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Background: This study aims to identify factors associated with disparities in receipt and outcomes of surgical interventions in patients with primary nonmetastatic liver cancers., Methods: Cases from 2010 to 2020 were identified using Louisiana Tumor Registry. Four surgical categories were utilized: none, ablation, resection, transplant. Bivariate relationships were assessed via Chi-square tests. Overall survival (OS) was visualized using Kaplan Meier plots, compared via log-rank test, and analyzed with Cox proportional hazards models., Results: Only 24.5 ​% of patients underwent surgical interventions. Black race had decreased odds of undergoing transplant and decreased OS with transplant. Uninsured, Medicaid, and rural residence had decreased odds of receiving surgical intervention. Older age and no domestic partner had decreased odds of transplant. Older age, male sex, no domestic partner, and rural residence had decreased OS post-transplant., Conclusions: Identifying the population at risk for not receiving surgical intervention and allocating resources to access care is crucial to improve outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare the work described has not been published previously and the article is not under consideration for publication elsewhere. The article's publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out. If accepted, the article will not be published elsewhere in the same form, in English or any other language, including electronically without the written consent of the copyright-holder. The authors declare they have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths. In recent years, the approach to managing this malignancy has evolved toward embracing neoadjuvant treatment (NAT), backed by studies reporting its survival benefit. This study aimed to identify factors that contribute to disparities in NAT utilization and their impact on outcomes in patients with PDAC who underwent resection in Louisiana., Methods: Data on diagnosed PDAC cases were obtained from the Louisiana Tumor Registry between 2000 and 2020. We conducted multivariable logistic regression to adjust for potential confounding factors in assessing the covariate relationships with NAT use. Multivariate Cox regression analysis was performed to determine which factors were associated with survival. Chained multiple imputation was performed on covariates with missing data in multivariable regressions., Results: The study encompassed 2121 patients who underwent resection for PDAC. Upon controlling for potential confounding variables, Black patients were on average 5.7% less likely to receive NAT than their White counterparts (ATE = 5.7, aOR= 0.56, 95% CI = 0.40-0.80, p = 0.001). After adjustment for confounding factors, there was a significant decrease in the risk of overall death for patients who received NAT (aHR = 0.82, 95% CI = 0.71-0.94, p = 0.006). There was no significant interaction between race and NAT for the risk of death., Conclusion: Black patients with PDAC were less likely to receive NAT before resection in Louisiana. Overall survival improved in patients who underwent NAT. These differences were independent of insurance status and poverty zip codes, and future investigations should identify modifiable barriers to access and receipt of NAT in patients with PDAC., (© 2024 Wiley Periodicals LLC.)

This work looks at the effects of a varying concentration, soak time, pH and temperature on the sorption of tetraammineplatinum(II) chloride (Pt-Ammine) in Nafion-117 films in the context of the electroless plating of ionic polymer-metal composites (IPMCs). Sorption is characterised by atomic absorption spectroscopy. A definitive screening design carried out determined all four factors to be significant for further analysis using response surface modelling. A duplicated central composite design (CCD) was utilised to characterise how the four factors affect the sorption amount and efficiency. Regression models for both responses were of poor fit. Nevertheless, key insights were obtained on the effects of the process parameters on sorption behaviour. The results indicate that above 0.5 g/L Pt-Ammine sorption, the platinisation of 10 × 50 mm IPMC samples through sodium borohydride reduction becomes redundant by the surface resistance metric. IPMCs with surface resistance values of approximately 2.5 Ω/square were obtained through only one round of chemical reduction. Varying surface morphologies and electrode thicknesses were analysed under a scanning electron microscope. The CCD parameter settings were validated. Recommended settings for optimised Pt-Ammine sorption in 10 × 50 mm Nafion-117 films were identified as follows: 1.0 g/L Pt-Ammine concentration, 24 h soak time, pH of 3 and temperature of 20 °C.

Children and adolescents with serious emotional disturbance represent 7-12 percent of all youth in the United States. In 2017, the State of Idaho implemented the Youth Empowerment Service program, which allows youth with serious emotional disturbance who are younger than age eighteen living in households with income up to 300 percent of the federal poverty level to qualify for Medicaid and receive intensive, community-based treatment. A uniquely detailed method was used to assess the need for services: the Child and Adolescent Needs and Strengths tool, a ninety-seven-indicator instrument administered by a clinician. We used these indicators and Idaho's 2018-22 administrative Medicaid claims data to study the association between children and adolescents' clinical needs complexity and their actual Medicaid behavioral and mental health service use. Our findings show that there was a substantial proportion of youth who were underusing Medicaid behavioral and mental health care services, and there were virtually no overusers. Our findings have implications for the appropriateness of Medicaid utilization management in behavioral health care and program efforts to maintain families with youth having serious emotional disturbance in the Youth Empowerment Service program.

While semiconductor nanocrystals provide versatile fluorescent materials for light-emitting devices, their brightness suffers from the "dark exciton"─an optically inactive electronic state into which nanocrystals relax before emitting. Recently, a theoretical mechanism, the Rashba effect, was discovered that can overcome this limitation by inverting the lowest-lying levels and creating a bright excitonic ground state. However, no methodology is available to systematically identify materials that exhibit this inversion, hindering the development of superbright nanocrystals and their devices. Here, based on a detailed understanding of the Rashba mechanism, we demonstrate a procedure that reveals previously unknown "bright-exciton" nanocrystals. We first define physical criteria to reduce over 500,000 known solids to 173 targets. Higher-level first-principles calculations then refine this list to 28 candidates. From these, we select five with high oscillator strength and develop effective-mass models to determine the nature of their lowest excitonic state. We confirm that four of the five solids yield bright ground-state excitons in nanocrystals. Thus, our results provide a badly needed roadmap for experimental investigation of bright-exciton nanomaterials.

This study presents a rare case of pure choriocarcinoma (PCC) with metastasis to the gastrointestinal tract in a 52-year-old male with a history of mixed germ cell tumor in remission. Despite negative oncology surveillance imaging, serum marker monitoring, and a recent colonoscopy, the patient presented with new-onset melena and dysphagia, leading to further diagnostic evaluation. Endoscopic examination revealed an ulcerated duodenal mass, and a computer tomography (CT)-guided liver biopsy confirmed metastatic PCC. This case highlights the aggressive nature of PCC and the importance of considering gastrointestinal metastasis in patients with atypical symptoms, even when in apparent remission., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Aujla et al.)

Programmed cell death mechanisms are important for the regulation of tumor development and progression. Evasion of and resistance to apoptosis are significant factors in tumorigenesis and drug resistance. Bypassing apoptotic pathways and eliciting another form of regulated cell death, namely necroptosis, an immunogenic cell death (ICD), may override apoptotic resistance. Here, we present the mechanistic rationale for combining tolinapant, an antagonist of the inhibitor of apoptosis proteins (IAP), with decitabine, a hypomethylating agent (HMA), in T-cell lymphoma (TCL). Tolinapant treatment alone of TCL cells in vitro and in syngeneic in vivo models demonstrated that ICD markers can be upregulated, and we have shown that epigenetic priming with decitabine further enhances this effect. The clinical relevance of ICD markers was confirmed by the direct measurement of plasma proteins from patients with peripheral TCL treated with tolinapant. We showed increased levels of necroptosis in TCL lines, along with the expression of cancer-specific antigens (such as cancer testis antigens) and increases in genes involved in IFN signaling induced by HMA treatment, together deliver a strong adaptive immune response to the tumor. These results highlight the potential of a decitabine and tolinapant combination for TCL and could lead to clinical evaluation., Significance: The IAP antagonist tolinapant can induce necroptosis, a key immune-activating event, in TCL. Combination with DNA hypomethylation enhances tolinapant sensitivity and primes resistant cells by re-expressing necrosome proteins. In addition, this combination leads to increases in genes involved in IFN signaling and neoantigen expression, providing further molecular rationale for this novel therapeutic option., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Background: Complex social determinants of health may not be easily recognized by health care providers and pose a unique challenge in the vulnerable pediatric population where patients may not be able to advocate for themselves. The goal of this study was to examine the acceptability and feasibility of health care providers using an integrated brief pediatric screening tool in primary care and hospital settings., Methods: The framework of the Child and Adolescent Needs and Strengths (CANS) and Pediatric Intermed tools was used to inform the selection of items for the 9-item Child and Adolescent Needs and Strengths-Pediatric Complexity Indicator (CANS-PCI). The tool consisted of three domains: biological, psychological, and social. Semi-structured interviews were conducted with health care providers in pediatric medical facilities in Ottawa, Canada. A low inference and iterative thematic synthesis approach was used to analyze the qualitative interview data specific to acceptability and feasibility., Results: Thirteen health care providers participated in interviews. Six overarching themes were identified: acceptability, logistics, feasibility, pros/cons, risk, and privacy. Overall, participants agreed that a routine, trained provider-led pediatric tool for the screening of social determinants of health is important (n = 10, 76.9%), acceptable (n = 11; 84.6%), and feasible (n = 7, 53.8%)., Interpretation: Though the importance of social determinants of health are widely recognized, there are limited systematic methods of assessing, describing, and communicating amongst health care providers about the biomedical and psychosocial complexities of pediatric patients. Based on this study's findings, implementation of a brief provider-led screening tool into pediatric care practices may contribute to this gap., (© 2024. The Author(s).)

Background: The COVID-19 pandemic has placed an unprecedented strain on the US healthcare system, greatly impacting transplant centers. Objective: The purpose of this survey was to evaluate the impact of the COVID-19 pandemic on the transplant pharmacist workforce. Methods: A survey was disseminated electronically to assess the impact of the COVID-19 pandemic on the transplant pharmacist workforce. Respondents were asked to give background regarding transplant center, patient, population, and departmental staffing. Results: There were 67 total respondents from 56 transplant centers. In response to the COVID-19 pandemic, 55% of centers reported stopping non-life saving transplants, and a majority (89%) stopped living donor transplants altogether. The banning of caregivers on-site during education, reduction of bedside education teaching, and cancelling of group teaching classes occurred at 46%, 40%, and 22% of centers, respectively. Consequently, 42% of pharmacists surveyed felt that their confidence in patient and caregiver's understanding of medications had decreased since these changes have been implemented. Conclusions: Pharmacist perception of patient and caregiver understanding of transplant medications has decreased since before the COVID-19 pandemic. As health systems strategize resource allocation throughout the pandemic, the importance of patient education must be prioritized to sustain and improve transplant outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Ultramassive transfusion (UMT) is a resource-demanding intervention for trauma patients in hemorrhagic shock, and associated mortality rates remains high. Current research has been unable to identify a transfusion ceiling or point where UMT transitions from lifesaving to futility. Furthermore, little consideration has been given to how time-specific patient data points impact decisions with ongoing high-volume resuscitation. Therefore, this study sought to use time-specific machine learning modeling to predict mortality and identify parameters associated with survivability in trauma patients undergoing UMT., Methods: A retrospective review was conducted at a Level I trauma (2018-2021) and included trauma patients meeting criteria for UMT, defined as ≥20 red blood cell products within 24 hours of admission. Cross-sectional data were obtained from the blood bank and trauma registries, and time-specific data were obtained from the electronic medical record. Time-specific decision-tree models predicating mortality were generated and evaluated using area under the curve., Results: In the 180 patients included, mortality rate was 40.5% at 48 hours and 52.2% overall. The deceased received significantly more blood products with a median of 71.5 total units compared with 55.5 in the survivors ( p < 0.001) and significantly greater rates of packed red blood cells and fresh frozen plasma at each time interval. Time-specific decision-tree models predicted mortality with an accuracy as high as 81%. In the early time intervals, hemodynamic stability, undergoing an emergency department thoracotomy, and injury severity were most predictive of survival, while, in the later intervals, markers of adequate resuscitation such as arterial pH and lactate level became more prominent., Conclusion: This study supports that the decision of "when to stop" in UMT resuscitation is not based exclusively on the number of units transfused but rather the complex integration of patient and time-specific data. Machine learning is an effective tool to investigate this concept, and further research is needed to refine and validate these time-specific decision-tree models., Level of Evidence: Prognostic and Epidemiological; Level IV., (Copyright © 2023 American Association for the Surgery of Trauma.)

Cell death proteins play a central role in host immune signaling during sepsis. These interconnected mechanisms trigger cell demise via apoptosis, necroptosis, and pyroptosis while also driving inflammatory signaling. Targeting cell death mediators with novel therapies may correct the dysregulated inflammation seen during sepsis and improve outcomes for septic patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Coopersmith and Lyons.)

A major shortcoming of ultrawide-bandgap (UWBG) semiconductors is unipolar doping, in which either n -type or p -type conductivity is typically possible, but not both within the same material. For UWBG oxides, the issue is usually the p -type conductivity, which is inhibited by a strong tendency to form self-trapped holes (small polarons) in the material. Recently, rutile germanium oxide (r-GeO 2 ), with a band gap near 4.7 eV, was identified as a material that might break this paradigm. However, the predicted acceptor ionization energies are still relatively high (∼0.4 eV), limiting p -type conductivity. To assess whether r-GeO 2 is an outlier due to its crystal structure, the properties of a set of rutile oxides are calculated and compared. Hybrid density functional calculations indicate that rutile TiO 2 and SnO 2 strongly trap holes at acceptor impurities, consistent with previous work. Self-trapped holes are found to be unstable in r-SiO 2 , a metastable polymorph that has a band gap near 8.5 eV. Group-III acceptor ionization energies are also found to be lowest among the rutile oxides and approach those of GaN. Acceptor impurities have sufficiently low formation energies to not be compensated by donors such as oxygen vacancies, at least under O-rich limit conditions. Based on the results, it appears that r-SiO 2 has the potential to exhibit the most efficient p -type conductivity when compared to other UWBG oxides., (Creative Commons Attribution license.)

Background: Children less than five years of age comprised approximately 30% in 2020 of foster care entries in the United States, and they are consistently the largest foster care entry group. Very young children can respond differently to the same adverse life events. Detection of complex interpersonal traumas is core to providing appropriate interventions and prevention of reoccurring negative outcomes in these children., Methods: Children who (1) were identified as having experienced complex interpersonal trauma, but (2) who did not have traumatic stress symptoms were identified using Child and Adolescent Needs and Strengths data in a large midwestern state from 2010 to 2021. A logistic model was fit to determine the effect of cumulative traumatic exposures (e.g., adverse childhood experiences such that increased events were hypothesized to predict an increased likelihood of symptomatic detection. We conducted a latent class analysis to understand the relationship between traumatic experiences, asset-based factors, and the detection of traumatic stress in children aged five years and under who had exposure to traumatic events but did not have detectable traumatic stress symptoms., Results: We detected three classes within this population of very young children, who were described as "resilient" (demonstrating asset-based resilience when faced with traumatic experiences), "missed" (those who exhibit behavioral and mental health types like those with detected traumatic stress symptoms but who were not detected as such), and "unfolding". Very young children do demonstrate asset-based resilience when faced with traumatic experiences., Conclusions: Detection of traumatic stress may be more difficult in young children. It is important to assess both traumatic stress and strengths to ensure that children who are resilient after exposure to traumatic experiences (i.e., do not demonstrate traumatic stress symptoms) are not referred to unnecessary interventions. Additional educational approaches are needed to help caseworkers identify symptoms of traumatic stress that mirror symptoms of other behavioral and emotional challenges. Precision medicine approaches are required to best match the interventions to specific needs of young children. Recognition of resilience in very young children is critical for designing systems that customize approaches of trauma-informed care., (© 2023. The Author(s).)

Introduction: The increased threat of natural disasters makes understanding the relationship between community resources and children's mental health critical. Mental health care efficacy and access are crucial to assessing the quality of community mental health care availability., Objectives: The primary objective of this scoping review is to investigate the relationship between children's mental health and community mental health resource efficacy and accessibility after a major disaster., Methods: Conducted a systematic search to identify epidemiologic and health service utilization studies assessing the relationship between disasters and subsequent health service utilization amongst children and adolescents., Results: The research returned 1682 potentially relevant studies and 31 articles were selected based on identified criteria from pre-selected databases., Conclusion: The studies conclude a gender and age-based disparity in access and efficiency of children's mental health services. The studies also identify the need for greater resource distribution and organizational structure.

Understanding and addressing the impact of adverse life events is an important priority in the design of helping systems. However, creating trauma-informed systems requires efforts to embed effective trauma-informed work in routine practice. This article discusses a model for developing trauma-informed systems using the Transformational Collaborative Outcomes Management (TCOM) framework, a strategy for engineering person-centered care. Person-centered care is naturally congruent with trauma-informed care. We describe the initial stages of implementation of a trauma-informed standardized assessment process to support the sustained evolution of trauma-informed care. Distinguishing between traumatic experiences and traumatic stress is fundamental to an effective trauma-informed system. We describe two sets of analyses-one in a statewide child welfare system and the other in a statewide behavioral health system. These projects found opportunities in the analysis of the detection of traumatic stress based on traumatic experiences to inform practice and policy. Being trauma-informed in child welfare is distinct from being trauma-informed in behavioral health. In child welfare, it appears that a number of children are resilient in the face of traumatic experiences and do not require trauma treatment interventions. However, delayed and missed traumatic stress responses are common. In behavioral health, misses often occur among adolescents, particularly boys, who engage in acting out behavior. Opportunities for the ongoing development of trauma-informed systems using the TCOM framework are discussed., Competing Interests: JL is the president of the Praed Foundation. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lyons and Fernando.)

Hepatocellular carcinoma (HCC) is a male-dominated disease. Currently, gender differences remain incompletely defined. Data from the state tumor registry were used to investigate differences in demographics, comorbidities, treatment patterns, and cancer-specific survival (HSS) among HCC patients according to gender. Additional analyses were performed to evaluate racial differences among women with HCC. 2627 patients with HCC were included; 498 (19%) were women. Women were mostly white (58%) or African American (39%)-only 3.8% were of another or unknown race. Women were older (65.1 vs. 61.3 years), more obese (33.7% vs. 24.2%), and diagnosed at an earlier stage (31.7% vs. 28.4%) than men. Women had a lower incidence of liver associated comorbidities (36.1% vs. 43%), and more often underwent liver-directed surgery (LDS; 27.5% vs. 22%). When controlling for LDS, no survival differences were observed between genders. African American women had similar HSS rates compared to white women (HR 1.14 (0.91,1.41), p = 0.239) despite having different residential and treatment geographical distributions. African American race and age >65 were predictive for worse HSS in men, but not in women. Overall, women with HCC undergo more treatment options-likely because of the earlier stage of the cancer and/or less severe underlying liver disease. However, when controlling for similar stages and treatments, HCC treatment outcomes were similar between men and women. African American race did not appear to influence outcomes among women with HCC as it did in men.

Objectives: Minimally invasive esophagectomy is a technically challenging procedure that been associated with better outcomes at high-volume tertiary care centers. Louisiana is one of the most impoverished states, and travel to a "destination center" is not an option for many patients. We hypothesize that patients can obtain excellent surgical outcomes following MIE in a comprehensive community cancer center., Methods: We identified all patients who underwent totally robotic MIE by a single surgeon at our center from July 2018 to November 2020. All cases were performed using totally robotic Ivor Lewis technique with intrathoracic isoperistaltic esophagogastrostomy. Incidence, demographics, treatment, and outcomes were compared before and after first 10 cases using Student's t-test., Results: We identified 21 patients: 16 male and 5 female. Mean age 65 (49-85). 19 patients underwent MIE for malignancy; 18 of these received neoadjuvant therapy. OR time decreased following the first 10 cases (502 vs. 408 minutes, P = 0.0127). Average lymph node harvest was 14 (4-23 nodes). Positive margin rate was 0%. Mean length of stay trended towards a decrease after the first 10 cases (11 vs. 9 days, P = NS). There were no leaks or strictures. Thirty-day readmission was five patients. Ninety-day mortality was 0%., Conclusion: These outcomes rival those of high-volume referral centers and demonstrate that totally robotic MIE can be performed with excellent outcomes in community center. These data call into question the need for all patients to travel to "destination centers" to receive complex oncologic surgery.

Objective: The authors quantified the impact of the use of telehealth services on patient-level clinical outcomes among children with complex behavioral and emotional needs in Idaho during the COVID-19 pandemic by comparing data collected in 2020 with data for the same months in 2019., Methods: Longitudinal statewide data of Child and Adolescent Needs and Strengths (CANS) assessments were extracted from Idaho's mental and behavioral health system. Prepandemic assessments were matched to midpandemic assessments. A linear mixed-effect model was used to explore four child-level outcomes: psychosocial strengths-building rate, rate of need resolution within a life-functioning domain, rate of need resolution within a behavior-emotional domain, and rate of need resolution within a high-risk behaviors domain., Results: The number of new patients admitted to Idaho's state-funded mental and behavioral health program decreased almost twofold from April-December 2019 to April-December 2020 (N=4,458 vs. 2,794). For most children with complex needs, the use of telehealth was as effective in terms of strengths building and needs resolution as in-person services; for children whose caregivers had issues with access to transportation, availability of telehealth services improved outcomes for the children., Conclusions: The COVID-19 pandemic in 2020 was associated with a dramatic drop in the number of children served by Idaho's mental health program. Telehealth may effectively bridge mental health service delivery while patients and providers work toward the resolution of transportation issues or may serve as a more acceptable permanent format of service delivery for some populations.

The overexpression of inhibitor of apoptosis (IAP) proteins is strongly related to poor survival of women with ovarian cancer. Recurrent ovarian cancers resist apoptosis due to the dysregulation of IAP proteins. Mechanistically, Second Mitochondrial Activator of Caspases (SMAC) mimetics suppress the functions of IAP proteins to restore apoptotic pathways resulting in tumor death. We previously conducted a phase 2 clinical trial of the single-agent SMAC mimetic birinapant and observed minimal drug response in women with recurrent ovarian cancer despite demonstrating on-target activity. Accordingly, we performed a high-throughput screening matrix to identify synergistic drug combinations with birinapant. SMAC mimetics in combination with an HDAC inhibitor showed remarkable synergy and was, therefore, selected for further evaluation. We show here that this synergy observed both in vitro and in vivo results from multiple convergent pathways to include increased caspase activation, HDAC inhibitor-mediated TNF-α upregulation, and alternative NF-kB signaling. These findings provide a rationale for the integration of SMAC mimetics and HDAC inhibitors in clinical trials for recurrent ovarian cancer where treatment options are still limited.

RIPK3 (receptor-interacting protein kinase 3) activity triggers cell death via necroptosis, whereas scaffold function supports protein binding and cytokine production. To determine if RIPK3 kinase or scaffold domains mediate pathology during Pseudomonas aeruginosa infection, control mice and those with deletion or mutation of RIPK3 and associated signaling partners were subjected to Pseudomonas pneumonia and followed for survival or killed for biologic assays. Murine immune cells were studied in vitro for Pseudomonas -induced cytokine production and cell death, and RIPK3 binding interactions were blocked with the viral inhibitor M45. Human tissue effects were assayed by infecting airway epithelial cells with Pseudomonas and measuring cytokine production after siRNA inhibition of RIPK3. Deletion of RIPK3 reduced inflammation and decreased animal mortality after Pseudomonas pneumonia. RIPK3 kinase inactivation did neither. In cell culture, RIPK3 was dispensable for cell killing by Pseudomonas and instead drove cytokine production that required the RIPK3 scaffold domain but not kinase activity. Blocking the RIP homotypic interaction motif (RHIM) with M45 reduced the inflammatory response to infection in vitro . Similarly, siRNA knockdown of RIPK3 decreased infection-triggered inflammation in human airway epithelial cells. Thus, the RIPK3 scaffold drives deleterious pulmonary inflammation and mortality in a relevant clinical model of Pseudomonas pneumonia. This process is distinct from kinase-mediated necroptosis, requiring only the RIPK3 RHIM. Inhibition of RHIM signaling is a potential strategy to reduce lung inflammation during infection.

Palliative care services (PCS) have improved quality of life for patients across various cancer subtypes. Minimal data exists regarding PCSfor metastatic hepatopancreaticobiliary (HPB) and gastrointestinal (GI) cancers. We assessed the impact of PCS on emergency department visits, hospital admissions, and survival among these patients. Patients with metastatic HPB and GI cancer referred to outpatient PCS between 2014 and 2018 at a single institution were included. We compared the demographics, outcomes, and end-of-life indicators between those who did and did not receive PCS. The study included 183 patients, with 118 (64.5%) having received PCS. There were no significant differences in age, gender, race, marital status, or insurance. Those receiving PCS were more likely to have colorectal cancer (p = 0.0082) and receive chemotherapy (p = 0.0098). On multivariate analysis, PCS was associated with fewer ED visits (p = 0.0319), hospital admissions (p = 0.0002), and total inpatient hospital days (p < 0.0001) per 30 days of life. Overall survival was greater among patients receiving PCS (HR: 0.65 (0.46-0.92)). Outpatient PCS for patients with metastatic HPB and GI cancer is associated with fewer emergency department visits, hospital admissions, and inpatient hospital days, and improved overall survival., (© 2022. The Author(s).)

Background: Efforts have been concentrated on improving vaccination administration during the pretransplant evaluation period. However, concern for human leukocyte antigen (HLA) sensitization subsequent to vaccination exists., Methods: A retrospective review of pediatric kidney transplant candidates (PKTCs) ≤18 years old who had received vaccinations between February 1, 2017 and November 30, 2019 was conducted. Emergence of de novo anti-HLA antibody (HLA-Ab) 3-4 weeks postvaccinations detected by the Luminex single antigen bead assay (SAB) was evaluated. Outcomes assessed included change in the HLA-Ab mean fluorescence intensity (MFI) ≥25% from baseline, and change in preexisting HLA-Ab MFI strength, categorized as weak: 1000-2999; moderate: 3000-9999; and strong: ≥10 000., Results: Sixty vaccinations were administered to 14 patients. Forty-one potential de novo HLA-Ab were detected in five patients. After additional antibody panel testing, 5/41 potential de novo HLA-Ab were determined to be HLA specific; the remaining 36 were deemed nonspecific. The 5 de novo HLA-Ab were observed in three patients and were deemed weak antibody (Ab). Median MFI showed a significant increase for nonspecific Ab, but not de novo HLA-Ab. Median MFI values were deemed transient at 7-10 week follow-up. No HLA-donor-specific Ab developed posttransplant in the patients who developed de novo HLA-Ab., Conclusion: Vaccination resulted in a transient increase in non-HLA-specific Ab. The majority of responses were non-HLA specific, hypothesized to be related to denatured antigens on single antigen beads. These data suggest limited clinical impact of vaccinations on the emergence of de novo HLA-Ab., (© 2022 Wiley Periodicals LLC.)

Introduction: Louisiana has one of the highest incidence and mortality rates of hepatocellular carcinoma (HCC) in the nation. The aim of this study was to analyze the trends in HCC incidence and relative survival rates in Louisiana and compare them with corresponding national rates, which can be used to formulate strategies to improve Louisiana HCC outcomes., Methods: Data on primary invasive HCC diagnosed in patients 20 years or older between 2005 and 2015 were obtained from the Surveillance, Epidemiology and End Results (SEER) program and Louisiana Tumor Registry. Time trends in HCC incidence and 12-month relative survival were analyzed using Joinpoint regression. Case characteristics were compared on 2 time periods (2005-2009 and 2010-2015) using Chi-squared tests. Cause-specific survival was analyzed via log-rank and multivariable Cox proportional hazard model., Results: Over the study period, the average annual percent change (AAPC) in age-adjusted HCC incidence in Louisiana was nearly double that of the national estimate, 6% (95% CI: 4.7, 7.3) compared to 3.1% (95% CI: 2.4, 3.7). 12-month relative survival among HCC patients in Louisiana was 40.7% (95% CI: 38.9, 42.4) which was significantly less than the US rate of 48.2% (95% CI: 47.8, 48.6). Relative survival did improve in Louisiana from 2000 to 2015 at a rate similar to that of the US (AAPC (95% CI): 2.9 (0.7, 5.2) vs. 2.7 (2.3, 3.1), p  = 0.8). In multivariable survival analysis, factors amongst Louisianans associated with worse survival were older age at diagnosis, advanced stage of disease, and lack of surgical therapy., Conclusion: The incidence of HCC continues to rise more dramatically in Louisiana than in the US. While some modest improvements in HCC survival have been realized, outcomes remain dismal. Future work identifying the most at-risk populations are needed to inform statewide public health initiatives., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Expression of the tight junction-associated protein junctional adhesion molecule-A (JAM-A) is increased in sepsis, although the significance of this is unknown. Here, we show that septic JAM-A -/- mice have increased gut permeability, yet paradoxically have decreased bacteremia and systemic TNF and IL-1β expression. Survival is improved in JAM-A-/- mice. However, intestine-specific JAM-A-/- deletion does not alter mortality, suggesting that the mortality benefit conferred in mice lacking JAM-A is independent of the intestine. Septic JAM-A-/- mice have increased numbers of splenic CD44hiCD4+ T cells, decreased frequency of TNF+CD4+ cells, and elevated frequency of IL-2+CD4+ cells. Septic JAM-A-/- mice have increased numbers of B cells in mesenteric lymph nodes with elevated serum IgA and intraepithelial lymphocyte IgA production. JAM-A-/- × RAG-/- mice have improved survival compared with RAG-/- mice and identical mortality as WT mice. Gut neutrophil infiltration and neutrophil phagocytosis are increased in JAM-A-/- mice, while septic JAM-A-/- mice depleted of neutrophils lose their survival advantage. Therefore, increased bacterial clearance via neutrophils and an altered systemic inflammatory response with increased opsonizing IgA produced through the adaptive immune system results in improved survival in septic JAM-A-/- mice. JAM-A may be a therapeutic target in sepsis via immune mechanisms not related to its role in permeability.

The 15 January 2022 climactic eruption of Hunga volcano, Tonga, produced an explosion in the atmosphere of a size that has not been documented in the modern geophysical record. The event generated a broad range of atmospheric waves observed globally by various ground-based and spaceborne instrumentation networks. Most prominent was the surface-guided Lamb wave (≲0.01 hertz), which we observed propagating for four (plus three antipodal) passages around Earth over 6 days. As measured by the Lamb wave amplitudes, the climactic Hunga explosion was comparable in size to that of the 1883 Krakatau eruption. The Hunga eruption produced remarkable globally detected infrasound (0.01 to 20 hertz), long-range (~10,000 kilometers) audible sound, and ionospheric perturbations. Seismometers worldwide recorded pure seismic and air-to-ground coupled waves. Air-to-sea coupling likely contributed to fast-arriving tsunamis. Here, we highlight exceptional observations of the atmospheric waves.

PLA (polylactide) is a bioresorbable polymer used in implantable medical and drug delivery devices. Like other bioresorbable polymers, PLA needs to be processed carefully to avoid degradation. In this work we combine in-process temperature, pressure, and NIR spectroscopy measurements with multivariate regression methods for prediction of the mechanical strength of an extruded PLA product. The potential to use such a method as an intelligent sensor for real-time quality analysis is evaluated based on regulatory guidelines for the medical device industry. It is shown that for the predictions to be robust to processing at different times and to slight changes in the processing conditions, the fusion of both NIR and conventional process sensor data is required. Partial least squares (PLS), which is the established 'soft sensing' method in the industry, performs the best of the linear methods but demonstrates poor reliability over the full range of processing conditions. Conversely, both random forest (RF) and support vector regression (SVR) show excellent performance for all criteria when used with a prior principal component (PC) dimension reduction step. While linear methods currently dominate for soft sensing of mixture concentrations in highly conservative, regulated industries such as the medical device industry, this work indicates that nonlinear methods may outperform them in the prediction of mechanical properties from complex physicochemical sensor data. The nonlinear methods show the potential to meet industrial standards for robustness, despite the relatively small amount of training data typically available in high-value material processing.

Background: Recent large retrospective studies suggest that breast-conserving therapy (BCT) plus radiation yielded better outcomes than mastectomy (MST) for women with early-stage breast cancer (ESBC). Whether this is applicable to the different subtypes is unknown. We hypothesize that BCT yielded better outcomes than MST, regardless of subtypes of ESBC., Study Design: Data on women diagnosed with first primary stage I to II breast cancer between 2010 and 2017 who underwent either BCT or MST were from the population-based 18 Surveillance, Epidemiology, and End Results cancer registries. The Kaplan-Meier method was used to estimate unadjusted 5-year overall survival and cause-specific survival. Univariable and multivariable Cox proportional regression models were used to determine the impact of surgical approaches on the hazard ratios adjusted for relevant demographic and clinical variables for molecular subtype (luminal A, luminal B, triple-negative, and HER2 enriched)., Results: Of the 214,128 patients with breast cancer, 41.6% received MST. For the different subtypes, BCT yielded better 5-year overall survival and cause-specific survival than MST. After adjusting for demographic and clinical factors, the risk of overall survival and cause-specific survival was still statistically significantly higher among MST recipients than BCT recipients for all subtypes., Conclusions: BCT yielded better survival rates than mastectomy for women with all subtypes of ESBC. The role of mastectomy for women with ESBC should be reassessed in future clinical trials., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Well-differentiated and dedifferentiated liposarcomas are rare soft tissue tumors originating in adipose tissue that share genetic abnormalities but have significantly different metastatic potential. Dedifferentiated liposarcoma (DDLPS) is highly aggressive and has an overall 5-year survival rate of 30% as compared to 90% for well-differentiated liposarcoma (WDLPS). This discrepancy may be connected to their potential to form adipocytes, where WDLPS is adipogenic but DDLPS is adipogenic-impaired. Normal adipogenesis requires Zinc Finger Protein 423 (ZFP423), a transcriptional coregulator of Perixosome Proliferator Activated Receptor gamma (PPARG2) mRNA expression that defines committed preadipocytes. Expression of ZFP423 in preadipocytes is promoted by Seven-In-Absentia Homolog 2 (SIAH2)-mediated degradation of Zinc Finger Protein 521 (ZFP521). This study investigated the potential role of ZFP423, SIAH2 and ZFP521 in the adipogenic potential of WDLPS and DDLPS., Methods: Human WDLPS and DDLPS fresh and paraffin-embedded tissues were used to assess the gene and protein expression of proadipogenic regulators. In parallel, normal adipose tissue stromal cells along with WDLPS and DDLPS cell lines were cultured, genetically modified, and induced to undergo adipogenesis in vitro., Results: Impaired adipogenic potential in DDLPS was associated with reduced ZFP423 protein levels in parallel with reduced PPARG2 expression, potentially involving regulation of ZFP521. SIAH2 protein levels did not define a clear distinction related to adipogenesis in these liposarcomas. However, in primary tumor specimens, SIAH2 mRNA was consistently upregulated in DDLPS compared to WDLPS when assayed by fluorescence in situ hybridization or real-time PCR., Conclusions: These data provide novel insights into ZFP423 expression in adipogenic regulation between WDLPS and DDLPS adipocytic tumor development. The data also introduces SIAH2 mRNA levels as a possible molecular marker to distinguish between WDLPS and DDLPS., (© 2022. The Author(s).)

Semiconductor nanoplatelets (NPLs), with their large exciton binding energy, narrow photoluminescence (PL), and absence of dielectric screening for photons emitted normal to the NPL surface, could be expected to become the fastest luminophores amongst all colloidal nanostructures. However, super-fast emission is suppressed by a dark (optically passive) exciton ground state, substantially split from a higher-lying bright (optically active) state. Here, the exciton fine structure in 2-8 monolayer (ML) thick Cs n - 1 Pb n Br 3n + 1 NPLs is revealed by merging temperature-resolved PL spectra and time-resolved PL decay with an effective mass model taking quantum confinement and dielectric confinement anisotropy into account. This approach exposes a thickness-dependent bright-dark exciton splitting reaching 32.3 meV for the 2 ML NPLs. The model also reveals a 5-16 meV splitting of the bright exciton states with transition dipoles polarized parallel and perpendicular to the NPL surfaces, the order of which is reversed for the thinnest NPLs, as confirmed by TR-PL measurements. Accordingly, the individual bright states must be taken into account, while the dark exciton state strongly affects the optical properties of the thinnest NPLs even at room temperature. Significantly, the derived model can be generalized for any isotropically or anisotropically confined nanostructure., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Tolinapant (ASTX660) is a potent, nonpeptidomimetic antagonist of cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1/2) and X-linked IAP, which is currently being evaluated in a phase 2 study in T-cell lymphoma (TCL) patients. Tolinapant has demonstrated evidence of single-agent clinical activity in relapsed/refractory peripheral TCL and cutaneous TCL. To investigate the mechanism of action underlying the single-agent activity observed in the clinic, we have used a comprehensive translational approach integrating in vitro and in vivo models of TCL confirmed by data from human tumor biopsies. Here, we show that tolinapant acts as an efficacious immunomodulatory molecule capable of inducing complete tumor regression in a syngeneic model of TCL exclusively in the presence of an intact immune system. These findings were confirmed in samples from our ongoing clinical study showing that tolinapant treatment can induce changes in gene expression and cytokine profile consistent with immune modulation. Mechanistically, we show that tolinapant can activate both the adaptive and the innate arms of the immune system through the induction of immunogenic forms of cell death. In summary, we describe a novel role for IAP antagonists as immunomodulatory molecules capable of promoting a robust antitumor immune response in TCL., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

The Rashba effect has been proposed to give rise to a bright exciton ground state in halide perovskite nanocrystals (NCs), resulting in very fast radiative recombination at room temperature and extremely fast radiative recombination at low temperature. In this paper we find the dispersion of the "Rashba exciton", i.e. , the exciton whose bulk dispersion reflects large spin-orbit Rashba terms in the conduction and valence bands and thus has minima at non-zero quasi-momenta. Placing Rashba excitonsin quasi-2D cylindrical quantum dots, we calculate size-dependent levels of confined excitons and their oscillator transition strengths. We consider the implications of this model for two-dimensional hybrid organic-inorganic perovskites, discuss generalizations of this model to 3D NCs, and establish criteria under which a bright ground exciton state could be realized.

The MAPK signaling pathway is commonly upregulated in human cancers. As the primary downstream effector of the MAPK pathway, ERK is an attractive therapeutic target for the treatment of MAPK-activated cancers and for overcoming resistance to upstream inhibition. ASTX029 is a highly potent and selective dual-mechanism ERK inhibitor, discovered using fragment-based drug design. Because of its distinctive ERK-binding mode, ASTX029 inhibits both ERK catalytic activity and the phosphorylation of ERK itself by MEK, despite not directly inhibiting MEK activity. This dual mechanism was demonstrated in cell-free systems, as well as cell lines and xenograft tumor tissue, where the phosphorylation of both ERK and its substrate, ribosomal S6 kinase (RSK), were modulated on treatment with ASTX029. Markers of sensitivity were highlighted in a large cell panel, where ASTX029 preferentially inhibited the proliferation of MAPK-activated cell lines, including those with BRAF or RAS mutations. In vivo , significant antitumor activity was observed in MAPK-activated tumor xenograft models following oral treatment. ASTX029 also demonstrated activity in both in vitro and in vivo models of acquired resistance to MAPK pathway inhibitors. Overall, these findings highlight the therapeutic potential of a dual-mechanism ERK inhibitor such as ASTX029 for the treatment of MAPK-activated cancers, including those which have acquired resistance to inhibitors of upstream components of the MAPK pathway. ASTX029 is currently being evaluated in a first in human phase I-II clinical trial in patients with advanced solid tumors (NCT03520075)., (©2021 American Association for Cancer Research.)

During infectious disease, pathogen load drives inflammation and immune response that together contribute to tissue injury often resulting in organ dysfunction. Pulmonary failure in SARS-CoV2-infected hospitalized COVID-19 patients is one such prominent example. Intervention strategies require characterization of the host-pathogen interaction by accurately assessing all of the above-mentioned disease parameters. To study infection in intact mammals, mice are often used as essential genetic models. Due to humane concerns, there is a constant unmet demand to develop studies that reduce the number of mice utilized while generating objective data. Here, we describe an integrated method of evaluating lung inflammation in mice infected with Pseudomonas aeruginosa or murine gammaherpesvirus (MHV)-68. This method conserves animal resources while permitting evaluation of disease mechanisms in both infection settings. Lungs from a single euthanized mouse were used for two purposes-biological assays to determine inflammation and infection load, as well as histology to evaluate tissue architecture. For this concurrent assessment of multiple parameters from a single euthanized mouse, we limit in-situ formalin fixation to the right lung of the cadaver. The unfixed left lung is collected immediately and divided into several segments for biological assays including determination of pathogen titer, assessment of infection-driven cytokine levels and appearance of cell death markers. In situ fixed right lung was then processed for histological determination of tissue injury and confirmation of infection-driven cell death patterns. This method reduces overall animal use and minimizes inter-animal variability that results from sacrificing different animals for different types of assays. The technique can be applied to any lung disease study in mice or other mammals., Competing Interests: NO authors have competing interests.

Background: Louisiana has the third highest breast cancer mortality in the US, despite ranking 30th in incidence. Whether surgical approach contributes to such a poor outcome is unknown. We compared outcomes of breast-conserving surgery plus radiation (BCT) vs mastectomy (MST) for Louisiana women with early-stage breast cancer., Study Design: Data on women diagnosed with Stage I-II breast cancer from 2004 to 2016 were analyzed from the Louisiana Tumor Registry. Overall survival (OS) and breast cancer-specific survival (CSS) were compared between BCT and MST. Kaplan-Meier method and log-rank test were used to compare survival curves, and logistic regression was used to examine the association of sociodemographic and clinical factors with the type of breast cancer surgery. Values of p < 0.05 were considered significant., Results: Of the 18,260 patients, 9,968 patients (54.6%) had BCT and 8,292 patients (45.4%) had MST. Compared with BCT, the MST group tended to be underinsured/Medicare/Medicaid, more impoverished, had higher stage 2 disease, were more likely to reside in rural regions, travel ≥25 miles to radiation treatment facility, be treated at low volume centers, and have T3, node positive, and poorly differentiated tumors. Ten-year OS and CSS were significantly better among those who had BCT (OS: 80.0%; 95% CI: 79.0%-81.1%; CSS: 92.7%; 95% CI: 92.1%-93.4%) than those having MST (OS: 69.3%; 95% CI: 68.0%-70.5%; CSS: 88.8%:95% CI: 87.9%-89.7%) (p < 0.05). Even after controlling for sociodemographic and clinical variables, MST was associated with a 28.6% increased risk of death from all causes (hazard ratio [HR]:1.286; 95% CI:1.197-1.380) and a 29.8% increased risk of breast-cancer specific death (HR:1.298; 95% CI: 1.150-1.465)., Conclusions: Surgical approach, a factor that is within the control of the surgeon, has an impact on mortality for Louisiana women with early-stage breast cancer., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Louisiana is one of the few Southern states that enacted the Medicaid expansion of the Patient Protection and Affordable Care Act (ACA). To the authors' knowledge, the issue of how this has affected the breast cancer landscape in Louisiana is unknown. The authors have postulated that ACA expansion had a positive impact for Louisiana women diagnosed with breast cancer., Methods: Data from the Louisiana Tumor Registry regarding 14,640 women aged 20 to 64 years who resided in Louisiana and were diagnosed with American Joint Committee on Cancer stage 0 to stage IV breast cancer between 2012 and 2018 were analyzed. The study period was divided into 2 groups: 1) before ACA expansion (January 1, 2012-May 31, 2016); and 2) after ACA expansion (June 1, 2016-December 31, 2018). The chi-square test and multivariable logistic regression models were used to assess the impact of ACA expansion. A P value <.05 was considered statistically significant., Results: After ACA expansion, the rate of uninsured patients decreased from 5.4% to 3.0% (P < .0001), and the rate of Medicaid recipients increased from 11.6% to 17.7% (P < .0001). The diagnosis of stage I breast cancer increased from 36.8% to 44.7% (P < .0001), whereas the diagnosis of stage III breast cancer decreased from 10.7% to 8.5% (P < .0001). The receipt of radiotherapy after breast-conserving surgery increased from 81.2% to 84.0% (P = .0035), and the receipt of radiotherapy within 90 days increased from 57.2% to 61.7% (P = .0012). After adjustment for sociodemographic and clinical variables, the models demonstrated that ACA expansion decreased the uninsured rate by 48% (odds ratio [OR], 0.52; 95% CI, 0.43-0.63), increased the diagnosis of early-stage disease (stage0 to stage II) by 27% (OR, 1.27; 95% CI, 1.15-1.41), increased receipt of radiotherapy after breast-conserving surgery by 19% (OR, 1.19; 95% CI, 1.03-1.37), and reduced the delay of receipt of radiotherapy by 16% (OR, 0.84; 95% CI, 0.74-0.95)., Conclusions: ACA expansion in Louisiana reduced the uninsured rate, increased the diagnosis of early-stage disease, and increased access to treatment., (© 2020 American Cancer Society.)

Purpose: We conducted a phase 1 trial of the HSP90 inhibitor onalespib in combination with the CDK inhibitor AT7519, in patients with advanced solid tumors to determine the safety profile and maximally tolerated dose, pharmacokinetics, preliminary antitumor activity, and to assess the pharmacodynamic (PD) effects on HSP70 expression in patient-derived PBMCs and plasma., Methods: This study followed a 3 + 3 trial design with 1 week of intravenous (IV) onalespib alone, followed by onalespib/AT7519 (IV) on days 1, 4, 8, and 11 of a 21-days cycle. PK and PD samples were collected at baseline, after onalespib alone, and following combination therapy., Results: Twenty-eight patients were treated with the demonstration of downstream target engagement of HSP70 expression in plasma and PBMCs. The maximally tolerated dose was onalespib 80 mg/m 2 IV + AT7519 21 mg/m 2 IV. Most common drug-related adverse events included Grade 1/2 diarrhea (79%), fatigue (54%), mucositis (57%), nausea (46%), and vomiting (50%). Partial responses were seen in a palate adenocarcinoma and Sertoli-Leydig tumor; a colorectal and an endometrial cancer patient both remained on study for ten cycles with stable disease as the best response. There were no clinically relevant PK interactions for either drug., Conclusions: Combined onalespib and AT7519 is tolerable, though below monotherapy RP2D. Promising preliminary clinical activity was seen. Further benefit may be seen with the incorporation of molecular signature pre-selection. Further biomarker development will require the assessment of the on-target impact on relevant client proteins in tumor tissue.

ScAlN is an emergent ultrawide-band-gap material with both a high piezoresponse and demonstrated ferroelectric polarization switching. Recent demonstration of epitaxial growth of ScAlN on GaN has unlocked prospects for new high-power transistors and nonvolatile memory technologies fabricated from these materials. An understanding of the band alignments between ScAlN and GaN is crucial in order to control the electronic and optical properties of engineered devices. To date, there have been no experimental studies of the band offsets between ScAlN and GaN. This work presents optical characterization of the band gap of molecular beam epitaxy grown Sc x Al 1- x N using spectroscopic ellipsometry and measurements of the band offsets of Sc x Al 1- x N with GaN using X-ray photoemission spectroscopy, along with a comparison to first-principles calculations. The band gap is shown to continuously decrease as a function of increasing ScN alloy fraction with a negative bowing parameter. Furthermore, a crossover from straddling (type-I) to staggered (type-II) band offsets is demonstrated as Sc composition increases beyond approximately x = 0.11. These results show that the ScAlN/GaN valence band alignment can be tuned by changing the Sc alloy fraction, which can help guide the design of heterostructures in future ScAlN/GaN-based devices.

We develop a microscopic theoretical model of AlN, GaN, and InN film growth by atomic layer epitaxy. To make the model realistic, we take into account the atomic hydrogen that is created by the hydrogen plasma commonly used in plasma-assisted atomic layer epitaxy. This growth technique relies on separate deposition steps for nitrogen and the group-III cation. Our model addresses the processes that occur after a complete monolayer of nitrogen has formed, that is, the deposition, adsorption, surface diffusion, island nucleation, and island growth of group-III cations. According to our model, the three nitrides grow in a standard and qualitatively similar manner: during a brief nucleation phase, a modest attractive interaction leads to stable island nuclei consisting of just a few atoms. These then grow in place at a nearly constant island density and with an island size distribution which obeys an expected universal scaling relationship that depends only on the critical island size.

Background: It is unknown whether rural patients with operable breast cancer do worse than urban patients in Louisiana. We performed an analysis of breast cancer based on rural versus urban residencies and evaluate factors associated with worse survival., Methods: Data on women diagnosed with stages I to III breast cancer from 2004 to 2016 were obtained from the Louisiana Tumor Registry. Overall survival and cancer-specific survival were compared between rural and urban residencies by sociodemographic, clinical-pathologic, and treatment variables. Kaplan-Meier method and the log-rank test were used to compare the survival curves. Cox regression model was used to assess independent factors associated with overall survival and cancer-specific survival., Results: Of the 27,780 patients, 2,441 patients (8.7%) resided in rural areas. Compared with urban patients, rural patients tended to be older, underinsured, more impoverished, less likely to be treated at an American College of Surgeons accredited institution, and more likely to be treated at a low-volume center (P < .005 each). For stages I and II diseases, there was a statistically significant difference in overall survival favoring urban regions, but no difference in cancer-specific survival. For stage III disease, there was no difference in either overall survival or cancer-specific survival between the 2 cohorts. Overall survival and cancer-specific survival curves for the entire cohort were not different at the 5-year mark, but become statistically significant with greater time; although rural patients had a lower long-term overall survival (P = .0001) and cancer-specific survival (P = .049) compared with urban patients, the rural-urban differences in overall survival and cancer-specific survival were no longer different after adjusting for other covariates, indicating the observed differences in univariate analysis were attributable to sociodemographic, clinicpathologic, and treatment factors., Conclusion: Despite rural patients with operable breast cancer having an overall lesser overall survival and cancer-specific survival than their urban counterpart, rural residence itself was not an independent predictor of outcome. In fact, particular socioeconomic factors increased the risk of death among patients residing in rural areas. Additional analysis at the patient-level is needed to understand the interactions between rurality and breast cancer outcomes in Louisiana., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Poly (ether ether ketone) (PEEK) is a high-performance engineering thermoplastic polymer with potential for use in a variety of metal replacement applications due to its high strength to weight ratio. This combination of properties makes it an ideal material for use in the production of bespoke replacement parts for out-of-earth manufacturing purposes, in particular on the International Space Station (ISS). Additive manufacturing (AM) may be employed for the production of these parts, as it has enabled new fabrication pathways for articles with complex design considerations. However, AM of PEEK via fused filament fabrication (FFF) encounters significant challenges, mostly stemming from the semi crystalline nature of PEEK and its associated high melting temperature. This makes PEEK highly susceptible to changes in processing conditions which leads to a large reported variation in the literature on the final performance of PEEK. This has limited the adaption of FFF printing of PEEK in space applications where quality assurance and reproducibility are paramount. In recent years, several research studies have examined the effect of printing parameters on the performance of the 3D-printed PEEK parts. The aim of the current review is to provide comprehensive information in relation to the process-structure-property relationships in FFF 3D-printing of PEEK to provide a clear baseline to the research community and assesses its potential for space applications, including out-of-earth manufacturing.

Rural hospitals in New Zealand face difficult workforce challenges to maintain services and quality outcomes. Ashburton Hospital has undergone a 10-year transition from a secondary specialist to a rural generalist medical model of care. Current senior medical staff (rural hospital medicine fellows) here explore their experience of the process and outcomes of this transition. Key drivers for change included commitment and support from management, senior medical staff and the local community, the new rural hospital medicine qualification and a core group of doctors willing to train in it. Challenges included the need to adapt rapidly to even a single doctor's departure, initial lack of credibility of the new qualification, and choice between a single or two-tier system of medical rostering. While acute and elective surgical services were lost, acute medical and rehabilitation services were maintained or increased. Presentations to the acute assessment unit, including high acuity cases, have more than doubled over the period described. Workforce stability has been enhanced and commitment to training contributes to future workforce sustainability. Long-term shared strategic commitment to transition was a key factor in successfully traversing challenges faced. Rural and provincial communities should consider rural generalism as a medical model to sustain and further develop their local hospital services., Competing Interests: Dr Kiuru and Dr Withington report grants from Advance Ashburton Trust during the conduct of the study.

Inorganic lead halide perovskite nanostructures show promise as the active layers in photovoltaics, light emitting diodes, and other optoelectronic devices. They are robust in the presence of oxygen and water, and the electronic structure and dynamics of these nanostructures can be tuned through quantum confinement. Here we create aligned bundles of CsPbBr 3 nanowires with widths resulting in quantum confinement of the electronic wave functions and subject them to ultrafast microscopy. We directly image rapid one-dimensional exciton diffusion along the nanowires, and we measure an exciton trap density of roughly one per nanowire. Using transient absorption microscopy, we observe a polarization-dependent splitting of the band edge exciton line, and from the polarized fluorescence of nanowires in solution, we determine that the exciton transition dipole moments are anisotropic in strength. Our observations are consistent with a model in which splitting is driven by shape anisotropy in conjunction with long-range exchange.

: The effect of cooling on the degree of crystallinity, solid-state and dissolution properties of multi-component hot-melt extruded solid dispersions [SD] is of great interest for the successful formulation of amorphous SDs and is an area that is unreported, especially in the context of improving the stability of these specific systems. The thermal solid-state properties, degree of crystallinity, drug-polymer interactions, solubility and physical stability over time were investigated. X-ray powder diffraction [XRPD] and hyper differential scanning calorimetry [DSC] confirmed that indomethacin [INM] was converted to the amorphous state; however, the addition of poloxamer 407 [P407] had a significant effect on the degree of crystallinity and the solubility of the SD formulations. Spectroscopy studies identified the mechanism of interaction and solubility studies, showing a higher dissolution rate compared to amorphous and pure INM in pH 1.2 with a kinetic solubility of 20.63 µg/mL and 34.7 µg/mL after 3 and 24 h. XRPD confirmed that INM remained amorphous after 5 months stability testing in solid solutions with Poly(vinylpyrrolidone-co-vinyl acetate) [PVP VA64] and Plasdone S-630 [PL-S630]. Although cooling had a significant effect on the degree of crystallinity and on solubility of INM, the cooling method used did not have any significant effect on the amorphous stability of INM over time.

We present an analysis of quantum confinement of carriers and excitons, and exciton fine structure, in metal halide perovskite (MHP) nanocrystals (NCs). Starting with coupled-band k · P theory, we derive a nonparabolic effective mass model for the exciton energies in MHP NCs valid for the full size range from the strong to the weak confinement limits. We illustrate the application of the model to CsPbBr 3 NCs and compare the theory against published absorption data, finding excellent agreement. We then apply the theory of electron-hole exchange, including both short- and long-range exchange interactions, to develop a model for the exciton fine structure. We develop an analytical quasicubic model for the effect of tetragonal and orthorhombic lattice distortions on the exchange-related exciton fine structure in CsPbBr 3 , as well as some hybrid organic MHPs of recent interest, including formamidinium lead bromide (FAPbBr 3 ) and methylammonium lead iodide (MAPbI 3 ). Testing the predictions of the quasicubic model using hybrid density functional theory (DFT) calculations, we find qualitative agreement in tetragonal MHPs but significant disagreement in the orthorhombic modifications. Moreover, the quasicubic model fails to correctly describe the exciton oscillator strength and with it the long-range exchange corrections in these systems. Introducing the effect of NC shape anisotropy and possible Rashba terms into the model, we illustrate the calculation of the exciton fine structure in CsPbBr 3 NCs based on the results of the DFT calculations and examine the effect of Rashba terms and shape anisotropy on the calculated fine structure.

The introduction of three-dimensional printing (3DP) has created exciting possibilities for the fabrication of dosage forms, paving the way for personalized medicine. In this study, oral dosage forms of two drug concentrations, namely 2.50% and 5.00%, were fabricated via stereolithography (SLA) using a novel photopolymerizable resin formulation based on a monomer mixture that, to date, has not been reported in the literature, with paracetamol and aspirin selected as model drugs. In order to produce the dosage forms, the ratio of poly(ethylene glycol) diacrylate (PEGDA) to poly(caprolactone) triol was varied with diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure TPO) utilized as the photoinitiator. The fabrication of 28 dosages in one print process was possible and the printed dosage forms were characterized for their drug release properties. It was established that both drugs displayed a sustained release over a 24-h period. The physical properties were also investigated, illustrating that SLA affords accurate printing of dosages with some statistically significant differences observed from the targeted dimensional range, indicating an area for future process improvement. The work presented in this paper demonstrates that SLA has the ability to produce small, individualized batches which may be tailored to meet patients' specific needs or provide for the localized production of pharmaceutical dosage forms.

The current distribution and abundance of the 40 species of Goodeidae fishes known from Mexico are described, and a total of 84 Evolutionarily Significant Units (ESUs) is designated within these species. Two species and four ESUs are likely extinct with no captive populations, and three species and eight ESUs are probably extinct in the wild but have at least one captive population in Mexico, the United States, or Europe. Of the 35 extant species, the analyses indicate that nine should be considered as critically endangered, 14 as endangered, nine as vulnerable, and only three as least concern. Twenty-seven of these species have experienced substantial declines in distribution or abundance or both since 2000, and only eight appear to have remained relatively stable. Of the 72 extant ESUs, our analyses indicate that 29 should be considered as critically endangered, 21 as endangered, 18 as vulnerable, and only four as least concern. Brief summaries of the historic and current distributions and abundance of each species are provided, as well as ESU. Three strategies are recommended to conserve Mexican goodeids: protect the best-quality remaining habitats where goodeids still persist, restore degraded habitat and re-introduce species or ESUs where practical, and establish captive populations to ensure continued survival of the many species and ESUs that will almost inevitably go extinct in the coming years. Limited resources require cooperation and collaboration between scientists, conservationists, and aquarium hobbyists for successful captive maintenance., (John Lyons, Kyle R. Piller, Juan Miguel Artigas-Azas, Omar Dominguez-Dominguez, Pablo Gesundheit, Michael Köck, Martina Medina-Nava, Norman Mercado-Silva, Arely Ramírez García, Kearstin M. Findley.)