contained with 0.59, 0.45, and 0.58 for macro, micro, and weighted precision and 0.63,0.41, and 0.63 for macro, micro, and weighted recall. This study is one of the first to attempt to classify patient portal messages by whether they involve medical decision-making and the complexity of that decision-making. Machine learning classifiers trained on message content resulted in better message thread classification than classifiers that employed medical terms in the messages alone. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening syndrome that occurs in response to a severe infection. In recent years, the understanding of the pathobiology of sepsis has been refined, with research describing an altered host response as the underlying cause. Survivors of sepsis often have long hospital stays and suffer from subsequent frailty and long-term health consequences. Predicting attributes of sepsis survivors remains challenging; however, an obesity paradox exists, wherein obese individuals survive sepsis at higher rates than their normal-weight counterparts. We present a model that describes the relationships between sepsis and obesity, focusing on inflammation as a shared pathway for dysregulation in obese and healthy-weight adults. Understanding the interaction of these complex variables is an important first step toward developing interventions and treatments to augment sepsis survival. [ABSTRACT FROM AUTHOR]

Background: The extent to which obesity and genetics determine postoperative complications is incompletely understood. Methods: We performed a retrospective study using two population cohorts with electronic health record (EHR) data. The first included 736,726 adults with body mass index (BMI) recorded between 1990 and 2017 at Vanderbilt University Medical Center. The second cohort consisted of 65,174 individuals from 12 institutions contributing EHR and genome-wide genotyping data to the Electronic Medical Records and Genomics (eMERGE) Network. Pairwise logistic regression analyses were used to measure the association of BMI categories with postoperative complications derived from International Classification of Disease-9 codes, including postoperative infection, incisional hernia, and intestinal obstruction. A genetic risk score was constructed from 97 obesity-risk single-nucleotide polymorphisms for a Mendelian randomization study to determine the association of genetic risk of obesity on postoperative complications. Logistic regression analyses were adjusted for sex, age, site, and race/principal components. Results: Individuals with overweight or obese BMI (≥25 kg/m2) had increased risk of incisional hernia (odds ratio [OR] 1.7–5.5, p < 3.1 × 10−20), and people with obesity (BMI ≥ 30 kg/m2) had increased risk of postoperative infection (OR 1.2–2.3, p < 2.5 × 10−5). In the eMERGE cohort, genetically predicted BMI was associated with incisional hernia (OR 2.1 [95% CI 1.8–2.5], p = 1.4 × 10−6) and postoperative infection (OR 1.6 [95% CI 1.4–1.9], p = 3.1 × 10−6). Association findings were similar after limitation of the cohorts to those who underwent abdominal procedures. Conclusions: Clinical and Mendelian randomization studies suggest that obesity, as measured by BMI, is associated with the development of postoperative incisional hernia and infection. [ABSTRACT FROM AUTHOR]

Purpose: In recent years, researchers have noted an "obesity paradox," where individuals with obesity survive sepsis at higher rates than their nonobese counterparts. This systematic review summarizes the literature on studies examining the association between obesity and 1-year mortality among patients admitted with sepsis, severe sepsis, or septic shock. Materials and Methods: Using a comprehensive search strategy, a systematic review was conducted to identify studies examining the association of obesity and sepsis mortality. PubMed, Cumulative Index of Nursing and Allied Health Literature, and Elton B. Stephens Company host databases were searched for the terms sepsis, obesity, mortality, and adult. Results: The initial search identified 189 studies, 9 of which met inclusion criteria. Of these, four provided evidence that obese or very obese patients with sepsis have lower mortality than nonobese patients. Methodologic differences in the remaining five studies, which reported conflicting results, limit generalizability. Conclusion: This systematic review on the association of obesity and sepsis mortality found three studies that demonstrated lower sepsis mortality among obese patients in the first 30 days and one showing that this protective effect extends up to 1 year. Given the increased number of patients surviving sepsis, it is important to consider long-term mortality and further describe the variables associated with increased survival. [ABSTRACT FROM AUTHOR]

Biliary atresia (BA) is a rare obstructive cholangiopathy that presents in early infancy. The Kasai portoenterostomy (PE) improves survival with the native liver. Epidural analgesia is an appealing option to control pain in this fragile patient population, yet its safety, efficacy, and potential benefits remain unproven. Patients undergoing PE for BA between 2001 and 2016 at a single institution were identified by ICD codes. Preoperative laboratories, procedure details, and recovery outcomes were reviewed retrospectively. Outcomes of interest were need for postoperative mechanical ventilation, pain scores, normalized opioid administration, return of bowel function, and length of hospital stay after PE. Of 47 infants undergoing PE for BA, 25 received epidural analgesia, and 22 did not. Infants with epidurals received less systemic opioids over the first 96 h postoperatively than those without (P < 0.001). Epidurals were associated with lower pain scores between 6 and 30 h postoperatively (P = 0.01 to 0.04), during which the highest median 6-h interval pain score was 0.2 (IQR 0-1.3) for patients with epidurals yet 2.1 (IQR 1.2-3.3) for patients without. Patients with epidurals (88%, n = 22) were more commonly extubated before leaving the operating room than those without (59%, n = 13; P = 0.02). No significant difference was observed in time to first bowel movement (P = 0.48) or first oral feed (P = 0.81). However, infants with epidurals had shorter hospital stays after PE than those without (6 d [IQR 5-7] versus 8 d [IQR 6.3-11], P = 0.01). No major complications were associated with epidural catheters. Epidural analgesia in patients undergoing PE for BA appears safe and effectively controls pain while minimizing the need for systemic opioids. Reduced need for mechanical ventilation postoperatively and shortened hospital stays serve as further evidence for using epidurals to enhance recovery after PE. [ABSTRACT FROM AUTHOR]

The complexity and cost of diabetes care are barriers to a free health clinic attempting to provide quality care to uninsured patients. The alphabet strategy intervention was selected to increase the number of patients with diabetes receiving care according to the American Diabetes Association guidelines because it is simple and cost-effective. The project results revealed statistically significant increases in clinic uptake of diabetes education, blood pressure interventions, proteinuria, glucose control measurement and intervention, eye exams, and foot exams. The findings may be useful to other free health clinics attempting to provide quality care to their patients with diabetes. [ABSTRACT FROM AUTHOR]

Abstract Background Patient portals are online applications that typically allow users to interact with providers using secure messaging. Portal messaging use and content have not been studied in pediatric surgical specialties. Materials and methods We obtained all message threads initiated by pediatric patients/caregivers and sent to pediatric surgical providers through the Vanderbilt University Medical Center patient portal from June 1, 2014 to December 31, 2014. We collected patient demographics and providers' surgical specialties. We determined the number of message threads and individual messages sent by patients/caregivers and providers by specialty. Message content was analyzed by semantic types using a validated consumer health taxonomy. Results Most threads were about male (176, 60.3%), white (239, 81.8%), non-Hispanic (278, 95.2%) patients with a median age of 6 y (range: 0-21 y). A total of 292 message threads containing 1679 individual messages were sent with mean 5.8 (standard deviation [SD] 5.0) messages per thread. Messages were sent more frequently regarding younger patients (P = 0.001). Physicians directly contributed to 161 (55%) message threads. Otolaryngology received the most threads (123, 42.1%) and messages (790, 47.1%). Specialties exchanging the most messages per thread were cardiac surgery (mean 7.0, SD 11.7), and dermatology (7.0, SD 6.9). Most message threads (273, 93.5%) involved delivery of medical care with 123 (42.1%) involving appointments/scheduling; 99 (33.9%) medical problems; 81 (27.7%) treatments; 68 (23.3%) testing; and 29 (9.9%) referrals. Conclusions Pediatric surgeons deliver substantial care within portal messages exchanged with pediatric patients and caregivers. Institutions adopting portals should consider effects on provider workload and potential disparities in access to care. [ABSTRACT FROM AUTHOR]

The article reports that the genome-wide association studies (GWAS) and phenomewide association studies (PheWAS) have give methods for investigating the impact of genetic variation on individual drug response. GWAS is a hypothesis-generating method to analyze variants across the entire genome for association with a phenotype of interest.

Background Patient portals are online applications that allow patients to interact with healthcare organizations and view information. Portal messages exchanged between patients and providers contain diverse types of communications, including delivery of medical care. The types of communications and complexity of medical decision-making in portal messages sent to surgeons have not been studied. Materials and methods We obtained all message threads initiated by patients and exchanged with surgical providers through the Vanderbilt University Medical Center patient portal from June 1 to December 31, 2014. Five hundred randomly selected messages were manually analyzed by two research team members to determine the types of communication (i.e., informational, medical, logistical, or social), whether medical care was delivered, and complexity of medical decision-making as defined for outpatient billing in each message thread. Results A total of 9408 message threads were sent to 401 surgical providers during the study period. In the 500 threads selected for detailed analysis, 1293 distinct issues were communicated, with an average of 2.6 issues per thread. Medical needs were communicated in 453 message threads (90.6%). Further, 339 message threads (67.8%) contained medical decision-making. Overall complexity of medical decision-making was straightforward in 210 messages (62%), low in 102 messages (30%), and moderate in 27 messages (8%). No highly complex decisions were made over portal messaging. Conclusions Through patient portal messages, surgeons deliver substantial medical care with varied levels of medical complexity. Models for compensation of online care must be developed as consumer and surgeon adoption of these technologies increases. [ABSTRACT FROM AUTHOR]

Objective: Systemic loxoscelism is a rare illness resulting from the bite of the recluse spider and, in its most severe form, can lead to widespread hemolysis, coagulopathy, and death. We aim to describe the clinical features and outcomes of the largest known cohort of individuals with moderate to severe loxoscelism. Methods: We performed a retrospective, cross sectional study from January 1, 1995, to December 31, 2015, at a tertiary-care academic medical center, to determine individuals with clinical records consistent with moderate to severe loxoscelism. Age-, sex-, and race-matched controls were compared. Demographics, clinical characteristics, laboratory measures, and outcomes of individuals with loxoscelism are described. Case and control groups were compared with descriptive statistics and phenome-wide association study (PheWAS). Results: During the time period, 57 individuals were identified as having moderate to severe loxoscelism. Of these, only 33% had an antecedent spider bite documented. Median age of individuals diagnosed with moderate to severe loxoscelism was 14 years old (IQR 9.0–24.0 years). PheWAS confirmed associations of systemic loxoscelism with 29 other phenotypes, e.g., rash, hemolytic anemia, and sepsis. Hemoglobin level dropped an average of 3.1 g/dL over an average of 2.0 days (IQR 2.0–6.0). Lactate dehydrogenase and total bilirubin levels were on average over two times their upper limit of normal values. Eighteen individuals of 32 tested had a positive direct antiglobulin (Coombs’) test. Mortality was 3.5% (2/57 individuals). Conclusion: Systemic loxoscelism is a rare but devastating process with only a minority of patients recalling the toxic exposure; hemolysis reaches a peak at 2 days after admission, with some cases taking more than a week before recovery. In endemic areas, suspicion for systemic loxoscelism should be high in individuals, especially children and younger adults, presenting with a cutaneous ulcer and hemolysis or coagulopathy, even in the absence of a bite exposure history. [ABSTRACT FROM AUTHOR]

Background Electronic health records (EHRs), computerized provider order entry (CPOE), and patient portals have experienced increased adoption by health care systems. The objective of this study was to review evidence regarding the impact of such health information technologies (HIT) on surgical practice. Materials and methods A search of Medline, EMBASE, CINAHL, and the Cochrane Library was performed to identify data-driven, nonsurvey studies about the effects of HIT on surgical care. Domain experts were queried for relevant articles. Two authors independently reviewed abstracts for inclusion criteria and analyzed full text of eligible articles. Results A total of 2890 citations were identified. Of them, 32 observational studies and two randomized controlled trials met eligibility criteria. EHR or CPOE improved appropriate antibiotic administration for surgical procedures in 13 comparative observational studies. Five comparative observational studies indicated that electronically generated operative notes had increased accuracy, completeness, and availability in the medical record. The Internet as an information resource about surgical procedures was generally inadequate. Surgical patients and providers demonstrated rapid adoption of patient portals, with increasing proportions of online versus inperson outpatient surgical encounters. Conclusions The overall quality of evidence about the effects of HIT in surgical practice was low. Current data suggest an improvement in appropriate perioperative antibiotic administration and accuracy of operative reports from CPOE and EHR applications. Online consumer health educational resources and patient portals are popular among patients and families, but their impact has not been studied well in surgical populations. With increasing adoption of HIT, further research is needed to optimize the efficacy of such tools in surgical care. [ABSTRACT FROM AUTHOR]

Background Delayed gastric emptying ( DGE) is a frequent cause of morbidity, prolonged hospital stay and readmission after a pancreaticoduodenectomy ( PD). We sought to evaluate predictive peri-operative factors for DGE after a PD. Methods Four hundred and sixteen consecutive patients who underwent a PD at our tertiary referral centre were identified. Univariate and multivariate ( MV) logistic regression models were used to assess peri-operative factors associated with the development of clinically significant DGE and a post-operative pancreatic fistula ( POPF). Results DGE occurred in 24% of patients ( n = 98) with Grades B and C occurring at 13.5% ( n = 55) and 10.5% ( n = 43), respectively. Using MV regression, a body mass index ( BMI) ≥35 [odds ratio ( OR) = 3.19], operating room ( OR) length >5.5 h ( OR = 2.72) and prophylactic octreotide use ( OR = 2.04) were independently associated with an increased risk of DGE. DGE patients had a significantly longer median hospital stay (12 versus 7 days), higher 90-day readmission rates (32% versus 18%) and an increased incidence of a pancreatic fistula (59% versus 27%). When controlling for POPF, only OR length >5.5 h ( OR 2.73) remained significantly associated with DGE. Conclusions DGE remains a significant cause of morbidity, increased hospital stay and readmission after PD. Our findings suggest patients with a BMI ≥35 or longer OR times have a higher risk of DGE either independently or through the development of POPF. These patients should be considered for possible enteral feeding tube placement along with limited octreotide use to decrease the potential risk and consequences of DGE. [ABSTRACT FROM AUTHOR]

Objective: To describe psychiatric symptoms in a sample of patients seeking treatment for "brain fog" due to Post-Acute Sequelae of COVID-19 (PASC). Method: Patients were referred for a neuropsychological evaluation from the University of Alabama at Birmingham (UAB) Post-COVID Treatment Program. Ninety-two patients completed a battery of self-report questionnaires to measure mood symptoms and behavior. Patients were on average 49 years of age (range: 18 to 74), female (77%), and White/Caucasian (73%)/Black/African American (25%), with 15.49 years of education (SD = 2.43). Results: On average, patients who sought treatment for PASC reported mild to moderate anxiety (Generalized Anxiety Disorder Assessment [GAD-7]; M = 9.83, SD = 6.07), moderate depression (Patient Health Questionnaire [PHQ-8]; M = 13.23, SD = 5.81), moderate stress levels (Perceived Stress Scale [PSS]; M = 22.97, SD = 7.99). They also reported overall functional impairment in activities of daily living (Functional Assessment Questionnaire [FAQ]; M = 9.57, SD = 8.29) and perceived cognitive impairment (Cognitive Failures Questionnaire [CFQ]; M = 55.22, SD = 18.66). Additionally, patients endorsed several somatic symptoms (PHQ-15; M = 13.90, SD = 5.16), mild insomnia (Insomnia Severity Index [ISI]; M = 14.80, SD = 6.85), and severe fatigue (Chalder's Fatigue Scale [CFS]; M = 25.53, SD = 5.72). Conclusion: Patients seeking treatment for "long-COVID" report a variety of clinically significant psychiatric symptoms, suggesting the need for incorporating behavioral, lifestyle, and psychological interventions in the treatment of this population. [ABSTRACT FROM AUTHOR]

Objective: Describe those with persistent neuropsychiatric symptoms seeking treatment for Post-Acute Sequelae of COVID-19 (PASC). Method: Patients were referred for neuropsychological evaluation from the University of Alabama at Birmingham (UAB) Post-COVID Treatment Program. Ninety-seven patients completed a comprehensive set of self-report questionnaires. Results: Patients were 49 years old (range: 18 to 74), had 15.49 years (SD = 2.43) of education, and identified as female (77%), married (51%), and White/Caucasian (73%) or Black/AA (25%). Reported annual income ranged from ≤ $20,000 (11%) to ≥ $100,000 (32%), with 75% currently employed. Confirmed positive test result for COVID-19 was reported in 88%, with 87% having the original virus and 13% the Delta variant, based on estimated dates of infection. Symptoms during the acute illness included: headache (76%), fever (51%), cough (57%), shortness of breath (56%), and loss of smell or taste (54%). Most of the participants were not hospitalized (76%) nor required oxygen therapy (78%). Persistent symptoms included: headache (55%), shortness of breath (53%), muscle and joint pain (53%), cough (17%), congestion (40%) and loss of smell or taste (25%). Of these participants, 87% reported they had not returned to their baseline health because of COVID-19 and most indicated impaired job performance following COVID-19 infection. Conclusion: Those who sought treatment for persistent neuropsychiatric symptoms following a symptomatic course of COVID-19 were commonly middle aged, White, women, with at least a high school education. "Brain fog" secondary to PASC can result in reported persistent health and neuropsychiatric issues that can impact ability to work. [ABSTRACT FROM AUTHOR]

Abstract: The Fosterville gold deposit hosted by a folded Ordovician turbidite sequence, in Victoria, Australia, contains major gold mineralisation. This is related to the reactivation of low-displacement faults and a network of hydrofractures adjacent to the faults. The location of the hydrofractures was controlled by the angular relationship between the fault and bedding within both the hangingwall and footwall of the fault. Numerical models are used to investigate how the orientations of faults and bedding influence dilation (positive volumetric strain) and fluid infiltration. The initial velocity boundary conditions applied to the models, as a compression direction and strike-slip to compression ratio, are constrained by the orientation of quartz-carbonate slickenline lineations associated with the reactivated mineralised faults. The models show that variations in the magnitudes of positive volumetric strain and fluid flow are associated with the orientations of bedding and faults. High magnitudes of positive volumetric strain and fluid flow occur at low (35–55°) and intermediate (90–110°) bedding-fault angles. The models also illustrate that fluid infiltration within meta-sandstones adjacent to a fault is affected by the dip angle of the fault with a 70° dipping fault promoting greater fluid infiltration than a 60° dipping fault. The magnitudes of positive volumetric strain and fluid flow increase as the magnitude of the applied strike-slip to compression ratio is increased. However, when a velocity field with a low strike-slip component is applied to the models higher fluid flows occur within steep-plunging (30°) folds, whereas a velocity field with a high strike-slip component results in higher fluid flows within gentle-plunging (15°) folds. These results suggest that the orientation of bedding and the plunge angle of folds are exerting a control on mineralisation. Such coupling of numerical simulations of deformation and fluid flow provides a useful framework that can be applied to better understand structural control on fluid infiltration in hydrothermal mineral systems. [Copyright &y& Elsevier]

The future of market-oriented health policy and practice lies in "managed consumerism," a blend of the patient-centric focus of consumer-driven health care and the provider-centric focus of managed competition. The optimal locus of incentives will vary among health services according to the nature of the illness, the clinical technology, and the extent of discretion in utilization. A competitive market will manifest a variety of comprehensive and limited benefit designs, broad and narrow contractual networks, and single- and multispecialty provider organizations. [ABSTRACT FROM AUTHOR]

The hexose and pentose sugars common to substrate mixtures used in yeast-catalyzed industrial processes are often affected by carbon catabolite repression, in which the presence of glucose significantly delays the consumption of other sugars. Screening experiments performed with wild-type Saccharomyces cerevisiae strains have identified a strain that exhibits exceptional fermentative performance on galactose, completely exhausting the sugar in significantly less time (6 h) than that typically required by other S. cerevisiae strains tested (10–24 h). This strain was also capable of initiating fermentation at very high concentrations of galactose (≥225 g L-1). Further experiments on mixed hexose sugar substrates (galactose, glucose, and mannose) indicated the absence of conventional catabolite repression in this strain, including a preference for galactose as carbon source and notable delays in the utilization of glucose and mannose. Additionally, the endogenous formation of extracellular glucose was observed during double sugar fermentations of galactose and mannose. Subsequent experiments illustrated differences between the selected strain and a reference strain in UDP-glucose-4-epimerase activity, and suggested other unique molecular properties. [Copyright &y& Elsevier]

America is facing a primary care provider shortage. Enhanced primary care RNs (EPC‐RNs), registered nurses working at the top of their practice scope, can be an important part of community‐based primary care provision. Typically, community health nursing education has not included primary care‐based clinical experiences, and there is a clinical site shortage. Teaching students about EPC‐RN roles can be an important domain of community/public health nursing education. Simulation is a creative pedagogical approach to learning about the EPC‐RN role. The purpose of this manuscript is to 1) describe EPC‐RN Telehealth Simulation development; and 2) describe student simulation feedback. Nursing faculty and simulation experts designed five simulations for community health students to teach about the EPC‐RN role, incorporating recommendations from the Quad Council Coalition of Public Health Nursing Organizations community/public health nursing competencies and the National Competencies for Registered Nurses in Primary Care. Retrospective, descriptive quantitative, and qualitative student feedback data (n = 519) was collected through QuestionPro over multiple semesters. Student feedback data demonstrated support of the use of the simulations in community/public health nursing education. The EPC‐RN Telehealth Simulations prepared pre‐licensure nursing students to practice in community‐based primary care settings. Innovative, sustainable experiences such as this can improve community/public health nursing education. [ABSTRACT FROM AUTHOR]

Historically, community health nursing education has not encompassed clinical sites in primary care. Primary care can be an important domain of community health nursing education. However, student practicum opportunities are limited by the number of and underutilization of RNs practicing at the full scope of their licensure (including assessment, client education, care planning and evaluation of care interventions) who can serve as student preceptors, especially in rural areas. This article describes the creation and implementation of the Enhanced Primary Care Registered Nurse (EPCRN) role in rural primary care clinics, as well as evaluates student perceptions of the EPCRN-precepted clinical experience. One nursing school used a federal training award to create the role of Enhanced Primary Care Registered Nurses (EPCRNs) to practice in federally-designated Rural Health Clinics. The EPCRNs worked in the Rural Health Clinics performing patient care and also functioned as student preceptors. Student experiences were evaluated through quantitative and qualitative methods, namely the Clinical Learning Experience, Supervision, and Nurse Teacher (CLES+T) scale and focus groups. This pilot project demonstrated positive pre-licensure student experience feedback as well as role value and sustainability for the health system. This pilot served as an example of a process for EPCRN role design within a primary care clinic site. It also demonstrated the importance of innovative, sustainable academic-practice partnerships. [ABSTRACT FROM AUTHOR]

Objective: In this study, we aimed to establish the causal effects of lowering sclerostin, target of the antiosteoporosis drug romosozumab, on atherosclerosis and its risk factors. Methods: A genome‐wide association study meta‐analysis was performed of circulating sclerostin levels in 33,961 European individuals. Mendelian randomization (MR) was used to predict the causal effects of sclerostin lowering on 15 atherosclerosis‐related diseases and risk factors. Results: We found that 18 conditionally independent variants were associated with circulating sclerostin. Of these, 1 cis signal in SOST and 3 trans signals in B4GALNT3, RIN3, and SERPINA1 regions showed directionally opposite signals for sclerostin levels and estimated bone mineral density. Variants with these 4 regions were selected as genetic instruments. MR using 5 correlated cis‐SNPs suggested that lower sclerostin increased the risk of type 2 diabetes mellitus (DM) (odds ratio [OR] 1.32 [95% confidence interval (95% CI) 1.03–1.69]) and myocardial infarction (MI) (OR 1.35 [95% CI 1.01–1.79]); sclerostin lowering was also suggested to increase the extent of coronary artery calcification (CAC) (β = 0.24 [95% CI 0.02–0.45]). MR using both cis and trans instruments suggested that lower sclerostin increased hypertension risk (OR 1.09 [95% CI 1.04–1.15]), but otherwise had attenuated effects. Conclusion: This study provides genetic evidence to suggest that lower levels of sclerostin may increase the risk of hypertension, type 2 DM, MI, and the extent of CAC. Taken together, these findings underscore the requirement for strategies to mitigate potential adverse effects of romosozumab treatment on atherosclerosis and its related risk factors. [ABSTRACT FROM AUTHOR]

Background: Gastroschisis is a challenging neonatal condition often with prolonged hospitalizations, need for parenteral nutrition, infectious complications, and can even result in death. Infection is reported to occur in up to two-thirds of patients with gastroschisis and is a strong risk factor for increased morbidity and mortality. Increased days with a central venous catheter, complex gastroschisis, and delayed abdominal wall closure have been consistently found to be associated with increased risk of infection, whereas sutureless gastroschisis closure has been associated with fewer infections. Although one of the most common complications of gastroschisis is infection, the use of antibiotic agents varies widely with variability in the literature to guide management. Antibiotic usage should be selective and short-term, especially in neonates with simple gastroschisis regardless of method for abdominal wall closure. Conclusions: Future initiatives should focus on development of evidence-based guidelines on the care of these patients with the goal of reducing variability and improve outcomes within and across institutions. [ABSTRACT FROM AUTHOR]

Objective: Describe cognitive function in patients seeking treatment for Post-Acute Sequelae of COVID-19 (PASC). Method: Ninety-two patients underwent neuropsychological evaluation secondary to reported "brain fog" following COVID-19 infection. Patients were referred from the University of Alabama at Birmingham (UAB) Post-COVID Treatment Program. Patients were on average 49 years of age (range: 18-74), female (77%), and White/Caucasian (73%)/Black/AA (25%), with 15.49 years of education (SD = 2.43). Results: Overall, many patients demonstrated mild impairment on a brief global cognitive screener (MoCA; M = 24.78, SD = 3.46). On specific tasks of cognitive abilities, processing speed was variable; ranging from low average (Oral TMT Part A; M = 88.31, SD = 28.78) to below average (Oral SDMT; M = 72.80, SD = 20.37). Memory for immediate recall was low average (CVLT3-Brief Form (BF) Trials 1-4, M = 88.01, SD = 17.11), while delayed recall was average (CVLT3-BF, M = 94.17, SD = 19.11). Performances on measures of attention/working memory (WAIS-IV Digit Span; M = 96.75, SD = 12.54), executive functioning (Oral TMT Part B; M = 92.71, SD = 28.48), language (COWAT; M = 92.03, SD = 14.19) and visuospatial abilities (RBANS Figure Copy M = 104.04, SD = 16.08) were intact. Performance on embedded validity measures was also intact (RDS [95% valid]; CVLT-3 FC [93% valid]). Conclusion: Overall, patients with "brain fog" following COVID-19 infection experience difficulties in specific domains of cognitive functioning. Further investigation of neuropsychological profiles associated with PASC is warranted to inform diagnosis, neurocognitive trajectory, and treatment planning. [ABSTRACT FROM AUTHOR]

Background: This study was to systematically test whether previously reported risk factors for chronic kidney disease (CKD) are causally related to CKD in European and East Asian ancestries using Mendelian randomization.Methods: A total of 45 risk factors with genetic data in European ancestry and 17 risk factors in East Asian participants were identified as exposures from PubMed. We defined the CKD by clinical diagnosis or by estimated glomerular filtration rate of <60 ml/min/1.73 m2. Ultimately, 51 672 CKD cases and 958 102 controls of European ancestry from CKDGen, UK Biobank and HUNT, and 13 093 CKD cases and 238 118 controls of East Asian ancestry from Biobank Japan, China Kadoorie Biobank and Japan-Kidney-Biobank/ToMMo were included.Results: Eight risk factors showed reliable evidence of causal effects on CKD in Europeans, including genetically predicted body mass index (BMI), hypertension, systolic blood pressure, high-density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein(a), type 2 diabetes (T2D) and nephrolithiasis. In East Asians, BMI, T2D and nephrolithiasis showed evidence of causality on CKD. In two independent replication analyses, we observed that increased hypertension risk showed reliable evidence of a causal effect on increasing CKD risk in Europeans but in contrast showed a null effect in East Asians. Although liability to T2D showed consistent effects on CKD, the effects of glycaemic phenotypes on CKD were weak. Non-linear Mendelian randomization indicated a threshold relationship between genetically predicted BMI and CKD, with increased risk at BMI of >25 kg/m2.Conclusions: Eight cardiometabolic risk factors showed causal effects on CKD in Europeans and three of them showed causality in East Asians, providing insights into the design of future interventions to reduce the burden of CKD. [ABSTRACT FROM AUTHOR]

Rural Health Clinics (RHCs) were created in 1977 to address the high health care needs, limited provider access, and poor health outcomes of rural Americans. Although innovative at their inception, the provider-centric model of RHC cost-based reimbursement structures has not evolved, leaving limited opportunities for change; many have failed. Comprehensive, proactive change is needed. Registered nurses (RNs) working at the top of their practice scope are a neglected clinical resource that can improve access, quality, value, and satisfaction for rural patient communities. RHC reimbursement policy must evolve to sustain and support this significant RN role. RNs have demonstrated value in care continuity and disease management, but there is little research on the utilization of RNs using their enhanced skill set in RHCs. Using the Bardach and Patashnik's eight steps of policy analysis, the authors will describe the background and regulations of RHCs, identify current barriers to improving the health of America's rural residents, and then provide evidence to support a new policy option according to the Quadruple Aim framework. The result is a sustainable policy recommendation designed to best serve rural communities. [ABSTRACT FROM AUTHOR]

Importance: Preclinical and epidemiological studies indicate a potential chemopreventive role of statins in epithelial ovarian cancer risk.Objective: To evaluate the association of genetically proxied inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (ie, genetic variants related to lower function of HMG-CoA reductase, target of statins) with epithelial ovarian cancer among the general population and in BRCA1/2 mutation carriers.Design, Setting, and Participants: Single-nucleotide polymorphisms (SNPs) in HMGCR, NPC1L1, and PCSK9 associated with low-density lipoprotein (LDL) cholesterol in a genome-wide association study (GWAS) meta-analysis (N ≤196 475) were used to proxy therapeutic inhibition of HMG-CoA reductase, Niemann-Pick C1-Like 1 (NPC1L1) and proprotein convertase subtilisin/kexin type 9 (PCSK9), respectively. Summary statistics were obtained for these SNPs from a GWAS meta-analysis of case-control analyses of invasive epithelial ovarian cancer in the Ovarian Cancer Association Consortium (OCAC; N = 63 347) and from a GWAS meta-analysis of retrospective cohort analyses of epithelial ovarian cancer among BRCA1/2 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA; N = 31 448). Across the 2 consortia, participants were enrolled between 1973 and 2014 and followed up through 2015. OCAC participants came from 14 countries and CIMBA participants came from 25 countries. SNPs were combined into multi-allelic models and mendelian randomization estimates representing lifelong inhibition of targets were generated using inverse-variance weighted random-effects models.Exposures: Primary exposure was genetically proxied inhibition of HMG-CoA reductase and secondary exposures were genetically proxied inhibition of NPC1L1 and PCSK9 and genetically proxied circulating LDL cholesterol levels.Main Outcomes and Measures: Overall and histotype-specific invasive epithelial ovarian cancer (general population) and epithelial ovarian cancer (BRCA1/2 mutation carriers), measured as ovarian cancer odds (general population) and hazard ratio (BRCA1/2 mutation carriers).Results: The OCAC sample included 22 406 women with invasive epithelial ovarian cancer and 40 941 control individuals and the CIMBA sample included 3887 women with epithelial ovarian cancer and 27 561 control individuals. Median ages for the cohorts ranged from 41.5 to 59.0 years and all participants were of European ancestry. In the primary analysis, genetically proxied HMG-CoA reductase inhibition equivalent to a 1-mmol/L (38.7-mg/dL) reduction in LDL cholesterol was associated with lower odds of epithelial ovarian cancer (odds ratio [OR], 0.60 [95% CI, 0.43-0.83]; P = .002). In BRCA1/2 mutation carriers, genetically proxied HMG-CoA reductase inhibition was associated with lower ovarian cancer risk (hazard ratio, 0.69 [95% CI, 0.51-0.93]; P = .01). In secondary analyses, there were no significant associations of genetically proxied inhibition of NPC1L1 (OR, 0.97 [95% CI, 0.53-1.75]; P = .91), PCSK9 (OR, 0.98 [95% CI, 0.85-1.13]; P = .80), or circulating LDL cholesterol (OR, 0.98 [95% CI, 0.91-1.05]; P = .55) with epithelial ovarian cancer.Conclusions and Relevance: Genetically proxied inhibition of HMG-CoA reductase was significantly associated with lower odds of epithelial ovarian cancer. However, these findings do not indicate risk reduction from medications that inhibit HMG-CoA reductase; further research is needed to understand whether there is a similar association with such medications. [ABSTRACT FROM AUTHOR]

Choledochal cysts are congenital malformations of the biliary tract that involve aberrant configurations of the pancreaticobiliary ductal system. The pathology exists on a spectrum from fusiform dilation of the common bile duct to multiple dilations involving the intra- and extrahepatic bile ducts with potential risks of malignant transformation and hepatic fibrosis. Advancements in ultrasound technology have increased the incidence of prenatal diagnosis of choledochal cysts. Here, we present the case of a prenatally diagnosed initially asymptomatic Type I choledochal cyst with rapid progression in the neonatal period to a complete gastric outlet obstruction within the first month of life. We demonstrate the feasibility of cyst resection and reconstruction with Roux-en-Y hepaticojejunostomy in the neonatal age group. Finally, we discuss management of the case based on evolving imaging findings and laboratory evidence of impending liver dysfunction. [ABSTRACT FROM AUTHOR]

Respectful maternity care research in Tanzania continues to increase. This is an overview of the literature summarizing research based on the domains which comprise this quality of care indicator, ranging from exploratory and descriptive to quantitative measurements of birth perinatal outcomes when respectful interventions are made. The domains of respectful care are reflected in the seven Universal Rights of Childbearing Women but go further to implicate facility administrators and policy makers to provide supportive infrastructure to allay disrespect and abuse. The research methodologies continue to be problematic and several ethical cautions restrict how much control is possible. Similarly, the barriers to collecting accurate accounts in qualitative studies of disrespect require astute interviewing and observation techniques. The participatory community-based and the critical sociology and human rights frameworks appear to provide a good basis for both researcher and participants to identify problems and determine possible solutions to the multiple factors that contribute to disrespect and abuse. The work-life conditions of midwives in the Global South are plagued with poor infrastructure and significantly low resources which deters respectful care while decreasing retention of workers. Researchers and policy-makers have addressed disrespectful care by building human resource capacity, by strengthening professional organizations and by educating midwives in low-resource countries. Furthermore, researchers encourage midwives not only to acquire attitudinal change and to adopt respectful maternity care skills, but also to emerge as leaders and change agents. Safe methods for conducting care while addressing low resources, skilled management of conflict and creative innovations to engage the community are all interventions that are being considered for quality improvement research. Tanzania is poised to evaluate the outcomes of education workshops that address all seven domains of respectful care. [ABSTRACT FROM AUTHOR]

A fed state in vitro methodology capable of use in commercial testing laboratories has been developed for measuring the human ingestion bioaccessibility of polyaromatic hydrocarbons (PAHs) in soil (Fed ORganic Estimation human Simulation Test- FOREhST). The protocol for measuring PAHs in the simulated gastro-intestinal fluids used methanolic KOH saponification followed by a combination of polymeric sorbent solid phase extraction and silica sorbent cartridges for sample cleanup and preconcentration. The analysis was carried out using high pressure liquid chromatography with fluorescence detection. The repeatability of the method, assessed by the measurement of the bioaccessibility of 6 PAHs (benz[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenz[ah]anthracene, and indeno[1,2,3-c,d]pyrene) in eleven gas works soils, was ∼10% RSD. The method compared well with the results from an independent dynamic human simulation reactor comprising of the stomach, duodenal and colon compartments tested on the same soils. The measured bioaccessible fraction of the soils varied from 10-60% for soils containing 10-300 mg kg-1 PAH (the sum of the six studied) with total organic carbon concentrations in the soils ranging from 1-13%. A multiple regression model showed that the PAH bioaccessible fraction could be explained using the PAH compound, the soil type and the total PAH to soil organic carbon content. The method described here has potential for site specific detailed quantitative risk assessment either to modify the risk estimation or to contribute to the risk evaluation. [ABSTRACT FROM AUTHOR]

Following a thorough site investigation, a biological Sequential Reactive Barrier (SEREBAR), designed to remove Polycyclic Aromatic Hydrocarbons (PAHs) and BTEX compounds, was installed at a Former Manufactured Gas Plant (FMGP) site. The novel design of the barrier comprises, in series, an interceptor and six reactive chambers. The first four chambers (2 nonaerated-2 aerated) were filled with sand to encourage microbial colonization. Sorbant Granular Activated Carbon (GAC) was present in the final two chambers in order to remove any recalcitrant compounds. The SEREBAR has been in continuous operation for 2 years at different operational flow rates (ranging from 320 L/d to 4000 L/d, with corresponding residence times in each chamber of 19 days and 1.5 days, respectively). Under low flow rate conditions (320–520 L/d) the majority of contaminant removal (>93%) occurred biotically within the interceptor and the aerated chambers. Under high flow rates (1000–4000 L/d) and following the installation of a new interceptor to prevent passive aeration, the majority of contaminant removal (>80%) again occurred biotically within the aerated chambers. The sorption zone (GAC) proved to be an effective polishing step, removing any remaining contaminants to acceptable concentrations before discharge down-gradient of the SEREBAR (overall removals >95%). [ABSTRACT FROM AUTHOR]

Information on age- and gender-specific prevalence of herpes simplex virus (HSV) types 1 and 2 infections is crucial to guide genital herpes control strategies. Such data are not available from the newly independent Eastern European countries. We present of study of the age- and gender-specific prevalence of HSV-1 and HSV-2 in low risk populations in Estonia. Serum samples from 1016 children, 794 first trimester antenatal women, and 1036 blood donors (462M, 574F) were tested for HSV IgG antibodies by type-specific HSV-1 and HSV-2 assays. High seroprevalence rates of HSV-1 among children, pregnant women and (non-paid) blood donors were found. HSV-2 infection was not detected among boys. Gender differences in HSV-2 seroprevalence rates among people of reproductive age were observed: higher rates were recorded among pregnant women (23%) and female blood donors (21%), compared to 11% among male blood donors. HSV-1 seroprevalence was high in adults. HSV-2 seroprevalence was higher among females than males and increased substantially with age. HSV-2 prevalence in these non-high risk populations was relatively high, and may indicate a risk for an impending sexually- and STI- driven HIV epidemic. [ABSTRACT FROM AUTHOR]

In 1993, the Institute for Healthcare Improvement (IHI) and the Health Resources and Services Administration (HRSA) formed the Interdisciplinary Professional Education Collaborative (IPEC). From the beginning, two potentially opposing challenges emerged. One reflects the first part of IPEC's aim 'to equip health professionals with the ability to continually improve'. The other reflects the second part of the aim 'to continually improve the health of the individuals and communities they serve.' Debate occurred around two questions: 'Are we educating students?' and 'Are we improving health?'. Each question reflects different and separate complex processes and systems. How can two systems-the system to educate health professionals and the system that influences the health of the community-interact so that each realises a mutual benefit? Through our work in the collaborative we identified six key factors that will lead to successful and mutually advantageous student/community projects. These are: (1) understand community health issues; (2) connect the educational institution and the community; (3) define a target community; (4) understand the people you wish to serve; (5) identify appropriate, short-term projects; (6) practice interdisciplinary teamwork. Work from two Local Interdisciplinary Teams (LIT's), Rochester, New York, and Philadelphia, Pennsylvania, illustrates these factors. [ABSTRACT FROM AUTHOR]