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Objective We analyzed application and match rates for pain medicine training in the United States and hypothesized that there would be (1) greater growth in the number of training positions than applicants, (2) higher match rates among US allopathic graduates relative to non-US allopathic graduates, and (3) greater number of unfilled training positions over time. Design Retrospective, cross-sectional study of all applicants for pain medicine training in the United States. Method National Resident Matching Program data were obtained over a ten-year period (2014-2023). Match rates and applicant-to-position ratios were calculated and compared over time with linear regression. Comparisons were made with chi-square tests. Results Growth in the number of annual training positions (261-377, 44% increase) exceeded growth in the number of interested applicants (398-415, 4% increase) (P  < .001). Annual applicant-to-training position ratios decreased (1.5-1.1, P  < .001). The representation of US allopathic graduates among incoming pain medicine fellows decreased over the study period (73%-58%, P  < .001) while US osteopathic graduates increased (9%-28%, P  < .001). Match rates increased for both US allopathic graduates (71%-91%, P  < .001) and non-US allopathic graduates (51%-81%, P  < .001). From 2018 to 2023, US allopathic graduates (79%) had higher match rates than US osteopathic graduates (60%, P  < .001) and international medical graduates (57%, P  < .001). More available annual training positions went unfilled over the study period (2%-5%, P  = .006). Conclusions Stagnant annual applicant volume and increasing number of available training positions have led to increasing match rates for pain medicine fellowship training. Fewer US allopathic graduates are pursuing pain medicine training. The increasing percentage of unfilled training positions warrants ongoing surveillance. [ABSTRACT FROM AUTHOR]

Importance: Large-scale estimates of bronchopulmonary dysplasia (BPD) are warranted for adequate prevention and treatment. However, systematic approaches to ascertain rates of BPD are lacking. Objective: To conduct a systematic review and meta-analysis to assess the prevalence of BPD in very low birth weight (≤ 1,500 g) or very low gestational age (< 32 weeks) neonates. Data sources: A search of MEDLINE from January 1990 until September 2019 using search terms related to BPD and prevalence was performed. Study selection: Randomized controlled trials and observational studies evaluating rates of BPD in very low birth weight or very low gestational age infants were eligible. Included studies defined BPD as positive pressure ventilation or oxygen requirement at 28 days (BPD28) or at 36 weeks postmenstrual age (BPD36). Data extraction and synthesis: Two reviewers independently conducted all stages of the review. Random-effects meta-analysis was used to calculate the pooled prevalence. Subgroup analyses included gestational age group, birth weight group, setting, study period, continent, and gross domestic product. Sensitivity analyses were performed to reduce study heterogeneity. Main outcomes and measures: Prevalence of BPD defined as BPD28, BPD36, and by subgroups. Results: A total of 105 articles or databases and 780,936 patients were included in this review. The pooled prevalence was 35% (95% CI, 28-42%) for BPD28 (n = 26 datasets, 132,247 neonates), and 21% (95% CI, 19-24%) for BPD36 (n = 70 studies, 672,769 neonates). In subgroup meta-analyses, birth weight category, gestational age category, and continent were strong drivers of the pooled prevalence of BPD. Conclusions and relevance: This study provides a global estimation of BPD prevalence in very low birth weight/low gestation neonates. [ABSTRACT FROM AUTHOR]

The RNA polymerase II (Pol II) elongation rate influences poly(A) site selection, with slow and fast Pol II derivatives causing upstream and downstream shifts, respectively, in poly(A) site utilization. In yeast, depletion of either of the histone chaperones FACT or Spt6 causes an upstream shift of poly(A) site use that strongly resembles the poly(A) profiles of slow Pol II mutant strains. Like slow Pol II mutant strains, FACT-and Spt6-depleted cells exhibit Pol II processivity defects, indicating that both Spt6 and FACT stimulate the Pol II elongation rate. Poly(A) profiles of some genes show atypical downstream shifts; this subset of genes overlaps well for FACT-or Spt6-depleted strains but is different from the atypical genes in Pol II speed mutant strains. In contrast, depletion of histone H3 or H4 causes a downstream shift of poly(A) sites for most genes, indicating that nucleosomes inhibit the Pol II elongation rate in vivo. Thus, chromatin-based control of the Pol II elongation rate is a potential mechanism, distinct from direct effects on the cleavage/polyadenylation machinery, to regulate alternative polyadenylation in response to genetic or environmental changes. [ABSTRACT FROM AUTHOR]

Background: Treat-all strategies improved patient outcomes, despite higher rates of loss to follow-up compared to the pre-treat era. Patients in Ethiopia experienced a higher rate of LTFU during the treat-all strategy period; however, studies did not identify contributing factors in comparison with previous strategies. This study aimed to assess the incidence and predictors of loss to follow-up before and after the start of the treat-all strategy among adults on anti-retroviral therapy in public health facilities in Hawassa City, Ethiopia. Methods: An institution-based retrospective follow-up study was conducted among 1190 randomly selected adults on antiretroviral therapy in public health facilities in Hawassa City. Using the Open Data Kit (ODK), data were collected from medical records and exported to Stata version 16 and R 4.2.1 for analysis. A Grays test and cumulative incidence curve were used to compare the cumulative incidence function of loss to follow-up. Bivariable and multivariable competing risk regression were fitted to identify predictors of LTFU and variables with a p-value <0.05 were considered significant. Results: The cumulative incidence of lost-to-follow-up was 4.92(3.84,6.3) and 8.67(7.26,10.3) per 100 person-years (PY) in pre-treat all and treat all cohorts, respectively. The cumulative incidence of mortality was 5.86(4.67,7.35) and 3(2.26,4.12) per 100 PY in pre-treat and treat all cohorts, respectively. Fair/poor adherence (aSHR:5.17; (95% CI 1.97, 13.51), underweight (aSHR:2.13; 95% CI: 1.15–3.93) and WHO stage III/IV (aSHR:2.69; 95% CI: 1.27, 5.71) were predictors of loss up in pre—treat all, whereas fair/poor adherence (aSHR = 2.07; 95% CI: 1.18, 3.68), underweight (aSHR:1.71; 95% CI: 1.13, 2.56), and CD4 cell >350 cell/m3 (aSHR: 1.67; 95% CI: 1.05, 2.65) predicts of loss up in treat all cohorts. Conclusion: This study demonstrated that the incidence of loss to follow-up was considerably higher in the treat-all period as compared to the pre-treat-all era. Poor medication compliance, underweight, and a CD4 level >350 cells/m3 contributed to the higher rate of LTFU in the treat-all strategy. Targeted interventions, such as nutritional support and strengthening medication adherence counseling, should be implemented to maintain treatment retention and reduce antiretroviral therapy dropout rates. [ABSTRACT FROM AUTHOR]

Genomic surveillance is crucial for tracking emergence and spread of novel variants of pathogens, such as SARS-CoV-2, to inform public health interventions and to enforce control measures. However, in some settings especially in low- and middle- income counties, where sequencing platforms are limited, only certain patients get to be selected for sequencing surveillance. Here, we show that patients with multiple comorbidities potentially harbour SARS-CoV-2 with higher mutation rates and thus deserve more attention for genomic surveillance. The relationship between the patient comorbidities, and type of amino acid mutations was assessed. Correlation analysis showed that there was a significant tendency for mutations to occur within the ORF1a region for patients with higher number of comorbidities. Frequency analysis of the amino acid substitution within ORF1a showed that nsp3 P822L of the PLpro protease was one of the highest occurring mutations. Using molecular dynamics, we simulated that the P822L mutation in PLpro represents a system with lower Root Mean Square Deviation (RMSD) fluctuations, and consistent Radius of gyration (Rg), Solvent Accessible Surface Area (SASA) values—indicate a much stabler protein than the wildtype. The outcome of this study will help determine the relationship between the clinical status of a patient and the mutations of the infecting SARS-CoV-2 virus. [ABSTRACT FROM AUTHOR]

Background: There has been little information on the actual diagnosis of pulmonary lesions in patients with a history of urinary tract transitional cell carcinoma (TCC) and short- and long- outcomes of pulmonary resection for these patients. Methods: In the present study, the data of 37 consecutive patients with a history of TCC who underwent pulmonary resection for solitary pulmonary lesions were reviewed, and the clinical factors and short- and long-term outcomes were analyzed. Results: The study population included 35 male patients, and 2 female patients. The mean age was 72.5 years. Twenty patients (80%) were smokers and showed a high incidence of chronic obstructive pulmonary disease. Pulmonary lesions and primary TCC were detected simultaneously in 5 patients and metachronously in 32 patients. The median interval between treatment for primary TCC and the detection of pulmonary lesion was 43 months. The mean tumor diameter was 23 mm. The types of resection included lobectomy (n = 19), segmentectomy (n = 8), and partial resection (n = 10). Twelve of 37 patients (32%) developed postoperative complications. The pathological diagnoses included primary lung cancer (n = 28), pulmonary metastasis from TCC (n = 7), and others (n = 2). The 5-year overall survival rate for all patients was 72%. The 5-year overall survival rate of patients with primary lung cancer was 74%, while that of patients with pulmonary metastasis from TCC was 57%. Conclusions: Surgery can be proactively considered for treating pulmonary lesions in patients with a previous history of TCC, as it provides favorable long-term outcomes. [ABSTRACT FROM AUTHOR]

To describe the burden and causes of disease in Mexican women in 1990 and 2019, based on the data disaggregation by age groups and states. Also, to evaluate the relationship of years of healthy life lost with the Socio-demographic Index (SDI) and with the Healthcare Access and Quality (HAQ) Index. This was an ecological descriptive study. Based on the Global Burden of Disease, Injuries, and Risk Factors Study study, the age-standardized and age-specific rates for mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) were reported. At the national level, the all-cause age-standardized rates for Mexican women decreased in mortality −28.8%; YLLs -39.8%; YLDs −1.3%; and DALYs −26.2%. For 2019, the indicators analyzed had the worst performances in Chiapas and Chihuahua, while women in Sinaloa had the lowest age-standardized rates. In 1990, it is worth noting that there was a remarkable presence of CDs, mainly in YLLs. In all age groups, diabetes mellitus was the leading cause of DALYs in Mexico's 32 states, followed by CKD (in 24 states), and ischemic heart disease (in 18 states). In both 1990 and 2019, a negative and statistically significant correlation between DALYs and the HAQ Index was evident. The correlation between DALYs and the SDI was only significant in 1990. In the last 30 years, the burden of disease on Mexican women has undergone substantial changes that reflect progress in the improvement of their health conditions. However, the current scenario is complex because the convergence of communicable diseases, non-communicable diseases, and injuries is evident, which implies important challenges that must be addressed as soon as possible. [ABSTRACT FROM AUTHOR]

Background: Relapse is a clinical concern in dogs diagnosed with immune‐mediated hemolytic anemia (IMHA), thrombocytopenia (ITP), or polyarthritis (IMPA). The average time to relapse is unknown, and evidence that vaccination is associated with disease relapse is lacking. Hypothesis/Objectives: Compare the incidence of relapse in groups of dogs with IMHA, ITP, or IMPA over a 24‐month period after diagnosis and compare proportions of dogs that received vaccines in those dogs that did and did not relapse. Animals: One hundred sixty client‐owned dogs (73 with IMHA, 55 with ITP, 32 with IMPA). Methods: Medical records of dogs were reviewed with the goal of following cases for a minimum of 2 years. Incidence of relapse was calculated for each disease, and relapse rates in dogs that were or were not vaccinated after diagnosis were compared. Results: Relapse rates at 12 months differed significantly among disease groups (P =.02), with a higher rate for IMPA (35%) compared to IMHA (11%) or ITP (11%). Relapse rate at 24 months was 41% for IMPA, 18% for IMHA, and 23% for ITP. Ninety percent of IMPA relapses occurred in the first 12 months after diagnosis, compared with 56% for IMHA and 50% for ITP. Vaccine administration after diagnosis was not associated with relapse (P =.78). Conclusions and Clinical Importance: Risk of disease relapse in IMPA is highest in the first year after diagnosis, with a higher relapse rate compared with IMHA and ITP. The role of vaccination in disease relapse remains unclear. [ABSTRACT FROM AUTHOR]

The impact of U.S. monetary policy (USMP) on domestic interest rates and goods markets in Emerging Market Economies (EMEs) remains a subject of ongoing debate. We investigate the fluctuations in U.S. interest rates across 17 inflation-targeting EMEs with flexible exchange rates from 2000–2020. Our findings reveal asymmetric contagion effects, with U.S. interest rate decrease having a more significant short-term impact than rate hikes. Long-term U.S. rates minimally influence EMEs’ domestic rates. Resilience is observed in EMEs with robust GDP growth and favorable trade balances, while increased capital inflows and stock market surges heighten contagion risks. Focusing on the short-term contagion effect on goods markets through international trade drivers, we find that global capital flows and US dollar fluctuations, combined with a rise in the FED rate, contribute to the deterioration of EMEs’ trade balance. The study underscores the need for EMEs to monitor and respond to U.S. monetary policy changes for financial stability and advocates for enhanced international dialogue among policymakers. [ABSTRACT FROM AUTHOR]

Purpose: Identify urinary catheter (UC)-associated urinary tract infections (CAUTI) incidence and risk factors (RF) in Latin American Countries. Methods: From 01/01/2014 to 02/10/2022, we conducted a prospective cohort study in 145 ICUs of 67 hospitals in 35 cities in nine Latin American countries: Argentina, Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Panama, and Peru. To estimate CAUTI incidence, we used the number of UC-days as the denominator, and the number of CAUTIs as numerator. To estimate CAUTI RFs, we analyzed the following 10 variables using multiple logistic regression: gender, age, length of stay (LOS) before CAUTI acquisition, UC-days before CAUTI acquisition, UC-device utilization (DU) ratio, UC-type, hospitalizationtype, ICU type, facility ownership, and time period. Results: 31,631 patients, hospitalized for 214,669 patient-days, acquired 305 CAUTIs. The pooled CAUTI rate per 1000 UC-days was 2.58, for those using suprapubic catheters, it was 2.99, and for those with indwelling catheters, it was 2.21. The following variables were independently associated with CAUTI: age, rising risk 1% yearly (aOR = 1.01; 95% CI 1.01–1.02; p < 0.0001 female gender (aOR = 1.28; 95% CI 1.01–1.61; p = 0.04), LOS before CAUTI acquisition, rising risk 7% daily (aOR = 1.07; 95% CI 1.06–1.08; p < 0.0001, UC/DU ratio (aOR = 1.14; 95% CI 1.08–1.21; p < 0.0001, public facilities (aOR = 2.89; 95% CI 1.75–4.49; p < 0.0001. The periods 2014–2016 and 2017–2019 had significantly higher risks than the period 2020–2022. Suprapubic catheters showed similar risks as indwelling catheters. Conclusion: The following CAUTI RFs are unlikely to change: age, gender, hospitalization type, and facility ownership. Based on these findings, it is suggested to focus on reducing LOS, UC/DU ratio, and implementing evidence-based CAUTI prevention recommendations. [ABSTRACT FROM AUTHOR]

Setting: Paraquat is a highly toxic, herbicide, extensively used in various parts of India. There is no effective treatment for paraquat poison and carries a very high mortality. In India, this compound can be misused for harmful purposes. Objective: A retrospective time-bound descriptive study of paraquat-consumed patients was conducted at Kasturba Hospital, Manipal, from January 1, 2014 to January 31, 2016. Materials and Methods: All the data were analyzed using the SPSS version 16. All the categorical data are expressed in terms of frequency and percentage. Continuous normal variables were expressed in terms of mean ± standard deviation, and skewed variables were expressed in terms of median and quartiles. Chi-square test was used to find the association between the categorical independent variables across the outcome in survivors, nonsurvivors, and those patients who were discharged from the hospital against medical advice. Similarly, Fisher's exact test was performed for those variables, for which 20% of the expected cell count was <5%. Kruskal--Wallis test was used to compare the relationship between the continuous skewed variables across the outcome. Results: A total of 55 paraquat-consumed patients were admitted, out of which 67.27% (n = 37) of patients were men. Only 32.7% (n = 18) of patients were farmers. Oral ulcers were seen in 43.6% (n = 24) of patients. About 65.5% (n = 36) of patients underwent hemoperfusion, 27.3% (n = 15) of patients survived, 47.3% (n = 26) of patients expired, and 25.5% (n = 14) of patients were discharged against medical advice in a critical condition. The presence of respiratory failure, hypotension, need for ventilator supportive therapy, the elevation of levels of blood urea, serum creatinine, and liver enzymes AST and ALT levels were statistically significant in three groups (P < 0.001). Conclusion: Paraquat poisoning is highly fatal. Treatment is expensive and available only in tertiary care hospitals in India. Central and state governments should ensure that it should not be readily accessible to ordinary people and it should be banned progressively. [ABSTRACT FROM AUTHOR]

This paper examines whether or to what extent San Francisco International Airport's (SFO's) purportedly high costs relative to other airports suppressed SFO's traffic demand and prolonged the recovery of passenger traffic in the period after the 11th September, 2001 terrorist attacks. A comparative analysis of the historical data shows that SFO's direct airport costs per enplanement (CPE) were higher than most other major airports in the post-9/11 period by a considerable margin, but that airport costs likely were not a significant factor in SFO's prolonged recovery. Airport costs likely did not affect airline profitability sufficiently to influence route and scheduling decisions, and it is unlikely that passenger demand was dampened by the pass-through of higher costs to airfares. This research suggests at best a tenuous relationship between airport rates and passenger activity, and at SFO the evidence does not suggest that an extremely high CPE relative to peer airports affected the pace of its slow return to pre-9/11 traffic levels. Rather, the slow return of traffic to SFO and its neighbour, Norman Y. Mineta San Jose International Airport (SJC), compared to the robust growth at Oakland International Airport (OAK) can be explained by traditional economic means. It also suggests that in a multi-airport region where each airport is somewhat specialised, an individual airport's over- or underperformance relative to its neighbours is more likely to be a function of economic geography than of any airport's rate-setting practices. If this conclusion holds true for other US airports, it emphasises the ability of airports to create capital plans and set rates and charges to make long-term investments in organic air traffic growth, ensuring that new entrant airlines have sufficient facilities to begin service and that existing airlines have sufficient capacity to grow. [ABSTRACT FROM AUTHOR]

Immigrants living in low hepatitis C (HCV) prevalence countries bear a disproportionate HCV burden, but there are limited HCV population‐based studies focussed on this population. We estimated rates and trends of reported HCV diagnoses over a 20‐year period in Quebec, Canada, to investigate subgroups with the highest rates and changes over time. A population‐based cohort of all reported HCV diagnoses in Quebec (1998–2018) linked to health administrative and immigration databases. HCV rates, rate ratios (RR) and trends overall and stratified by immigrant status and country of birth were estimated using Poisson regression. Among 38,348 HCV diagnoses, 14% occurred in immigrants, a median of 7.5 years after arrival. The average annual HCV rate/100,000 decreased for immigrants and nonimmigrants, but the risk (RR) among immigrants increased over the study period [35.7 vs. 34.5 (RR = 1.03) and 18.4 vs. 12.7 (1.45) between 1998–2008 and 2009–2018]. Immigrants from middle‐income Europe & Central Asia [55.8 (RR = 4.39)], sub‐Saharan Africa [51.7 (RR = 4.06)] and South Asia [32.8 (RR = 2.58)] had the highest rates between 2009 and 2018. Annual HCV rates decreased more slowly among immigrants vs. nonimmigrants (−5.9% vs. −8.9%, p < 0.001), resulting in a 2.5‐fold (9%–21%) increase in the proportion of HCV diagnoses among immigrants (1998–2018). The slower decline in HCV rates among immigrants over the study period highlights the need for targeted screening for this population, particularly those from sub‐Saharan Africa, Asia and middle‐income Europe. These data can inform micro‐elimination efforts in Canada and other low‐HCV‐prevalence countries. [ABSTRACT FROM AUTHOR]

Objective: To examine injury and concussion rates, mechanisms, locations, and types of injury in Canadian high school male rugby. Design: Prospective cohort study. Setting: High school male rugby. Participants: A total of 429 high school players (2018: n = 225, 2019: n = 256) were recruited from 12 teams in 7 schools in Calgary, Canada. Interventions: None. Main Outcome Measures: Injury surveillance included baseline questionnaires, weekly exposure, and injury reports. Injuries included those requiring medical attention, resulted in time loss and/or inability to complete a session. Concussion was defined as per the fifth Consensus on Concussion in Sport, and all players with a suspected concussion were referred to a study sport medicine physician. Results: A total of 134 injuries were captured, leading to an injury incidence rate (IR) of 57.9/1000 hours [95% confidence intervals (CIs): 45.4-73.8]. Median time loss was 6 days (range: 0-90). Injuries to the head were the most common (40%), followed by shoulder (12%) and ankle (10%). The concussion IR was 22.0/1000 hours (95% CIs: 15.9-30.4), which was the most common injury type (38%), followed by sprain (20%) and strain (15%). Sixty-five percent of injuries occurred in the tackle (ball carrier 35%, tackler 30%) and 76% of concussions (ball carrier 41%, tackler 35%). Conclusions: The rate of injury and concussion in Canadian youth high school male rugby is high, with tackle-related injuries and concussions the most common. Given this, there is a critical need for implementation of prevention strategies, in particular targeting concussion and the tackle event (eg, neuromuscular, tackle training, and law changes). [ABSTRACT FROM AUTHOR]

Background: Programmed cell death‐1/ligand 1 inhibitors are a new treatment strategy for advanced urothelial carcinoma. Therefore, a comparative evaluation of their efficacy and toxicity compared with chemotherapy is necessary. Methods: We comprehensively searched PubMed, Web of Science, Embase, and Cochrane Library databases and performed a meta‐analysis of randomized controlled trials up to July 2021. We considered overall survival as the primary outcome, and progression‐free survival, objective response rate, and treatment‐related adverse events as secondary outcomes. Results: Overall, 3584 patients from five studies were evaluated. Compared with first‐line chemotherapy, programmed cell death‐1/ligand 1 inhibitors were significantly associated with worse progression‐free survival (p < 0.001) and adverse objective response rates (p < 0.001). However, the treatments were not significantly different in terms of overall survival (p = 0.33). Compared with second‐line chemotherapy, programmed cell death‐1/ligand 1 inhibitors significantly improved overall survival (p < 0.001), and there was no statistically significant difference in progression‐free survival (p = 0.89) or objective response rate (p = 0.34). Compared with chemotherapy, programmed cell death‐1/ligand 1 inhibitors were well tolerated (first‐line chemotherapy: p < 0.001; second‐line chemotherapy: p < 0.001). Conclusions: The efficacy of programmed cell death‐1/ligand 1 inhibitors in patients with advanced urothelial carcinoma is not superior to that of first‐line platinum‐based chemotherapy but is better than second‐line chemotherapy; however, programmed cell death‐1/ligand 1 inhibitors are safer than first‐ and second‐line chemotherapy and have a broader prospect for use in combination therapy. [ABSTRACT FROM AUTHOR]

Obesity has been recognized as one of the most significant risk factors for the deterioration and mortality associated with COVID-19, but the significance of obesity itself differs among ethnicity. Multifactored analysis of our single institute-based retrospective cohort revealed that high visceral adipose tissue (VAT) burden, but not other obesity-associated markers, was related to accelerated inflammatory responses and the mortality of Japanese COVID-19 patients. To elucidate the mechanisms how VAT-dominant obesity induces severe inflammation after severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, we infected two different strains of obese mice, C57BL/6JHamSlc-ob/ob (ob/ob), C57BLKS/J-db/db (db/db), genetically impaired in the leptin ligand and receptor, respectively, and control C57BL/6 mice with mouse-adapted SARS-CoV-2. Here, we revealed that VAT-dominant ob/ob mice were extremely more vulnerable to SARS-CoV-2 due to excessive inflammatory responses when compared to SAT-dominant db/db mice. In fact, SARS-CoV-2 genome and proteins were more abundant in the lungs of ob/ob mice, engulfed in macrophages, resulting in increased cytokine production including interleukin (IL)-6. Both an anti-IL-6 receptor antibody treatment and the prevention of obesity by leptin replenishment improved the survival of SARS-CoV-2-infected ob/ob mice by reducing the viral protein burden and excessive immune responses. Our results have proposed unique insights and clues on how obesity increases the risk of cytokine storm and death in patients with COVID-19. Moreover, earlier administration of antiinflammatory therapeutics including anti-IL-6R antibody to VAT-dominant patients might improve clinical outcome and stratification of the treatment for COVID-19, at least in Japanese patients. [ABSTRACT FROM AUTHOR]

Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones. Postmortem liver biopsies were collected to assess the presence of SARS-CoV-2 and its transporters in hepatocytes. In human hepatocytes, we studied the mechanistic bases of SARS-CoV-2 entrance and its gluconeogenic effect. SARS-CoV-2 infection was independently associated with hyperglycemia, regardless of diabetic history and beta cell function. We detected replicating viruses in human hepatocytes from postmortem liver biopsies and in primary hepatocytes. We found that SARS-CoV-2 variants infected human hepatocytes in vitro with different susceptibility. SARS-CoV-2 infection in hepatocytes yields the release of new infectious viral particles, though not causing cell damage. We showed that infected hepatocytes increase glucose production and this is associated with induction of PEPCK activity. Furthermore, our results demonstrate that SARS-CoV-2 entry in hepatocytes occurs partially through ACE2- and GRP78-dependent mechanisms. SARS-CoV-2 infects and replicates in hepatocytes and exerts a PEPCK-dependent gluconeogenic effect in these cells that potentially is a key cause of hyperglycemia in infected patients. [ABSTRACT FROM AUTHOR]

This study presents the trends of age-standardised incidence and mortality rates of common cancers in Brunei Darussalam from 2011 to 2020. All cancer cases diagnosed among Brunei Darussalam citizens and permanent residents in the period 2011 to 2020 were included in the study. De-identified data were provided by the CanReg5 based BDCR, Ministry of Health Brunei Darussalam. The annual age-standardised incidence and mortality rates per 100,000 persons were standardised by the direct method using the World Health Organization (WHO) world standard population distribution. Joinpoint regression analyses were used to study the incidence and mortality trends of cancer in Brunei Darussalam over the 2011–2020 period. Trends were expressed as average annual percent change (AAPC) over 2011 to 2020, or annual percent change (APC) for a given time period. There were a total of 6,495 new cancer cases diagnosed and 3,359 death cases recorded from 2011 to 2020, in Brunei Darussalam. The five common cancers for males were colorectal, lung and bronchus, prostate, liver, and non-Hodgkin lymphoma. Among females, the five most common cancers were breast, colorectal, lung and bronchus, corpus uteri and cervix uteri. The five leading cancer deaths for males were lung and bronchus, colorectal, liver, prostate, and stomach, while for females, the five leading cancer deaths were breast, lung and bronchus, colorectal, ovary, and cervix uteri. There was a significant increase in the incidence trend of corpus uteri (AAPC : 13.3 ) and a significant decline in the incidence trend for cervical cancer (AAPC : - 4.5 ) from 2011 to 2020. There was a significant increase in the mortality trend of female breast cancer from 2011 to 2015 (APC : 16.3 ), but the trend significantly declined from 2015 to 2020 (APC : - 12.5 ). We also found a significant decrease in mortality trends for stomach cancer (AAPC : - 4.7 ) from 2011 to 2020 for both genders combined. The burden of common cancers is expected to continue to grow with ageing population, effective public health interventions targeting high burden cancers and high-risk groups, and control of modifiable risk factors will continue to be the essential approaches in reducing cancer burden. [ABSTRACT FROM AUTHOR]

Mexico is among the countries with the highest estimated excess mortality rates due to the COVID–19 pandemic, with more than half of reported deaths occurring in adults younger than 65 years old. Although this behavior is presumably influenced by the young demographics and the high prevalence of metabolic diseases, the underlying mechanisms have not been determined. The age–stratified case fatality rate (CFR) was estimated in a prospective cohort with 245 hospitalized COVID–19 cases, followed through time, for the period October 2020–September 2021. Cellular and inflammatory parameters were exhaustively investigated in blood samples by laboratory test, multiparametric flow cytometry and multiplex immunoassays. The CFR was 35.51%, with 55.2% of deaths recorded in middle–aged adults. On admission, hematological cell differentiation, physiological stress and inflammation parameters, showed distinctive profiles of potential prognostic value in patients under 65 at 7 days follow–up. Pre–existing metabolic conditions were identified as risk factors of poor outcomes. Chronic kidney disease (CKD), as single comorbidity or in combination with diabetes, had the highest risk for COVID–19 fatality. Of note, fatal outcomes in middle–aged patients were marked from admission by an inflammatory landscape and emergency myeloid hematopoiesis at the expense of functional lymphoid innate cells for antiviral immunosurveillance, including NK and dendritic cell subsets. Comorbidities increased the development of imbalanced myeloid phenotype, rendering middle–aged individuals unable to effectively control SARS–CoV–2. A predictive signature of high–risk outcomes at day 7 of disease evolution as a tool for their early stratification in vulnerable populations is proposed. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: This study provides an overview of opioid dispensing in Queensland from 2008 to 2018 by recipient age, drug, oral morphine equivalent and remoteness. Methods: Data were obtained from the Queensland Monitoring of Drugs of Dependence System database for 2008–18 and analysed using data from the Australian Bureau of Statistics to account for population growth. Opioid dispensing by age, drug, oral morphine equivalent and remoteness were assessed. Results: The number of prescriptions for Schedule 8 opioid medicines dispensed in Queensland increased from 190 to 430 per 1000 population over the study period (2.3-fold increase). Oxycodone had the largest increase in dispensing over the study period of 3.1-fold, with tapentadol increasing rapidly since initial Pharmaceutical Benefits Scheme listing in 2013 to the third most dispensed opioid by 2018. By 2018, opioid dispensing among the oldest Queenslanders, those aged 85+ years, occurred at triple the rate for those aged 65–84 years. When adjusted to report oral morphine equivalents (OME) in milligrams (mg), there has been an increase of approximately 1.9-fold over the study period. Results were also presented by geographical area, including a heatmap and analysis by remoteness. Prescriptions dispensed per 1000 population were 416 for major cities, 551 for inner regional and 445 for outer regional, and highlight that inner and outer regional areas have higher rates of prescriptions when compared to major cities (32 and 7% higher, respectively). Conclusion: This study highlights changes in opioid prescription dispensing by drug and OME, as well as the variation in dispensing rates when accounting for remoteness. Further studies to link statewide databases, and to better understand drivers for differences in dispensing by location, will provide valuable insights to further inform policy and service provision. What is known about the topic? Opioid dispensing is known to have increased in Australia over recent decades. However, most existing data hails from the Pharmaceutical Benefits Scheme (PBS), which has small gaps in quantifying opioids that are not subsidised. What does this paper add? This retrospective study uses an alternative database, adding information about non-PBS dispensing of tapentadol and buprenorphine, accompanied by rates of opioid dispensing in Queensland by age, oral morphine equivalent and geographical area. What are the implications for practitioners? This research highlights recent changes in opioid dispensing and opportunities for further studies to best inform practice improvement. [ABSTRACT FROM AUTHOR]

COVID‐19 vaccines have so far been the most powerful weapon in the current pandemic, yet many people still show hesitancy towards them. This paper is one of the first studies that examine the factors affecting the COVID‐19 vaccine uptake decision from a spatial perspective in Turkey. The study setting allows us to specify the spatial effects that are influential in this decision without which the true nature of the association between vaccination rates and various socio‐economic factors can be determined. Our findings reveal the existence of global spatial interactions in vaccination rates. In addition, age, the level of conservatism, and low education levels show spillovers that amplify their total effects on vaccination rates. [ABSTRACT FROM AUTHOR]

Frenkel exciton population dynamics of an excitonic dimer is studied by comparing the results from a quantum master equation involving rates from second-order perturbative treatment with respect to the excitonic coupling with the non-perturbative results from "Hierarchical Equations of Motion" (HEOM). By formulating generic Liouville-space expressions for the rates, we can choose to evaluate them either via HEOM propagations or by applying the cumulant expansion. The coupling of electronic transitions to bath modes is modeled either as overdamped oscillators for the description of thermal bath components or as underdamped oscillators to account for intramolecular vibrations. Cases of initial nonequilibrium and equilibrium vibrations are discussed. In the case of HEOM, initial equilibration enters via a polaron transformation. Pointing out the differences between the nonequilibrium and equilibrium approach in the context of the projection operator formalism, we identify a further description, where the transfer dynamics is driven only by fluctuations without involvement of dissipation. Despite this approximation, this approach can also yield meaningful results in certain parameter regimes. While for the chosen model, HEOM has no technical advantage for evaluation of the rate expressions compared to cumulant expansion, there are situations where only evaluation with HEOM is applicable. For instance, a separation of reference and interaction Hamiltonian via a polaron transformation to account for the interplay between Coulomb coupling and vibrational oscillations of the bath at the level of a second-order treatment can be adjusted for a treatment with HEOM. [ABSTRACT FROM AUTHOR]

Kinetic rate factors of crystallization have a direct effect on formation and growth of an ordered solid phase in supercooled liquids and glasses. Using the crystallizing Lennard-Jones liquid as an example, in the present work, we perform a direct quantitative estimation of values of the key crystallization kinetic rate factors—the rate g+ of particle attachments to a crystalline nucleus and the rate g− of particle detachments from a nucleus. We propose a numerical approach, according to which a statistical treatment of the results of molecular dynamics simulations was performed without using any model functions and/or fitting parameters. This approach allows one to accurately estimate the critical nucleus size nc. We find that for the growing nuclei, whose sizes are larger than the critical size nc, the dependence of these kinetic rate factors on the nucleus size n follows a power law. In the case of the subnucleation regime, when the nuclei are smaller than nc, the n-dependence of the quantity g+ is strongly determined by the inherent microscopic properties of a system, and this dependence cannot be described in the framework of any universal law (for example, a power law). It has been established that the dependence of the growth rate of a crystalline nucleus on its size goes into the stationary regime at the size n > 3nc particles. [ABSTRACT FROM AUTHOR]

We address the calculation of microcanonical reaction rates for processes involving significant nuclear quantum effects using ring-polymer molecular dynamics (RPMD), both with and without electronically non-adiabatic transitions. After illustrating the shortcomings of the naive free-particle direct-shooting method, in which the temperature of the internal ring-polymer modes is set to the translational energy scale, we investigate alternative strategies based on the expression for the microcanonical rate in terms of the inverse Laplace transform of the thermal reaction rate. It is shown that simple application of the stationary-phase approximation (SPA) dramatically improves the performance of the microcanonical rates using RPMD, particularly in the low-energy region where tunneling dominates. Using the SPA as a Bayesian prior, numerically exact RPMD microcanonical rates are then obtained using maximum entropy inversion of the thermal reaction rates for both electronically adiabatic and non-adiabatic model systems. Finally, the direct-shooting method is revisited using the SPA-determined temperature for the internal ring-polymer modes, leading to a simple, direct-simulation method with improved accuracy in the tunneling regime. This work suggests a general strategy for the extraction of microcanonical dynamical quantities from RPMD (or other approximate thermal) simulations. [ABSTRACT FROM AUTHOR]

Chemical reactions in multidimensional driven systems are typically described by a time-dependent rank-1 saddle associated with one reaction and several orthogonal coordinates (including the solvent bath). To investigate reactions in such systems, we develop a fast and robust method—viz., local manifold analysis (LMA)—for computing the instantaneous decay rate of reactants. Specifically, it computes the instantaneous decay rates along saddle-bound trajectories near the activated complex by exploiting local properties of the stable and unstable manifold associated with the normally hyperbolic invariant manifold (NHIM). The LMA method offers substantial reduction in numerical effort and increased reliability in comparison with direct ensemble integration. It provides an instantaneous flux that can be assigned to every point on the NHIM and which is associated with a trajectory—regardless of whether it is periodic, quasiperiodic, or chaotic—that is bound on the NHIM. The time average of these fluxes in the driven system corresponds to the average rate through a given local section containing the corresponding point on the NHIM. We find good agreement between the results of the LMA and direct ensemble integration obtained using numerically constructed, recrossing-free dividing surfaces. [ABSTRACT FROM AUTHOR]

The recombination rates in InGaN/AlGaN/GaN multiple quantum wells (MQWs) emitting in the green-yellow and grown with different Al compositions in the AlGaN interlayer (IL) are shown. By transforming measurements on radiative efficiency, absorption, and differential carrier lifetime, the radiative and nonradiative rates are determined. The IL Al composition controls lattice relaxation of the MQWs, as determined by X-ray reciprocal space mapping, and, therefore, defect formation. For the most pseudomorphic MQWs, the Shockley-Read-Hall (SRH) A coefficient is minimized and is similar to reports at shorter (blue and green) wavelengths. It is an order of magnitude smaller than a conventional InGaN/GaN MQW and is the most significant factor behind the improvement in radiative efficiency using the IL. The radiative B coefficient is also reduced and a minimum for the most pseudomorphic MQWs due to a reduction in the electron-hole wavefunction overlap. However, the decrease in A is more significant and leads to an overall improvement in the radiative efficiency. These recombination rate measurements confirm that if the SRH recombination is controlled, then the severe reduction of radiative recombination with an increased emitting wavelength is one of the main challenges in realizing high efficiency, long-wavelength InGaN-based MQW emitters operating at low to moderate current densities. [ABSTRACT FROM AUTHOR]

Clinical Scenario: Current studies have identified body checking as the most common cause of sports-related concussion in ice hockey across all divisions and levels. As a result, many hockey organizations, particularly in youth sports, have implemented rules making body checking to the head, face, and/or neck illegal. Such a rule, in Canada, makes age 13 the first age in which individuals can engage in body checking. Despite these changes, effectiveness of their implementation on the incidence of concussion in Canadian male youth ice hockey players remains unclear. Clinical Question: What is the effect of body checking policy changes on concussion incidence in male youth ice hockey players? Summary of Key Findings: Of the 3 included studies, 2 studies reported a decrease in the incidence of concussion once a body checking policy change was implemented. The third study showed an increase; however, it is important to note that this may be due, in part, to increased awareness leading to better reporting of injuries. Clinical Bottom Line: Current evidence supports a relationship between body checking policy implementation and decreased concussion incidence; however, more research is needed to understand the long-term implications of policy change and the effects in other leagues. In addition, further data are needed to differentiate between increased concussion incidence resulting from concussion education efforts that may improve disclosure and increased concussion incidence as a direct result of policy changes. Strength of Recommendation: Grade B evidence exists that policy changes regarding body checking decrease concussion incidence in male youth ice hockey players. [ABSTRACT FROM AUTHOR]

The change in electronic state from one spin multiplicity to another, known as intersystem crossing, occurs in molecules via the relativistic phenomenon of spin-orbit coupling. Current means of estimating intersystem crossing rates rely on the perturbative evaluation of spin-orbit coupling effects. This perturbative approach, valid in lighter atoms where spin-orbit coupling is weaker, is expected to break down for heavier elements where relativistic effects become dominant. Methods which incorporate spin-orbit effects variationally, such as the exact-two-component (X2C) method, will be necessary to treat this strong-coupling regime. We present a novel procedure which produces a diabatic basis of spin-pure electronic states coupled by spin-orbit terms, generated from fully variational relativistic calculations. This method is implemented within X2C using time-dependent density-functional theory and is compared to results from a perturbative relativistic study in the weak spin-orbit coupling regime. Additional calculations on a more strongly spin-orbit-coupled [ U O 2 C l 4 ] 2 − complex further illustrate the strengths of this method. This procedure will be valuable in the estimation of intersystem crossing rates within strongly spin-coupled species. [ABSTRACT FROM AUTHOR]

Aims: To (i) assess the population mortality rates of cocaine‐related deaths in Australia, 2000 to 2021; (ii) determine the circumstances of death and case characteristics; and (iii) determine their toxicological profile. Design: Retrospective study of cocaine‐related deaths in Australia, 2000 to 2021, retrieved from the National Coronial Information System. Setting: Australia‐wide. Cases A total of 884 cases, mean age = 33.8 (SD, 10.0) years and 86.5% (n = 765) male. Measurements Information was collected on characteristics, manner of death and toxicology. Only cases in which the presence of blood cocaine and/or metabolites were included. Findings Population rates did not significantly increase during 2001–2011 (annual percentage change [APC] = 1.5; CI, −3.2, 6.5), but from 2012, there was a marked acceleration (APC = 20.0, 95% CI, 15.5, 25.3). Circumstances of death were unintentional drug toxicity (70.7%, n = 625), intentional self‐harm (17.8%, n = 157), traumatic accident (11.5%, n = 102). The proportion of cases constituted by unintentional toxicity declined across the study period (APC = −2.6; CI, −3.1, −2.1). There was a substantial decline in the proportion of cases with a history of injecting drug use (APC = −5.7; CI, −6.5, −4.9) and with a history of substance use problems (APC = −3.2; CI, −3.9, −2.5). Both cocaine (0.100 vs 0.050 mg/L, P < 0.001) and benzoylecgonine (0.590 vs 0.240 mg/L, P < 0.001) concentrations were higher amongst toxicity cases than in cases of death from traumatic injury. Cocaethylene was present in 26.4% (n = 233), levamisole in 18.6% (n = 164) and lignocaine in 11.5% (n = 102). Psychoactive drugs in addition to cocaine were present in 92.9% (n = 821), most commonly opioids (50.5%, n = 446), alcohol (47.1%, n = 416), hypnosedatives (43.2%, n = 382) and psychostimulants (30.3%, n = 268). There was a steady decline in the proportion of opioid positive cases (APC = −5.4; CI, −6.3, −4.5). Conclusions: There was a large increase in cocaine‐related deaths across Australia from 2000 to 2021. This was accompanied by changes in case profiles, with histories of injecting drug use and substance use problems, as well as recent opioid use, becoming less prominent. [ABSTRACT FROM AUTHOR]

Participants can optimize encoding of an immediate verbal memory test for item or for order information, or they can try to be ready for either type of test. Dividing encoding between both kinds of information, however, comes at a cost. Recently, it has been shown that the cost is more severe for order information compared to item information (Guitard et al., 2022). Here, for the first time, we evaluated which factor can better account for this asymmetry by contrasting two hypotheses. According to a rate hypothesis, divided attention affects the rate of encoding more for order than for items. According to an alternative, asymptote hypothesis, divided attention does not affect the rates but diminishes the endpoint, or asymptotic level, of order encoding more than item encoding. In three experiments to distinguish these hypotheses, participants prepared for an item fragment completion test, an order reconstruction test, or both types of tests, in trials with different durations of presentation. Overall, our results were better accounted for by a model which assumes that dividing attention between preparation for item and order testing affects the asymptote of encoding more for order than for items, with no effects on the rates of order or item encoding compared to preparation for a single test. The findings not only replicate our prior results, but also demonstrate that the allocation of attention to item or order processing can be disentangled from the time on task. [ABSTRACT FROM AUTHOR]

Given a geodesic space (E, d), we show that full ordinal information (quadruple comparison of distances) on the metric d determines uniquely—up to a constant factor—the metric d. Moreover, given any sequence { E n } of subsets E n ⊂ E of size n such that E n → E in Hausdorff distance we construct a metric d n on E n from only ordinal information on (E n , d) and prove rates of convergence of (E n , d n) to (E, d) in Gromov–Hausdorff distance. [ABSTRACT FROM AUTHOR]

We derive and analyze a generic, recursive algorithm for estimating all splits in a finite cluster tree as well as the corresponding clusters. We further investigate statistical properties of this generic clustering algorithm when it receives level set estimates from a kernel density estimator. In particular, we derive finite sample guarantees, consistency, rates of convergence, and an adaptive data-driven strategy for choosing the kernel bandwidth. For these results we do not need continuity assumptions on the density such as Hölder continuity, but only require intuitive geometric assumptions of non-parametric nature. In addition, we compare our results to other guarantees found in the literature and also present some experiments comparing our algorithm to k-means and hierarchical clustering. [ABSTRACT FROM AUTHOR]

Fringescale sardinella is one of the largest fishery resources and has the highest economic value in the Savu Sea. The increasing demand for this fish makes it one of the main fishing targets, which allows overfishing to occur. Therefore, the purpose of this study was to determine the population dynamics of sardinella fringescale through growth and mortality, recruitment and exploitation rate of fringescale sardinella in Rote Island in the Savu Sea. A total of 1095 fish sampled from Rote Island were assessed and showed the total length (TL) range from 90 mm to 157 mm. Further, the data were analyzed using FISAT II software with the following results: the length-weight relationship was W= 0.0004L2.2523, while the negative allometric growth pattern and growth equation was Lt = 165.26 (1 - exp1,500 (t + 0.0585)). The age of S. fimbriata consisted of 1-2 cohorts. Recruitment of S. fimbriata in Rote Island occurred throughout the year with the highest peaks in May and August. The size of the first caught fish (Lc) was 96.98 mm TL. The total mortality rate (Z) was 2.41 yr-1, natural mortality (M) was 1.45 yr-1 and fishing mortality (F) was 0.97 yr-1. The exploitation rate of S. fimbriata is estimated at 0.40 yr-1; this implies that the stock does not exceed the optimum exploitation rate (E = 0.5) or that overfishing has not occurred in the Savu Sea. Nevertheless, this study's results are sufficiently robust to anticipate that the unprecedented overexploitation of S. fimbriata in Rote Island has nearly occurred. Therefore, regular monitoring and surveillance of surface gillnet fishing gear are urgently needed. [ABSTRACT FROM AUTHOR]

We present a theory and accompanying importance sampling method for computing rate constants in spatially inhomogeneous systems. Using the relationship between rate constants and path space partition functions, we illustrate that the relative change in the rate of a rare event through space is isomorphic to the calculation of a free energy difference, albeit in a trajectory ensemble. Like equilibrium free energies, relative rate constants can be estimated by importance sampling. An extension to transition path sampling is proposed that combines biased path ensembles and weighted histogram analysis to accomplish this estimate. We show that rate constants can also be decomposed into different contributions, including relative changes in stability, barrier height, and flux. This decomposition provides a means of interpretation and insight into rare processes in complex environments. We verify these ideas with a simple model of diffusion with spatially varying diffusivity and illustrate their utility in a model of ion pair dissociation near an electrochemical interface. [ABSTRACT FROM AUTHOR]

The relative orientation and alignment of colliding molecules plays a key role in determining the rates of chemical processes. Here, we examine in detail a prototypical example: rotational quenching of HD in cold collisions with H2. We show that the rotational quenching rate from j = 2 → 0, in the v = 1 vibrational level, can be maximized by aligning the HD along the collision axis and can be minimized by aligning the HD at the so called magic angle. This follows from quite general helicity considerations and suggests that quenching rates for other similar systems can also be controlled in this manner. [ABSTRACT FROM AUTHOR]

Quasiclassical trajectories are used to compute nonthermal rate constants, k*, for abstraction reactions involving highly-excited methane CH4* and the radicals H, O, OH, and O2. Several temperatures and internal energies of methane, Evib, are considered, and significant nonthermal rate enhancements for large Evib are found. Specifically, when CH4* is internally excited close to its dissociation threshold (Evib ≈ D0 = 104 kcal/mol), its reactivity with H, O, and OH is shown to be collision-rate-limited and to approach that of comparably-sized radicals, such as CH3, with k* > 10−10 cm3 molecule−1 s−1. Rate constants this large are more typically associated with barrierless reactions, and at 1000 K, this represents a nonthermal rate enhancement, k*/k, of more than two orders of magnitude relative to thermal rate constants k. We show that large nonthermal rate constants persist even after significant internal cooling, with k*/k > 10 down to Evib ≈ D0/4. The competition between collisional cooling and nonthermal reactivity is studied using a simple model, and nonthermal reactions are shown to account for up to 35%–50% of the fate of the products of H + CH3 = CH4* under conditions of practical relevance to combustion. Finally, the accuracy of an effective temperature model for estimating k* from k is quantified. [ABSTRACT FROM AUTHOR]

Surface-facilitated, front-propagated softening of glassy materials is now a well-known phenomenon, which is common to stable vapor deposited glasses. As we demonstrate in our recent communication, this softening pathway is not unique to vapor-deposited vitreous phases and can be observed in ordinary melt-cooled glasses in the limit of high heating rates [Cubeta et al., J. Chem. Phys. 147(7), 071101 (2017)]. Expanding on this preliminary report, we use our thin-wire, quasi-adiabatic fast scanning calorimetry technique to investigate softening kinetics of micrometer scale, viscous liquid methylbenzene, and 2-propanol films, which are fully equilibrated at distinct temperatures near the compounds' standard glass hardening transition ranges. Heating of each sample with rates in excess of 105 K·s−1 results in softening kinetics that are well approximated by an Arrhenius temperature function. Remarkably, the apparent activation energy barriers to non-equilibrium, front-propagated softening matches the barriers to near-equilibrium self-diffusivity at the samples' initial temperatures. Furthermore, our analysis also shows an exceptionally strong correlation between the high temperature softening rate and the self-diffusion coefficients at low initial temperatures. Finally, our front softening velocities are also strongly dependent on the samples' initial states, much more so than previously observed. Based on these results, we propose an extended Wilson-Frenkel model of non-equilibrium phase transformations as a general theoretical framework to describe front propagated softening in glassy materials. [ABSTRACT FROM AUTHOR]

In this paper, we will see how an eleven-year-old girl discusses and presents her solution to a problem involving fractions and rates. The readers will be able to watch a video of the girl's presentation of a middle school problem. An analysis of the solution and the presentation is discussed in the context of current mathematics education research. [ABSTRACT FROM AUTHOR]

Objective: To describe the characteristics of offenders found not guilty on the grounds of mental illness (NGMI) in New South Wales and rates of NGMI and other homicide verdicts. Method: Demographic, legal and clinical data after referral to the NSW Mental Health Review Tribunal following an NGMI verdict for homicide matched with results from the National Homicide Monitoring Program. Results: Between 1993 and 2016, a total of 2159 homicide offenders were dealt with by the NSW courts, including 169 (7.8%) who were found NGMI. Over this period, the rate of non-NGMI homicide convictions fell from 1.83 per 100,000 per annum to 0.65 per 100,000 per annum (Kendall's tau = −0.79, p ⩽ 0.001) while the rate of NGMI homicide fluctuated, with an average annual rate of about 0.1 per 100,000 per annum (Kendall's tau = 0.17, p = 0.23). There was no association between the annual rates of NGMI and non-NGMI homicides (Pearson r = −0.3, p = 0.16) but falling rate of non-NGMI homicide meant that the proportion of NGMI offences doubled from 5.5% in the first 12 years to 11% in the second 12 years. Nearly all (88.7%) of those found NGMI had a schizophrenia-related psychosis. However, there were high rates of psychiatric comorbidity including substance use disorder (60.7%) and a history of a prior head injury (41.1%). Most (83.4%) of the NGMI offenders had previous contact with mental health services, but only half of these had received treatment with antipsychotic medication. Conclusion: The fall in conviction for homicide offences in the last 24 years has not been matched by a reduction in NGMI homicide verdicts. More assertive treatment of emerging psychosis and comorbid substance use disorders, and improved continuity of care of chronic psychosis might prevent some homicides. [ABSTRACT FROM AUTHOR]

As one of the malignant tumors with rising incidence, early diagnosis and accurate treatment of liver cancer play a crucial role in improving the cure rate of patients. Alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) are two important tumor markers in the diagnosis of liver cancer. Although antibody analysis methods such as immunoassay have been developed, they are still challenging considering the sensitivity and operating cost. Here, we describe a fluorescent RNA aptamer-based rolling circle transcription (FRA-RCT) test, which can ultra-sensitively and accurately detect the presence of both AFP and CEA target proteins at the same time. The dual-targets sensor integrating the aptamers of AFP and CEA can be protectively bound to the target proteins in advance, while the remaining complements are bound by the trigger chains. Through the in vitro transcription process of FRA-RCT, the amount of the targets is successfully converted to the amount of the remaining triggers and thus amplified into two fluorescent RNA aptamer products. This collection of modular components greatly improves the signal gain and specificity of the FRA-RCT technology. In addition, we have successfully distinguished the positive serum samples of liver cancer patients from the negative healthy controls, and realized the point of care testing (POCT) of different targets by using portable chips. The differential fluorescence output proved its effectiveness and practicability. Therefore, this dual-targets aptamer sensor has a promising prospect in simultaneous cancer diagnosis at low cost and high efficiency. [Display omitted] • A dual-aptamer biosensor was used for ultrasensitive and simultaneous detection of AFP and CEA. • Quantitative analysis of AFP and CEA was achieved by rolling circle transcription amplification based on fluorescent RNA aptamer. • The chip-based FRA-RCT owns advantages of portability, label-free and low-cost. • The assay can effectively meet the requirements of point-of-care diagnosis of AFP and CEA. [ABSTRACT FROM AUTHOR]

• We study the effect of emergency department crowding due to low severity patients. • We unpack welfare implications for high severity patients along their pathway in ED. • We show the slack in capacity by looking at the distribution of unplanned demand. • Emergency departments efficiently prioritise high severity patients. • Care rationing at very high levels of demand explains crowding effects on outcomes. Unexpected peaks in volumes of attendances at hospital emergency departments (EDs) have been found to affect waiting times, intensity of care and outcomes. We ask whether these effects of ED crowding on patients are caused by poor clinical prioritisation or a quality-quantity trade-off generated by a binding capacity constraint. We study the effects of crowding created by lower-severity patients on the outcomes of approximately 13 million higher-severity patients attending the 140 public EDs in England between April 2016 and March 2017. Our identification approach relies on high-dimensional fixed effects to account for planned capacity. Unexpected demand from low-severity patients has very limited effects on the care provided to higher-severity patients throughout their entire pathway in ED. Detrimental effects of crowding caused by low-severity patients materialise only at very high levels of unexpected demand, suggesting that binding resource constraints impact patient care only when demand greatly exceeds the ED's expectations. These effects are smaller than those caused by crowding induced by higher-severity patients, suggesting an efficient prioritisation of incoming patients in EDs. [ABSTRACT FROM AUTHOR]

Background: Safety data reported from the large-scale clinical trials of the coronavirus disease 2019 (COVID-19) vaccine are extremely limited in patients with decompensated cirrhosis. The vaccination campaign in this specific population could be difficult due to uncertainty about the adverse events following vaccination. We aimed to assessed the COVID-19 vaccination rate, factors associated with unvaccinated status, and the adverse events following vaccination in patients with decompensated cirrhosis. Methods: This is a retrospective study from Ruijin Hospial (Shanghai, China) on an ongoing prospective cohort designed for long-term survival analysis of decompensated cirrhotic patients who recovered from decompensating events or acute-on-chronic liver failure (ACLF) between 2016 and 2018. We assessed the COVID-19 vaccination rate, the number of doses, type of vaccine, safety data, patient-reported reasons for remaining unvaccinated, factors associated with unvaccinated status, and the adverse events of COVID-19 vaccine. Binary logistic regression was used for identifying factors associated with unvaccinated status. Results: A total of 229 patients with decompensated cirrhosis without previous SARS-CoV-2 infection participated (mean age, 56 ± 12.2 years, 75% male, 65% viral-related cirrhosis). Mode of decompensation were grade II‒III ascites (82.5%), gastroesophageal varices bleeding (7.9%), hepatic encephalopathy (7.9%). Eighty-five participants (37.1%) received at least one dose of vaccination (1 dose: n = 1, 2 doses: n = 65, 3 doses: n = 19) while 62.9% remained unvaccinated. Patient-reported reasons for remaining unvaccinated were mainly fear of adverse events (37.5%) and lack of positive advice from healthcare providers (52.1%). The experience of hepatic encephalopathy (OR = 5.61, 95% CI: 1.24–25.4) or ACLF (OR = 3.13, 95% CI: 1.12–8.69) and post-liver transplantation status (OR = 2.47, 95% CI: 1.06–5.76) were risk factors of remaining unvaccinated independent of residential areas. The safety analysis demonstrated that 75.3% had no adverse events, 23.6% had non-severe reactions (20% injection-site pain, 1.2% fatigue, 2.4% rash) and 1.2% had a severe event (development of acute decompensation requiring hospitalization). Conclusions: Patients with decompensated cirrhosis in eastern China are largely remained at unvaccinated status, particularly those with previous episodes of ACLF or hepatic encephalopathy and liver transplantation recipients. Vaccination against COVID-19 in this population is safe. [ABSTRACT FROM AUTHOR]

Academic and government research regarding the affordability of household drinking water and sewer utility (water utility) costs have resulted in the development of several methodologies that have been tested at various geographic levels. A New Jersey study on potential household affordability stresses from water utility costs at or below the Census tract‐level estimates that approximately one‐fifth of all New Jersey households could face affordability stresses, assuming that they directly pay all water utility costs. The methodology is adapted from the Affordability Ratio method of Teodoro. The results show the potential for use of county‐level household essential expenditure estimates in areas with high‐density populations. They also show the value of the methodology as a basis for policy discussions regarding the severity and geographic distribution of affordability stresses, as the analysis clearly indicates that significant affordability stresses exist in many suburban municipalities and rural town centers, not just historic urban cities. [ABSTRACT FROM AUTHOR]

Microbial communities often face external perturbations that can induce lasting changes in their composition and functions. Our understanding of how multispecies communities respond to perturbations such as antibiotics is limited, with susceptibility assays performed on individual, isolated species our primary guide in predicting community transitions. Here, we studied how bacterial growth dynamics can overcome differences in antibiotic susceptibility in determining community resilience: the recovery of the original community state following antibiotic exposure. We used an experimental community containing Corynebacterium ammoniagenes and Lactobacillus plantarum that displays two alternative stable states as a result of mutual inhibition. Although C. ammoniagenes was more susceptible to chloramphenicol in monocultures, we found that chloramphenicol exposure nonetheless led to a transition from the L. plantarumdominated to the C. ammoniagenes-dominated community state. Combining theory and experiments, we demonstrated that growth rate differences between the two species made the L. plantarum-dominated community less resilient to several antibiotics with different mechanisms of action. Taking advantage of an observed cooperativity--a dependence on population abundance--in the growth of C. ammoniagenes, we next analyzed in silico scenarios that could compromise the high resilience of the C. ammoniagenes-dominated state. The model predicted that lowering the dispersal rate, through interacting with the growth at low population densities, could make the C. ammoniagenes state fragile against virtually any kind of antibiotic, a prediction that we confirmed experimentally. Our results highlight that species susceptibility to antibiotics is often uninformative of community resilience, as growth dynamics in the wake of antibiotic exposure can play a dominant role. [ABSTRACT FROM AUTHOR]

The paper covers the research into the productivity of sorghum (Sorghum bicolor (L.) Moench) grain for its widest use: nutrition, fodder for animals, and as a bioenergy crop, depending on the rates of mineral fertilisation. The purpose of the experiment was to analyse the effect of the fertiliser rates on the productivity of sorghum grain, its biofuel output, and energy received from it. The following methods were used: the field method, to investigate biological and ecological features of growth and development of the crop productivity and quality; the laboratory method, to determine the correlation between the crop and the environment (plant and soil analysis); the generalised method, to identify common properties and features. The application of fertilisers improved the quality of sorghum grain considerably: protein and fat content increased from 9.7% to 12.4% and from 3.37% to 3.62%, respectively; with higher fertiliser rates, starch content increased from 67.1% to 70.1% for cultivar 'Dniprovskyi 39' and from 65.8% to 68.8% for cultivar 'Vinets'. Compared with the control treatment (without fertilisers) and under the effect fertiliser rates, grain yield capacity and above-ground mass increased. In the case of 'Dniprovskyi 39', at fertiliser rates N90P90K90, N120P120K120 and estimated rate of N50P40K70, grain yield capacity increased reliably, compared with the control treatment, and it amounted to 7.1, 7.9, and 7.3 tha-1; grain yield capacity of 'Vinets' was 7.2, 7.8 and 7.0 tha-1, respectively. Biomass yield capacity of 'Dniprovskyi 39' and 'Vinets' increased reliably only at the highest and estimated fertiliser rates. When 'Dniprovskyi 39' was grown, the highest total energy output was equal to 181.0 and 187.8 GJ ha-1; this indicator was 169.8 and 178.3 GJ ha-1 for 'Vinets'. This was due to the estimated and maximal fertiliser rates. More than 80% of this energy is concentrated in solid biofuel and only 20% in bio-ethanol. The decrease in fertiliser rates led to a lower energy output of 1 ha. [ABSTRACT FROM AUTHOR]

This study uses an embedded survey experiment to evaluate the effects of issue framing on willingness to pay water and sewer rate increases. Government‐owned utilities require public support for financial resources, and so managers must communicate the value of their services to their customers. Water and wastewater utilities provide several benefits; little systematic evidence exists on which resonate with the public. In this study, respondents in a U.S. national survey were randomly assigned to one of four framing treatments in a question about support for a hypothetical rate increase: reduced pollution, safer drinking water, better tasting drinking water, and low‐income affordability. Compared with the other treatments, the safer drinking water framing yielded 11.2% greater average willingness to pay a rate increase. Multivariate analysis shows that Republican partisans and women responded especially positively to safe drinking water framing. Results have important implications for utilities' outreach and public communications efforts. [ABSTRACT FROM AUTHOR]

Background: Clostridioides difficile infection (CDI) frequently complicates allogeneic hematopoietic stem cell (allo‐HCT) and solid organ transplantation (SOT). Methods: We retrospectively analyzed risk factors and outcomes of CDI occurring within 30 days of transplant. Results: Between March 2010 and June 2015, 466 allo‐HCT and 1454 SOT were performed. The CDI cumulative incidence (95% CI) was 10% (8–13) and 4% (3–5), following allo‐HCT and SOT, respectively (p <.01), occurring at a median (range) 7.5 days (1–30) and 11 (1–30), respectively (p =.18). In multivariate analysis, fluoroquinolones use within 14 days pre‐transplantation was a risk factor for CDI following allo‐HCT (HR 4.06 [95% CI 1.31–12.63], p =.02), and thoracic organ(s) transplantation was a risk factor for CDI following SOT (HR 3.03 [95% CI 1.31–6.98]) for lung and 3.90 (1.58–9.63) for heart and heart/kidney transplant, p =.02. Compared with no‐CDI patients, the length of stay (LOS) was prolonged in both allo‐HCT (35 days [19–141] vs. 29 [13–164], p <.01) and SOT with CDI (16.5 [4–101] vs. 7 [0–159], p <.01), though not directly attributed to CDI. In allo‐HCT, severe acute graft‐versus‐host disease (aGVHD) occurred more frequently in patients with CDI (33.3% vs. 15.8% without CDI, p =.01) and most aGVHD (87.5%) followed CDI. Non‐relapse mortality or overall survival, not attributed to CDI, were also similar in both allo‐HCT and SOT. Conclusions: Early post‐transplant CDI is frequent, associated with fluoroquinolones use in allo‐HCT and the transplanted organ in SOT, and is associated with longer LOS in both the groups without difference in survival but with increased aGVHD in allo‐HCT. [ABSTRACT FROM AUTHOR]

Anaerobic microbial respiration in suboxic and anoxic environments often involves particulate ferric iron (oxyhydr-)oxides as terminal electron acceptors. To ensure efficient respiration, a widespread strategy among iron-reducing microorganisms is the use of extracellular electron shuttles (EES) that transfer two electrons from the microbial cell to the iron oxide surface. Yet, a fundamental understanding of how EES-oxide redox thermodynamics affect rates of iron oxide reduction remains elusive. Attempts to rationalize these rates for different EES, solution pH, and iron oxides on the basis of the underlying reaction free energy of the two-electron transfer were unsuccessful. Here, we demonstrate that broadly varying reduction rates determined in this work for different iron oxides and EES at varying solution chemistry as well as previously published data can be reconciled when these rates are instead related to the free energy of the less exergonic (or even endergonic) first of the two electron transfers from the fully, two-electron reduced EES to ferric iron oxide. We show how free energy relationships aid in identifying controls on microbial iron oxide reduction by EES, thereby advancing a more fundamental understanding of anaerobic respiration using iron oxides. [ABSTRACT FROM AUTHOR]