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Retrograde BMP signaling and canonical pMad/Medea-mediated transcription regulate diverse target genes across subsets of Drosophila efferent neurons, to differentiate neuropeptidergic neurons and promote motor neuron terminal maturation. How a common BMP signal regulates diverse target genes across many neuronal subsets remains largely unresolved, although available evidence implicates subset-specific transcription factor codes rather than differences in BMP signaling. Here we examine the cis-regulatory mechanisms restricting BMP-induced FMRFa neuropeptide expression to Tv4-neurons. We find that pMad/Medea bind at an atypical, low affinity motif in the FMRFa enhancer. Converting this motif to high affinity caused ectopic enhancer activity and eliminated Tv4-neuron expression. In silico searches identified additional motif instances functional in other efferent neurons, implicating broader functions for this motif in BMP-dependent enhancer activity. Thus, differential interpretation of a common BMP signal, conferred by low affinity pMad/Medea binding motifs, can contribute to the specification of BMP target genes in efferent neuron subsets.

Recent theories suggest that low frequency dynamic intramolecular and intermolecular motions in organic semiconductors (OSCs) are critical to determining the hole mobility. So far, however, it has not been possible to probe these motions directly experimentally and therefore no unequivocal and quantitative link exists between molecular-scale thermal disorder and macroscale hole mobility in OSCs. Here we use inelastic neutron scattering to probe thermal disorder directly by measuring the phonon spectrum in six different small molecule OSCs, which we accurately reproduce with first principles simulations. We use the simulated phonons to generate a set of electron-phonon coupling parameters. Using these parameters, the theoretical mobility is in excellent agreement with macroscopic measurements. Comparison of mobility between different materials reveals routes to improve mobility by engineering phonon and electron-phonon coupling.

Paiche (Arapaima gigas), is a colossal freshwater fish native to the Amazon basin. Its geographic distribution spans various regions, including Brazil, Peru, Colombia, and Guyana, making it a significant component of the aquatic ecosystems in this area. Beyond its ecological role, the paiche holds substantial importance as a valuable fish resource for local communities, providing sustenance and economic opportunities. This review provides a comprehensive analysis of the reproductive aspects of the paiche, based on information published from January 2000 to January 2022. It encompasses a wide range of reproductive characteristics, including sexual differentiation, age at first maturity, and identification techniques. Additionally, it offers an evaluation of various mating behaviors, highlighting their respective advantages and disadvantages. The review also explores genetic and behavioral traits observed in both wild and captive specimens, offering valuable insights for the effective management of breeding programs.

Self-healing cementitious materials containing microcapsules filled with healing agents can autonomously seal cracks and restore structural integrity. However, optimising the microcapsule mechanical properties to survive concrete mixing whilst still rupturing at the cracked interface to release the healing agent remains challenging. This study develops an integrated numerical modelling and machine learning approach for tailoring acrylate-based microcapsules for triggering within cementitious matrices. Microfluidics is first utilised to produce microcapsules with systematically varied shell thickness, strength, and cement compatibility. The capsules are characterised and simulated using a continuum damage mechanics model that is able to simulate cracking. A parametric study investigates the key microcapsule and interfacial properties governing shell rupture versus matrix failure. The simulation results are used to train an artificial neural network to rapidly predict the triggering behaviour based on capsule properties. The machine learning model produces design curves relating the microcapsule strength, toughness, and interfacial bond to its propensity for fracture. By combining advanced simulations and data science, the framework connects tailored microcapsule properties to their intended performance in complex cementitious environments for more robust self-healing concrete systems.

Abstract Background Geriatric co-management is advocated to manage frail patients in the hospital, but there is no guidance on how to implement such programmes in practice. This paper reports our experiences with implementing the ‘Geriatric CO-mAnagement for Cardiology patients in the Hospital’ (G-COACH) programme. We investigated if G-COACH was feasible to perform after the initial adoption, investigated how well the implementation strategy was able to achieve the implementation targets, determined how patients experienced receiving G-COACH, and determined how healthcare professionals experienced the implementation of G-COACH. Methods A feasibility study of the G-COACH programme was performed using a one-group experimental study design. G-COACH was previously implemented on two cardiac care units. Patients and healthcare professionals participating in the G-COACH programme were recruited for this evaluation. The feasibility of the programme was investigated by observing the reach, fidelity and dose using registrations in the electronic patient record and by interviewing patients. The success of the implementation reaching its targets was evaluated using a survey that was completed by 48 healthcare professionals. The experiences of 111 patients were recorded during structured survey interviews. The experiences of healthcare professionals with the implementation process was recorded during 6 semi-structured interviews and 4 focus groups discussions (n = 27). Results The programme reached 91% in a sample of 151 patients with a mean age of 84 years. There was a high fidelity for the major components of the programme: documentation of geriatric risks (98%), co-management by specialist geriatrics nurse (95%), early rehabilitation (80%), and early discharge planning (74%), except for co-management by the geriatrician (32%). Both patients and healthcare professionals rated G-COACH as acceptable (95 and 94%) and feasible (96 and 74%). The healthcare professionals experienced staffing, competing roles and tasks of the geriatrics nurse and leadership support as important determinants for implementation. Conclusions The implementation strategy resulted in the successful initiation of the G-COACH programme. G-COACH was perceived as acceptable and feasible. Fidelity was influenced by context factors. Further investigation of the sustainability of the programme is needed. Trial registration ISRCTN22096382 (21/05/2020).

Abstract Background Transplantation offers the best survival for patients with end stage organ disease. Transplant of hepatitis C virus (HCV) nucleic acid test (NAT) positive organs into negative recipients is a novel strategy that can expand the donor pool. We aim to evaluate our centre’s experience. Methods We preformed a retrospective review of anti-HCV NAT positive and negative organs into negative recipients transplanted over 27 months. Primary outcome was the success rate of eradication of HCV post-transplant. Secondary outcomes were rate of transmission of HCV, treatment adverse events, and graft failure. Results 33 anti-HCV positive organs were transplanted into negative recipients. 22 (66.7%) were NAT positive. Median recipients age was 49 years (interquartile range [IQR] 44.5–62.0) with the majority being males (57.6%). NAT positive organ transplantations included 16 kidneys, 3 livers, 1 kidney-pancreas, 1 liver-kidney, and 1 heart. The most common HCV genotype was 1a (59.1%). The median time to initiating therapy was 41.5 days. SVR12 was 100% in patients who finished therapy. There were no adverse events with therapy and no graft failure. Conclusions Anti-HCV NAT positive organ transplantation into negative recipients is safe with excellent eradication rates and no significant adverse events or graft failure. This would expand donor pool to close the gap between supply and demand.

Late-onset combined immunodeficiency (LOCID), considered now a subset of common variable immunodeficiency (CVID) disorders, is characterized by a predominantly T-cell immune defect. LOCID has a distinct phenotype from CVID with a greater risk of lymphoproliferative complications. As compared to the CVID cohort, LOCID patients also have increased rates of splenomegaly and granulomatous disease. We report a case of central nervous system (CNS) T-cell lymphoma in a 67-year-old male as the presenting manifestation of LOCID. The patient achieved a complete response to therapy after 4 cycles of MATRix (methotrexate, cytarabine, and thiotepa) and 2 cycles of ICE (etoposide, carboplatin, and ifosfamide) chemotherapy followed by CNS-directed autologous stem cell transplantation. Intravenous immunoglobulin replacement was commenced to address the underlying immunodeficiency. Pulmonary lesions consistent with a diagnosis of granulomatous and lymphocytic interstitial lung disease (GLILD) were identified as a second noninfectious complication of LOCID. The pulmonary lesions resolved after chemotherapy and immunoglobulin replacement. The patient remains well with no evidence of disease recurrence now more than 18 months after completion of therapy. This is the first reported case of T-cell lymphoma in an adult patient with LOCID. Further study is needed to elucidate the mechanisms of transformation of B- or T-cells to lymphoproliferation in primary immunodeficiency patients as well as research to inform evidence-based therapeutic strategies for this challenging cohort of patients.

Abstract Polyhydroxyalkanoates (PHA) are biodegradable biopolymers of microbial origin that can be alternative materials to decrease the extensive use of plastics of petrochemical or synthetic origin. Thus, the selection of microorganisms with potential for PHA production from unexplored natural sources is a strategy to find bacterial species of high value. In the current study, 55 microbial strains related to bacteria were isolated from agricultural soils from Cascas, Peru. Initially, 4 strains were selected by Sudan Black B staining and Nile blue A fluorescence methods, subsequently, they were screened to examine its production capacity of PHA. Bacillus thuringiensis SP7-1 strain was selected based on its high production of PHA at 0.54 ± 0.16 g/L with an accumulation of 19 % by weight of cell biomass, during 72 h at 30 ºC. The isolate was characterized by its morphology, biochemical and molecular tests through the 16S rRNA gene. The extracted PHA was characterized quantitatively by HPLC and qualitatively by FT-IR. Its thermal properties were determined by TGA and DSC, revealing a thermal degradation temperature of up to 270-303 ºC and a melting temperature of 166.88 °C. Therefore, Bacillus thuringiensis SP7-1 can be used as a model system for the production of PHA with efficient thermal stability, and optimize its performance in future research, as well as being applied in obtaining of molded bioplastics.

Abstract Background Patients with acute low back pain frequently request diagnostic imaging, and clinicians feel pressure to acquiesce to such requests to sustain patient trust and satisfaction. Spinal imaging in patients with acute low back pain poses risks from diagnostic evaluation of false-positive findings, patient labeling and anxiety, and unnecessary treatment (including spinal surgery). Watchful waiting advice has been an effective strategy to reduce some low-value treatments, and some evidence suggests a watchful waiting approach would be acceptable to many patients requesting diagnostic tests. Methods We will use key informant interviews of clinicians and focus groups with primary care patients to refine a theory-informed standardized patient-based intervention designed to teach clinicians how to advise watchful waiting when patients request low-value spinal imaging for low back pain. We will test the effectiveness of the intervention in a randomized clinical trial. We will recruit 8–10 primary care and urgent care clinics (~ 55 clinicians) in Sacramento, CA; clinicians will be randomized 1:1 to intervention and control groups. Over a 3- to 6-month period, clinicians in the intervention group will receive 3 visits with standardized patient instructors (SPIs) portraying patients with acute back pain; SPIs will instruct clinicians in a three-step model emphasizing establishing trust, empathic communication, and negotiation of a watchful waiting approach. Control physicians will receive no intervention. The primary outcome is the post-intervention rate of spinal imaging among actual patients with acute back pain seen by the clinicians adjusted for rate of imaging during a baseline period. Secondary outcomes are use of targeted communication techniques during a follow-up visit with an SP, clinician self-reported use of watchful waiting with actual low back pain patients, post-intervention rates of diagnostic imaging for other musculoskeletal pain syndromes (to test for generalization of intervention effects beyond back pain), and patient trust and satisfaction with physicians. Discussion This trial will determine whether standardized patient instructors can help clinicians develop skill in negotiating a watchful waiting approach with patients with acute low back pain, thereby reducing rates of low-value spinal imaging. The trial will also examine the possibility that intervention effects generalize to other diagnostic tests. Trial registration ClinicalTrials.gov NCT 04255199 . Registered on January 20, 2020

Nearly 80% of American adults between the ages of 33-44 have at least some postsecondary education, which ranges from vocational training to a doctorate or professional degree. However, in education-health studies, postsecondary credentials are often grouped into a limited number of categories. This is an important omission as it obscures differentiations between the various types of postsecondary credentials. This study provides the first comprehensive analysis of disparities in health behaviors across detailed levels of postsecondary education. Data comes from Wave 5 of the 2018 National Longitudinal Study of Adolescent to Adult Health (Add Health). A covariance-weighting technique is used to produce behavioral index scores that identify the full spectrum of health behaviors influenced by postsecondary educational attainment. Estimates are initially produced in aggregate for the total sample population, with interaction models subsequently being used to test differences across gender and race/ethnicity population subgroups. The aggregate results indicate that adults with at least a bachelor's degree exhibit healthier lifestyles; however, no difference is observed among adults with lower-level postsecondary credentials, compared to high school graduates. Women experience steeper gradients at higher levels of postsecondary education, compared to men. Both White and Hispanic American adults exhibit comparable health lifestyles across levels of postsecondary education; however, Black Americans were found to experience no returns except at the doctorate or professional degree level. These findings have important implications particularly as adults in their thirties and forties continue to exhibit troubling health and mortality trends.

Abstract Background Up to one in three of older patients who are hospitalised develop functional decline, which is associated with sustained disability, institutionalisation and death. This study developed and validated a clinical prediction model that identifies patients who are at risk for functional decline during hospitalisation. The predictive value of the model was compared against three models that were developed for patients admitted to a general medical ward. Methods A prospective cohort study was performed on two cardiac care units between September 2016 and June 2017. Patients aged 75 years or older were recruited on admission if they were admitted for non-surgical treatment of an acute cardiovascular disease. Hospitalisation-associated functional decline was defined as any decrease on the Katz Index of Activities of Daily Living between hospital admission and discharge. Predictors were selected based on a review of the literature and a prediction score chart was developed based on a multivariate logistic regression model. Results A total of 189 patients were recruited and 33% developed functional decline during hospitalisation. A score chart was developed with five predictors that were measured on hospital admission: mobility impairment = 9 points, cognitive impairment = 7 points, loss of appetite = 6 points, depressive symptoms = 5 points, use of physical restraints or having an indwelling urinary catheter = 5 points. The score chart of the developed model demonstrated good calibration and discriminated adequately (C-index = 0.75, 95% CI (0.68–0.83) and better between patients with and without functional decline (chi2 = 12.8, p = 0.005) than the three previously developed models (range of C-index = 0.65–0.68). Conclusion Functional decline is a prevalent complication and can be adequately predicted on hospital admission. A score chart can be used in clinical practice to identify patients who could benefit from preventive interventions. Independent external validation is needed.

Agricultural producers and enterprises face a dizzying array of decisions every day, and the many factors that influence them are incredibly complex. Agricultural planning relies heavily on accurately calculating the yields of the various crops that will be used. If you want realistic and successful solutions, data mining is an essential component. Researchers in this study are looking for ways to evaluate agricultural data and extract valuable information from the results in order to increase agricultural output. Use of the CART and random forest algorithms is a data mining technique that may be used to various datasets. It is possible to recognise the effects of various climatic and other factors on agricultural output using the MATLAB software and data mining methods, and a potential strategy is highlighted.

Background Multimorbidity is common, and care is impacted by patient life context. Effective, efficient interventions to improve patient-centered outcomes such as perceived treatment burden are limited. There is a need for interventions that integrate patient contextual information into primary care encounters to improve such outcomes. Patient life context is a multitude of factors that influence a patient’s life and healthcare, including social determinants of health and broader elements such as family and work demands. Methods This pilot randomized controlled trial (RCT) protocol will compare standard pre-visit planning to context-informed pre-visit planning that incorporates the patient’s life context, for patients with diabetes plus other chronic comorbid conditions. Primary outcomes include measures of trial protocol and intervention feasibility and acceptability: physician study and visit perceived burden, patient satisfaction, and patient, physician and staff experience with the trial. Additional measurements of intervention impact include: initial estimates of effect size on patient treatment burden and other patient-oriented outcomes, change in glycemic control, and other intermediate medical outcomes. Discussion This intervention is novel as it collects patient life context information using a direct person-to-person approach, allows physicians to review the information prior to patient arrival at the clinic and, where appropriate, incorporate it when negotiating treatment plans, and is longitudinal, summarizing evolving contextual information over time. This pilot RCT has the potential to demonstrate trial protocol and intervention feasibility and acceptability, and estimate effect size on patient and provider outcomes, to inform for a future, definitive RCT. Trial Registration: This trial was registered at ClinicalTrials.gov prior to patient enrollment: NCT04568382

Background: The COVID-19 pandemic impacted the psychological wellbeing of populations worldwide. In this study, we assess changes in mental health during the early months of the pandemic in Canada and examine its relationship with another prominent problem during this time, economic concerns. Methods: Analyses were based on two cycles of the nationally representative repeated cross-sectional Canadian Perspectives Survey Series (N=4627 in March and 4600 in May). We described the changes in mental health and economic concerns between March and May, and assessed the relationship between the two characteristics. Results: Mental health declined significantly during the early months of the COVID-19 pandemic: the proportion of Canadian adults who reported only good/fair/poor mental health grew from 46% to 52% from March to May. Economic concerns including food insecurity were an important correlate of ‘bad’ mental health, as was younger age, female gender, and Canada-born status. Contrary to expectations, however, economic concerns lessened during this time frame. Conclusions: These findings suggest that policies to mitigate economic stress, such as Canada's Emergency Response Benefit, may have eased mental health deterioration in early pandemic months through a reduction in financial hardship. Interventions to increase the economic security of the population will have far-reaching consequences in terms of improved mental health, and should be continued throughout the pandemic.

Background: In Ontario, kidney transplants have risen by 4% annually in recent years. An understanding of how this will affect the future annual number of posttransplant follow-up visits informs how to organize and deliver care. Objective: We projected the required number of annual posttransplant follow-up nephrology visits to inform posttransplant care delivery. Design: Population-based retrospective cohort study. Setting: Linked databases from Ontario, Canada (population 14 million). Patients: Incident kidney transplant recipients from years 2008 to 2013. Measurements: Frequency, distance traveled, and current and projected visits for posttransplant follow-up. Methods: Assuming a graft survival of 13 years and using the mean number of posttransplant clinic visits in years 1, 2, and 3, we forecasted the number of clinic visits needed in the year 2027. Results: Using data from 2443 recipients, the mean (SD) number of clinic visits per recipient was 14.0 (9.2) in the first year after transplant, and 3.9 (6.2) and 3.0 (5.3) in the second and third year, respectively. If transplant rates rise by 4% per year until 2027, the estimated annual visits number will increase from 30 622 to 43 948. The median (25th, 75th percentile) distance between transplant center and patient’s home was 30 (13, 65) km. The median round-trip travel distance for these visits in the first year after transplantation was 603 km per recipient, and median driving cost was Can$344 (2017). Limitations: Regarding patient expense, limitations include that distances traveled were calculated orthodromically, and we did not account for patient cost of follow-up beyond that of vehicular travel. Regarding follow-up projections, limitations include the assumption that graft life span will not change, follow-up patterns do not differ between donor kidney type, and we did not survey stakeholders as to their preferred method of follow-up. Conclusion: We quantified the increase in posttransplant visits when regional annual rates of transplantation rise. Strategies recognizing the burden of these visits may enhance patient-centered care, as it is unclear how some patients manage costs, nor how the current health care system will manage the demand.

Abstract Background Many medical schools use admissions Multiple Mini-Interviews (MMIs) rather than traditional interviews (TIs), partly because MMIs are thought to be more reliable. Yet prior studies examined single-school samples of candidates completing either an MMI or TI (not both). Using data from five California public medical schools, the authors examined the within- and between-school reliabilities of TIs and MMIs. Methods The analyses included applicants interviewing at ≥1 of the five schools during 2011–2013. Three schools employed TIs (TI1, TI2, TI3) and two employed MMIs (MMI1, MMI2). Mixed linear models accounting for nesting of observations within applicants examined standardized TI and MMI scores (mean = 0, SD = 1), adjusting for applicant socio-demographics, academic metrics, year, number of interviews, and interview date. Results A total of 4993 individuals (completing 7516 interviews [TI = 4137, MMI = 3379]) interviewed at ≥1 school; 428 (14.5%) interviewed at both MMI schools and 687 (20.2%) at more than one TI school. Within schools, inter-interviewer consistency was generally qualitatively lower for TI1, TI2, and TI3 (Pearson’s r 0.07, 0.13, and 0.29, and Cronbach’s α, 0.40, 0.44, and 0.61, respectively) than for MMI1 and MMI 2 (Cronbach’s α 0.68 and 0.60, respectively). Between schools, the adjusted intraclass correlation coefficient was 0.27 (95% CI 0.20–0.35) for TIs and 0.47 (95% CI 0.41–0.54) for MMIs. Conclusions Within and between-school reliability was qualitatively higher for MMIs than for TIs. Nonetheless, TI reliabilities were higher than anticipated from prior literature, suggesting TIs may not need to be abandoned on reliability grounds if other factors favor their use.

Esta investigación mixta, cualitativa de abordaje IAP. OMS (1997), tuvo como objetivo mejorar la calidad de vida en personas con VIH del Grupo de Autoayuda Mutua a través del Modelo de Calidad de Vida relacionado con la salud. La muestra lo conformaron 37 personas, a quienes se aplicó la entrevista semiestructurada y el cuestionario de GENCAT. El estudio tuvo el rigor científico de Hernández (1998) y los principios de la Bioética Personalista de Sgreccia (2001). Los datos fueron procesados por análisis temático según Minayo (2003) y la descripción en gráficos estadísticos. Se obtuvieron las categorías, en primer momento: Malestar biorgánico por TARGA y seropositividad. Trastornos psicológicos con subcategorías: depresión; comportamiento suicida y baja autoestima. Tercera categoría: dificultad en las relaciones sociofamiliares, con subcategorías: exclusión social, discriminación y problemas en la relación de pareja y sexualidad. Posterior a proyectos de acción emergieron: incrementando el autocuidado para hacer frente los efectos adversos de la TARGA y seropositividad. Expresando bienestar psicológico para adquirir conocimientos y mejorando relaciones sociofamiliares y sexualidad. Se concluyó que las afecciones orgánicas, consecuencia de la TARGA y seropositividad, van acompañados de trastornos psicológicos dado el proceso de adaptación al diagnóstico, que están o pasaron crisis de depresión, comportamientos suicidas, baja autoestima y vivenciaron discriminación por familiares, pareja y sociedad; afectando su calidad de vida. Posterior a la intervención, los resultados fueron positivos, observándose cambios notorios.

Materials for Life (M4L) was a 3 year, EPSRC funded, research project carried out by the Universities of Cardiff, Bath and Cambridge to investigate the development of self-healing cementitious construction materials. This paper describes the UK's first site trial of self-healing concrete, which was the culmination of that project. The trial comprised the in-situ construction of five concrete panels using a range of self-healing technologies within the site compound of the A465 Heads of the Valleys Highway upgrading project. Four self-healing techniques were used both individually and in combination with one another. They were: (i) the use of microcapsules developed by the University of Cambridge, in collaboration with industry, containing mineral healing agents, (ii) bacterial healing using the expertise developed at Bath University, (iii) the use of a shape memory polymer (SMP) based system for crack closure and (iv) the delivery of a mineral healing agent through a vascular flow network. Both of the latter, (iii) and (iv), were the product of research undertaken at Cardiff University. This paper describes the design, construction, testing, and monitoring of these trial panels and presents the primary findings of the exercise. The challenges that had to be overcome to incorporate these self-healing techniques into full-scale structures on a live construction site are highlighted, the impact of the different techniques on the behavior of the panels when subject to loading is presented and the ability of the techniques used to heal the cracks that were generated is discussed.

Background: Renal transplant recipients (RTRs) are at significantly higher risk for morbidity and mortality compared with the general population, largely attributed to cardiovascular disease (CVD). Previous estimates of CVD events have come from health care databases and retrospective studies. Objective: The objective of this study was to prospectively determine the prevalence of risk factors and incidence of CVD events in a Canadian cohort of RTRs. Design: Study of Cardiovascular Outcomes in Renal Transplantation (SCORe) was a prospective, longitudinal, multicenter observational study. Setting: Adult RTRs were recruited from 6 participating transplant sites in Ontario, Canada. Patients: Eligible patients were those receiving a living or deceased donor renal transplant. Patients who received simultaneous transplant of any other organ were excluded. Measurements: Primary outcomes included myocardial infarction (MI) defined by American College of Cardiology (ACC-MI) criteria, and major adverse cardiac events (MACE), defined as cardiovascular (CV) death, ACC-MI, coronary revascularization, and nonhemorrhagic stroke. CV events were adjudicated by a single, independent cardiologist. Methods: CV and transplant-specific risk factors that predict MACE and ACC-MI were identified by stepwise regression analysis using the Cox proportional hazards model. Results: A total of 1303 patients enrolled across 6 transplant centers were followed for 4.5 ± 1.6 years (mean ± SD). Incidence of MACE was 7.0%, with significant independent predictors/risk factors including age, diabetes, coronary revascularization, nonhemorrhagic stroke, and renal replacement therapy (RRT). ACC-MI incidence was 4.0%, with significant independent predictors/risk factors including age, coronary revascularization, and duration of RRT in excess of the median value (2.91 years). Limitations: Patients were recruited from a single province, so may not reflect the experience of RTRs in other areas of Canada. Conclusions: Using a prospective design and rigorous methodology, this study found that the incidence of CV events after renal transplantation was elevated relative to the general Canadian population and was comparable with that reported in patient registries, thus helping validate the utility of retrospective analysis in this field. SCORe highlights the importance of monitoring RTRs for traditional cardiac and transplant-specific CV risk factors to help prevent CV morbidity and mortality. Further research is needed to investigate a broader range of potential risk factors and their combined effects on incident CV events.

Anthony Jerant1, Peter Franks1, Daniel J Tancredi2, Naomi Saito3, Richard L Kravitz41Department of Family and Community Medicine, Center for Healthcare Policy and Research, University of California Davis School of Medicine, Sacramento, CA, USA; 2Department of Pediatrics, Center for Healthcare Policy and Research, University of California Davis School of Medicine, Sacramento, CA, USA; 3Center for Healthcare Policy and Research, University of California Davis School of Medicine, Sacramento, CA, USA; 4Department of Internal Medicine, Division of General Medicine, Center for Healthcare Policy and Research, University of California Davis School of Medicine, Sacramento, CA, USABackground: Patients’ general tendency to adhere to health care provider-recommended treatments is associated with a number of health outcomes, but whether it influences pain severity over time among individuals with cancer is unclear. We explored the relationship between adherence tendency and subsequent pain severity among cancer patients participating in a randomized controlled trial of coaching to enhance communication with physicians and reduce pain severity.Methods: Associations between baseline Medical Outcomes Study general adherence measure score and pain severity over 12 weeks were examined with repeated-measures regression models. Model 1 included sociodemographics, study group and site, follow-up point, and baseline pain; Model 2 included these variables plus partner status, physical and mental health status (12-item Short Form Health Survey [SF-12®]), and pain control self-efficacy.Results: Of 307 patients randomized, 224 (73%) had at least one follow-up pain severity assessment plus complete data for other model variables and were included in the analyses. In Model 1, adherence tendency was associated with less subsequent pain severity: a one standard deviation increase in adherence tendency was associated with a 0.22-point adjusted mean decrease in pain severity on a 0–10 scale (95% confidence interval 0.40, 0.03). The association was diminished and not statistically significant in Model 2, primarily due to adjustment for the SF-12.Conclusion: Tendency to adhere to provider-recommended treatments was associated with subsequent pain severity among individuals with cancer, suggesting a potential way of predicting and intervening to improve cancer pain control. However, the association was attenuated after adjusting for health status, suggesting mediation or confounding of the relationship by health status.Keywords: health status, longitudinal studies, neoplasms, outcome assessment (health care)

This study is dedicated to the experimental characterisation and phenomenological modeling of the bake hardening effect of a thin steel sheet, to predict the static dent resistance and perform an experimental validation on a bulged part. In a first step, rectangular samples are submitted to a thermo-mechanical loading to characterise the bake hardening magnitude in tension. A three-step procedure is considered, involving first a pre-strain in tension up to several values followed by unloading. Secondly, a heat treatment during a fixed time and a given temperature is performed, and finally, a reloading in tension in the same direction as the pre-strain is applied. Then, a specific device is developed to perform dent tests on a bulged specimen, to evaluate the influence of bake hardening on the dent resistance. A three-step procedure is also considered, with a pre-strain applied with a hydraulic bulge test followed by a heat treatment and then static dent test at the maximum dome height. An original phenomenological model is proposed to represent the yield stress increase after the heat treatment and the second reloading. Material parameters are identified from the tensile tests and are input data to a finite element model. The numerical prediction of the load evolution during the dent test is then compared with experimental data and shows an overall good correlation.

Ischemia reperfusion (I/R) injury is an unavoidable event occurring during heart transplantation, leading to graft failures and lower long-term survival rate of the recipient. Several studies have demonstrated that microRNAs (miRNAs) are vital regulators of signalling pathways involved in I/R injury. The present study aims to quantify the altered expression levels of miRNA and mRNA upon I/R injury in a mouse heart transplantation model, and to investigate whether these miRNA can regulate genes involved in I/R injury. We performed heterotopic heart transplantation on mouse models to generate heart tissue samples with I/R and non-I/R (control). The expression levels of miRNAs as well as genes were measured in heart grafts by microarray and real time RT-PCR. miRNA alteration in cardiomyocytes exposed to hypoxia was also detected by qRT-PCR. We observed significant alterations in miRNA and gene expression profile after I/R injury. There were 39 miRNAs significantly downregulated and 20 upregulated up to 1.5 fold in heart grafts with I/R injury compared with the grafts without I/R. 48 genes were observed with 3 fold change and p

Abstract Objective To assess the confidence, practices and perceived training needs in diabetes care of post-graduate trainee doctors in the UK. Methods An anonymised postal questionnaire using a validated 'Confidence Rating' (CR) scale was applied to aspects of diabetes care and administered to junior doctors from three UK hospitals. The frequency of aspects of day-to-day practice was assessed using a five-point scale with narrative description in combination with numeric values. Respondents had a choice of 'always' (100%), 'almost always' (80–99%), 'often' (50–79%), 'not very often' (20–49%) and 'rarely' (less than 20%). Yes/No questions were used to assess perception of further training requirements. Additional 'free-text' comments were also sought. Results 82 doctors completed the survey. The mean number of years since medical qualification was 3 years and 4 months, (range: 4 months to 14 years and 1 month). Only 11 of the respondents had undergone specific diabetes training since qualification. 4(5%) reported 'not confident' (CR1), 30 (37%) 'satisfactory but lacked confidence' (CR2), 25 (30%) felt 'confident in some cases' (CR3) and 23 (28%) doctors felt fully confident (CR4) in diagnosing diabetes. 12 (15%) doctors would always, 24 (29%) almost always, 20 (24%) often, 22 (27%) not very often and 4 (5%) rarely take the initiative to optimise gcaemic control. 5 (6%) reported training in diagnosis of diabetes was adequate while 59 (72%) would welcome more training. Reported confidence was better in managing diabetes emergencies, with 4 (5%) not confident in managing hypoglycaemia, 10 (12%) lacking confidence, 22 (27%) confident in some cases and 45 (55%) fully confident in almost all cases. Managing diabetic ketoacidosis, 5 (6%) doctors did not feel confident, 16 (20%) lacked confidence, 20 (24%) confident in some cases, and 40 (50%) felt fully confident in almost all cases. Conclusion There is a lack of confidence in managing aspects of diabetes care, including the management of diabetes emergencies, amongst postgraduate trainee doctors with a perceived need for more training. This may have considerable significance and further research is required to identify the causes of deficiencies identified in this study.

Abstract Background As many as 30% of doctors working for the National Health System (NHS) of the United Kingdom of Great Britain and Northern Ireland (UK) have obtained their primary qualifications from a country outside the European Union. However, factors driving this migration of doctors to the UK merit continuing exploration. Our objective was to obtain training and employment profile of UK doctors who obtained their primary medical qualification outside the European Union (non-European doctors) and to assess self-reported reasons for their migration. Methods We conducted an online survey of non-European doctors using a pre-validated questionnaire. Results One thousand six hundred and nineteen doctors of 26 different nationalities completed the survey. Of the respondents, 90.1% were from India and over three-quarters migrated to the UK mainly for 'training'. Other reasons cited were 'better pay' (7.2%), 'better work environment' (7.1%) and 'having family and friends in the UK' (2.8%). Many of the respondents have been in the UK for more than a year (88.8%), with 31.3% having spent more than 3 years gaining experience of working in the NHS. Most respondents believe they will be affected by recent changes to UK immigration policy (86.6%), few report that they would be unaffected (3.7%) and the rest are unsure (9.8%). Conclusion The primary reason for many non-European doctors to migrate to the UK is for training within the NHS. Secondary reasons like better pay, better work environment and having friends and family in the UK also play a role in attracting these doctors, predominantly from the Indian subcontinent and other British Commonwealth countries.

In the pursuit of achieving high-performance and high-throughput organic transistors, this study highlights two critical aspects: designing new soluble acenes and optimizing their solution processing. A fundamental understanding of the crystallization mechanism inherent to these customized soluble acenes, as they undergo a transformation during the evaporation of residual solvent, is deemed essential. Here, the pathway to crafting ideal solution processing conditions is elucidated, meticulously tailored to the molecular structure of soluble acenes when blended with polymers. Employing a comprehensive array of analytical and computational methodologies, this investigation delves directly into the intricate interplay between processing parameters and crystallization mechanisms, firmly rooted in the domains of thermodynamics and kinetics. Notably, a delicate equilibrium where the optimal weight of residual solvent harmoniously aligns is uncovered with the specific attributes of soluble acene molecules, exerting influence over vertical phase separation with the blended polymer and the crystallization process of soluble acenes at the surface. Consequently, transistors showcasing remarkable field-effect mobility exceeding 8 cm 2  V -1  s -1 are successfully developed. These findings provide invaluable guidance for navigating the path toward determining optimal solution processing conditions across a diverse array of soluble acene/polymer blend systems, all achieved through the strategic application of crystal and residual solvent engineering., (© 2024 Wiley‐VCH GmbH.)

A seventh blind test of crystal structure prediction has been organized by the Cambridge Crystallographic Data Centre. The results are presented in two parts, with this second part focusing on methods for ranking crystal structures in order of stability. The exercise involved standardized sets of structures seeded from a range of structure generation methods. Participants from 22 groups applied several periodic DFT-D methods, machine learned potentials, force fields derived from empirical data or quantum chemical calculations, and various combinations of the above. In addition, one non-energy-based scoring function was used. Results showed that periodic DFT-D methods overall agreed with experimental data within expected error margins, while one machine learned model, applying system-specific AIMnet potentials, agreed with experiment in many cases demonstrating promise as an efficient alternative to DFT-based methods. For target XXXII, a consensus was reached across periodic DFT methods, with consistently high predicted energies of experimental forms relative to the global minimum (above 4 kJ mol -1 at both low and ambient temperatures) suggesting a more stable polymorph is likely not yet observed. The calculation of free energies at ambient temperatures offered improvement of predictions only in some cases (for targets XXVII and XXXI). Several avenues for future research have been suggested, highlighting the need for greater efficiency considering the vast amounts of resources utilized in many cases., (open access.)

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern. The use of CSP in the prediction of likely cocrystal stoichiometry was also explored, demonstrating multiple possible approaches. Crystallographic disorder emerged as an important theme throughout the test as both a challenge for analysis and a major achievement where two groups blindly predicted the existence of disorder for the first time. Additionally, large-scale comparisons of the sets of predicted crystal structures also showed that some methods yield sets that largely contain the same crystal structures., (open access.)

Singlet fission, the process of transforming a singlet excited state into two lower energy triplet excited states, is a promising strategy for improving the efficiency of dye-sensitized solar cells. The difficulty in utilizing singlet fission molecules in this architecture is understanding and controlling the orientation of dyes on mesoporous metal oxide surfaces to maximize triplet production and minimize detrimental deactivation pathways, such as electron injection from the singlet or excimer formation. Here, we varied the concentration of loading solutions of two anthradithiophene dyes derivatized with either one or two carboxylic acid groups for binding to a metal oxide surface and studied their photophysics using ultrafast transient absorption spectroscopy. For the single carboxylic acid case, an increase in dye surface coverage led to an increase in apparent triplet excited-state growth via singlet fission, while the same increase in coverage with two carboxylic acids did not. This study represents a step toward controlling the interactions between molecules at mesoporous interfaces., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

A previously unreported polymorph of 5,11-bis(triisopropylsilylethynyl)anthradithiophene (TIPS ADT), Form II, crystallizes from melt-processed TIPS ADT films blended with 16 ± 1 wt % medium density polyethylene (PE). TIPS ADT/PE blends that initially are crystallized from the melt produce twisted TIPS ADT crystals of a metastable polymorph (Form IV, space group P 1̅) with a brickwork packing motif distinct from the slipstack packing by solution-processed TIPS ADT crystals (Form I, space group P 2 1 / c ) at room temperature. When these films were cooled to room temperature and subsequently annealed at 100 °C, near a PE melting temperature of 110 °C, Form II crystals nucleated and grew while consuming Form IV. The growth rate and orientations of Form II crystals were predetermined by the twisting pitch and growth direction of the original banded spherulites in the melt-processed films of the blends. Notably, the Form IV → II transition was not observed during thermal annealing of neat TIPS ADT films without PE. The presence of the mobile PE phase during thermal annealing of TIPS ADT/PE blend films increases the diffusion rate of TIPS ADT molecules, and the rate of nucleation of Form II. Form IV crystals are more conductive but less emissive compared to Form II crystals., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Tetraceno[2,3- b ]thiophene is regarded as a strong candidate for singlet fission-based solar cell applications due to its mixed characteristics of tetracene and pentacene that balance exothermicity and triplet energy. An electronically weakly coupled tetraceno[2,3- b ]thiophene dimer (Et 2 Si(TIPSTT) 2 ) with a single silicon atom bridge has been synthesized, providing a new platform to investigate the singlet fission mechanism involving the two acene chromophores. We study the excited state dynamics of Et 2 Si(TIPSTT) 2 by monitoring the evolution of multiexciton coupled triplet states, 1 TT to 5 TT to 3 TT to T 1 + S 0 , upon photoexcitation with transient absorption, temperature-dependent transient absorption, and transient/pulsed electron paramagnetic resonance spectroscopies. We find that the photoexcited singlet lifetime is 107 ps, with 90% evolving to form the TT state, and the complicated evolution between the multiexciton states is unraveled, which can be an important reference for future efforts toward tetraceno[2,3- b ]thiophene-based singlet fission solar cells.

Blends comprising organic semiconductors and inorganic quantum dots (QDs) are relevant for many optoelectronic applications and devices. However, the individual components in organic-QD blends have a strong tendency to aggregate and phase-separate during film processing, compromising both their structural and electronic properties. Here, we demonstrate a QD surface engineering approach using electronically active, highly soluble semiconductor ligands that are matched to the organic semiconductor host material to achieve well-dispersed inorganic-organic blend films, as characterized by X-ray and neutron scattering, and electron microscopies. This approach preserves the electronic properties of the organic and QD phases and also creates an optimized interface between them. We exemplify this in two emerging applications, singlet-fission-based photon multiplication (SF-PM) and triplet-triplet annihilation-based photon upconversion (TTA-UC). Steady-state and time-resolved optical spectroscopy shows that triplet excitons can be transferred with near unity efficiently across the organic-inorganic interface, while the organic films maintain efficient SF (190% yield) in the organic phase. By changing the relative energy between organic and inorganic components, yellow upconverted emission is observed upon 790 nm NIR excitation. Overall, we provide a highly versatile approach to overcome longstanding challenges in the blending of organic semiconductors with QDs that have relevance for many optical and optoelectronic applications.

ConspectusPreparing and manipulating pure magnetic states in molecular systems are the key initial requirements for harnessing the power of synthetic chemistry to drive practical quantum sensing and computing technologies. One route for achieving the requisite higher spin states in organic systems exploits the phenomenon of singlet fission, which produces pairs of triplet excited states from initially photoexcited singlets in molecular assemblies with multiple chromophores. The resulting spin states are characterized by total spin (quintet, triplet, or singlet) and its projection onto a specified molecular or magnetic field axis. These excited states are typically highly polarized but exhibit an impure spin population pattern. Herein, we report the prediction and experimental verification of molecular design rules that drive the population of a single pure magnetic state and describe the progress toward its experimental realization.A vital feature of this work is the close partnership among theory, chemical synthesis, and spectroscopy. We begin by presenting our theoretical framework for understanding spin manifold interconversion in singlet fission systems. This theory makes specific testable predictions about the intermolecular structure and orientation relative to an external magnetic field that should lead to pure magnetic state preparation and provides a powerful tool for interpreting magnetic spectra. We then test these predictions through detailed magnetic spectroscopy experiments on a series of new molecular architectures that meet one or more of the identified structural criteria. Many of these architectures rely on the synthesis of molecules with features unique to this effort: rigid bridges between chromophores in dimers, heteroacenes with tailored singlet/triplet-pair energy level matching, or side-group engineering to produce specific crystal structures. The spin evolution of these systems is revealed through our application and development of several magnetic resonance methods, each of which has different sensitivities and relevance in environments relevant to quantum applications.Our theoretical predictions prove to be remarkably consistent with our experimental results, though experimentally meeting all the structural prescriptions demanded by theory for true pure-state preparation remains a challenge. Our magnetic spectra agree with our model of triplet-pair behavior, including funneling of the population to the m s = 0 magnetic sublevel of the quintet under specified conditions in dimers and crystals, showing that this phenomenon is subject to control through molecular design. Moreover, our demonstration of novel and/or highly sensitive detection mechanisms of spin states in singlet fission systems, including photoluminescence (PL), photoinduced absorption (PA), and magnetoconductance (MC), points the way toward both a deeper understanding of how these systems evolve and technologically feasible routes toward experiments at the single-molecule quantum limit that are desirable for computational applications.

Organic dosimeters offer unique advantages over traditional technologies, and they can be used to expand the capabilities of current radiation detection systems. In-depth knowledge of the mechanisms underlying the interaction between radiation and organic materials is essential for their widespread adoption. Here, we identified and quantitatively characterized the electronic traps generated during the operation of radiation dosimeters based on organic field-effect transistors. Spectral analysis of the trap density of states, along with optical and structural studies, revealed the origin of trap states as local structural disorder within the crystalline films. Our results provide new insights into the radiation-induced defects in organic dosimeters, and pave the way for the development of more efficient and reliable radiation detection devices.

The multiexciton quintet state, 5 TT, generated as a singlet fission intermediate in pairs of molecular chromophores, is a promising candidate as a qubit or qudit in future quantum information science schemes. In this work, we synthesize a pyrene-bridged parallel tetracene dimer, TPT, with an optimized interchromophore coupling strength to prevent the dissociation of 5 TT to two decorrelated triplet (T 1 ) states, which would contaminate the spin-state mixture. Long-lived and strongly spin-polarized pure 5 TT state population is observed via transient absorption spectroscopy and transient/pulsed electron paramagnetic resonance spectroscopy, and its lifetime is estimated to be >35 µs, with the dephasing time ( T 2 ) for the 5 TT-based qubit measured to be 726 ns at 10 K. Direct relaxation from 1 TT to the ground state does diminish the overall excited state population, but the exclusive 5 TT population at large enough persistent density for pulsed echo determination of spin coherence time is consistent with recent theoretical models that predict such behavior for strict parallel chromophore alignment and large exchange coupling., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Controlling the dispersibility of nanocrystalline inorganic quantum dots (QDs) within organic semiconductor (OSC):QD nanocomposite films is critical for a wide range of optoelectronic devices. This work demonstrates how small changes to the OSC host molecule can have a dramatic detrimental effect on QD dispersibility within the host organic semiconductor matrix as quantified by grazing incidence X-ray scattering. It is commonplace to modify QD surface chemistry to enhance QD dispersibility within an OSC host. Here, an alternative route toward optimizing QD dispersibilities is demonstrated, which dramatically improves QD dispersibilities through blending two different OSCs to form a fully mixed OSC matrix phase.

Singlet fission proceeds through a manifold of triplet-pair states that are exceedingly difficult to distinguish spectroscopically. Here, we introduce a new implementation of photoinduced-absorption-detected magnetic resonance (PADMR) and use it to understand the excited-state absorption spectrum of a tri-2-pentylsilylethynyl pentadithiophene (TSPS-PDT) film. These experiments allow us to directly correlate magnetic transitions driven by RF with electronic transitions in the visible and near-infrared spectrum with high sensitivity. We find that the new near-infrared excited-state transitions that arise in thin films of TSPS-PDT are correlated with the magnetic transitions of T 1 , not 5 TT. Thus, we assign these features to the excited-state absorption of 1 TT, which is depleted when T 1 states are driven to a spin configuration that forbids subsequent fusion. These results clarify the disputed origin of triplet-associated near-infrared absorption features in singlet-fission materials and demonstrate an incisive general purpose tool for studying the evolution of high-spin excited states.

Molecular spin systems based on photoexcited triplet pairs formed via singlet fission (SF) are attractive as carriers of quantum information because of their potentially pure and controllable spin polarization, but developing systems that offer optical routes to readout as well as initialization is challenging. Herein, we characterize the electron spin magnetic resonance change in the photoluminescence intensity for a tailored organic molecular crystal while sweeping a microwave drive up to 10 GHz in a broadband loop structure. We observe resonant transitions for both triplet and quintet spin sublevel populations showing their optical sensitivity and revealing the zero-field parameters for each. We map the evolution of these spectra in both microwave frequency and magnetic field, producing a pattern of optically detected magnetic resonance (ODMR) peaks. Fits to these data using a suitable model suggest significant spin polarization in this system with orientation selectivity. Unusual excitation intensity dependence is also observed, which inverts the sign of the ODMR signal for the triplet features, but not for the quintet. These observations demonstrate optical detection of the spin sublevel population dictated by SF and intermolecular geometry, and highlight anisotropic and multi-scale dynamics of triplet pairs.

Quantum dot-organic semiconductor hybrid materials are gaining increasing attention as spin mixers for applications ranging from solar harvesting to spin memories. Triplet energy transfer between the inorganic quantum dot (QD) and organic semiconductor is a key step to understand in order to develop these applications. Here we report on the triplet energy transfer from PbS QDs to four energetically and structurally similar tetracene ligands. Even with similar ligands we find that the triplet energy transfer dynamics can vary significantly. For TIPS-tetracene derivatives with carboxylic acid, acetic acid and methanethiol anchoring groups on the short pro- cata side we find that triplet transfer occurs through a stepwise process, mediated via a surface state, whereas for monosubstituted TIPS-tetracene derivative 5-(4-benzoic acid)-12-triisopropylsilylethynyl tetracene (BAT) triplet transfer occurs directly, albeit slower, via a Dexter exchange mechanism. Even though triplet transfer is slower with BAT the overall yield is greater, as determined from upconverted emission using rubrene emitters. This work highlights that the surface-mediated transfer mechanism is plagued with parasitic loss pathways and that materials with direct Dexter-like triplet transfer are preferred for high-efficiency applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The photo-driven process of singlet fission generates coupled triplet pairs (TT) with fundamentally intriguing and potentially useful properties. The quintet 5 TT 0 sublevel is particularly interesting for quantum information because it is highly entangled, is addressable with microwave pulses, and could be detected using optical techniques. Previous theoretical work on a model Hamiltonian and nonadiabatic transition theory, called the JDE model, has determined that this sublevel can be selectively populated if certain conditions are met. Among the most challenging, the molecules within the dimer undergoing singlet fission must have their principal magnetic axes parallel to one another and to an applied Zeeman field. Here, we present time-resolved electron paramagnetic resonance (TR-EPR) spectroscopy of a single crystal sample of a tetracenethiophene compound featuring arrays of dimers aligned in this manner, which were mounted so that the orientation of the field relative to the molecular axes could be controlled. The observed spin sublevel populations in the paired TT and unpaired (T+T) triplets are consistent with predictions from the JDE model, including preferential 5 TT 0 formation at z ‖ B 0 , with one caveat-two 5 TT spin sublevels have little to no population. This may be due to crossings between the 5 TT and 3 TT manifolds in the field range investigated by TR-EPR, consistent with the intertriplet exchange energy determined by monitoring photoluminescence at varying magnetic fields.