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Background Topical fluoride hesitancy is a well-documented and growing public health problem. Despite extensive evidence that topical fluoride is safe and prevents tooth decay, an increasing number of caregivers are hesitant about their children receiving topical fluoride, leading to challenges in clinical settings where caregivers refuse preventive care. Purpose To explore the determinants of topical fluoride hesitancy for caregivers with dependent children. Methods In this qualitative study, we interviewed 56 fluoride-hesitant caregivers to develop an inductive conceptual model of reasons why caregivers are hesitant. Results The core construct of the conceptual model of topical fluoride hesitancy centered on caregivers “wanting to protect and not mess up their child”. Six domains comprised this core construct: thinking topical fluoride is unnecessary, wanting to keep chemicals out of my child’s body, thinking fluoride is harmful, thinking there is too much uncertainty about fluoride, feeling pressured to get topical fluoride, and feeling fluoride should be a choice. Conclusions Topical fluoride hesitancy is complex and multifactorial. Study findings provide insight for future efforts to understand and optimize caregivers’ preventive care decision making.

Background:. Mortality rates following major lower extremity amputations (LEAs) 30 days–365 days postoperative have decreased, but 5-year rates remain high at 40.4%–70%. These data may not reflect recent advances in peripheral arterial disease (PAD) care, and comorbidities of chronic PAD may lead to mortality more frequently than the amputation itself. Mortality rates between diabetic and nondiabetic patients were also analyzed. Methods:. The California Office of Statewide Health Planning and Development hospital database was queried for patients admitted January 1, 2007–December 31, 2018. ICD-9-CM codes identified patients with vascular disease and an amputation procedure. Results:. There were 26,669 patients. The 30-day, 90-day, 1-year, and 5-year major LEA mortality rates were 4.82%, 8.62%, 12.47%, and 18.11%, respectively. Weighted averages of 30-day, 90-day, 1-year, and 5-year major LEA mortality rates in the literature are 13%, 15.40%, 47.93%, and 60.60%, respectively. Mortality risk associated with vascular disease after amputation (hazard ratio = 22.07) was 11 times greater than risk associated with amputation-specific complications from impaired mobility (hazard ratio = 1.90; P < 0.01). Having diabetes was associated with lower mortality at 30 days, 90 days, and 1 year (P < 0.01) but not at 5 years (P = 0.22). Conclusions:. This study suggests that people may be living longer after their major LEA than was previously thought. This study suggests that patients’ PAD may play a bigger role in contributing to their mortality than complications from loss of mobility postamputation. Although having diabetes was associated with lower postamputation mortality, the difference was no longer significant by 5 years.

Introduction: Brain atrophy in Parkinson’s disease occurs to varying degrees in different brain regions, even at the early stage of the disease. While cortical morphological features are often considered independently in structural brain imaging studies, research on the co-progression of different cortical morphological measurements could provide new insights regarding the progression of PD. This study’s aim was to examine the interplay between cortical curvature and thickness as a function of PD diagnosis, motor symptoms, and cognitive performance. Methods: A total of 359 de novo PD patients and 159 healthy controls (HC) from the Parkinson’s Progression Markers Initiative (PPMI) database were included in this study. Additionally, an independent cohort from four databases (182 PD, 132 HC) with longer disease durations was included to assess the effects of PD diagnosis in more advanced cases. Pearson correlation was used to determine subject-specific associations between cortical curvature and thickness estimated from T1-weighted MRI images. General linear modeling (GLM) was then used to assess the effect of PD diagnosis, motor symptoms, and cognitive performance on the curvature-thickness association. Next, longitudinal changes in the curvature-thickness correlation as well as the predictive effect of the cortical curvature-thickness association on changes in motor symptoms and cognitive performance across four years were investigated. Finally, Akaike information criterion (AIC) was used to build a GLM to model PD motor symptom severity cross-sectionally. Results: A significant interaction effect between PD motor symptoms and age on the curvature-thickness correlation was found (βstandardized = 0.11; t(350) = 2.12; p = 0.03). This interaction effect showed that motor symptoms in older patients were related to an attenuated curvature-thickness association. No significant effect of PD diagnosis was observed for the PPMI database (β = 0.03; t(510) = 0.35; p = 0.72). However, in patients with a longer disease duration, a significant effect of diagnosis on the curvature-thickness association was found (βstandardized = 0.31; t(306.7) = 3.49; p = 0.0006). Moreover, rigidity, but not tremor, in PD was significantly related to the curvature-thickness correlation (βstandardized = 0.11, t(350) = 2.24, p = 0.03; βstandardized = -0.03, t(350) = -0.58, p = 0.56, respectively). The curvature-thickness association was attenuated over time in both PD and HC, but the two groups did not show a significantly different effect (βstandardized = 0.03, t(184.7) = 0.78, p = 0.44). No predictive effects of the CC-CT correlation on longitudinal changes in cognitive performance or motor symptoms were observed (all p-values > 0.05). The best cross-sectional model for PD motor symptoms included the curvature-thickness correlation, cognitive performance, and putamen dopamine transporter (DAT) binding, which together explained 14 % of variance. Conclusion: The association between cortical curvature and thickness is related to PD motor symptoms and age. This research shows the potential of modeling the curvature-thickness interplay in PD.

Purpose: While disparities in the inclusion and advancement of women and minorities in science, technology, engineering, mathematics, and medical fields have been well documented, less work has focused on medical physics specifically. In this study, we evaluate historical and current diversity within the medical physics workforce, in cohorts representative of professional advancement (PA) in the field, and within National Institutes of Health (NIH)–funded medical physics research activities. Methods and Materials: The 2020 American Association of Physicists in Medicine (AAPM) membership was queried as surrogate for the medical physics workforce. Select subsets of the AAPM membership were queried as surrogate for PA and early career professional advancement (ECPA) in medical physics. Self-reported AAPM-member demographics data representative of study analysis groups were identified and analyzed. Demographic characteristics of the 2020 AAPM membership were compared with those of the PA and ECPA cohorts and United States (US) population. The AAPM-NIH Research Database was appended with principal investigator (PI) demographics data and analyzed to evaluate trends in grant allocation by PI demographic characteristics. Results: Women, Hispanic/Latinx/Spanish individuals, and individuals reporting a race other than White or Asian alone comprised 50.8%, 18.7%, and 32.4% of the US population, respectively, but only 23.9%, 9.1%, and 7.9% of the 2020 AAPM membership, respectively. In general, representation of women and minorities was further decreased in the PA cohort; however, significantly higher proportions of women (P < .001) and Hispanic/Latinx/Spanish members (P < .05) were observed in the ECPA cohort than the 2020 AAPM membership. Analysis of historical data revealed modest increases in diversity within the AAPM membership since 2002. Across NIH grants awarded to AAPM members between 1985 and 2020, only 9.4%, 5.3%, and 1.7% were awarded to women, Hispanic/Latinx/Spanish, and non-White, non-Asian PIs, respectively. Conclusions: Diversity within medical physics is limited. Proactive policy should be implemented to ensure diverse, equitable, and inclusive representation within research activities, roles representative of PA, and the profession at large.

Abstract Peptide receptor radionuclide therapy (PRRT) is an increasingly used treatment for unresectable neuroendocrine tumours (NETs) that express somatostatin receptors. Normal pituitary tissue expresses somatostatin receptors so patients receiving PRRT may be at risk of developing hypopituitarism. The aim was to assess the prevalence of clinically significant hypopituitarism a minimum of 2 years following radioisotope therapy for metastatic NET. This was a multicentre study (Australia and New Zealand). Sixty‐six patients with unresectable NETs were included–34 had received PRRT and 32 comparison patients. Median follow‐up after PRRT was 68 months. Male hypogonadism was the most common hormonal abnormality (16 of 38 men [42%]) from the total cohort. Of these, seven men had primary hypogonadism (five from PRRT group) and nine had secondary hypogonadism (six in PRRT group). There was no difference in either male hypogonadism or other hormonal dysfunction between patients who had received PRRT and those that had not. Patients who have received PRRT out to 68 months following treatment do not show concerning hypopituitarism although there may be the suggestion of growth hormone deficiency developing. However, hypogonadism is common in men with NETs so the gonadal axis should be assessed in men with suggestive symptoms as the treatment of testosterone deficiency may improve the quality of life.

Abstract Background Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. COPD patients with cachexia or weight loss have increased risk of death independent of body mass index (BMI) and lung function. We tested the hypothesis genetic variation is associated with weight loss in COPD using a genome‐wide association study approach. Methods Participants with COPD (N = 4308) from three studies (COPDGene, ECLIPSE, and SPIROMICS) were analysed. Discovery analyses were performed in COPDGene with replication in SPIROMICS and ECLIPSE. In COPDGene, weight loss was defined as self‐reported unintentional weight loss > 5% in the past year or low BMI (BMI

IntroductionCurrent evidence shows that serum miR-371a-3p can identify disease recurrence in testicular germ cell tumour (TGCT) patients and correlates with tumour load. Despite convincing evidence showing the advantages of including miR-371a-3p testing to complement and overcome the classical serum tumour markers limitations, the successful introduction of a serum miRNA based test into clinical practice has been impeded by a lack of consensus regarding optimal methodologies and lack of a universal protocol and thresholds. Herein, we investigate two quantitative real-time PCR (qRT-PCR) based pipelines in detecting disease recurrence in stage I TGCT patients under active surveillance, and compare the sensitivity and specificity for each method.MethodsSequential serum samples collected from 33 stage I TGCT patients undergoing active surveillance were analysed for miR-371a-3p via qRT-PCR with and without an amplification step included.ResultsUsing a pre-amplified protocol, all known recurrences were detected via elevated miR-371a-3p expression, while without pre-amplification, we failed to detect recurrence in 3/10 known recurrence patients. For pre-amplified analysis, sensitivity and specificity was 90% and 94.4% respectively. Without amplification, sensitivity dropped to 60%, but exhibited 100% specificity.DiscussionWe conclude that incorporating pre-amplification increases sensitivity of miR-371a-3p detection, but produces more false positive results. The ideal protocol for quantification of miR-371a-3p still needs to be determined. TGCT patients undergoing active surveillance may benefit from serum miR-371a-3p quantification with earlier detection of recurrences compared to current standard methods. However, larger cross-institutional studies where samples are processed and data is analysed in a standardised manner are required prior to its routine clinical implementation.

PurposePathologic complete response (pCR) is a critical factor in determining whether patients with rectal cancer (RC) should have surgery after neoadjuvant chemoradiotherapy (nCRT). Currently, a pathologist's histological analysis of surgical specimens is necessary for a reliable assessment of pCR. Machine learning (ML) algorithms have the potential to be a non-invasive way for identifying appropriate candidates for non-operative therapy. However, these ML models' interpretability remains challenging. We propose using explainable boosting machine (EBM) to predict the pCR of RC patients following nCRT.MethodsA total of 296 features were extracted, including clinical parameters (CPs), dose-volume histogram (DVH) parameters from gross tumor volume (GTV) and organs-at-risk, and radiomics (R) and dosiomics (D) features from GTV. R and D features were subcategorized into shape (S), first-order (L1), second-order (L2), and higher-order (L3) local texture features. Multi-view analysis was employed to determine the best set of input feature categories. Boruta was used to select all-relevant features for each input dataset. ML models were trained on 180 cases from our institution, with 37 cases from RTOG 0822 clinical trial serving as the independent dataset for model validation. The performance of EBM in predicting pCR on the test dataset was evaluated using ROC AUC and compared with that of three state-of-the-art black-box models: extreme gradient boosting (XGB), random forest (RF) and support vector machine (SVM). The predictions of all black-box models were interpreted using Shapley additive explanations.ResultsThe best input feature categories were CP+DVH+S+R_L1+R_L2 for all models, from which Boruta-selected features enabled the EBM, XGB, RF, and SVM models to attain the AUCs of 0.820, 0.828, 0.828, and 0.774, respectively. Although EBM did not achieve the best performance, it provided the best capability for identifying critical turning points in response scores at distinct feature values, revealing that the bladder with maximum dose >50 Gy, and the tumor with maximum2DDiameterColumn >80 mm, elongation 50 mm and lower variance of CT intensities were associated with unfavorable outcomes.ConclusionsEBM has the potential to enhance the physician's ability to evaluate an ML-based prediction of pCR and has implications for selecting patients for a “watchful waiting” strategy to RC therapy.

Protocols that enhance communication between nurses, physicians and patients have had a variable impact on the quality and safety of patient care. We combined standardised nursing and physician interdisciplinary bedside rounds with a mnemonic checklist to assure all key nursing care components were modified daily. The mnemonic TEMP allowed the rapid review of 11 elements. T stands for tubes assuring proper management of intravenous lines and foleys; E stands for eating, exercise, excretion and sleep encouraging a review of orders for diet, exercise, laxatives to assure regular bowel movements, and inquiry about sleep; M stands for monitoring reminding the team to review the need for telemetry and the frequency of vital sign monitoring as well as the need for daily blood tests; and P stands for pain and plans reminding the team to discuss pain medications and to review the management plan for the day with the patient and family. Faithful implementation eliminated central line-associated bloodstream infections and catheter-associated urinary tract infections and resulted in a statistically significant reduction in average hospital length of stay of 13.3 hours, one unit achieving a 23-hour reduction. Trends towards reduced 30-day readmissions (20% down to 10%–11%) were observed. One unit improved the percentage of patients who reported nurses and doctors always worked together as a team from a 56% baseline to 75%. However, the combining of both units failed to demonstrate statistically significant improvement. Psychologists well versed in implementing behavioural change were recruiting to improve adherence to our protocols. Following training physicians and nurses achieved adherence levels of over 70%. A high correlation (r2=0.69) between adherence and reductions in length of stay was observed emphasising the importance of rigorous training and monitoring of performance to bring about meaningful and reliable improvements in the efficiency and quality of patient care.

Incidental detection of urogenital tumors has increased in recent decades owing to the greater use of ultrasonography and cross-sectional imaging. For patients with low-risk prostate cancer or small renal masses, active surveillance represents a valid treatment option. Similarly, for men with small testicular masses

We review the extent and nature of scientific knowledge of the Big-headed Amazon River Turtle, Peltocephalus dumerilianus, covering distribution, morphology, taxonomy, diet, behaviour, reproduction, and ecology. We discuss the phylogenetic position of the species and its evolutionary relationships with the other podocnemidids, comparing morphological, karyological and molecular information. Also, we describe the importance of this species and its relationship with traditional Amazonian communities, including capture techniques, uses, beliefs and taboos. Finally, we comment on the conservation status of the species and the urgent need for additional studies. Besides discussing and reinterpreting published data, we provide new information from recent genetic studies, field activities and captive observations.

Background: Noninvasive transcranial electrical stimulation (tES) research has been plagued with inconsistent effects. Recent work has suggested neuroanatomical and neurophysiological variability may alter tES efficacy. However, direct evidence is limited. Objective: We have previously replicated effects of transcranial alternating current stimulation (tACS) on improving multitasking ability in young adults. Here, we attempt to assess whether these stimulation parameters have comparable effects in older adults (aged 60–80 years), which is a population known to have greater variability in neuroanatomy and neurophysiology. It is hypothesized that this variability in neuroanatomy and neurophysiology will be predictive of tACS efficacy. Methods: We conducted a pre-registered study where tACS was applied above the prefrontal cortex (between electrodes F3-F4) while participants were engaged in multitasking. Participants were randomized to receive either 6-Hz (theta) tACS for 26.67 min daily for three days (80 min total; Long Exposure Theta group), 6-Hz tACS for 5.33 min daily (16-min total; Short Exposure Theta group), or 1-Hz tACS for 26.67 min (80 min total; Control group). To account for neuroanatomy, magnetic resonance imaging data was used to form individualized models of the tACS-induced electric field (EF) within the brain. To account for neurophysiology, electroencephalography data was used to identify individual peak theta frequency. Results: Results indicated that only in the Long Theta group, performance change was correlated with modeled EF and peak theta frequency. Together, modeled EF and peak theta frequency accounted for 54%–65% of the variance in tACS-related performance improvements, which sustained for a month. Conclusion: These results demonstrate the importance of individual differences in neuroanatomy and neurophysiology in tACS research and help account for inconsistent effects across studies.

Introduction Ambulances services are asked to further reduce avoidable conveyances to emergency departments (EDs). Risk of Adverse Outcomes after a Suspected Seizure seeks to support this by: (1) clarifying the risks of conveyance and non-conveyance, and (2) developing a risk prediction tool for clinicians to use ‘on scene’ to estimate the benefits an individual would receive if conveyed to ED and risks if not.Methods and analysis Mixed-methods, multi-work package (WP) project. For WP1 and WP2 we shall use an existing linked data set that tracks urgent and emergency care (UEC) use of persons served by one English regional ambulance service. Risk tools are specific to clinical scenarios. We shall use suspected seizures in adults as an exemplar.WP1: Form a cohort of patients cared for a seizure by the service during 2019/2020. It, and nested Knowledge Exchange workshops with clinicians and service users, will allow us to: determine the proportions following conveyance and non-conveyance that die and/or recontact UEC system within 3 (/30) days; quantify the proportion of conveyed incidents resulting in ‘avoidable ED attendances’ (AA); optimise risk tool development; and develop statistical models that, using information available ‘on scene’, predict the risk of death/recontact with the UEC system within 3 (/30) days and the likelihood of an attendance at ED resulting in an AA.WP2: Form a cohort of patients cared for a seizure during 2021/2022 to ‘temporally’ validate the WP1 predictive models.WP3: Complete the ‘next steps’ workshops with stakeholders. Using nominal group techniques, finalise plans to develop the risk tool for clinical use and its evaluation.Ethics and dissemination WP1a and WP2 will be conducted under database ethical approval (IRAS 307353) and Confidentiality Advisory Group (22/CAG/0019) approval. WP1b and WP3 have approval from the University of Liverpool Central Research Ethics Committee (11450). We shall engage in proactive dissemination and knowledge mobilisation to share findings with stakeholders and maximise evidence usage.

Background: Persistent posttraumatic symptoms (PPS) may manifest after a mild-moderate traumatic brain injury (mmTBI) even when standard brain imaging appears normal. Transcranial direct current stimulation (tDCS) represents a promising treatment that may ameliorate pathophysiological processes contributing to PPS.Objective/Hypothesis: We hypothesized that in a mmTBI population, active tDCS combined with training would result in greater improvement in executive functions and post-TBI cognitive symptoms and increased resting state connectivity of the stimulated region, i.e., left dorsolateral prefrontal cortex (DLPFC) compared to control tDCS.Methods: Thirty-four subjects with mmTBI underwent baseline assessments of demographics, symptoms, and cognitive function as well as resting state functional magnetic resonance imaging (rsfMRI) in a subset of patients (n = 24). Primary outcome measures included NIH EXAMINER composite scores, and the Neurobehavioral Symptom Inventory (NSI). All participants received 10 daily sessions of 30 min of executive function training coupled with active or control tDCS (2 mA, anode F3, cathode right deltoid). Imaging and assessments were re-obtained after the final training session, and assessments were repeated after 1 month. Mixed-models linear regression and repeated measures analyses of variance were calculated for main effects and interactions.Results: Both active and control groups demonstrated improvements in executive function (EXAMINER composite: p < 0.001) and posttraumatic symptoms (NSI cognitive: p = 0.01) from baseline to 1 month. Active anodal tDCS was associated with greater improvements in working memory reaction time compared to control (p = 0.007). Reaction time improvement correlated significantly with the degree of connectivity change between the right DLPFC and the left anterior insula (p = 0.02).Conclusion: Anodal tDCS improved reaction time on an online working memory task in a mmTBI population, and decreased connectivity between executive network and salience network nodes. These findings generate important hypotheses for the mechanism of recovery from PPS after mild-moderate TBI.

Background Gait is a complex task requiring coordinated efforts of multiple brain networks. To date, there is little evidence on whether gait is altered in cerebral amyloid angiopathy (CAA). We aimed to identify impairments in gait performance and associations between gait impairment and neuroimaging markers of CAA, cognition, and falls. Methods and Results Gait was assessed using the Zeno Walkway during preferred pace and dual task walks, and grouped into gait domains (Rhythm, Pace, Postural Control, and Variability). Participants underwent neuropsychological testing and neuroimaging. Falls and fear of falling were assessed through self‐report questionnaires. Gait domain scores were standardized and analyzed using linear regression adjusting for age, sex, height, and other covariates. Participants were patients with CAA (n=29), Alzheimer disease with mild dementia (n=16), mild cognitive impairment (n=24), and normal elderly controls (n=47). CAA and Alzheimer disease had similarly impaired Rhythm, Pace, and Variability, and higher dual task cost than normal controls or mild cognitive impairment. Higher Pace score was associated with better global cognition, processing speed, and memory. Gait measures were not correlated with microbleed count or white matter hyperintensity volume. Number of falls was not associated with gait domain scores, but participants with low fear of falling had higher Pace (odds ratio [OR], 2.61 [95% CI, 1.59–4.29]) and lower Variability (OR, 1.64 [95% CI, 1.10–2.44]). Conclusions CAA is associated with slower walking, abnormal rhythm, and greater gait variability than in healthy controls. Future research is needed to identify the mechanisms underlying gait impairments in CAA, and whether they predict future falls.

The provision of electricity in rural areas has been an outstanding need in trying to achieve the United Nations sustainable development goals (SDGs) by 2030. However, most sub-Saharan countries have found this difficult due to financial constraints. Uganda tried to increase rural electrification to more than 20% of its population by 2020 through Rural Electrification Agency programmes. In an attempt to realise SDGs and the National Vision by 2040, Uganda is investing more in renewable energy sources, especially solar photovoltaic mini-grids to ensure that rural areas access affordable, reliable, and sustainable modern energy. This paper assesses the operation, causes of failure, causes of discomfort for mini-grid connected customers, and customer behavior of two solar photovoltaic mini-grids located in Kyenjojo District in western Uganda. It was found that the current energy demand exceeds the generation supply and that the systems need phase upgrades and clustering to remain economically viable and sustainable. The methodology involved re-sizing the existing load demand of the connected users, well-designed and administered questionnaires, analysis of published literature, review of the existing records, and interviews. Analysis was done in an Excel software program. The paper concludes by identifying the benefits and challenges of solar photovoltaic mini-grids in Kyenjojo District.

This manuscript introduces an exploratory case study of the SIMFAC’s (Sistema de Información Meteorológica de la Fuerza Aérea Colombiana) operational implementation of the Weather Research and Forecasting (WRF) model with a 3DVAR (three-dimensional variational) data assimilation scheme that provides meteorological information for military, public, and private aviation. In particular, it investigates whether the assimilation scheme in SIMFAC’s implementation improves the prediction of the variables of interest compared to the implementation without data assimilation (CTRL). Consequently, this study compares SIMFAC’S 3DVAR-WRF operational implementation in Colombia with a CTRL with the same parameterization (without 3DVAR assimilation) against the ground and satellite observations in two operational forecast windows. The simulations are as long as an operational run, and the evaluation is performed using the root mean square error, the mean fractional bias, the percent bias, the correlation factor, and metrics based on contingency tables. It also evaluates the model’s results according to the regions of Colombia, accounting for the country’s topographical differences. The findings reveal that, in general, the operational forecast (3DVAR) is similar to the CTRL without data assimilation, indicating the need for further improvement of the 3DVAR-WRF implementation.

Sarcoma is a rare cancer that has a significant impact on patients’ and carers’ quality of life. Despite this, there has been a paucity of research exploring the diverse experiences of patients and carers following sarcoma treatment. The aim of this study was to explore patients’ and carers’ reflections on life after treatment for sarcoma. A qualitative research design with a social constructionist epistemology was used. Participants included patients previously treated for sarcoma (n = 21) and family carers of patients treated for sarcoma (n = 16). Participants completed semi-structured interviews which were analysed using thematic analysis. Three primary themes were identified: “This journey is never going to be over”, “But what happens when I am better?”, and finding a silver lining. Participants represented sarcoma as having a long-term, and sometimes indefinite, threat on their life that they had limited control over. Conclusions: This study highlight the heterogeneous and ongoing needs of sarcoma survivors and their families. Patients and carers strove to translate their experiences in a meaningful way, such as by improving outcomes for other people affected by sarcoma. Parental carers in particular attempted to protect the patient from the ongoing stress of managing the disease.

BackgroundGait disturbances are critical motor symptoms in Parkinson’s disease (PD). The mechanisms of gait impairment in PD are not entirely understood but likely involve changes in the Pedunculopontine Nucleus (PPN), a critical locomotion center, and its associated connections. Exercise is universally accepted as helpful in PD, but the extent and intensity of exercise required for plastic changes are unclear.MethodsTwenty-seven PD subjects participated in a 3-month gait training intervention. Clinical assessments and resting-state functional magnetic resonance imaging were performed at baseline and 3 months after exercise. Functional connectivity of PPN was assessed by combining the methods of partial least squares, conditional dependence and partial correlation. In addition, paired t-tests were used to examine the effect of exercise on PPN functional connectivity and clinical measures, and Pearson’s correlation was used to assess the association between altered PPN functional connectivity and clinical measures.ResultsExercise significantly improved Unified Parkinson’s Disease Rating Scale-III (UPDRS-III). A significant increase in right PPN functional connectivity was observed after exercise, which did not correlate with motor improvement. However, the decrease in left PPN functional connectivity significantly correlated with the improvement in UPDRS-III and was linearly related to both number of walks and the duration of walks. In addition, exercise induced a significant increase in the laterality of PPN connectivity strength, which correlated with motor improvement.ConclusionPPN functional connectivity is modifiable by walking exercise in both a dose-independent (right PPN and laterality of PPN connectivity strength) and dose-dependent (left PPN) manner. The PPN may contribute to pathological and compensatory processes in PD gait control. The observed gait improvement by walking exercise is most likely due to the reversal of the maladaptive compensatory mechanism. Altered PPN functional connectivity can be a marker for exercise-induced motor improvement in PD.

Objectives Settings in identifying need for emergency care amongst those with suspected COVID-19 infection and identify factors which affect triage accuracy. Approach An observational cohort study of adults who contacted the NHS 111 telephone triage service provided by Yorkshire Ambulance Service between March and June 2020 with symptoms indicating possible COVID-19 infection. Patient-level data encompassing triage call, primary care, hospital care and death registration records relating to 40,261 adults were linked. The accuracy of triage outcome (self-care/non-urgent assessment versus ambulance/urgent assessment) was assessed for death or organ support 30 days from first contact. Multivariable logistic regression was used to identify factors associated with risk of false negative or false positive triage. Results Callers had a 3% (1,200/40,261) risk of serious adverse outcomes. Telephone triage recommended self-care or non-urgent assessment for 60% (24,335/40,261), with a 1.3% (310/24,335) risk of adverse outcomes 30 days from first contact. Telephone triage had 74.2% sensitivity (95% CI: 71.6 to 76.6%) and 61.5% specificity (61% to 62%) for the primary outcome. Analysis suggested respiratory comorbidities may be over-appreciated and diabetes under-appreciated as predictors of deterioration. Repeat contact with triage service appears to be an important under-recognised predictor of deterioration. Conclusion Patients advised to self-care or receive non-urgent clinical assessment had a small but non-negligible risk of serious clinical deterioration. Repeat contact with telephone services needs recognition as an important predictor of subsequent adverse outcomes.

Background The prevalence of diverticulitis has steadily increased during the past century. One possible complication of large bowel diverticulitis (LBD) is the concurrent development of a small bowel obstruction (SBO). The literature regarding these joint diagnoses is primarily limited to small case series from the 1950s. Consequently, no official recommendations or recent literature exists to guide decision making.Methods This is a retrospective case–control study with 5:1 matching by demographics, comorbidities, and Hinchey classification of patients presenting with concomitant LBD and SBO and patients with LBD alone. The primary outcome assessed was the need for same admission surgical intervention.Results Patients with concurrent LBD and SBO were more likely to require surgical intervention (OR 4.2, p

BackgroundGait impairment is a debilitating and progressive feature of Parkinson’s disease (PD). Increasing evidence suggests that gait control is partly mediated by cholinergic signaling from the pedunculopontine nucleus (PPN).ObjectiveWe investigated whether PPN structural connectivity correlated with quantitative gait measures in PD.MethodsTwenty PD patients and 15 controls underwent diffusion tensor imaging to quantify structural connectivity of the PPN. Whole brain analysis using tract-based spatial statistics and probabilistic tractography were performed using the PPN as a seed region of interest for cortical and subcortical target structures. Gait metrics were recorded in subjects’ medication ON and OFF states, and were used to determine if specific features of gait dysfunction in PD were related to PPN structural connectivity.ResultsTract-based spatial statistics revealed reduced structural connectivity involving the corpus callosum and right superior corona radiata, but did not correlate with gait measures. Abnormalities in PPN structural connectivity in PD were lateralized to the right hemisphere, with pathways involving the right caudate nucleus, amygdala, pre-supplementary motor area, and primary somatosensory cortex. Altered connectivity of the right PPN-caudate nucleus was associated with worsened cadence, stride time, and velocity while in the ON state; altered connectivity of the right PPN-amygdala was associated with reduced stride length in the OFF state.ConclusionOur exploratory analysis detects a potential correlation between gait dysfunction in PD and a characteristic pattern of connectivity deficits in the PPN network involving the right caudate nucleus and amygdala, which may be investigated in future larger studies.

Abstract Background In response to the rising concern with promoting the wellbeing of university students and relative lack of domain-specific wellbeing measurement instruments in China, the current study aimed to validate a Chinese version of the College Student Subjective Wellbeing Questionnaire (CSSWQ), a 16-item self-report English-language rating scale assessing four aspects of wellbeing (academic satisfaction, academic efficacy, school connectedness, and college gratitude). Methods The Chinese translation of the CSSWQ, the Students’ Life Satisfaction Scale, the Positive and Negative Affect Schedule, the 10-Item Big Five Personality Inventory, and demographic questions were completed by 252 Chinese students at a university in Suzhou, China. Results Exploratory factor analysis found four factors each with the same four items as in the original English scale. Each subscale showed good internal consistency. Test–retest for a one-month interval showed generally moderate reliability. As predicted, Pearson correlational analysis found positive correlations between the Chinese CSSWQ and life satisfaction, positive affect, extraversion, and GPA, and negative correlations with neuroticism and negative affect. Monthly income had small negative correlations with academic satisfaction and academic efficacy, smoking had a small positive correlation with school connectedness, and exercise had a small positive correlation with academic efficacy. Conclusion Data for the Chinese CSSWQ in the current study showed validity and reliability, supporting the use of this instrument as a measurement of college student wellbeing in China.

Abstract Background We previously reported a Phase 1/2 randomized placebo-controlled trial of systemic administration of bone marrow-derived allogeneic MSCs (remestemcel-L) in COPD. While safety profile was good, no functional efficacy was observed. However, in view of growing recognition of effects of inflammatory environments on MSC actions we conducted a post-hoc analysis with stratification by baseline levels of a circulating inflammatory marker, C-reactive protein (CRP) to determine the effects of MSC administration in COPD patients with varying circulating CRP levels. Methods Time course of lung function, exercise performance, patient reported responses, and exacerbation frequency following four monthly infusions of remestemcel-L vs. placebo were re-assessed in subgroups based on baseline circulating CRP levels. Results In COPD patients with baseline CRP ≥ 4 mg/L, compared to COPD patients receiving placebo (N = 17), those treated with remestemcel-L (N = 12), demonstrated significant improvements from baseline in forced expiratory volume in one second, forced vital capacity, and six minute walk distance at 120 days with treatment differences evident as early as 10 days after the first infusion. Significant although smaller benefits were also detected in those with CRP levels ≥ 2 or ≥ 3 mg/L. These improvements persisted variably over the 2-year observational period. No significant benefits were observed in patient reported responses or number of COPD exacerbations between treatment groups. Conclusion In an inflammatory environment, defined by elevated circulating CRP, remestemcel-L administration yielded at least transient meaningful pulmonary and functional improvements. These findings warrant further investigation of potential MSC-based therapies in COPD and other inflammatory pulmonary diseases. Trial registration: Clinicaltrials.gov NCT00683722.

Abstract Background Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection. Methods CONCOR-1 is an open-label, multicentre, randomized trial. Inclusion criteria include the following: patients > 16 years, admitted to hospital with COVID-19 infection, receiving supplemental oxygen for respiratory complications of COVID-19, and availability of blood group compatible CCP. Exclusion criteria are : onset of respiratory symptoms more than 12 days prior to randomization, intubated or imminent plan for intubation, and previous severe reactions to plasma. Consenting patients are randomized 2:1 to receive either approximately 500 mL of CCP or standard of care. CCP is collected from donors who have recovered from COVID-19 and who have detectable anti-SARS-CoV-2 antibodies quantified serologically. The primary outcome is intubation or death at day 30. Secondary outcomes include ventilator-free days, length of stay in intensive care or hospital, transfusion reactions, serious adverse events, and reduction in SARS-CoV-2 viral load. Exploratory analyses include patients who received CCP containing high titre antibodies. A sample size of 1200 patients gives 80% power to detect a 25% relative risk reduction assuming a 30% baseline risk of intubation or death at 30 days (two-sided test; α = 0.05). An interim analysis and sample size re-estimation will be done by an unblinded independent biostatistician after primary outcome data are available for 50% of the target recruitment (n = 600). Discussion This trial will determine whether CCP will reduce intubation or death non-intubated adults with COVID-19. The trial will also provide information on the role of and thresholds for SARS-CoV-2 antibody titres and neutralization assays for donor qualification. Trial registration Clinicaltrials.gov NCT04348656 . Registered on 16 April 2020.

In the past of the earth several asteroids and meteoroids have been impacted, but most of these collisions have been eroded and today there are only sometimes direct and indirect indications, such as massive extinctions of species in the form of fossils, layers with content of extraterrestrial material among others. Based on our recent reconnaissance in the field in 2017, we have been able to identify a new impact of a meteorite on volcanic rock of the Miocene Tarqui Formation in central Ecuador. We were able to reveal and reconstruct the corresponding trajectory as well as its impact day being in 1995. Based on known impacts in South America, this is the very first to have been impacted on rocks, which would lead to a clear shock metamorphism. This discovery of the impact on a rock may soon be a major tourist attraction of the country due to its accessibility and importance for being unique in Ecuador and on the continent.

Silica-supported, single site, main group Zn(II) and Ga(III) ions catalyze ethylene and propylene oligomerization. Here, experimental and theoretical evidence suggests a Cossee-Arlman reaction mechanism similar to that for transition metal catalysts.

Background: A classic debate concerns whether absolute or relative income is more salient. Absolute values resources as constant across time and place while relative contextualizes one's hierarchical location in the distribution of a time and place. Objective: This study investigates specifically whether absolute income or relative income matters more for health and well-being. Methods: We exploit within-person, within-age, and within-time variation with higher-quality income measures and multiple health and well-being outcomes in the United States. Using the Panel Study of Income Dynamics and the Cross-National Equivalent File, we estimate three-way fixed effects models of self-rated health, poor health, psychological distress, and life satisfaction. Results: For all four outcomes, relative income has much larger standardized coefficients than absolute income. Robustly, the confidence intervals for relative income do not overlap with zero. By contrast, absolute income mostly has confidence intervals that overlap with zero, and its coefficient is occasionally signed in the wrong direction. A variety of robustness checks support these results. Conclusions: Relative income has far greater predictive validity than absolute income for self-reported health and well-being. Contribution: Compared to earlier studies, this study provides a more rigorous comparison and test of the predictive validity of absolute and relative income that is uniquely conducted with data on the United States. This informs debates on income measurement, the sources of health and well-being, and inequalities generally. Plausibly, these results can guide any analysis that includes income in models.

With the increase in rainfall intensity, population, and urbanised areas, surface water flooding (SWF) is an increasing concern impacting properties, businesses, and human lives. Previous studies have shown that microtopography significantly influences flow paths, flow direction, and velocity, impacting flood extent and depth, particularly for the shallow flow associated with urban SWF. This study compares two survey strategies commonly used by flood practitioners, S1 (using Unmanned Aerial Systems-based RGB data) and S2 (using manned aircraft with LiDAR scanners), to develop guidelines on where to use each strategy to better characterise microtopography for a range of flood features. The difference between S1 and S2 in elevation and their accuracies were assessed using both traditional and robust statistical measures. The results showed that the difference in elevation between S1 and S2 varies between 11 cm and 37 cm on different land use and microtopographic flood features. Similarly, the accuracy of S1 ranges between 3 cm and 70 cm, and the accuracy of S2 ranges between 3.8 cm and 30.3 cm on different microtopographic flood features. Thus, this study suggests that the flood features of interest in any given flood study would be key to select the most suitable survey strategy. A decision framework was developed to inform data collection and integration of the two surveying strategies to better characterise microtopographic features. The findings from this study will help improve the microtopographic representation of flood features in flood models and, thus, increase the ability to identify high flood-risk prompt areas accurately. It would also help manage and maintain drainage assets, spatial planning of sustainable drainage systems, and property level flood resilience and insurance to better adapt to the effects of climate change. This study is another step towards standardising flood extent and impact surveying strategies.

Abstract Background Bone-targeted agents (BTAs) are widely used in the management of patients with bone metastases from solid tumors. Knowledge of the impact of their routine care use on patient-reported pain and bone pain-related quality of life (QoL) is limited. Methods This real world, cross-sectional study enrolled patients over a 3-month period through oncologists across Switzerland. Patients were ≥ 18 years, had solid tumors and at least one bone metastasis, and received routine care for bone metastases. Physicians provided data on BTA-related practices, risk of bone complications and BTA regimen. Patients completed questionnaires about pain (BPI-SF), general and bone pain-related QoL (FACT-G, FACT-BP) and treatment satisfaction (FACIT-TS-G). Results Eighteen sites recruited 417 patients. Based on the FACT-BP, 42% of the patients indicated not having bone pain. According to the BPI-SF, 28% reported no, 43% mild, 14% moderate, and 15% severe pain, respectively. Patients not treated with a BTA had better overall QoL (FACT-G: p = 0.031) and bone pain-related QoL (FACT-BP, p = 0.007) than those treated with a BTA. All pain and other QoL scales did not differ between groups. Patients perceived at ‘low risk of bone complications’ by their physician not receiving a BTA reported less pain and better QoL than those considered at ‘low risk’ but receiving BTA treatment or those considered at ‘high risk’ regardless of BTA treatment. Overall satisfaction with the treatment was good; almost 50% of patients reporting that they were completely satisfied. Conclusions Overall, pain and QoL did not differ according to BTA treatment or physicians’ risk perception. Patient with low risks not receiving BTA treatment reported least pain and highest QoL scores. These results may suggest that treating physicians assess bone complication risk appropriately and treat patients accordingly, but they need to be confirmed by objective determination of longitudinal skeletal complication risk.

Abstract Utilization of biologic skin substitutes for the management of soft tissue defects as an alternative to autologous skin grafts has expanded over the past 2 decades. The purpose of this case series study was to report our experience with Integra® bilayer wound matrix for reconstruction of intraoral oncologic defects. Case records of 6 patients with intraoral oncologic defects reconstructed with Integra® bilayer wound matrix were retrospectively reviewed. The surgical defect location, size, and time to removal of surgical splint varied. Clinically, normal oral epithelialization was noted for all patients. One patient demonstrated a small area of dehiscence and bone exposure after adjuvant radiation therapy which resolved with minimal intervention. Integra bilayer wound matrix is a viable and versatile option for reconstruction of intraoral oncologic surgical defects. Further exploration of wound healing with Integra® matrix, surgical techniques, and cost‐effectiveness is advocated.

Objective To assess accuracy of emergency medical service (EMS) telephone triage in identifying patients who need an EMS response and identify factors which affect triage accuracy.Design Observational cohort study.Setting Emergency telephone triage provided by Yorkshire Ambulance Service (YAS) National Health Service (NHS) Trust.Participants 12 653 adults who contacted EMS telephone triage services provided by YAS between 2 April 2020 and 29 June 2020 assessed by COVID-19 telephone triage pathways were included.Outcome Accuracy of call handler decision to dispatch an ambulance was assessed in terms of death or need for organ support at 30 days from first contact with the telephone triage service.Results Callers contacting EMS dispatch services had an 11.1% (1405/12 653) risk of death or needing organ support. In total, 2000/12 653 (16%) of callers did not receive an emergency response and they had a 70/2000 (3.5%) risk of death or organ support. Ambulances were dispatched to 4230 callers (33.4%) who were not conveyed to hospital and did not deteriorate. Multivariable modelling found variables of older age (1 year increase, OR: 1.05, 95% CI: 1.04 to 1.05) and presence of pre-existing respiratory disease (OR: 1.35, 95% CI: 1.13 to 1.60) to be predictors of false positive triage.Conclusion Telephone triage can reduce ambulance responses but, with low specificity. A small but significant proportion of patients who do not receive an initial emergency response deteriorated. Research to improve accuracy of EMS telephone triage is needed and, due to limitations of routinely collected data, this is likely to require prospective data collection.

Background: Infective endocarditis is a heart infection with a first-year mortality rate of ≈ 30%. It has long been thought that infective endocarditis is causally associated with bloodstream seeding with oral bacteria in ≈ 40–45% of cases. This theorem led guideline committees to recommend that individuals at increased risk of infective endocarditis should receive antibiotic prophylaxis before undergoing invasive dental procedures. However, to the best of our knowledge, there has never been a clinical trial to prove the efficacy of antibiotic prophylaxis and there is no good-quality evidence to link invasive dental procedures with infective endocarditis. Many contend that oral bacteria-related infective endocarditis is more likely to result from daily activities (e.g. tooth brushing, flossing and chewing), particularly in those with poor oral hygiene. Objective: The aim of this study was to determine if there is a temporal association between invasive dental procedures and subsequent infective endocarditis, particularly in those at high risk of infective endocarditis. Design: This was a self-controlled, case-crossover design study comparing the number of invasive dental procedures in the 3 months immediately before an infective endocarditis-related hospital admission with that in the preceding 12-month control period. Setting: The study took place in the English NHS. Participants: All individuals admitted to hospital with infective endocarditis between 1 April 2010 and 31 March 2016 were eligible to participate. Interventions: This was an observational study; therefore, there was no intervention. Main outcome measure: The outcome measure was the number of invasive and non-invasive dental procedures in the months before infective endocarditis-related hospital admission. Data sources: NHS Digital provided infective endocarditis-related hospital admissions data and dental procedure data were obtained from the NHS Business Services Authority. Results: The incidence rate of invasive dental procedures decreased in the 3 months before infective endocarditis-related hospital admission (incidence rate ratio 1.34, 95% confidence interval 1.13 to 1.58). Further analysis showed that this was due to loss of dental procedure data in the 2–3 weeks before any infective endocarditis-related hospital admission. Limitations: We found that urgent hospital admissions were a common cause of incomplete courses of dental treatment and, because there is no requirement to record dental procedure data for incomplete courses, this resulted in a significant loss of dental procedure data in the 2–3 weeks before infective endocarditis-related hospital admissions. The data set was also reduced because of the NHS Business Services Authority’s 10-year data destruction policy, reducing the power of the study. The main consequence was a loss of dental procedure data in the critical 3-month case period of the case-crossover analysis (immediately before infective endocarditis-related hospital admission), which did not occur in earlier control periods. Part of the decline in the rate of invasive dental procedures may also be the result of the onset of illness prior to infective endocarditis-related hospital admission, and part may be due to other undefined causes. Conclusions: The loss of dental procedure data in the critical case period immediately before infective endocarditis-related hospital admission makes interpretation of the data difficult and raises uncertainty over any conclusions that can be drawn from this study. Future work: We suggest repeating this study elsewhere using data that are unafflicted by loss of dental procedure data in the critical case period. Trial registration: This trial is registered as ISRCTN11684416. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 28. See the NIHR Journals Library website for further project information.

ObjectivesThe histidine kinase (HK) CHK1 and other protein kinases in Candida albicans are key players in the development of hyphae. This study is designed to determine the functional roles of the S_Tkc domain (protein kinase) and the GAF domain of C. albicans CHK1 in hyphal formation and mucosal invasion.MethodsThe domain mutants CHK25 (ΔS_TkcCHK1/Δchk1) and CHK26 (ΔS_TkcΔgafCHK1/Δchk1) were first constructed by the his1-URA3-his1 method and confirmed by sequencing and Southern blots. A mouse tongue infection model was used to evaluate the hyphal invasion and fungal loads in each domain mutant, full-gene deletion mutant CHK21 (chk1Δ/chk1Δ), re-constituted strain CHK23 (chk1Δ/CHK1), and wild type (WT) from day 1 to day 5. The degree of invasion and damage to the oral mucosa of mice in each strain-infected group was evaluated in vivo and compared with germ tube rate and hyphal formation in vitro.ResultWhen compared with severe mucosal damage and massive hyphal formation in WT- or CHK23-infected mouse tongues, the deletion of S_Tkc domain (CHK25) caused mild mucosal damage, and fungal invasion was eliminated as we observed in full-gene mutant CHK21. However, the deletion of S_Tkc and GAF (CHK26) partially restored the hyphal invasion and mucosal tissue damage that were exhibited in WT and CHK23. Regardless of the in vivo results, the decreased hyphal formation and germ tube in vitro were less apparent and quite similar between CHK25 and CHK26, especially at the late stage of the log phase where CHK26 was closer to WT and CHK23. However, growth defect and hyphal impairment of both domain mutants were similar to CHK21 in the early stages.ConclusionOur data suggest that both protein kinase (S_Tkc) and GAF domains in C. albicans CHK1 are required for hyphal invasiveness in mucosal tissue. The appropriate initiation of cell growth and hyphal formation at the lag phase is likely mediated by these two functional domains of CHK1 to maintain in vivo infectivity of C. albicans.

NADPH oxidase deficiency exacerbates lupus in murine models and patients, but the mechanisms remain unknown. It is hypothesized that NADPH oxidase suppresses autoimmunity by facilitating dead cell clearance via LC3-associated phagocytosis (LAP). The absence of LAP reportedly causes an autoinflammatory syndrome in aged, nonautoimmune mice. Prior work implicated cytochrome b-245, β polypeptide (CYBB), a component of the NADPH oxidase complex, and the RUN and cysteine-rich domain-containing Beclin 1–interacting protein (RUBICON) as requisite for LAP. To test the hypothesis that NADPH oxidase deficiency exacerbates lupus via a defect in LAP, we deleted Rubicon in the B6.Sle1.Yaa and MRL.Faslpr lupus mouse models. Under this hypothesis, RUBICON deficiency should phenocopy NADPH oxidase deficiency, as both work in the same pathway. However, we observed the opposite — RUBICON deficiency resulted in reduced mortality, renal disease, and autoantibody titers to RNA-associated autoantigens. Given that our data contradict the published role for LAP in autoimmunity, we assessed whether CYBB and RUBICON are requisite for LAP. We found that LAP is not dependent on either of these 2 pathways. To our knowledge, our data reveal RUBICON as a novel regulator of SLE, possibly by a B cell–intrinsic mechanism, but do not support a role for LAP in lupus.

TRPM3 is a calcium-permeable cation channel expressed in a range of sensory neurons that can be activated by heat and the endogenous steroid pregnenolone sulfate (PS). During inflammation, the expression and function of TRPM3 are both augmented in somatosensory nociceptors. However, in isolated dorsal root ganglion (DRG) neurons application of inflammatory mediators like prostaglandins and bradykinin (BK) inhibit TRPM3. Therefore, the aim of this study was to examine the effect of preceding activation of cultured 1 day old mouse DRG neurons by the inflammatory mediator BK on TRPM3-mediated calcium responses. Calcium signals were recorded using the intensity-based dye Fluo-8. We found that TRPM3-mediated calcium responses to PS were enhanced by preceding application of BK in cells that responded to BK with a calcium signal, indicating BK receptor (BKR) expression. The majority of cells that co-expressed TRPM3 and BKRs also expressed TRPV1, however, only a small fraction co-expressed TRPA1, identified by calcium responses to capsaicin and supercinnamaldehyde, respectively. Signaling and trafficking pathways responsible for sensitization of TRPM3 following BK were characterized using inhibitors of second messenger signaling cascades and exocytosis. Pharmacological blockade of protein kinase C, calcium–calmodulin-dependent protein kinase II and diacylglycerol (DAG) lipase did not affect BK-induced sensitization, but inhibition of DAG kinase did. In addition, release of calcium from intracellular stores using thapsigargin also resulted in TRPM3 sensitization. Finally, BK did not sensitize TRPM3 in the presence of exocytosis inhibitors. Collectively, we show that preceding activation of DRG neurons by BK sensitized TRPM3-mediated calcium responses to PS. Our results indicate that BKR-mediated activation of intracellular signaling pathways comprising DAG kinase, calcium and exocytosis may contribute to TRPM3 sensitization during inflammation.

Background: The level of radiation exposure received by operators performing transcatheter aortic valve replacement (TAVR) is not well investigated. The aim of this study is to measure the amount of radiation received by operators performing transfemoral TAVR and to identify various patient and procedural characteristics associated with increased radiation exposure. Methods: Primary (operator 1) and secondary (operator 2) operators' equivalent radiation doses in micro Sieverts (µSv) were calculated prospectively using real-time radiation dosimeters for a total of 140 consecutive transfemoral TAVRs. Corresponding eye and thorax radiation exposures between the operators were compared. Associations between various patient and procedural characteristics and the radiation exposure were tested using the t-test and Wilcoxon Mann-Whitney rank-sum test with Monte Carlo estimation. Multivariable regression analysis was also conducted. Results: Operator 1 had significantly higher cumulative equivalent radiation exposure than operator 2 (86 µSv vs 38 µSv, p-value:

Chelonians represent an important resource in the Amazon, either as a source of protein at the base of the food chain of aquatic and transition ecosystems, or in the dispersion of seeds of plants from floodplains and flooded forests. The consumption and predatory exploitation of their meat and eggs by local populations has been, and still is, one of the main threats to these animals. Community-based conservation projects allied to official protection programs have been restoring populations of chelonians of the genus Podocnemis throughout the Amazon since 1974. In this study, we analyzed the historical time series of protection data of Podocnemis expansa, P. unifilis, P. sextuberculata and P. erythrocephala in areas protected by the government and communities in the Amazonas state and northwest of Pará state. Between 1974 and 2019, 230,444 nests and 21,350,201 hatchlings of P. expansa, 170,076 nests and 3,229,821 hatchlings of P. unifilis, 647,715 nests and 6,410,092 hatchlings of P. sextuberculata and 24,617 nests and 168,856 hatchlings of P. erythrocephala were protected. Community protection schemes emerged in 1990, and covered 80.7% of the areas and produced 64.2% of P. unifilis hatchlings and 44.6% of P. sextuberculata hatchlings. The areas with the highest production of P. expansa remain under government protection (57.4%). Using the time series of production of nests and hatchlings per beach, logistic growth curves were estimated, and the values of r and K were compared between the two protection systems (government and community). Beaches controlled by the government showed higher support capacity in the production of nests (1,910.7 ± 1,035) and hatchlings (211,513 ± 93,031) of P. expansa and P. sextuberculata (81,160 ± 34,924 hatchlings). However, the communities were more efficient in protecting nests (r = 0.102 ± 0.2315) and hatchlings (r = 0.282 ± 0.166) of P. unifilis. Community-based protection and monitoring programs are an important component that should be incorporated by the government’s environmental agencies for the management and conservation of turtles in the Amazon.