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The cause of death in people affected by sickle cell disease (SCD) is often challenging to define as prior studies have used retrospective or administrative data for analysis. We used a prospective longitudinal registry to assess mortality and clinical co-morbidities among subjects enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. At enrollment, we collected the following data: patient-reported demographics, SCD phenotype, baseline laboratory values, comorbidities, and current medications. Subjects were followed for a median of 4.7 years before the present analysis. The relationship of clinical co-morbidities (at time of enrollment) to mortality was determined using survival analysis, adjusting for SCD phenotype and gender. There was a total of 2439 people with SCD enrolled in the SCDIC registry. One hundred and twenty-eight participants (5%) died during the observation period (2017-2022). Six people died from trauma and were excluded from further analysis. Proximate cause of death was unwitnessed in 17% of the deaths, but commonest causes of death include cardiac (18%), acute chest or respiratory failure (11%), sudden unexplained death (8%). Enrollment characteristics of the individuals who died (n = 122) were compared to those of survivors (n = 2317). Several co-morbidities at enrollment increased the odds of death on univariate analysis. All co-morbidities were included in a multivariable model. After backward elimination, iron overload, pulmonary hypertension, and depression, remained statistically significant predictors of the risk of death. SCD reduces life expectancy. Improved comprehensive and supportive care to prevent end-organ damage and address comorbidities is needed for this population.

OBJECTIVE: The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticosteroid Randomization After Significant Head Injury (CRASH) prognostic models for mortality and outcome after traumatic brain injury (TBI) were developed using data from 1984 to 2004. This study examined IMPACT and CRASH model performances in a contemporary cohort of US patients. METHODS: The prospective 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years 2014-2018) enrolled subjects aged ≥ 17 years who presented to level I trauma centers and received head CT within 24 hours of TBI. Data were extracted from the subjects who met the model criteria (for IMPACT, Glasgow Coma Scale [GCS] score 3-12 with 6-month Glasgow Outcome Scale-Extended [GOSE] data [n = 441]; for CRASH, GCS score 3-14 with 2-week mortality data and 6-month GOSE data [n = 831]). Analyses were conducted in the overall cohort and stratified on the basis of TBI severity (severe/moderate/mild TBI defined as GCS score 3-8/9-12/13-14), age (17-64 years or ≥ 65 years), and the 5 top enrolling sites. Unfavorable outcome was defined as GOSE score 1-4. Original IMPACT and CRASH model coefficients were applied, and model performances were assessed by calibration (intercept [< 0 indicated overprediction; > 0 indicated underprediction] and slope) and discrimination (c-statistic). RESULTS: Overall, the IMPACT models overpredicted mortality (intercept -0.79 [95% CI -1.05 to -0.53], slope 1.37 [1.05-1.69]) and acceptably predicted unfavorable outcome (intercept 0.07 [-0.14 to 0.29], slope 1.19 [0.96-1.42]), with good discrimination (c-statistics 0.84 and 0.83, respectively). The CRASH models overpredicted mortality (intercept -1.06 [-1.36 to -0.75], slope 0.96 [0.79-1.14]) and unfavorable outcome (intercept -0.60 [-0.78 to -0.41], slope 1.20 [1.03-1.37]), with good discrimination (c-statistics 0.92 and 0.88, respectively). IMPACT overpredicted mortality and acceptably predicted unfavorable outcome in the severe and moderate TBI subgroups, with good discrimination (c-statistic ≥ 0.81). CRASH overpredicted mortality in the severe and moderate TBI subgroups and acceptably predicted mortality in the mild TBI subgroup, with good discrimination (c-statistic ≥ 0.86); unfavorable outcome was overpredicted in the severe and mild TBI subgroups with adequate discrimination (c-statistic ≥ 0.78), whereas calibration was nonlinear in the moderate TBI subgroup. In subjects ≥ 65 years of age, the models performed variably (IMPACT-mortality, intercept 0.28, slope 0.68, and c-statistic 0.68; CRASH-unfavorable outcome, intercept -0.97, slope 1.32, and c-statistic 0.88; nonlinear calibration for IMPACT-unfavorable outcome and CRASH-mortality). Model performance differences were observed across the top enrolling sites for mortality and unfavorable outcome. CONCLUSIONS: The IMPACT and CRASH models adequately discriminated mortality and unfavorable outcome. Observed overestimations of mortality and unfavorable outcome underscore the need to update prognostic models to incorporate contemporary changes in TBI management and case-mix. Investigations to elucidate the relationships between increased survival, outcome, treatment intensity, and site-specific practices will be relevant to improve models in specific TBI subpopulations (e.g., older adults), which may benefit from the inclusion of blood-based biomarkers, neuroimaging features, and treatment data.

Agronomic crops, including grains, forages, and fiber, are central to California agriculture, yet face many challenges. To ensure resilience, a statewide survey was conducted by the University of California Cooperative Extension service (UCCE) to identify high-priority needs and inform extension programming based on grower, consultant, and allied industry input. The goal was to compare the importance of different topics with the level of satisfaction regarding UCCE’s delivery of information on these topics. Survey respondents identified integrated pest management, nutrient and irrigation management, and variety testing as high-priority needs, with overall high satisfaction regarding UCCE’s program delivery on these topics. Topics needing more focus (high priority but below-average level of satisfaction) included testing new products, soil health management, and water conservation and storage. Areas of low priority and low satisfaction included niche marketing, emerging crops, organic production, harvest/post-harvest technology, salinity management, compost and manure management, and greenhouse gas emission reductions. To address stakeholder challenges, results from this study suggest that research and extension efforts should prioritize issues directly impacting on-farm crop production. At the same time, areas of low interest reflect a need for more support to engage farmers on these topics, particularly those concerning state environmental regulations and challenges to local and global food production and security.

Abstract: Long bean (Vigna unguiculata subsp. sesquipedalis, asparagus bean, Asian yardlong bean), the vegetable type of cowpea [Vigna unguiculata (L.) Walp], is a climate‐resilient and nutritious food legume grown by Southeast Asian farmers in the Central Valley of California and marketed to Asian immigrant communities across the United States. Insect pests are major threats, reducing yield and quality of all current lines. Modern plant breeding protocols and extension activities were implemented to develop resistant lines using sources of natural resistance found in African cowpea germplasm. Three aphid‐resistant long bean lines, Dark Green 1994 (Reg no. GP‐320, PI 702995), Light Green 2055 (Reg. no. GP‐321, PI 702996), and Purple 2056 (Reg. no. GP‐322, PI 702997), were developed by introgression of two known quantitative trait loci (QTL) for aphid resistance into three local elite lines through marker‐assisted backcrossing (MABC). One bush‐type long bean line, Bush 2074 (Reg. no. GP‐319, PI 702994), carrying two known QTL for root‐knot nematode resistance, was also developed to enable scaling up production and to improve nematode management in large‐scale commercial farming. These improved lines were evaluated in controlled experiments which also served in outreach activities to enable adoption. Each of these advanced lines, when forming a near‐isogenic pair with its recurrent parent, can provide useful genetic materials for resistance gene discovery.

Academic staff members (academics) are central social agents in providing accessible higher education (AHE) to students with disabilities (SWD). The literature demonstrates gaps between academics' positive attitudes and self-efficacy to apply AHE. This study explores factors explaining their willingness and self-efficacy to provide AHE through the lens of organizational theories on work engagement. The 210 academics recruited from 10 universities and colleges completed four questionnaires: personal and organizational characteristics, engagement in AHE, Multidimensional Attitudes Scale toward Persons with Disabilities, and workload related to AHE. Hierarchical linear regressions revealed that gender, contact with SWD, familiarity with support centers, training, and cognitive attitudes toward people with disabilities explained 31% of the participants' self-efficacy. Gender, workload, and cognitive attitudes toward people with disabilities explained 28% of their willingness to provide AHE. The gender difference regarding female academics' higher commitment to AHE than male academics is one of the study's important findings. This research revealed the institutions' responsibility to develop resources for academics to implement AHE, encourage training that addresses gender differences, strengthen support centers, and acknowledge the benefits of and commitment to diversity, inclusion, and social justice.

Hydroxyurea reduces sickle cell disease (SCD) complications, but medication adherence is low. We tested 2 mobile health (mHealth) interventions targeting determinants of low adherence among patients (InCharge Health) and low prescribing among providers (HU Toolbox) in a multi-center, non-randomized trial of individuals with SCD ages 15-45. We compared the percentage of days covered (PDC), labs, healthcare utilization, and self-reported pain over 24 weeks of intervention and 12 weeks post-study with a 24-week preintervention interval. We enrolled 293 patients (51% male; median age 27.5 years, 86.8% HbSS/HbSβ0-thalassemia). The mean change in PDC among 235 evaluable subjects increased (39.7% to 56.0%; P < 0.001) and sustained (39.7% to 51.4%, P < 0.001). Mean HbF increased (10.95% to 12.78%; P = 0.03). Self-reported pain frequency reduced (3.54 to 3.35 events/year; P = 0.041). InCharge Health was used ≥1 day by 199 of 235 participants (84.7% implementation; median usage: 17% study days; IQR: 4.8-45.8%). For individuals with ≥1 baseline admission for pain, admissions per 24 weeks declined from baseline through 24 weeks (1.97 to 1.48 events/patient, P = 0.0045) and weeks 25-36 (1.25 events/patient, P = 0.0015). PDC increased with app use (P < 0.001), with the greatest effect in those with private insurance (P = 0.0078), older subjects (P = 0.033), and those with lower pain interference (P = 0.0012). Of the 89 providers (49 hematologists, 36 advanced care providers, 4 unreported), only 11.2% used HU Toolbox ≥1/month on average. This use did not affect change in PDC. Tailoring mHealth solutions to address barriers to hydroxyurea adherence can potentially improve adherence and provide clinical benefits. A definitive randomized study is warranted. This trial was registered at www.clinicaltrials.gov as #NCT04080167.

Aim: Determining the anthropometric characteristics of the nose, which is located in the center of the face, plays an important role not only in surgical procedures but also in identifying ethnic differences. This study aimed to examine the nasal similarities and differences between Kazakhs and Turks who have lived in different regions for more than a thousand years.Material and Methods: The study included 200 Turkish students and 200 Kazakh students. For each student, sixteen distance measurements and five angle measurements of the nose were taken. The photographs were taken using a digital camera mounted on a tripod, with a distance of 1.50 meters between the photographer and the student participating in the study. Digital photographs of the front, left side, and base of the nose were taken in the Frankfurt Horizontal Plan, which is the standard head position. The photographs were transferred to the DIGIMIZER software, where measurements were made using anthropometric points previously determined.Results: The findings reveal that among both societies, nasal measurements tend to be greater for males compared to females. Conversely, females exhibit higher nasofrontal (p=0.001) and nasolabial (p=0.001) angles compared to males. Moreover, Turks generally exhibit greater nasal length (p=0.001), width (p=0.001), and height (p=0.037) than Kazakhs, whereas tend to have lower nasofrontal (p=0.001) and nasolabial (p=0.001) angles than Kazakhs.Conclusion: Nasal anthropometric measurements for males were generally higher than for females. In addition, all measurements differed between Turks and Kazakhs. The results of this study will be useful for future anthropometric studies.

Objectives: This study aimed to identify the incidence and risk factors for contrast-associated acute kidney injury nephropathy (CA-AKI) in patients undergoing contrast-enhanced computed tomography (CCT) in the emergency department. Materials and Methods: In this retrospective single-center study, patients aged 18 and older who visited the emergency department and underwent CCT between January and February 2022 were included. The Mehran score, calculated from patient data, was used to assess risk. CA-AKI development was determined by measuring serum creatinine (SCr) levels 48–72 h post-contrast administration. Results: The study included 532 patients, with a mean age of 57 ± 19 years; 53.2% were male. CA-AKI developed in 16% of cases, 5.82% required hemodialysis, and 7.9% died. The Mehran score was the only significant predictor of CA-AKI development. Patients with a Mehran score of 16 or higher had a 161-fold increased risk of developing CA-AKI compared to those with a score of 5 or lower. The model achieved a 91.3% correct classification rate. Logistic regression analysis showed that CA-AKI significantly increased mortality risk by 15.7 times. Conclusion: The Mehran score, originally developed for predicting CA-AKI risk post-coronary intervention, is also effective for predicting CA-AKI risk after CCT. While CA-AKI is a significant factor affecting mortality, it is not the sole cause of death (Nagelkerke R2 value 0.310).

Abstract Therapy-related myeloid neoplasms (t-MN) arise as a complication of chemo- and/or radiotherapy. Although t-MN can occur both in adult and childhood cancer survivors, the mechanisms driving therapy-related leukemogenesis likely vary across different ages. Chemotherapy is thought to induce driver mutations in children, whereas in adults pre-existing mutant clones are selected by the exposure. However, selective pressures induced by chemotherapy early in life are less well studied. Here, we use single-cell whole genome sequencing and phylogenetic inference to show that the founding cell of t-MN in children starts expanding after cessation of platinum exposure. In patients with Li-Fraumeni syndrome, characterized by a germline TP53 mutation, we find that the t-MN already expands during treatment, suggesting that platinum-induced growth inhibition is TP53-dependent. Our results demonstrate that germline aberrations can interact with treatment exposures in inducing t-MN, which is important for the development of more targeted, patient-specific treatment regimens and follow-up.

PURPOSE: To report the incidence and risk factors for secondary neoplasm after transplantation for sickle cell disease. METHODS: Included are 1,096 transplants for sickle cell disease between 1991 and 2016. There were 22 secondary neoplasms. Types included leukemia/myelodysplastic syndrome (MDS; n = 15) and solid tumor (n = 7). Fine-Gray regression models examined for risk factors for leukemia/MDS and any secondary neoplasm. RESULTS: The 10-year incidence of leukemia/MDS was 1.7% (95% CI, 0.90 to 2.9) and of any secondary neoplasm was 2.4% (95% CI, 1.4 to 3.8). After adjusting for other risk factors, risks for leukemia/MDS (hazard ratio, 22.69; 95% CI, 4.34 to 118.66; P = .0002) or any secondary neoplasm (hazard ratio, 7.78; 95% CI, 2.20 to 27.53; P = .0015) were higher with low-intensity (nonmyeloablative) regimens compared with more intense regimens. All low-intensity regimens included total-body irradiation (TBI 300 or 400 cGy with alemtuzumab, TBI 300 or 400 cGy with cyclophosphamide, TBI 200, 300, or 400 cGy with cyclophosphamide and fludarabine, or TBI 200 cGy with fludarabine). None of the patients receiving myeloablative and only 23% of those receiving reduced-intensity regimens received TBI. CONCLUSION: Low-intensity regimens rely on tolerance induction and establishment of mixed-donor chimerism. Persistence of host cells exposed to low-dose radiation triggering myeloid malignancy is one plausible etiology. Pre-existing myeloid mutations and prior inflammation may also contribute but could not be studied using our data source. Choosing conditioning regimens likely to result in full-donor chimerism may in part mitigate the higher risk for leukemia/MDS.

OBJECTIVE: Observational studies can impact patient care but must be robust and reproducible. Nonreproducibility is primarily caused by unclear reporting of design choices and analytic procedures. This study aimed to: (1) assess how the study logic described in an observational study could be interpreted by independent researchers and (2) quantify the impact of interpretations variability on patient characteristics. MATERIALS AND METHODS: Nine teams of highly qualified researchers reproduced a cohort from a study by Albogami et al. The teams were provided the clinical codes and access to the tools to create cohort definitions such that the only variable part was their logic choices. We executed teams cohort definitions against the database and compared the number of subjects, patient overlap, and patient characteristics. RESULTS: On average, the teams interpretations fully aligned with the master implementation in 4 out of 10 inclusion criteria with at least 4 deviations per team. Cohorts size varied from one-third of the master cohort size to 10 times the cohort size (2159-63 619 subjects compared to 6196 subjects). Median agreement was 9.4% (interquartile range 15.3-16.2%). The teams cohorts significantly differed from the master implementation by at least 2 baseline characteristics, and most of the teams differed by at least 5. CONCLUSIONS: Independent research teams attempting to reproduce the study based on its free-text description alone produce different implementations that vary in the population size and composition. Sharing analytical code supported by a common data model and open-source tools allows reproducing a study unambiguously thereby preserving initial design choices.

The global food system, and animal agriculture in particular, is a major and growing contributor to climate change, land system change, biodiversity loss, water consumption and contamination, and environmental pollution. The copious production and consumption of animal products are also contributing to increasingly negative public health outcomes, particularly in wealthy and rapidly industrializing countries, and result in the slaughter of trillions of animals each year. These impacts are motivating calls for reduced reliance on animal-based products and increased use of replacement plant-based products. However, our understanding of how the production and consumption of animal products, as well as plant-based alternatives, interact with important dimensions of human and environment systems is incomplete across space and time. This inhibits comprehensively envisioning global and regional food system transitions and planning to manage the costs and synergies thereof. We therefore propose a cross-disciplinary research agenda on future target-based scenarios for food system transformation that has at its core three main activities: (1) data collection and analysis at the intersection of animal agriculture, the environment, and societal well-being, (2) the construction of target-based scenarios for animal products informed by these new data and empirical understandings, and (3) the evaluation of impacts, unintended consequences, co-benefits, and trade-offs of these target-based scenarios to help inform decision-making.

IntroductionNeuroworsening may be a sign of progressive brain injury and is a factor for treatment of traumatic brain injury (TBI) in intensive care settings. The implications of neuroworsening for clinical management and long-term sequelae of TBI in the emergency department (ED) require characterization.MethodsAdult TBI subjects from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study with ED admission and disposition Glasgow Coma Scale (GCS) scores were extracted. All patients received head computed tomography (CT) scan

lovo-cel (bb1111; LentiGlobin for sickle cell disease [SCD]) gene therapy (GT) comprises autologous transplantation of hematopoietic stem and progenitor cells transduced with the BB305 lentiviral vector encoding a modified β-globin gene (βA-T87Q ) to produce anti-sickling hemoglobin (HbAT87Q ). The efficacy and safety of lovo-cel for SCD are being evaluated in the ongoing phase 1/2 HGB-206 study (ClinicalTrials.gov: NCT02140554). The treatment process evolved over time, using learnings from outcomes in the initial patients to optimize lovo-cel's benefit-risk profile. Following modest expression of HbAT87Q in the initial patients (Group A, n = 7), alterations were made to the treatment process for patients subsequently enrolled in Group B (n = 2, patients B1 and B2), including improvements to cell collection and lovo-cel manufacturing. After 6 months, median Group A peripheral blood vector copy number (≥0.08 c/dg) and HbAT87Q levels (≥0.46 g/dL) were inadequate for substantial clinical effect but stable and sustained over 5.5 years; both markedly improved in Group B (patient B1: ≥0.53 c/dg and ≥2.69 g/dL; patient B2: ≥2.14 c/dg and ≥6.40 g/dL, respectively) and generated improved biologic and clinical efficacy in Group B, including higher total hemoglobin and decreased hemolysis. The safety of the lovo-cel for SCD treatment regimen largely reflected the known side effects of HSPC collection, busulfan conditioning regimen, and underlying SCD; acute myeloid leukemia was observed in two patients in Group A and deemed unlikely related to insertional oncogenesis. Changes made during development of the lovo-cel treatment process were associated with improved outcomes and provide lessons for future SCD GT studies.

Abstract Recently, the underlying mechanism for successful deep learning (DL) was presented based on a quantitative method that measures the quality of a single filter in each layer of a DL model, particularly VGG-16 trained on CIFAR-10. This method exemplifies that each filter identifies small clusters of possible output labels, with additional noise selected as labels outside the clusters. This feature is progressively sharpened with each layer, resulting in an enhanced signal-to-noise ratio (SNR), which leads to an increase in the accuracy of the DL network. In this study, this mechanism is verified for VGG-16 and EfficientNet-B0 trained on the CIFAR-100 and ImageNet datasets, and the main results are as follows. First, the accuracy and SNR progressively increase with the layers. Second, for a given deep architecture, the maximal error rate increases approximately linearly with the number of output labels. Third, similar trends were obtained for dataset labels in the range [3, 1000], thus supporting the universality of this mechanism. Understanding the performance of a single filter and its dominating features paves the way to highly dilute the deep architecture without affecting its overall accuracy, and this can be achieved by applying the filter’s cluster connections (AFCC).

Abstract Background Adults with sickle cell disease (SCD) suffer early mortality and high morbidity. Many are not affiliated with SCD centers, defined as no ambulatory visit with a SCD specialist in 2 years. Negative social determinants of health (SDOH) can impair access to care. Hypothesis: Negative SDOH are more likely to be experienced by unaffiliated adults than adults who regularly receive expert SCD care. Methods Cross-sectional analysis of the SCD Implementation Consortium (SCDIC) Registry, a convenience sample at 8 academic SCD centers in 2017–2019. A Distressed Communities Index (DCI) score was assigned to each registry member’s zip code. Insurance status and other barriers to care were self-reported. Most patients were enrolled in the clinic or hospital setting. Results The SCDIC Registry enrolled 288 Unaffiliated and 2110 Affiliated SCD patients, ages 15-45y. The highest DCI quintile accounted for 39% of both Unaffiliated and Affiliated patients. Lack of health insurance was reported by 19% of Unaffiliated versus 7% of Affiliated patients. The most frequently selected barriers to care for both groups were “previous bad experience with the healthcare system” (40%) and “Worry about Cost” (17%). SCD co-morbidities had no straightforward trend of association with Unaffiliated status. The 8 sites’ results varied. Conclusion The DCI economic measure of SDOH was not associated with Unaffiliated status of patients recruited in the health care delivery setting. SCDIC Registrants reside in more distressed communities than other Americans. Other SDOH themes of affordability and negative experiences might contribute to Unaffiliated status. Recruiting Unaffiliated SCD patients to care might benefit from systems adopting value-based patient-centered solutions.

Backround: The aim of this study is to evaluate how competent family medicine residents see themselves in the interventional competency goals targeted in emergency medicine rotation and the factors associated with their competency levels. Methods: The study is a methodological and cross-sectional study carried out between 01 May-31 October 2022. 138 family medicine residents who completed their emergency medicine rotation and agreed to participate in the study were included in the study. In the questionnaire used to collect data in the study, there were the Emergency Medicine Rotation Interventional Competence Scale (EMRICS) developed by the researchers based on the family medicine specialty training curriculum and sociodemographic characteristics. Results: The mean ages of the study group 29.71±4.27 (Mean±SD) years, and 60.10% (n:83) were women. The mean scores obtained from the scale in the study group were 59.86±11.72 (Mean±SD). While the interventional competence in which family physician residents had the highest proficiency was arterial blood gas with 97.80% (n:135), the lowest was tracheostomy with 15.20% (n:21). Evaluation of BLS (p:0.037), intubation (p:0.028), tracheostomy (p:0.034), trauma patient assessment (p:0.004) in the study group who applied five or more applications received higher EMRICS than those who did not apply at all. Conclusion: In order to achieve the desired competence in interventional competency goals, it is recommended to be repeated at least 5 times.