Design of a volumetric cylindrical coil-tuned at 298 MHz for 7 T imaging.

The concept of a 2D cylindrical High Pass Ladder (2D c-HPL) is used in the development of this ultra high radio frequency (UHRF) volumetric head coil for 7T tuned at the Larmor frequency of 298 MHz. The architecture of the 2D c-HPL helps to overcome the challenges associated with non-uniform magnetic field distribution. The prototype consists of an individual resonating array of inductance-capacitance (LC) elements and each component is tuned to the precise f o frequency. The tuning of the (i) inductance, (ii) capacitance, (iii) mesh size, and (iv) coupling coefficient play critical roles to attain the desired Larmor frequency. For this proof-of-concept, the prototype of a volumetric head coil consists of a cylindrical array size of 4 ×6, with individual LC components of inductance magnitude, 98 nH and four fixed value capacitors and one tunable capacitor that allowed to achieve the desired precession frequency, f r = 298 M H z . The model was tested for three different f o values of 269 MHz, 275 MHz and 286 MHz. The mutual coupling and the eigenfrequencies were compared through bench testing and dispersion equation. The experimental data were in good agreement (< 5%) with the theoretical eigenfrequencies from the dispersion relation. The theoretical eigenfrequencies and the experimental eigenfrequencies are in good agreement for eigenmodes (1,2), (1,3), (2,2), (2,3) and (4,3).

Revision of the Essential Core Competencies: Domains of Competence and Associated Competencies for Pediatric Physical Therapy Professional Education.

PURPOSE: The purpose of this Special Communication is to describe the processes of Education Summit III, sponsored by the Academy of Pediatric Physical Therapy, with an emphasis on the review, update, and integration of contemporary language and the Competency-Based Education framework into a revision of the Essential Core Competencies (ECCs). SUMMARY OF KEY POINTS: The Academy of Pediatric Physical Therapy has consistently supported pediatric professional education, including sponsoring 3 Education Summits in 2012, 2016, and 2023. The most recent summit focused on a revision of the ECCs and the development of materials to support their implementation. RECOMMENDATIONS FOR PRACTICE: These revised domains of competence and associated competencies will support and guide pediatric physical therapy education for professional students. Educators are encouraged to use their creativity and resources to integrate these into teaching and learning activities.

Attitudes, Self-Confidence, and Knowledge of Primary Care Professionals towards School Bullying.

Attitudes, practices, and knowledge about bullying were evaluated in a sample of 274 primary care professionals, including general practitioners, pediatricians, community, pediatric and school nurses, and residents of these specialties. This study was based on a mixed method with a parallel convergent design without dominance between phases, data were collected concurrently, and conversion of the results from both phases was carried out during data interpretation. The quantitative phase had a cross-sectional observational design, using The Healthcare Provider's Practices, Attitudes, Self-confidence, and Knowledge Regarding Bullying Questionnaire as an instrument. Descriptive and bivariate analyses were performed, which showed a positive correlation between higher self-confidence and knowledge scores and a greater predisposition to detect cases. However, although the dimensions of attitudes and knowledge yielded generally high data, low self-confidence was evident in addressing this problem. In addition, a lack of clear guidelines in the workplace was expressed, highlighting the need to create and provide specific resources to intervene in bullying in said context, which could develop an improvement in self-confidence, leading to greater well-being for the educational community regarding bullying.

Machine learning prediction model for postoperative ileus following colorectal surgery.

BACKGROUND: Postoperative ileus (POI) continues to be a major cause of morbidity following colorectal surgery. Despite best efforts, the incidence of POI in colorectal surgery remains high (~30%). This study aimed to investigate machine learning techniques to identify risk factors for POI in colorectal surgery patients, to help guide further preventative strategies. METHODS: A TRIPOD-guideline-compliant retrospective study was conducted for major colorectal surgery patients at a single tertial care centre (2018-2022). The primary outcome was the occurrence of POI, defined as not achieving GI-2 (outcome measure of time to first stool and tolerance of oral diet) by day four. Multivariate logistic regression, decision trees, radial basis function and multilayer perceptron (MLP) models were trained using a random allocation of patients to training/testing data sets (80/20). The area under the receiver operating characteristic (AUROC) curves were used to evaluate model performance. RESULTS: Of 504 colorectal surgery patients, 183 (36%) experienced POI. Multivariate logistic regression, decision trees, radial basis function and MLP models returned an AUROC of 0.722, 0.706, 0.712 and 0.800, respectively. The MLP model had the highest sensitivity and specificity values. In addition to well-known risk factors for POI, such as postoperative hypokalaemia, surgical approach, and opioid use, the MLP model identified sarcopenia (ranked 4/30) as a potentially modifiable risk factor for POI. CONCLUSION: MLP outperformed other models in predicting POI. Machine learning can provide valuable insights into the importance and ranking of specific predictive variables for POI. Further research into the predictive value of preoperative sarcopenia for POI is required.

Assessing ethical behavior and self-control in elite ultimate championships: a cross-sectional study using the spirit of the game scoring system.

Introduction: Implementing a self-refereeing system presents a unique challenge in sports education, particularly in academic and training settings where officiated sports prevail. However, Ultimate Frisbee stands out by entrusting players with both athlete and referee roles, introducing distinctive ethical complexities. This manuscript is intended to evaluate ethical behavior and self-control within the Spirit of the Game (SOTG) scoring system in Elite Ultimate. To address these, Ultimate employs the (SOTG) scoring system, integral since the sport's inception in the late 1980s. SOTG aims to enhance and evaluate athletes' ethical conduct. This study evaluates SOTG's effectiveness in elite-level Ultimate, analyzing variations across divisions and age groups in three high-level tournaments. Methods: Using a cross-sectional design, data were collected from five international Ultimate tournaments in 2022. Teams spanned diverse age groups (under 17 to over 50) and divisions (women's, mixed, open). Post-match, teams assessed opponents' SOTG in five domains: Rules knowledge, fouls, fairness, attitude/self-control, and communication. Ratings used a 5-point Likert scale ("poor" to "excellent"). An overall SOTG score was calculated by aggregating domain scores. Results: Our study consistently revealed high SOTG scores, reflecting strong sportsmanship. "Positive attitude and self-control" consistently ranked highest, while "Knowledge and use of the rules" scored lowest. Divisional differences in SOTG were statistically insignificant. Notably, WMUCC2022 (participants aged 30+) had significantly higher SOTG scores, possibly indicating age-related self-control improvement or evolving sport culture. Lower rules knowledge scores may stem from linguistic translation challenges. Conclusion: Self-refereeing promotes ethical behavior across divisions and age groups. SOTG underscores sportsmanship's importance and aligns with International Olympic Committee (IOC) and with Sustainable Development Goals (SDGs), particularly SDG 3, 4, 5 and 16 fostering a fairer, healthier, and more peaceful world.

Improvement of Emergency Department Chest Pain Evaluation Using Hs-cTnT and a Risk Stratification Pathway.

BACKGROUND: Chest pain is among the most common reasons for presentation to the emergency department (ED) worldwide. Additional studies on most cost-effective ways of differentiating serious vs. benign causes of chest pain are needed. OBJECTIVES: Our study aimed to evaluate the effectiveness of a novel risk stratification pathway utilizing 5th generation high-sensitivity cardiac troponin T assay (Hs-cTnT) and HEART score (History, Electrocardiogram, Age, Risk factors, Troponin) in assessing nontraumatic chest pain patients in reducing ED resource utilization. METHODS: A retrospective chart review was performed 6 months prior to and after the implementation of a novel risk stratification pathway that combined hs-cTnT with HEART score to guide evaluation of adult patients presenting with nontraumatic chest pain at a large academic quaternary care ED. Primary outcome was ED length of stay (LOS); secondary outcomes included cardiology consult rates, admission rates, number of ED boarders, and number of eloped patients. RESULTS: A total of 1707 patients and 1529 patients were included pre- and postimplementation, respectively. Median overall ED LOS decreased from 317 to 286 min, an absolute reduction of 31 min (95% confidence interval 22-41 min), after pathway implementation (p < 0.001). Furthermore, cardiology consult rate decreased from 26.9% to 16.0% (p < 0.0001), rate of admission decreased from 30.1% to 22.7% (p < 0.0001), and number of ED boarders as a proportion of all nontraumatic chest pain patients decreased from 25.13% preimplementation to 18.63% postimplementation (p < 0.0001). CONCLUSIONS: Implementation of our novel chest pain pathway improved numerous ED throughput metrics in the evaluation of nontraumatic chest pain patients.

Pyridostigmine to Reduce the duration of postoperative Ileus after Colorectal surgery (PyRICo-RCT): randomized clinical trial.

BACKGROUND: Postoperative ileus, driven by the cholinergic anti-inflammatory pathway, is the most common complication in patients undergoing colorectal surgery. By inhibiting acetylcholinesterase, pyridostigmine can potentially modulate the cholinergic anti-inflammatory pathway and accelerate gastrointestinal recovery. This study aimed to assess the efficacy of pyridostigmine in improving gastrointestinal recovery after colorectal surgery. METHODS: This double-blinded RCT enrolled adult patients undergoing elective colorectal surgery at two hospitals in South Australia. Patients were randomized to 60 mg oral pyridostigmine or placebo twice daily starting 6 h after surgery until the first passage of stool. The primary outcome was GI-2, a validated composite measure of time to first stool and tolerance of oral diet. Secondary outcomes included incidence of postoperative ileus (defined as GI-2 greater than 4 days), duration of hospital stay, and 30-day complications, evaluated by intention-to-treat univariate analysis. RESULTS: Of 130 patients recruited (mean(s.d.) age 58.4(16.4) years; 73 men, 56%), 65 were allocated to each arm. The median GI-2 was 1 day shorter with pyridostigmine compared with placebo (2 (i.q.r. 1-3) versus 3 (2-4) days; P = 0.015). However, there were no significant differences in postoperative ileus (17.2 versus 21.5%; P = 0.532) or duration of hospital stay (median 5 (i.q.r. 4-8.75) versus 5 (4-7.5) days; P = 0.921). Similarly, there were no significant differences in overall complications, anastomotic leak, cardiac complications, or patient-reported side effects. CONCLUSION: Pyridostigmine resulted in a quicker return of GI-2 and was well tolerated. Larger multicentre studies are required to determine the optimal dosing and evaluate the impact of pyridostigmine in different surgical settings. Registration number: ACTRN12621000530820 (https://anzctr.org.au).

The Association of Weight With Surgical Morbidity in Infants Undergoing Enterostomy Reversal: A Study of the NSQIP-Pediatrics Database.

INTRODUCTION: Optimal criteria and timing for enterostomy closure (EC) in neonates is largely based on clinical progression and adequate weight, with most institutions using 2.0-2.5 kg as the minimum acceptable weight. It is unclear how the current weight cutoff affects post-operative morbidity. AIM: To determine how infant weight at the time of EC influences 30-day complications. METHODS: Infants weighing ≤4000 g who underwent EC were identified in the 2012-2019 ACS NSQIP-P database. Demographics, comorbidities, and 30-day outcomes were assessed using univariate analysis. Multivariable logistic regression controlling for ASA score, nutritional support, and ventilator support was used to estimate the independent association of weight on risk of 30-day complications. RESULTS: A total of 1692 neonates from the NSQIP-P database during the years 2012-2019 met inclusion criteria. Neonates weighing <2.5 kg were significantly more likely to have a younger gestational age, require ventilator support, and have concurrent comorbidities. Major morbidity, a composite outcome of the individual postoperative complications, was observed in 283 (16.7%) infants. ASA classifications 4 and 5, dependence on nutritional support, and ventilator support were independently associated with increased risk of 30-day complications. With respect to weight, we found no significant difference in major morbidity between infants weighing <2.5 kg and infants weighing ≥2.5 kg. CONCLUSION: Despite using a robust, national dataset, we could find no evidence that a defined weight cut-off was associated with a reduction in major morbidity, indicating that weight should not be a priority factor when determining eligibility for neonatal EC. LEVEL OF EVIDENCE: III.

Cross-Cultural Validation of the Healthcare Provider's Practices, Attitudes, Self-Confidence, and Knowledge Regarding Bullying Questionnaire.

How can we know the reality of the context of bullying in the field of primary health care? The aim of this study is to obtain a validated and reliable tool that allows measurement of the involvement of primary care professionals in addressing bullying through a systematic content validation process. A cross-cultural validation of the Healthcare Provider's Practices, Attitudes, Self-Confidence, and Knowledge Regarding Bullying Questionnaire was conducted for the Spanish perspective. This involved linguistic adaptation through translation-back-translation, content validity index (CVI) analysis, construct validity using confirmatory factor analysis (CFA), and internal consistency (Cronbach's α). The total CVI was 0.95, with individual item scores ≥ 0.78. CFA revealed a good fit for the three subscales, with discrimination indices (item-total correlation within the dimension) > 0.30. Cronbach's α for each dimension indicated a high level of reliability, with values of 0.735 for attitudes, 0.940 for self-confidence, and 0.895 for knowledge. The questionnaire is valid and reliable for evaluating the knowledge, attitudes, and self-confidence of primary care professionals in Spain regarding bullying. Its validity and reliability guarantee its potential use in other health settings and may lead to better training of professionals and school biopsychosocial health.

Evaluation of a mobile COVID-19 vaccination van outreach service in an outer South London borough.

BACKGROUND: This study aimed to explore differences in users of a COVID-19 mobile vaccine van service and users of a COVID-19 static vaccination hub, and the impact of changes in national COVID-19 vaccine policy on vaccine uptake. METHODS: The age distribution of male and female service users in each service was compared. The average number of vaccines administered per hour per week was analysed. RESULTS: Females aged 80-89 represented 51.9% (95% CI 49.5-54.3%) of female vaccine van users compared with 2.8% (95% CI 2.5-3.1%) of female static hub users. The static hub had significantly greater proportions of female service users in all other age brackets.For males, the greatest difference was in those aged 70-79 who represented 29.8% (95% CI 27-32.6%) of vaccine van users and 16.6% (95% CI 16-17.2%) static hub users.Fewer vaccines were administered 2-3 weeks before the COVID-19 autumn booster policy change compared with 2-3 weeks after; 1.92 versus 6.25 vaccines per hour, respectively (Mann-Whitney U = 7, n1 = 11, n2 = 8, P < 0.01 two-tailed). CONCLUSIONS: These findings suggest that a mobile vaccine van service is an effective model for increasing COVID-19 vaccination uptake in elderly residents, particularly after a national policy change.

Two artificial intelligence models underperform on examinations in a veterinary curriculum.

OBJECTIVE: Advancements in artificial intelligence (AI) and large language models have rapidly generated new possibilities for education and knowledge dissemination in various domains. Currently, our understanding of the knowledge of these models, such as ChatGPT, in the medical and veterinary sciences is in its nascent stage. Educators are faced with an urgent need to better understand these models in order to unleash student potential, promote responsible use, and align AI models with educational goals and learning objectives. The objectives of this study were to evaluate the knowledge level and consistency of responses of 2 platforms of ChatGPT, namely GPT-3.5 and GPT-4.0. SAMPLE: A total of 495 multiple-choice and true/false questions from 15 courses used in the assessment of third-year veterinary students at a single veterinary institution were included in this study. METHODS: The questions were manually entered 3 times into each platform, and answers were recorded. These answers were then compared against those provided by the faculty members coordinating the courses. RESULTS: GPT-3.5 achieved an overall performance score of 55%, whereas GPT-4.0 had a significantly (P < .05) greater performance score of 77%. Importantly, the performance scores of both platforms were significantly (P < .05) below that of the veterinary students (86%). CLINICAL RELEVANCE: Findings of this study suggested that veterinary educators and veterinary students retrieving information from these AI-based platforms should do so with caution.

Sense of agency in joint action: a critical review of we-agency.

The sense of agency refers to the experience of control over voluntary actions and their effects. There is growing interest in the notion of we-agency, whereby individual sense of agency is supplanted by a collective agentic experience. The existence of this unique agentic state would have profound implications for human responsibility, and, as such, warrants further scrutiny. In this paper, we review the concept of we-agency and examine whether evidence supports it. We argue that this concept entails multiplying hypothetical agentic states associated with joint action, thus ending up with an entangled phenomenology that appears somewhat speculative when weighted against the available evidence. In light of this, we suggest that the concept of we-agency should be abandoned in favor of a more parsimonious framework for the sense of agency in joint action.

Development of an FRα Companion Diagnostic Immunohistochemical Assay for Mirvetuximab Soravtansine.

CONTEXT.­: Folate receptor-α (FRα, encoded by the FOLR1 gene) is overexpressed in several solid tumor types, including epithelial ovarian cancer (EOC), making it an attractive biomarker and target for FRα-based therapy in ovarian cancer. OBJECTIVE.­: To describe the development, analytic verification, and clinical performance of the VENTANA FOLR1 Assay (Ventana Medical Systems Inc) in EOC. DESIGN.­: We used industry standard studies to establish the analytic verification of the VENTANA FOLR1 Assay. Furthermore, the VENTANA FOLR1 Assay was used in the ImmunoGen Inc-sponsored SORAYA study to select patients for treatment with mirvetuximab soravtansine (MIRV) in platinum-resistant EOC. RESULTS.­: The VENTANA FOLR1 Assay is highly reproducible, demonstrated by a greater than 98% overall percent agreement (OPA) for repeatability and intermediate precision studies, greater than 93% OPA for interreader and greater than 96% for intrareader studies, and greater than 90% OPA across all observations in the interlaboratory reproducibility study. The performance of the VENTANA FOLR1 Assay in the SORAYA study was evaluated by the overall staining acceptability rate, which was calculated using the number of patient specimens that were tested with the VENTANA FOLR1 Assay that had an evaluable result. In the SORAYA trial, data in patients who received MIRV demonstrated clinically meaningful efficacy, and the overall staining acceptability rate of the assay was 98.4%, demonstrating that the VENTANA FOLR1 Assay is safe and effective for selecting patients who may benefit from MIRV. Together, these data showed that the assay is highly reliable, consistently producing evaluable results in the clinical setting. CONCLUSIONS.­: The VENTANA FOLR1 Assay is a robust and reproducible assay for detecting FRα expression and identifying a patient population that derived clinically meaningful benefit from MIRV in the SORAYA study.

Understanding Near-Infrared Spectroscopy: An Update.

Near-infrared spectroscopy (NIRS) is a novel technology that uses infrared light to noninvasively and continuously measure regional oxygen extraction in real time at the bedside. Neonatal research using this device supports its use as an adjunct to routine cardiovascular monitoring because NIRS serves as a surrogate marker for end-organ perfusion and can detect minute changes in cerebral, intestinal, and kidney tissue beds. Multiple conditions affecting premature infants are frequently associated with hypoperfusion; therefore, methods to detect early tissue-specific perfusion alterations may substantially improve the clinician's ability to intervene and prevent further deterioration.

Identifying Perspectives on Physical Therapist Residency Program Goals: Hallmarks of Success and Excellence.

OBJECTIVE: The purpose of this study was to describe common perspectives important to achieving excellence and success in physical therapist residency education programs. METHODS: Individuals with direct responsibility for creating and revising physical therapist residency program goals participated in a mixed-methods study using Q-methodology. They sorted 31 goal topics based on the level of importance for achieving excellence and success in physical therapist residency education. By-participant factor analysis identified dominant perspectives, which were interpreted based on emergent themes from the topics identified as the most important. Participants' rationale for selecting goal topics as the most important were extracted from the post-survey. RESULTS: Seventy-three individuals responded, representing 9 of the 11 clinical residency areas of practice. Three main perspectives emerged: resident behaviors, resident achievements, and program attributes. One shared perspective emerged across all 3 factors that emphasized the residents' ability to become self-regulated, lifelong learners who integrate learning into practice: preparation for future learning. CONCLUSIONS: Variability in weighting the importance of program goals associated with each perspective may include a program's organization and mission, individual beliefs and experiences related to program leadership, and resource availability. Although respondent emphasis placed importance of some items over others, the findings do not suggest that items ranked lower were unnecessary or unimportant in achieving program excellence. The relative importance of items was weighted differently based on the perspective of program leadership and the individual completing the sorting activity. IMPACT: The results of this study suggest that physical therapist residency programs should have at least 1 or 2 goals in each of the 3 distinct perspectives, as well as the 1 shared perspective identified in our findings. Some consistency in program goals based on the perspectives identified here may enable further research exploring excellence, value, and outcomes in physical therapist residency education.

Deep learning to predict lymph node status on pre-operative staging CT in patients with colon cancer.

INTRODUCTION: Lymph node (LN) metastases are an important determinant of survival in patients with colon cancer, but remain difficult to accurately diagnose on preoperative imaging. This study aimed to develop and evaluate a deep learning model to predict LN status on preoperative staging CT. METHODS: In this ambispective diagnostic study, a deep learning model using a ResNet-50 framework was developed to predict LN status based on preoperative staging CT. Patients with a preoperative staging abdominopelvic CT who underwent surgical resection for colon cancer were enrolled. Data were retrospectively collected from February 2007 to October 2019 and randomly separated into training, validation, and testing cohort 1. To prospectively test the deep learning model, data for testing cohort 2 was collected from October 2019 to July 2021. Diagnostic performance measures were assessed by the AUROC. RESULTS: A total of 1,201 patients (median [range] age, 72 [28-98 years]; 653 [54.4%] male) fulfilled the eligibility criteria and were included in the training (n = 401), validation (n = 100), testing cohort 1 (n = 500) and testing cohort 2 (n = 200). The deep learning model achieved an AUROC of 0.619 (95% CI 0.507-0.731) in the validation cohort. In testing cohort 1 and testing cohort 2, the AUROC was 0.542 (95% CI 0.489-0.595) and 0.486 (95% CI 0.403-0.568), respectively. CONCLUSION: A deep learning model based on a ResNet-50 framework does not predict LN status on preoperative staging CT in patients with colon cancer.

Use of Acetylcholinesterase Inhibitors in Reducing Time to Gastrointestinal Function Recovery following Abdominal Surgery: A Systematic Review.

INTRODUCTION: Postoperative ileus (POI) is a significant complication following abdominal surgery, increasing morbidity and mortality. The cholinergic anti-inflammatory response is one of the major pathways involved in developing POI, but current recommendations to prevent POI do not target this. This review aims to summarise evidence for the use of acetylcholinesterase inhibitors, neostigmine and pyridostigmine, to reduce the time to return of gastrointestinal function (GI) following abdominal surgery. METHODS: A systematic search of various databases was performed from 1946 to May 2023. Randomised controlled trials (RCTs) on acetylcholinesterase inhibitors in intra-abdominal surgery were included. Data on time to flatus and/or stool and side effects were extracted. RESULTS: Among 776 screened manuscripts, 8 RCTs (703 patients) investigating acetylcholinesterase inhibitors in intra-abdominal surgery were analysed. Five studies showed a significant reduction in time to flatus and/or stool by 17-47.6 h. Methodological variations, differing procedure types, and potential bias were observed. Limited studies reported side effects or length of stay. CONCLUSION: Acetylcholinesterase inhibitors may reduce the time for GI to return. However, current evidence is limited and biased. Further studies incorporating acetylcholinesterase inhibitors in an enhanced recovery protocol are required to address this question, especially for patients undergoing colorectal surgery.

The right face at the wrong place: How motor intentions can override outcome monitoring.

The concept of intentions is often taken for granted in the cognitive and neural sciences, and comparing outcomes with internal goals is seen as critical for our sense of agency. We created an experiment where participants decided which face they preferred, and we either created outcome errors by covertly switching the position of the chosen face or induced motor errors by deviating the mouse cursor, or we did both at the same time. In the final case, participants experienced a motor error, but the outcome ended up correct. The result showed that when they received the right face, but at the wrong place, participants rejected the outcome they actually wanted in a majority of the trials. Thus, contrary to common belief, higher-order outcomes do not always regulate our actions. Instead, motor "wrongness" might sometimes override goal "rightness" and lead us to reject the outcome we actually want.

Mistranslation-associated perturbations of proteostasis do not promote accumulation of amyloid beta and plaque deposition in aged mouse brain.

A common perception in age-related neurodegenerative diseases posits that a decline in proteostasis is key to the accumulation of neuropathogenic proteins, such as amyloid beta (Aß), and the development of sporadic Alzheimer's disease (AD). To experimentally challenge the role of protein homeostasis in the accumulation of Alzheimer's associated protein Aß and levels of associated Tau phosphorylation, we disturbed proteostasis in single APP knock-in mouse models of AD building upon Rps9 D95N, a recently identified mammalian ram mutation which confers heightened levels of error-prone translation together with an increased propensity for random protein aggregation and which is associated with accelerated aging. We crossed the Rps9 D95N mutation into knock-in mice expressing humanized Aß with different combinations of pathogenic mutations (wild-type, NL, NL-F, NL-G-F) causing a stepwise and quantifiable allele-dependent increase in the development of Aß accumulation, levels of phosphorylated Tau, and neuropathology. Surprisingly, the misfolding-prone environment of the Rps9 D95N ram mutation did not affect Aß accumulation and plaque formation, nor the level of phosphorylated Tau in any of the humanized APP knock-in lines. Our findings indicate that a misfolding-prone environment induced by error-prone translation with its inherent perturbations in protein homeostasis has little impact on the accumulation of pathogenic Aß, plaque formation and associated phosphorylated Tau.

Protocol summary and statistical analysis plan for the low oxygen intervention for cardiac arrest injury limitation (LOGICAL) trial.

Background: The effect of conservative vs. liberal oxygen therapy on outcomes of intensive care unit (ICU) patients with hypoxic ischaemic encephalopathy (HIE) is uncertain and will be evaluated in the Low Oxygen Intervention for Cardiac Arrest injury Limitation (LOGICAL) trial. Objective: The objective of this study was to summarise the protocol and statistical analysis plans for the LOGICAL trial. Design setting and participants: LOGICAL is a randomised clinical trial in adults in the ICU who are comatose with suspected HIE (i.e., those who have not obeyed commands following return of spontaneous circulation after a cardiac arrest where there is clinical concern about possible brain damage). The LOGICAL trial will include 1400 participants and is being conducted as a substudy of the Mega Randomised registry trial comparing conservative vs. liberal oxygenation targets in adults receiving unplanned invasive mechanical ventilation in the ICU (Mega-ROX). Main outcome measures: The primary outcome is survival with favourable neurological function at 180 days after randomisation as measured with the Extended Glasgow Outcome Scale (GOS-E). A favourable neurological outcome will be defined as a GOS-E score of lower moderate disability or better (i.e. a GOS-E score of 5-8). Secondary outcomes include survival time, day 180 mortality, duration of invasive mechanical ventilation, ICU length of stay, hospital length of stay, the proportion of patients discharged home, quality of life assessed at day 180 using the EQ-5D-5L, and cognitive function assessed at day 180 using the Montreal Cognitive Assessment (MoCA-blind). Conclusions: The LOGICAL trial will provide reliable data on the impact of conservative vs. liberal oxygen therapy in ICU patients with suspected HIE following resuscitation from a cardiac arrest. Prepublication of the LOGICAL protocol and statistical analysis plan prior to trial conclusion will reduce the potential for outcome-reporting or analysis bias. Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN12621000518864).