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Cohort scheduling intentionally places students in the same sections of several classes (e.g., biology, algebra, and writing) with a consistent peer group and is typically done for small groups (<30 students) to enable better interaction among students. The goal of this study was to compare cohort scheduling to traditional scheduling methods among freshmen in a physiology-related program. Outcomes included retention to the university and major, semester grades, and institutional integration and perceived group cohesion. Incoming freshmen ( n = 209) were randomized into control ( n = 43; scheduled with traditional methods) and intervention ( n = 166; coenrolled in first-year seminar course, biology, and medical terminology) groups. Outcomes were collected via surveys or requested from the university registrar. There was no significant difference in the likelihood of retention to the university or major and no differences between groups in pass/fail rates for the first-year seminar or biology courses. At the end of the semester, there were no differences between groups in Perceived Cohesion for Small Groups ( P = 0.102) or the Institutional Integration Scale ( P = 0.357). However, the intervention group scored higher on the Institutional Integration Scale's subscales related to social integration and faculty. Cohort scheduling did not impact retention to the university or major but improved secondary outcomes related to retention, specifically social integration and student perceptions of faculty. NEW & NOTEWORTHY Compared with traditional scheduling methods, cohort scheduling freshman in physiology programs does not improve retention but improves students' social integration and perceptions of faculty.

Continuous subcutaneous (SubQ) treprostinil is an effective therapy for pediatric patients diagnosed with pulmonary hypertension (PH). To date, the clinical characteristics and factors associated with failure to tolerate this therapy have not been described. The purpose was to describe patient-reported factors contributing to SubQ treprostinil intolerance in pediatric patients with PH. A retrospective descriptive study was performed at 11 participating sites in the United States and Canada for patients younger than 21 years of age diagnosed with PH who failed treatment to tolerate SubQ treprostinil between January 1, 2009, and December 31, 2019. All data were summarized using descriptive statistics. Forty-one patients met the inclusion criteria. The average age at SQ treprostinil initiation, and length of treatment, was 8.6 years and 22.6 months, respectively. The average maximum dose, concentration, and rate were 95.8 ng/kg/min, 6.06 mg/mL, and 0.040 mL/h, respectively. The reasons for failure to tolerate SubQ treprostinil included intractable site pain (73.2%), frequent site changes (56.1%), severe site reactions (53.7%), infections (26.8%), and noncompliance/depression/anxiety (17.1%). Thirty-nine (95.1%) patients transitioned to a prostacyclin therapy with 23 patients transitioning to intravenous prostacyclin, 5 to inhaled prostacyclin, 5 to oral prostacyclin, and 7 to a prostacyclin receptor agonist. A subset of pediatric PH patients failed to tolerate SubQ treprostinil infusions despite advances in SubQ site maintenance and pain management strategies. Intractable site pain, frequent SubQ site changes, and severe localized skin reactions were the most common reasons for failure., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Haberlea rhodopensis is a resurrection plant that can tolerate extreme and prolonged periods of desiccation with a rapid restoration of physiological function upon rehydration. Specialized mechanisms are required to minimize cellular damage during desiccation and to maintain integrity for rapid recovery following rehydration. In this study we used respiratory activity measurements, electron microscopy, transcript, protein and blue native-PAGE analysis to investigate mitochondrial activity and biogenesis in fresh, desiccated and rehydrated detached H. rhodopensis leaves. We demonstrate that unlike photosynthesis, mitochondrial respiration was almost immediately activated to levels of fresh tissue upon rehydration. The abundance of transcripts and proteins involved in mitochondrial respiration and biogenesis were at comparable levels in fresh, desiccated and rehydrated tissues. Blue native-PAGE analysis revealed fully assembled and equally abundant OXPHOS complexes in mitochondria isolated from fresh, desiccated and rehydrated detached leaves. We observed a high abundance of alternative respiratory components which correlates with the observed high uncoupled respiration capacity in desiccated tissue. Our study reveals that during desiccation of vascular H. rhodopensis tissue, mitochondrial composition is conserved and maintained at a functional state allowing for an almost immediate activation to full capacity upon rehydration. Mitochondria-specific mechanisms were activated during desiccation which probably play a role in maintaining tolerance., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Radiotherapy is a key treatment modality for cancers of the head and neck, being used for curative intent either alone or in combination with surgery and chemotherapy. The treatment-related toxicities of these treatments can be significant in both the short and longer term. Many of these toxicities manifest orally, even in patients whose primary malignancy was outside the oral cavity, as radiotherapy often involves elective treatment of high-risk areas, such as locally draining lymph nodes in the neck. Reducing the burden of treatment is an area of intense focus in head and neck oncology. New technology and imaging techniques, such as proton therapy and magnetic resonance imaging, are being integrated into radiotherapy treatment to minimise radiation dose outside of the target areas. In parallel, tumour biology is being explored as a means of identifying patients who might be suitable for de-escalated therapy. This review will cover the latest advances in the oncology treatment available for patients with head and neck cancers, with a focus on how these might help reduce oral toxicity., (© 2022. The Author(s), under exclusive licence to the British Dental Association.)

While care models adapt to the COVID-19 pandemic with virtual and hybrid visits, clinical factors associated with treatment changes among ambulatory pediatric pulmonary arterial hypertension (PAH) patients are not well characterized. To understand which data critically altered treatment recommendations, we conducted a retrospective review among ambulatory children with Group 1 PAH to determine optimal visit and diagnostic strategies. Changes in management included: unplanned new treatments, dose modifications of vasodilators or diuretics, unscheduled hospitalizations, or changes to activity recommendations, catheterization schedule, or other testing. Factors prompting management changes were classified as symptoms, exam findings, or diagnostic tests. Across 398 ambulatory visits by 48 patients, 38 patients (79%) at 88 visits (22%) required change in management, most commonly in targeted PH medication. Changes were driven by symptoms alone (15%), diagnostic testing alone (47%), exam only (2%), symptoms and exam (2%), combination of testing and symptoms or testing and exam (25%), and other reasons (9%). Patients with World Health Organization functional Class IV (odds ratio [OR] 9.04 vs. Class I, p  = 0.014) or Class III (OR 2.08 vs. Class I, p  = 0.050) were more likely to undergo change in management. However, among Class I patients, 18% of visits generated changes in management because of test findings. While multiple factors affect management in ambulatory pediatric PH, neither symptoms nor exam was sufficient for identifying patients warranting clinical change in management. Testing accounted for most changes. Thus, in-person or hybrid surveillance including history, exam, and diagnostic testing remains essential for optimal management of pediatric PAH., Competing Interests: Dr. M. P. Mullen reports Altavant Sciences and Actelion scientific advisory board participation, outside the content of the manuscript. The remaining authors declare no conflict of interest., (© 2022 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

The 15th edition of the Workshop on Recent Issues in Bioanalysis (15th WRIB) was held on 27 September to 1 October 2021. Even with a last-minute move from in-person to virtual, an overwhelmingly high number of nearly 900 professionals representing pharma and biotech companies, contract research organizations (CROs), and multiple regulatory agencies still eagerly convened to actively discuss the most current topics of interest in bioanalysis. The 15th WRIB included three Main Workshops and seven Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on biomarker assay development and validation (BAV) (focused on clarifying the confusion created by the increased use of the term "context of use" [COU]); mass spectrometry of proteins (therapeutic, biomarker and transgene); state-of-the-art cytometry innovation and validation; and critical reagent and positive control generation were the special features of the 15th edition. This 2021 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2021 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations on ISR for Biomarkers, Liquid Biopsies, Spectral Cytometry, Inhalation/Oral & Multispecific Biotherapeutics, Accuracy/LLOQ for Flow Cytometry. Part 1A (Endogenous Compounds, Small Molecules, Complex Methods, Regulated Mass Spec of Large Molecules, Small Molecule, PoC), Part 1B (Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine) and Part 3 (TAb/NAb, Viral Vector CDx, Shedding Assays; CRISPR/Cas9 & CAR-T Immunogenicity; PCR & Vaccine Assay Performance; ADA Assay Comparability & Cut Point Appropriateness) are published in volume 14 of Bioanalysis, issues 9 and 11 (2022), respectively.

Tissue factor pathway inhibitor (TFPI) exhibits multiple isoforms, which are known to present in multiple locations such as plasma, endothelium, and platelets. TFPI is an endogenous negative modulator of the coagulation pathway, and therefore, neutralization of TFPI function can potentially increase coagulation activity. A human monoclonal antibody, PF-06741086, which interacts with all isoforms of TFPI is currently being tested in clinic for treating hemophilia patients with and without inhibitors. To support clinical development of PF-06741086, pharmacokinetics (PK) and pharmacodynamics of PF-06741086 were characterized in monkeys. In addition, a mechanistic model approach was used to estimate PK parameters in monkeys and simulate PK profiles in human. The results show that PF-06741086 exhibited target-mediated drug disposition and had specific effects on various hemostatic markers including diluted prothrombin time, thrombin generation, and thrombin-antithrombin complex in monkeys after administration. The model-predicted and observed human exposures were compared retrospectively, and the result indicates that the exposure prediction was reasonable within less than 2-fold deviation. This study demonstrated in vivo efficacy of PF-06741086 in monkeys and the utility of a rational mechanistic approach to describe PK for a monoclonal antibody with complex target binding., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

FXa I16L is a recombinant human FXa variant which is currently being evaluated in the clinic for treating intracerebral hemorrhage. The aim of our studies is to investigate overall pharmacokinetics, pharmacodynamics, and distribution of FXa I16L in preclinical species, and to understand its potential implication in human. Pharmacokinetics of FXa I16L was examined using active site probes and the results showed that FXa I16L displayed fast clearance, low volume of distribution, and a very short plasma resident time in mice, rats, and monkeys. When pharmacodynamics was examined in monkeys, concentration effects of FXa I16L on shortening of active partial prothrombin time and formation of thrombin-antithrombin complex were observed. Furthermore, biodistribution study was conducted in mice using radiolabeled FXa I16L , and showed that 125 I-FXa I16L has high plasma protein binding and significant liver and kidney distribution. Human pharmacokinetic prediction for first-in-human dosing was evaluated using allometric scaling, liver blood flow, and a fixed coefficient method, and single species allometric scaling using monkey data was most predictive for human pharmacokinetics of FXa I16L ., (Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

During the nineteenth century homoeopaths claimed better results than their conventional colleagues did for the treatment of epidemic cholera. Those of the London Homoeopathic Hospital in 1854 have been put forward, for 150 years, as evidence of the efficacy of homoeopathy. The evidence is examined in this paper. Failure to inflict exhausting allopathic treatments must have contributed considerably to the homoeopathic success. However it appears probable that the homoeopathic remedies themselves played an active part in the successful treatment of cholera cases.

We analyzed our initial 381 endoscopic cholecystectomies with particular emphasis on postoperative complications. The rate of conversion to open cholecystectomy was 3%. A technical complication occurred in 2% and a non-technical complication in 4%, for a total complication incidence of 6%. There were three postoperative fatalities (0.9%). Two fatal technical complications consisted of unrecognized intestinal injuries at the time of endoscopic cholecystectomy that were obvious when the abdomen was opened. One patient died of a cerebrovascular accident. Nonfatal technical complications included five bile leaks that required treatment. There were no common bile duct injuries, but excessive caution to prevent common bile duct injury may have contributed to the high incidence of bile leaks. Examination of the case numbers of the technical complications and conversion to open cholecystectomy suggests that the learning curve is real and somewhat prolonged, and that a willingness to convert to open cholecystectomy is necessary if technical complications are to be avoided.

Emergency department (ED) and morgue visits to view the results of accidents have recently been instituted as an alternative sentence for adolescents convicted of driving under the influence of alcohol (DUI). Although many DUI offenders are alcoholic, and educational programs intended to reduce recidivism in adults are generally not effective, scant data exist on adolescent offenders. Initial assessment of 59 of our program participants diagnosed 41% as alcoholic. This finding prompted further participant evaluation to define our population. Fifty-four participants evaluated by self-administered diagnostic questionnaire revealed an alcoholism rate of 54%. Additionally, recidivism rates for alcohol-related moving violations for 176 program participants and matched controls were 28% and 23%, respectively. The significance of these findings represents the serious alcohol problems faced by the study population and indicates that visitation programs are not effective for addressing the problems of alcoholic offenders or in reducing recidivism.