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Research and policy often focus on reducing attrition from educational trajectories leading to careers in science, technology, engineering, and mathematics (STEM), but many students change career plans "within" STEM. This study examined how changing career plans within STEM fields was associated with psychological indicators of career readiness. We conducted a large online survey of undergraduate students (N = 1,727) across 42 courses covering every major STEM discipline at a large U.S. research-intensive public university. Students reported about their career plans, whether plans had changed, motivation for those career plans, and satisfaction with and certainty of persisting with those plans. A trained team of coders classified whether students reported having STEM career plans at the time of the survey and at the beginning of college. Students who said they had changed career plans within STEM fields during college also reported lower motivation for their new career plans, satisfaction with those plans, and certainty of persisting in them, compared to students who retained consistent STEM career plans. With few exceptions, these associations held across students' gender, race, year in school, and STEM field of study. Within-STEM career plan changes were very common, reported by 55% of fourth-year STEM students. Women reported changing career plans within STEM fields more often than men. Results suggest that changing career plans within STEM is an important phenomenon to consider in preparing a qualified and diverse STEM workforce. Students who change career plans within STEM fields may need additional supports for their career motivation and satisfaction compared to students who do not change plans.

Background: Common genetic variants with small effect sizes have been associated with rotator cuff tearing although very few rare, highly penetrant variants have been identified. The purpose of this pilot study was to identify dominant coding variants that segregated with affected individuals in pedigrees at high risk for rotator cuff tears (RCTs). We hypothesize that rare variants contribute to symptomatic RCTs and that they can be identified in related cases with a full-thickness tear requiring surgical management. Methods: We used the Utah Population Database to identify pedigrees that exhibited a significant excess of individuals who had undergone surgical repair of a full-thickness RCT. We analyzed whole exome sequence analysis to identify rare coding variants in 9 independent affected cousin pairs (first or second cousins) who had undergone arthroscopic surgery for repair of a full-thickness RCT (mean age at diagnosis 68 years). Validation of association of the candidate variants with risk for rotator cuff tearing was accomplished utilizing data from the UK Biobank and a separate cohort of unrelated cases of full-thickness RCTs. Results: A total of 82 rare (minor allele frequency

PurposeTo describe the application of the light adjustable lens (LAL) using an intrascleral haptic fixation (ISHF) technique for the correction of aphakia and post-operative refractive error.ObservationThe LAL was placed using a modified trocar-based ISHF technique for visual rehabilitation following removal of bilateral cataracts in a patient with ectopia lentis. She ultimately obtained an excellent refractive outcome after adjustment with micro-monovision.Conclusions and importanceSecondary intraocular lens placement has a much higher risk of residual ametropia than traditional in-the-bag lens placement. The ISHF technique with the LAL presents a solution for eliminating postoperative refractive error in patients requiring scleral-fixated lenses.

BackgroundDecades of research have transformed hemophilia from severely limiting children's lives to a manageable disorder compatible with a full, active life, for many in high-income countries. The direction of future research will determine whether exciting developments truly advance health equity for all people with hemophilia (PWH). National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive inclusive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them.Research design and methodsWorking group (WG) 1 of the NHF State of the Science Research Summit distilled the community-identified priorities for hemophilia A and B into concrete research questions and scored their feasibility, impact, and risk.ResultsWG1 defined 63 top priority research questions concerning arthropathy/pain/bone health, inhibitors, diagnostics, gene therapy, the pediatric to adult transition of care, disparities faced by the community, and cardiovascular disease. This research has the potential to empower PWH to thrive despite lifelong comorbidities and achieve new standards of wellbeing, including psychosocial.ConclusionsCollaborative research and care delivery will be key to capitalizing on current and horizon treatments and harnessing technical advances to improve diagnostics and testing, to advance health equity for all PWH.

Abstract Background Research and policy often focus on reducing attrition from educational trajectories leading to careers in science, technology, engineering, and mathematics (STEM), but many students change career plans within STEM. This study examined how changing career plans within STEM fields was associated with psychological indicators of career readiness. We conducted a large online survey of undergraduate students (N = 1,727) across 42 courses covering every major STEM discipline at a large U.S. research-intensive public university. Students reported about their career plans, whether plans had changed, motivation for those career plans, and satisfaction with and certainty of persisting with those plans. A trained team of coders classified whether students reported having STEM career plans at the time of the survey and at the beginning of college. Results Students who said they had changed career plans within STEM fields during college also reported lower motivation for their new career plans, satisfaction with those plans, and certainty of persisting in them, compared to students who retained consistent STEM career plans. With few exceptions, these associations held across students’ gender, race, year in school, and STEM field of study. Within-STEM career plan changes were very common, reported by 55% of fourth-year STEM students. Women reported changing career plans within STEM fields more often than men. Implications Results suggest that changing career plans within STEM is an important phenomenon to consider in preparing a qualified and diverse STEM workforce. Students who change career plans within STEM fields may need additional supports for their career motivation and satisfaction compared to students who do not change plans.

Accurate isolation and identification of pathogens for an animal with bovine respiratory disease are of critical importance to direct appropriate decision-making related to the treatment of individual animals, as well as control and prevention options in a herd setting. The objective of this study was to compare nasopharyngeal sampling approaches to evaluate accuracy and agreement for the recovery of Mannheimia haemolytica (MH) and Pasteurella multocida (PM) from deep nasopharyngeal swabs (DNS) using 3 different swabs. Deep nasopharyngeal samples were collected from 45 dairy calves using 3 swabs: (1) double-guarded culture swab (DGS); (2) single-guarded culture swab (SGS); and (3) unguarded culture swab (UGS). To evaluate the degree of agreement between DGS, SGS, and UGS, culture results were compared for each calf sampled by using a kappa agreement test. Overall, findings from our study support that when using either SGS or DGS for DNS sampling of preweaning calves, a high agreement for recovery of PM is observed. A low recovery of MH was observed in the study, limiting the conclusion comparing the 3 DNS methods. Use of UGS is considered a potential alternative; however, a higher percentage of polymicrobial growth was found with UGS samples.

In this study, we used online photovoice and community-based participatory research to understand and address facilitators and barriers to online distance education for college students in Turkey. Out of 260 students who consented to the study, 240 shared the most important facilitator, 190 shared the most important barriers, and 190 completed our contextual questions related to their education. We used online interpretative phenomenological analysis to identify key facilitators and barriers. Ten main facilitator themes emerged, including advantages of using Internet and technology (n = 104; 43%); enjoyable feelings (n = 61; 25%); saving time (n = 37; 15%); and social support (n = 28; 12%). Nine main barrier themes emerged, including challenges of online education (n = 51; 31%); psychopathology and unenjoyable feelings, thoughts, and bodily sensations (n = 37; 19%); Internet problems (n = 34; 18%); and COVID-19 restrictions (n = 30; 16%).

This case report explores the intricacies of utilising intrathecal baclofen (ITB) therapy for spasticity management and its impact on neurological recovery. Baclofen, a GABAB agonist with antispasmodic properties, has gained prominence in treating spasticity and muscle spasms related to neurological conditions. This report sheds light on a patient who was under ITB treatment and experienced unexpected late-stage improvements in motor function after the dose was inadvertently reduced. The study underscores the need for careful dosing adjustments to unveil potential neurological recovery masked by ITB therapy. The case highlights the importance of multi-physician communication and frequent dosage evaluation in long-term intrathecal therapy. Moreover, it calls attention to the possibility of motor recovery years following a traumatic brain injury, emphasising the role of neuroplasticity in such cases.

Summary: Background: To date, economic analyses of tissue-based next generation sequencing genomic profiling (NGS) for advanced solid tumors have typically required models with assumptions, with little real-world evidence on overall survival (OS), clinical trial enrollment or end-of-life quality of care. Methods: Cost consequence analysis of NGS testing (555 or 161-gene panels) for advanced solid tumors through the OCTANE clinical trial (NCT02906943). This is a longitudinal, propensity score-matched retrospective cohort study in Ontario, Canada using linked administrative data. Patients enrolled in OCTANE at Princess Margaret Cancer Centre from August 2016 until March 2019 were matched with contemporary patients without large gene panel testing from across Ontario not enrolled in OCTANE. Patients were matched according to 19 patient, disease and treatment variables. Full 2-year follow-up data was available. Sensitivity analyses considered alternative matched cohorts. Main Outcomes were mean per capita costs (2019 Canadian dollars) from a public payer's perspective, OS, clinical trial enrollment and end-of-life quality metrics. Findings: There were 782 OCTANE patients with 782 matched controls. Variables were balanced after matching (standardized difference 0.40), and greater in two (ovary, biliary, both p

Introduction: Polymorphisms in genes responsible for the metabolism and transport of tacrolimus have been demonstrated to influence clinical outcomes for patients following allogeneic hematologic stem cell transplant (allo-HSCT). However, the clinical impact of germline polymorphisms specifically for oral formulations of tacrolimus is not fully described.Methods: To investigate the clinical impact of genetic polymorphisms in CYP3A4, CYP3A5, and ABCB1 on oral tacrolimus pharmacokinetics and clinical outcomes, we prospectively enrolled 103 adult patients receiving oral tacrolimus for the prevention of graft-versus-host disease (GVHD) following allo-HSCT. Patients were followed in the inpatient and outpatient phase of care for the first 100 days of tacrolimus therapy. Patients were genotyped for CYP3A5 *3 (rs776746), CYP3A4 *1B (rs2740574), ABCB1 exon 12 (rs1128503), ABCB1 exon 21 (rs2032582), ABCB1 exon 26 (rs1045642).Results: Expression of CYP3A5 *1 was highly correlated with tacrolimus pharmacokinetics in the inpatient phase of care (p < 0.001) and throughout the entirety of the study period (p < 0.001). Additionally, Expression of CYP3A5 *1 was associated with decreased risk of developing AKI as an inpatient (p = 0.06). Variants in ABCB1 were not associated with tacrolimus pharmacokinetics in this study. We were unable to discern an independent effect of CYP3A4 *1B or *22 in this population.Conclusion: Expression of CYP3A5 *1 is highly influential on the pharmacokinetics and clinical outcomes for patients receiving oral tacrolimus as GVHD prophylaxis following allo-HSCT.

A new series of chiral 4,5-dihydro-1H-[1,2,4]-triazoline molecules, featuring a β-ᴅ-glucopyranoside appendage, were synthesized via a 1,3-dipolar cycloaddition reaction between various hydrazonyl chlorides and carbohydrate Schiff bases. The isolated enantiopure triazolines (8a–j) were identified through high-resolution mass spectrometry (HRMS) and vibrational spectroscopy. Subsequently, their solution structures were elucidated through NMR spectroscopic techniques. Single-crystal X-ray analysis of derivative 8b provided definitive evidence for the 3-D structure of this compound and revealed important intermolecular forces in the crystal lattice. Moreover, it confirmed the (S)-configuration at the newly generated stereo-center. Selected target compounds were investigated for anti-tumor activity in 60 cancer cell lines, with derivative 8c showing the highest potency, particularly against leukemia. Additionally, substituent-dependent anti-fungal and anti-bacterial behavior was observed.

Abstract Background Little is known about the association between the COVID‐19 pandemic and early survival among newly diagnosed cancer patients. Methods This retrospective population‐based cohort study used linked administrative datasets from Ontario, Canada. Adults (≥18 years) who received a cancer diagnosis between March 15 and December 31, 2020, were included in a pandemic cohort, while those diagnosed during the same dates in 2018/2019 were included in a pre‐pandemic cohort. All patients were followed for one full year after the date of diagnosis. Cox proportional hazards regression models were used to assess survival in relation to the pandemic, patient characteristics at diagnosis, and the modality of first cancer treatment as a time‐varying covariate. Interaction terms were explored to measure the pandemic association with survival for each cancer type. Results Among 179,746 patients, 53,387 (29.7%) were in the pandemic cohort and 37,741 (21.0%) died over the first post‐diagnosis year. No association between the pandemic and survival was found when adjusting for patient characteristics at diagnosis (HR 0.99 [95% CI 0.96–1.01]), while marginally better survival was found for the pandemic cohort when the modality of treatment was additionally considered (HR 0.97 [95% CI 0.95–0.99]). When examining each cancer type, only a new melanoma diagnosis was associated with a worse survival in the pandemic cohort (HR 1.25 [95% CI 1.05–1.49]). Conclusions Among patients able to receive a cancer diagnosis during the pandemic, one‐year overall survival was not different than those diagnosed in the previous 2 years. This study highlights the complex nature of the COVID‐19 pandemic impact on cancer care.

Abstract Background The efficacy‐effectiveness gap between randomized trial and real‐world evidence regarding the clinical benefit of ipilimumab for metastatic melanoma (MM) has been well characterized by previous literature, consistent with initial concerns raised by health technology assessment agencies (HTAs). As these differences can significantly impact cost‐effectiveness, it is critical to assess the real‐world cost‐effectiveness of second‐line ipilimumab versus non‐ipilimumab treatments for MM. Methods This was a population‐based retrospective cohort study of patients who received second‐line non‐ipilimumab therapies between 2008 and 2012 versus ipilimumab treatment between 2012 and 2015 (after public reimbursement) for MM in Ontario. Using a 5‐year time horizon, censor‐adjusted and discounted (1.5%) costs (from the public payer's perspective in Canadian dollars) and effectiveness were used to calculate incremental cost‐effectiveness ratios (ICERs) in life‐years gained (LYGs) and quality‐adjusted life years (QALYs), with bootstrapping to capture uncertainty. Varying the discount rate and reducing the price of ipilimumab were done as sensitivity analyses. Results In total, 329 MM were identified (Treated: 189; Controls: 140). Ipilimumab was associated with an incremental effectiveness of 0.59 LYG, incremental cost of $91,233, and ICER of $153,778/LYG. ICERs were not sensitive to discounting rate. Adjusting for quality of life using utility weights resulted in an ICER of $225,885/QALY, confirming the original HTA estimate prior to public reimbursement. Reducing the price of ipilimumab by 100% resulted in an ICER of $111,728/QALY. Conclusion Despite its clinical benefit, ipilimumab as second‐line monotherapy for MM patients is not cost‐effective in the real world as projected by HTA under conventional willingness‐to‐pay thresholds.

The title compound, 2,2′:4,4′′:4′,4′′′-quaterpyridine (Qtpy), C20H14N4, crystallizes in the triclinic P\overline{1} space group and has half of the molecule in the asymmetric unit, corresponding to 4,4′-bipyridine (4,4′-bpy) that serves as the building block for the molecule. C4,4′-bpy—N—C4,4′-bpy and/or N—C4,4′-bpy—C4,4′-bpy bond-angle parameters show that the 4,4′-bpy ligands are highly rigid, displaying values lower than the linear bond angle of 180°. In the crystal, the 4,4′-bpy units are seen to be facing each other in relatively close proximity. The most important interactions on the Hirshfeld Surface of the compound are C—H...N/H...N—C interactions (constituting 10.6% and 7.6% of the total surface).

Thermo-acoustic instability has been observed in gas turbines, rocket engines, and aero-engines. Acoustic perturbations grow and change the characteristics of the flow due to instability. The present work describes the use of pulsating air jets to suppress the thermo-acoustic instabilities. In present study pulsatile micro-jets are placed downstream of the burner radially which breaks the coupling between acoustic waves and unsteady heat release.A microphone connected to LIFA (LabVIEW Interface for Arduino) was used to detect the sound pressure levels. By controlling the airflow rate of the pulsatile jets, the sound pressure levels were suppressed down to the background noise level using minimum energy and time. A closed-loop control system is developed for this purpose, which works on the feedback signal acquired from microphone. To simulate the one dimensional combustion phenomenon, an experimental setup called Rijke tube was used. The suppression was most effective for the pulsatile jets of 27-33 Hz pulsation frequency range and at a flow rate of 6.8 LPM. This control strategy effectively controlled the combustion instability of around 35-42 dB. • The closed loop control method is built on DAQ and Arduino using the LabVIEW interface for Arduino (LIFA). • Developed closed loop active control method was observed to be effective for suppression of thermo-acoustic instability. • Optimum position of the radial planes of micro-jets with respect to the burner was decided to improve the efficacy of the pulsatile jets towards suppression of thermo-acoustic instability.

Eukaryotic cells regulate 5'-triphosphorylated RNAs (ppp-RNAs) to promote cellular functions and prevent recognition by antiviral RNA sensors. For example, RNA capping enzymes possess triphosphatase domains that remove the γ phosphates of ppp-RNAs during RNA capping. Members of the closely related PIR-1 (phosphatase that interacts with RNA and ribonucleoprotein particle 1) family of RNA polyphosphatases remove both the β and γ phosphates from ppp-RNAs. Here, we show that C. elegans PIR-1 dephosphorylates ppp-RNAs made by cellular RNA-dependent RNA polymerases (RdRPs) and is required for the maturation of 26G-RNAs, Dicer-dependent small RNAs that regulate thousands of genes during spermatogenesis and embryogenesis. PIR-1 also regulates the CSR-1 22G-RNA pathway and has critical functions in both somatic and germline development. Our findings suggest that PIR-1 modulates both Dicer-dependent and Dicer-independent Argonaute pathways and provide insight into how cells and viruses use a conserved RNA phosphatase to regulate and respond to ppp-RNA species.

Abstract Background To understand the facet capsular ligament's (FCL) role in cervical spine mechanics, the interactions between the FCL and other spinal components must be examined. One approach is to develop a subject‐specific finite element (FE) model of the lower cervical spine, simulating the motion segments and their components' behaviors under physiological loading conditions. This approach can be particularly attractive when a patient's anatomical and kinematic data are available. Methods We developed and demonstrated methodology to create 3D subject‐specific models of the lower cervical spine, with a focus on facet capsular ligament biomechanics. Displacement‐controlled boundary conditions were applied to the vertebrae using kinematics extracted from biplane videoradiography during planar head motions, including axial rotation, lateral bending, and flexion–extension. The FCL geometries were generated by fitting a surface over the estimated ligament–bone attachment regions. The fiber structure and material characteristics of the ligament tissue were extracted from available human cervical FCL data. The method was demonstrated by application to the cervical geometry and kinematics of a healthy 23‐year‐old female subject. Results FCL strain within the resulting subject‐specific model were subsequently compared to models with generic: (1) geometry, (2) kinematics, and (3) material properties to assess the effect of model specificity. Asymmetry in both the kinematics and the anatomy led to asymmetry in strain fields, highlighting the importance of patient‐specific models. We also found that the calculated strain field was largely independent of constitutive model and driven by vertebrae morphology and motion, but the stress field showed more constitutive‐equation‐dependence, as would be expected given the highly constrained motion of cervical FCLs. Conclusions The current study provides a methodology to create a subject‐specific model of the cervical spine that can be used to investigate various clinical questions by coupling experimental kinematics with multiscale computational models.