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Sharp edge eye syndrome (SEES), sometimes known as visual looming syndrome, is a condition in which the patient experiences ocular pain or discomfort when viewing or mentally picturing sharp objects and edges. Patients may present for medical care because they perceive the condition to represent an ophthalmic problem or a sign of a more serious underlying condition. An individual case report of SEES is included to aid in illustrating syndrome characteristics. Our aim is to describe the syndrome, vision-related quality of life (VRQOL), and psychosocial characteristics in patients with self-identified SEES.A cross-sectional web-based survey was made available on social media webpages dedicated to SEES. The study included 22 questions developed by the research team, demographic questions, and 4 standardized questionnaires [ID Migraine, the National Eye Institute's Visual Function Questionnaire (NEI-VFQ-25), General Anxiety Disorder-2 (GAD-2), and Patient Health Questionnaire (depression) Scale-2].Seventy-seven respondents had an average age of 29 and were 57% male. 92% reported symptoms before age 18. The main site of pain or discomfort was the eyes, with onset resulting from viewing or thinking of sharp objects and edges. Symptoms lasted from seconds to hours and could be prolonged even after closing eyes or avoiding viewing the trigger. The composite and subscale scores on the NEI-VFQ-25 were low, with a mean composite score of 78 and selected subscores of general health (61), general vision (73), ocular pain (68), driving (79), mental health (61), and role difficulties (72). Anxiety was reported in 58% of participants, and depression in 57%. Migraine or headache was reported in 46% of participants. Participants reported Alice in Wonderland syndrome, visual snow, obsessive-compulsive disorder, attention deficit hyperactivity disorder, stripe-induced visual discomfort, and synesthesia.From this survey, we have the beginnings of an understanding of the characteristics of SEES, as well as VRQOL impacts. These survey responses lead us to postulate that SEES may be a distinct visual phenomenon and to propose SEES criteria. Systematic studies of this condition's clinical features and treatment responses will be additional steps toward improving patient care.

The current classification of atrial fibrillation (AF) is mainly focused on the clinical presentation according to the duration of AF episodes and the mode of termination, which incompletely reflect the severity and progressive nature of the underlying atrial disease. In this review article, "atrial cardiomyopathy" is discussed as a new concept in AF pathophysiology. Electrogram-, imaging-, and biomarker-derived measures and parameters to assess atrial cardiomyopathy, which will likely impact how AF is clinically classified and managed in the future, are presented.Die aktuelle Klassifikation von Vorhofflimmern (VHF) basiert hauptsächlich auf der klinischen Präsentation unter Berücksichtigung der Dauer einzelner VHF-Episoden und der Art, wie eine VHF-Episode spontan endet. Dies beschreibt allerdings den Schweregrad und den progressiven Charakter der zugrunde liegenden atrialen Erkrankung nicht ausreichend. Im vorliegenden Übersichtsbeitrag wird die „atriale Kardiomyopathie“ als ein neues Konzept der Pathophysiologie von VHF diskutiert. Wir stellen elektrogramm-, bildgebungs- und biomarkerbasierte Parameter für die Beurteilung der atrialen Kardiomyopathie vor, die in der Zukunft wahrscheinlich die klinische Klassifikation und Behandlung von VHF beeinflussen werden.

The genus Haemaphysalis Koch, 1844 (Acari: Ixodidae) is the second-largest genus, with more than 170 described species that primarily parasitize mammals and birds (Guglielmone et al. 2014, Guglielmone et al. 2020). Haemaphysalis species are three-host ticks, mainly distributed in southern and southeastern Asia and tropical Africa (Guglielmone et al. 2014). The present study identified a tick, Haemaphysalis hoodi Warburton & Nuttall, 1909, collected from a human in Yaoundé, Cameroon. This tick species feed on birds in sub-Saharan Africa. To the best of our knowledge, this is the second record of H. hoodi from humans. In addition, 16S ribosomal RNA and cytochrome oxidase I sequences were generated for this species for the first time. Screening pan-Rickettsia-PCR infection gave a negative result.

Aims We assessed the value of the Clinical Frailty Scale (CFS) in the prediction of adverse outcome after hip fracture. Methods Of 1,577 consecutive patients aged > 65 years with a fragility hip fracture admitted to one institution, for whom there were complete data, 1,255 (72%) were studied. Clinicians assigned CFS scores on admission. Audit personnel routinely prospectively completed the Standardised Audit of Hip Fracture in Europe form, including the following outcomes: 30-day survival; in-hospital complications; length of acute hospital stay; and new institutionalization. The relationship between the CFS scores and outcomes was examined graphically and the visual interpretations were tested statistically. The predictive values of the CFS and Nottingham Hip Fracture Score (NHFS) to predict 30-day mortality were compared using receiver operating characteristic area under the curve (AUC) analysis. Results Significant non-linear associations between CFS and outcomes were observed. Risk of death within 30 days rose linearly for CFS 1 to 5, but plateaued for CFS > 5. The incidence of complications and length of stay rose linearly for CFS 1 to 4, but plateaued for CFS > 4. In contrast, the risk of new institutionalization rose linearly for CFS 1 to 8. The AUCs for 30-day mortality for the CFS and NHFS were very similar: CFS AUC 0.63 (95% CI 0.57 to 0.69) and NHFS AUC 0.63 (95% CI 0.57 to 0.69). Conclusion Use of the CFS may provide useful information on outcomes for fitter patients presenting with hip fracture, but completion of the CFS by the admitting orthopaedic team does not appear successful in distinguishing between higher CFS categories, which define patients with frailty. This makes a strong case for the role of the orthogeriatrician in the early assessment of these patients. Further work is needed to understand why patients assessed as being of mild, moderate, and severe frailty do not result in different outcomes. Cite this article: Bone Joint J 2022;104-B(8):980–986.

Few functional measures related to time-trial display diurnal variation. The diversity of tests/protocols used to assess time-trial performance on diurnal effects and the lack of a standardised approach hinder agreement in the literature. Therefore, the aims of the present study were to investigate and systematically review the evidence relating to time-of-day differences in time-trial measures and to examine the main aspects related to research design important for studies of a chronobiological nature. The entire content of Manipal Academy of Higher Education electronic library and Qatar National Library, and electronic databases: PubMed (MEDLINE), Scopus and Web of Science were searched. Research studies published in peer-reviewed journals and non-peer reviewed studies, conducted in male adult participants aged ≥18 y before November 2021 were screened/included. Studies assessing tests related to time-trials in any modality between a minimum of 2 time-points during the day (morning [06:30-10:30 h]

In adults, alcohol intoxication is associated with prolongation of the QT interval corrected for heart rate (QTc). The QTc is influenced by age and sex. Although alcohol intoxication is increasingly common in adolescents, there are no data on the prevalence of QTc prolongation in adolescents with alcohol intoxication. This study aimed to determine the prevalence of QTc prolongation in adolescents with alcohol intoxication and identify at-risk adolescents. In this observational study including adolescents aged 10–18 years, heart rate and QT interval were automatically assessed from an electrocardiogram (ECG) at alcohol intoxication using a validated algorithm. The QTc was calculated using both the Bazett formula (QTcB) and Fridericia formula (QTcF). If present, an ECG recorded within 1 year of the date of admission to the emergency department was obtained as a reference ECG. A total of 317 adolescents were included; 13.3% had a QTcB and 7.9% a QTcF longer than the sex- and age-specific 95th-percentile. None of the adolescents had a QTcB or QTcF > 500 ms, but 11.8% of the adolescents with a reference ECG had a QTcB prolongation of > 60 ms, while no adolescents had a QTcF prolongation of > 60 ms. QTc prolongation was mainly attributable to an increase in heart rate rather than QT prolongation, which underlies the differences between QTcB and QTcF. Male sex and hypokalaemia increased the likelihood of QTc prolongation.Conclusion: QTc prolongation was seen in approximately 10% of the adolescents presenting with alcohol intoxication, and although no ventricular arrhythmias were observed in this cohort, QTc prolongation increases the potential for malignant QT-related arrhythmias. Clinicians must be aware of the possibility of QTc prolongation during alcohol intoxication and make an effort to obtain an ECG at presentation, measure the QT interval, and give an adequate assessment of the findings. We advocate admitting adolescents with alcohol intoxication and QTc prolongation. During hospital admission, we recommend limiting exposure to QTc-prolonging medication, increasing potassium levels to a high-normal range (4.5–5.0 mmol/L) and obtaining a reference ECG at discharge. What is Known:• One out of five deaths in adolescents is alcohol-related. Alcohol intoxication has been related to cardiac arrhythmias and sudden cardiac death.•In adults, alcohol intoxication is associated with QTc prolongation. What is New:•Approximately 10% of the adolescents with alcohol intoxication had a QTc longer than the age- and sexspecific cut-off. In contrast to adults, in adolescents with alcohol intoxication, QTc prolongation is attributable to an increase in heart rate, rather than a prolongation of the QT interval.•Especially males and adolescents with hypokalaemia are at risk of QTc prolongation.

Immunohistochemical staining can be of great utility in differentiating various cutaneous spindle cell neoplasms, particularly when the histomorphologic appearance of the lesions is inconclusive. Nuclear staining for ETS-related gene (ERG), a highly sensitive endothelial cell marker, has seldom been studied in the context of cutaneous spindle cell neoplasms. Little is known about its specificity for vascular differentiation. In this pilot study, immunohistochemical analysis for ERG was performed on 15 dermatofibromas (DF), 10 keloids, and 9 dermatofibrosarcoma protuberans (DFSP) tumors. Consistent nuclear expression of ERG was found in DF [100% (15/15) of the lesions demonstrated50% labeling of tumor cells with moderate to strong intensity]. However, ERG expression was largely absent in DFSP [89% (8/9) of the lesions demonstrating50% labeling staining, generally of mild intensity] and hypertrophic scars-keloids [80% (8/10) without expression]. On the basis of the results of this pilot study, immunohistochemical staining for ERG may prove useful in helping to differentiate DF from DFSP and hypertrophic scars in the context of partial biopsy sampling. If replicated in a larger number of samples, this finding could mitigate the use of costly sequencing panels and potentially avoid unnecessary reexcisions in certain contexts.

Aims Cervical radiculopathy is a significant cause of pain and morbidity. For patients with severe and poorly controlled symptoms who may not be candidates for surgical management, treatment with transforaminal epidural steroid injections (CTFESI) has gained widespread acceptance. However, a paucity of high-quality evidence supporting their use balanced against perceived high risks of the procedure potentially undermines the confidence of clinicians who use the technique. We undertook a systematic review of the available literature regarding CTFESI to assess the clinical efficacy and complication rates of the procedure. Methods OVID, MEDLINE, and Embase database searches were performed independently by two authors who subsequently completed title, abstract, and full-text screening for inclusion against set criteria. Clinical outcomes and complication data were extracted, and a narrative synthesis presented. Results Six studies (three randomized controlled trials and three non-randomized observational studies; 443 patients) were included in the final review. The aggregate data support the efficacy of CTFESI in excess of the likely minimal clinically important difference. No major complications were described. Conclusion There is increasing evidence supporting the efficacy of CTFESI. Concerns regarding the occurrence of catastrophic complications, widely shared in the case report and anecdotal literature, were not found when reviewing the best available evidence. However, the strength of these findings remains limited by the lack of highly powered high-level studies and the heterogeneity of the studies available. Further high-quality studies are recommended to address the issues of efficacy and safety with CTFESI. Cite this article: Bone Joint J 2022;104-B(5):567–574.

Purpose To quantify the damage to the corneal endothelium from the flow of balanced salt solution during phacoemulsification. Setting John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Design Experimental Study. Methods Twelve New Zealand white rabbits received bilateral surgery. Six eyes served as controls with no irrigation (incision only). In 18 eyes, the Intrepid Balanced tip of the Centurion (Alcon) Ozil handpiece was inserted into the anterior chamber for continuous irrigation at 50mL/minute with either 250 mL or 500 mL of balanced salt solution (BSS). After euthanasia and enucleation, the corneas were removed, stained with trypan blue/alizarin red, and photographed in a standardized manner (X400 photographs from 5 specific areas, and 1 overview photograph from each corneal button). The ImageJ program was used to evaluate cell damage and loss in the photographs obtained from each cornea. Results Analysis of the X400 photographs showed no statistical differences between control, 250 mL, and 500 mL groups in the percentage of intact, damaged, or lost cells (P= 0.896, 0.851, and 0.972 respectively). For the overview photos, the differences in areas of intact and damaged cells among the groups were statistically significant, likely due to the peripheral areas of damage related to touches between the phaco tip and the endothelium during irrigation. Conclusion The volume of BSS flow alone does not appear to be a major contributing source of endothelial cell damage and loss, providing further insight on mechanisms of corneal endothelium damage during phacoemulsification.

Mesoporous silica particles (MSPs) are emerging as an interesting option to reduce calorific uptake as a treatment for obesity and other metabolic conditions. However, their further development under the pharmaceutical regulatory framework is hindered by poor understanding of the mechanisms by which they exert their effects. In the current study the interaction of MSPs with the lipid digestion process is investigated, specifically interactions with lipase enzymes and lipid digestion products as a key contributing factor to lipid absorption and calorific intake. The impact of exposing lipase to MSPs on the enzyme activity was assessed directly using the tributyrin digestion test. The extent of interaction of digestion products with MSPs was studied using selectively radiolabeled bile components and lipids, while the impact on in vivo absorption of lipids was studied by incorporation of radiolabelled lipid (triolein) into milk and administration with and without particles. The studies showed that particles that inhibited lipase activity also tended to interact more extensively with lipid digestion products. In vitro X-ray scattering studies revealed the interaction of some MSPs with lipid digestion products through changes in lipid self-assembly during digestion. The MSPs led to reduced lipid absorption in vivo compared to the control particles and MSP-free milk. While the specific properties of the MSPs that drive the differences between the behavior of MSPs during lipid digestion remain elusive, the studies highlight that interactions with the lipid digestion and absorption pathways are a likely mechanism for reducing calorific uptake.

Purpose: To investigate the impact of hyperthermia thermal dose (TD) on locoregional control (LRC), overall survival (OS) and toxicity in locoregional recurrent breast cancer patients treated with postoperative re-irradiation and hyperthermia.Methods: In this retrospective study, 112 women with resected locoregional recurrent breast cancer treated in 2010-2017 with postoperative re-irradiation 8frx4Gy (n = 34) or 23frx2Gy (n = 78), combined with 4-5 weekly hyperthermia sessions guided by invasive thermometry, were subdivided into 'low' (n = 56) and 'high' TD (n = 56) groups by the best session with highest median cumulative equivalent minutes at 43 degrees C (Best CEM43T50) < 7.2 min and >7.2 min, respectively. Actuarial LRC, OS and late toxicity incidence were analyzed. Backward multivariable Cox regression and inverse probability weighting (IPW) analysis were performed.Results: TD subgroups showed no significant differences in patient/treatment characteristics. Median follow-up was 43 months (range 1-107 months). High vs. low TD was associated with LRC (p = 0.0013), but not with OS (p = 0.29) or late toxicity (p = 0.58). Three-year LRC was 74.0% vs. 92.3% in the low and high TD group, respectively (p = 0.008). After three years, 25.0% and 0.9% of the patients had late toxicity grade 3 and 4, respectively. Multivariable analysis showed that distant metastasis (HR 17.6; 95%CI 5.2-60.2), lymph node involvement (HR 2.9; 95%CI 1.2-7.2), recurrence site (chest wall vs. breast; HR 4.6; 95%CI 1.8-11.6) and TD (low vs. high; HR 4.1; 95%CI 1.4-11.5) were associated with LRC. TD was associated with LRC in IPW analysis (p = 0.0018).Conclusions: High thermal dose (best CEM43T50 >= 7.2 min) was associated with significantly higher LRC for patients with locoregional recurrent breast cancer treated with postoperative re-irradiation and hyperthermia, without augmenting toxicity. (C) 2021 The Authors. Published by Elsevier B.V.

Contains fulltext : 248376.pdf (Publisher’s version ) (Open Access) For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

Special Issue: The ENIGMA Consortium: the first 10 years., Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes., European Community's Seventh Framework Programme, Grant/Award Numbers: 278948, 602450, 603016, 602805; US National Institute of Child Health and Human Development, Grant/Award Numbers: RO1HD050735, 1009064, 496682; QIMR Berghofer Medical Research Institute and the Centre for Advanced Imaging, University of Queensland; ICTSI NIH/NCRR, Grant/Award Number: RR025761; European Community's Horizon 2020 Programme, Grant/Award Numbers: 667302, 643051; Vici Innovation Program, Grant/Award Numbers: #91619115, 016-130-669; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433-09-229; Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL); Spinozapremie, Grant/Award Number: NWO-56-464-14192; Biobanking and Biomolecular Resources Research Infrastructure, Grant/Award Numbers: 184.033.111, 184.021.007; Netherlands Organization for Health Research and Development (ZonMW), Grant/Award Numbers: 480-15-001/674, 024.001.003, 911-09-032, 056-32-010, 481-08-011, 016-115-035, 31160008, 400-07-080, 400-05-717, 451-04-034, 463-06-001, 480-04-004, 904-61-193, 912-10-020, 985-10-002, 904-61-090; NIMH, Grant/Award Number: R01 MH090553; Geestkracht programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: NWO/SPI 56-464-14192, NWO-MagW 480-04-004, 433-09-220, NWO 51.02.062, NWO 51.02.061; National Center for Advancing Translational Sciences, National Institutes of Health, Grant/Award Number: UL1 TR000153; National Center for Research Resources; National Center for Research Resources at the National Institutes of Health, Grant/Award Numbers: NIH 1U24 RR025736-01, NIH 1U24 RR021992; NIH Institutes contributing to the Big Data to Knowledge; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Numbers: U54EB020403, G0500092; National Institute of Mental Health, Grant/Award Numbers: R01MH117014, R01MH042191; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; Swedish Research Council, Grant/Award Numbers: 523-2014-3467, 2017-00949, 521-2014-3487; South-Eastern Norway Health Authority; the Research Council of Norway, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Icahn School of Medicine at Mount Sinai; Seventh Framework Programme (FP7/2007-2013), Grant/Award Number: 602450; National Institutes of Health, Grant/Award Numbers: R01 MH116147, R01 MH113619, R01 MH104284; South London and Maudsley NHS Foundation Trust; the National Institute for Health Research (NIHR)

ObjectiveTo provide insight into professionals’ perceptions of and experiences with shared decision-making (SDM) in the treatment of symptomatic patients with severe aortic stenosis (AS).MethodsA semistructured interview study was performed in the heart centres of academic and large teaching hospitals in the Netherlands between June and December 2020. Cardiothoracic surgeons, interventional cardiologists, nurse practitioners and physician assistants (n=21) involved in the decision-making process for treatment of severe AS were interviewed. An inductive thematic analysis was used to identify, analyse and report patterns in the data.ResultsFour primary themes were generated: (1) the concept of SDM, (2) knowledge, (3) communication and interaction, and (4) implementation of SDM. Not all respondents considered patient participation as an element of SDM. They experienced a discrepancy between patients’ wishes and treatment options. Respondents explained that not knowing patient preferences for health improvement hinders SDM and complicating patient characteristics for patient participation were perceived. A shared responsibility for improving SDM was suggested for patients and all professionals involved in the decision-making process for severe AS.ConclusionsProfessionals struggle to make highly complex treatment decisions part of SDM and to embed patients’ expectations of treatment and patients’ preferences. Additionally, organisational constraints complicate the SDM process. To ensure sustainable high-quality care, professionals should increase their awareness of patient participation in SDM, and collaboration in the pathway for decision-making in severe AS is required to support the documentation and availability of information according to the principles of SDM.

International audience; Young children are most vulnerable to develop severe forms of tuberculosis (TB) and are over-represented among TB deaths. Almost all children estimated to have died from TB were never diagnosed or offered TB treatment. Improved access to TB preventive treatment (TPT) requires major upscaling of household contact investigation with allocation of adequate resources. Symptom-based screening is often discouraged in adults for fear of generating drug resistance, if TB cases are missed. However, the situation in vulnerable young children is different, as they present minimal risk of drug resistance generation. Further, the perceived need for additional diagnostic evaluation presents a major barrier to TPT access and underlies general reluctance to consider pragmatic decentralised models of care. Widespread roll-out of Xpert MTB/RIF Ultra® represents an opportunity for improved case detection in young children, but attaining full impact will require the use of non-sputum specimens. The new Fujifilm SILVAMP TB LAM® urine assay demonstrated good diagnostic accuracy in HIV-positive and malnourished children, but further validation is required. Given the limited accuracy of all available tests and the excellent tolerance of TB drugs in children, the global community may have to accept some over-treatment if we want to close the persistent case detection gap in young children.

Highlights • Globally, Zoonotic TB remains a poorly monitored and an important unaddressed burden. • Zoonotic TB primarily from consumption M. bovis contaminated unpasteurized dairy products. • Novel zoonotic TB strains (e.g. M. orygis), warrants more attention and intervention. • Early detection and control of M. bovis in cattle remains the mainstay of reducing zoonotic TB risk. • Reverse zoonosis to animals of treatment resistant TB strains is a threat to eliminating TB., Despite slow reductions in the annual burden of active human tuberculosis (TB) cases, zoonotic TB (zTB) remains a poorly monitored and an important unaddressed global problem. There is a higher incidence in some regions and countries, especially where close association exists between growing numbers of cattle (the major source of Mycobacterium bovis) and people, many suffering from poverty, and where dairy products are consumed unpasteurised. More attention needs to be focused on possible increased zTB incidence resulting from growth in dairy production globally and increased demand in low income countries in particular. Evidence of new zoonotic mycobacterial strains in South Asia and Africa (e.g. M. orygis), warrants urgent assessment of prevalence, potential drivers and risk in order to develop appropriate interventions. Control of M. bovis infection in cattle through detect and cull policies remain the mainstay of reducing zTB risk, whilst in certain circumstances animal vaccination is proving beneficial. New point of care diagnostics will help to detect animal infections and human cases. Given the high burden of human tuberculosis (caused by M. tuberculosis) in endemic areas, animals are affected by reverse zoonosis, including multi-drug resistant strains. This, may create drug resistant reservoirs of infection in animals. Like COVID-19, zTB is evolving in an ever-changing global landscape.

BACKGROUND: Open tibial fracture research has traditionally focused on surgical techniques; however, despite technological advances, outcomes from these injuries remain poor, with patients facing a sustained reduced quality of life. Research has rarely asked patients what is important to them after an open tibial fracture, and this question could potentially offer great insight into how to support patients. A qualitative study may assist in our understanding of this subject. QUESTIONS/PURPOSES: We asked: (1) What common themes did patients who have experienced open tibial fractures share? (2) What stresses and coping strategies did those patients articulate? (3) What sources for acquiring coping strategies did patients say they benefited from? METHODS: Semistructured interviews were conducted with patients who had sustained an open tibial fracture between January 1, 2016 and January 1, 2019. All participants were recruited from a Level 1 trauma center in England, and 26 participants were included. The mean age was 44 ± 17 years, and 77% (20 of 26) were men. The patients’ injuries ranged in severity, and they had a range of treatments and complications. Transcripts were analyzed using framework analysis, with codes subsequently organized into themes and subthemes. RESULTS: Four themes were identified, which included recouping physical mobility, values around treatment, fears about poor recovery, and coping strategies to reduce psychological burden. Coping strategies were important in mitigating the psychological burden of injury. Task-focused coping strategies were preferred by patients and perceived as taking a proactive approach to recovery. Healthcare practitioners, and others with lived experience were able to educate patients on coping, but such resources were scant and therefore probably less accessible to those with the greatest need. CONCLUSION: Most individuals fail to return to previous activities, and it is unlikely that improvements in surgical techniques will make major improvements in patient outcomes in the near future. Investment in psychosocial support could potentially improve patient experience and outcomes. Digital information platforms and group rehabilitation clinics were identified as potential avenues for development that could offer individuals better psychosocial support with minimal additional burden for surgeons. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Background and purpose Positional verification during single fraction lung SBRT could increase confidence and reduce the chance of geographic miss. As planar 2DkV imaging during VMAT irradiation is already available on current linear accelerators, markerless tracking based on these images could offer widely available and low-cost verification. We evaluated treatment delivery data and template matching and triangulation for 3D-positional verification during free-breathing, single fraction (34 Gy), 10 MV flattening-filter-free VMAT lung SBRT. Methods and materials Tumor tracking based on kV imaging at 7 frames/second was performed during irradiation in 6 consecutive patients (7 lesions). Tumor characteristics, tracking ability, comparison of tracking displacements with CBCT-based shifts, tumor position relative to the PTV margin, and treatment times are reported. Results For all 7 lesions combined, 3D tumor position could be determined for, on average, 71% (51–84%) of the total irradiation time. Visually estimated tracked and automated match +/− manually-corrected CBCT-derived displacements generally agreed within 1 mm. During the tracked period, the longitudinal, lateral and vertical position of the tumor was within a 5 mm/3 mm PTV margin 95.5/85.3% of the time. The PTV was derived from the ITV including all tumor motion. The total time from first set-up imaging to end of the last arc was 18.3–31.4 min (mean = 23.4, SD = 4.1). Conclusion 3D positional verification during irradiation of small lung targets with limited motion, was feasible. However, tumor position could not be determined for on average 29% of the time. Improvements are needed. Margin reduction may be feasible. Imaging and delivery of a single 34 Gy fraction was fast.

The role of postoperative radiation therapy (PORT) in stage III N2 nonsmall cell lung cancer patients remains controversial. PORT is still widely used among European thoracic radiation oncology experts with a clear decrease in its use for patients with completely resected pN+ NSCLC after the presentation of LungART trial results at ESMO 2020. The full publication of the LungART trial hopefully will shed additional light on the dilemma of the decision-making process for PORT in completely resected pN+ patients and identify the appropriate patients who might benefit from PORT.Background: The role of postoperative radiation therapy (PORT) in stage III N2 NSCLC is controversial. We analyzed decision-making for PORT among European radiation oncology experts in lung cancer. Methods: Twenty-two experts were asked before and after presentation of the results of the LungART trial to describe their decision criteria for PORT in the management of pN+ NSCLC patients. Treatment strategies were subsequently converted into decision trees and analyzed. Results: Following decision criteria were identified: extracapsular nodal extension, incomplete lymph node resection, multistation lymph nodes, high nodal tumor load, poor response to induction chemotherapy, ineligibility to receive adjuvant chemotherapy, performance status, resection margin, lung function and cardiopulmonary comorbidities. The LungART results had impact on decision-making and reduced the number of recommendations for PORT. The only clear indication for PORT was a R1/2 resection. Six experts out of ten who initially recommended PORT for all R0 resected pN2 patients no longer used PORT routinely for these patients, while four still recommended PORT for all patients with pN2. Fourteen experts used PORT only for patients with risk factors, compared to eleven before the presentation of the LungART trial. Four experts stated that PORT was never recommended in R0 resected pN2 patients regardless of risk factors. Conclusion: After presentation of the LungART trial results at ESMO 2020, 82% of our experts still used PORT for stage III pN2 NSCLC patients with risk factors. The recommendation for PORT decreased, especially for patients without risk factors. Cardiopulmonary comorbidities became more relevant in the decision-making for PORT. (C) 2021 Elsevier Inc. All rights reserved.

The reality of climate change and biodiversity collapse is irrefutable in the 21st century, with urgent action required not only to conserve threatened species but also to protect human life and wellbeing. This existential threat forces us to recognise that our existence is completely dependent upon well-functioning ecosystems that sustain the diversity of life on our planet, including that required for human health. By synthesising data on the ecology, epidemiology and evolutionary biology of various pathogens, we are gaining a better understanding of factors that underlie disease emergence and spread. However, our knowledge remains rudimentary with limited insight into the complex feedback loops that underlie ecological stability, which are at risk of rapidly unravelling once certain tipping points are breached. In this paper, we consider the impact of climate change and biodiversity collapse on the ever-present risk of infectious disease emergence and spread. We review historical and contemporaneous infectious diseases that have been influenced by human environmental manipulation, including zoonoses and vector- and water-borne diseases, alongside an evaluation of the impact of migration, urbanisation and human density on transmissible diseases. The current lack of urgency in political commitment to address climate change warrants enhanced understanding and action from paediatricians - to ensure that we safeguard the health and wellbeing of children in our care today, as well as those of future generations.

Palisaded neutrophilic and granulomatous dermatitis (PNGD) represents a cutaneous histopathologic reaction spectrum associated with several underlying disorders. Few cases of PNGD have been associated with chronic myelomonocytic leukemia (CMML), a malignant hematopoietic disorder with features in between those of a myeloproliferative neoplasm and myelodysplastic syndrome. We present a patient with a generalized papular skin reaction involving the neck, chest, and shoulders with histomorphological features on the spectrum of PNGD. Subsequent laboratory workup demonstrated a persistent mild monocytosis, raising concern for CMML. The diagnosis was ultimately confirmed with a bone marrow biopsy and associated mutational analysis through next-generation sequencing which identified deleterious variants in SRSF2, IDH2, and ASXL1. The findings in this case strengthen the previously made association between PNGD and SRSF2-mutated CMML and may help better define a unique recognizable clinical-histopathological-molecular subtype for dermatopathologists.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

KCNT1 (K

In the current study, the concept of multiparticulate drug delivery systems (MDDS) was applied to tablets intended for the amorphisation of supersaturated granular ASDs in situ, i.e. amorphisation within the final dosage form by microwave irradiation. The MDDS concept was hypothesised to ensure geometric and structural stability of the dosage form and to improve the in vitro disintegration and dissolution characteristics. Granules were prepared in two sizes (small and large) containing the crystalline drug celecoxib (CCX) and polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA) at a 50 % w/w drug load as well as sodium dihydrogen phosphate monohydrate as the microwave absorbing excipient. The granules were subsequently embedded in an extra-granular tablet phase composed of either the filler microcrystalline cellulose (MCC) or mannitol (MAN), as well as the disintegrant crospovidone and the lubricant magnesium stearate. The tensile strength and disintegration time were investigated prior to and after 10 min of microwave irradiation (800 and 1000 W) and the formed ASDs were characterised by X-ray powder diffraction and modulated differential scanning calorimetry. Additionally, the internal structure was elucidated by X-ray micro-Computed Tomography (XµCT) and, finally, the dissolution performance of selected tablets was investigated. The MDDS tablets displayed no geometrical changes after microwave irradiation, however, the tensile strength and disintegration time generally increased. Complete amorphisation of CCX was achieved only for the MCC-based tablets at a power input of 1000 W, while MAN-based tablets displayed partial amorphisation independent of power input. The complete amorphisation of CCX was associated with the fusion of individual ASD granules within the tablets, which negatively impacted the subsequent disintegration and dissolution performance. For these tablets, supersaturation was only observed after 60 min. On the other hand, the partially amorphised MDDS tablets displayed complete disintegration during the dissolution experiments, resulting in a fast onset of supersaturation within 5 min and an approx. 3.5-fold degree of supersaturation within the experimental timeframe (3 h). Overall, the MDDS concept was shown to potentially be a feasible dosage form for in situ amorphisation, however, there is still room for improvement to obtain a both fully amorphous and disintegrating system.

Three common symmetries exist in the natural visual world: (i) mirror symmetry, i.e., reflections around a vertical axis, (ii) radial symmetry, i.e., rotations around a point, and (iii) translational symmetry, i.e., shifted repetitions. Are these processed by a common class of visual mechanism? Using stimuli comprising arrays of Gaussian blobs we examined this question using a visual search protocol in which observers located a single symmetric target patch among varying numbers of random-blob distractor patches. The testing protocol used a blocked present/absent task and both search times and accuracy were recorded. Search times for mirror and radial symmetry increased significantly with the number of distractors, as did translational-symmetry patterns containing few repetitions. However translational-symmetry patterns with four repeating sectors produced search slopes close to zero. Fourier analysis revealed that, as with images of natural scenes, the structural information in both mirror- and radial-symmetric patterns is carried by the phase spectrum. However, for translational patterns with four repeating sectors, the amplitude spectrum appears to capture the structure, consistent with previous analyses of texture regularity. Modeling revealed that while the mirror and radial patterns produced an approximately Gaussian-shaped energy response profile as a function of spatial frequency, the translational pattern profiles contained a distinctive spike, the magnitude of which increased with the number of repeating sectors. We propose distinct mechanisms for the detection of different symmetry types: a mechanism that encodes local positional information to detect mirror- and radial-symmetric patterns and a mechanism that computes energy in narrowband filters for the detection of translational symmetry containing many sectors. Canadian Institute if Health Research grant ~MOP 123349.

BackgroundPoor physical activity and excessive sedentary behaviour are well-established risk factors for morbidity and mortality. In the presence of emerging social problems, including loneliness and social isolation, these risks may be even greater. We aimed to investigate the joint effects of social health and movement behaviours on mortality and cardiovascular disease (CVD).Methods497,544 UK Biobank participants were followed for an average of 11 years. Loneliness and social isolation were measured via self-report. Physical activity was categorised around current World Health Organisation (WHO) guidelines as low ( 5.5). We derived 24 social health–movement behaviour combinations, accordingly. Mortality and hospitalisations were ascertained to May 2020 for all-cause and CVD mortality, and non-fatal cardiovascular events.ResultsSocial isolation amplified the risk of both all-cause and CVD death across all physical activity and sedentary levels (hazard ratio, 95% confidence interval [HR, 95% CIs] for all-cause mortality; 1.58 [1.49 to 1.68] for low active-isolated vs. 1.26 [1.22 to 1.30] for low active-not isolated). Loneliness was only found to amplify the risk of death from cardiovascular disease among the high active and low sedentary participants. Loneliness and social isolation did not add to the risk of non-fatal cardiovascular events across most activity levels.ConclusionThe detrimental associations of poor physical activity and sedentary behaviour with mortality were consistently amplified by social isolation. Our study supports the need to target the socially isolated as a priority group in preventive public health strategies.

Microcystic lymphatic malformation (MiLM), also known as lymphangioma circumscriptum, is a superficial collection of lymphatic vessels measuring1 cm in the largest diameter, often with a more extensive deeper malformation. It commonly presents as discrete or grouped plaques of clear or hemorrhagic vesicles classically described as "frogspawn"; however, here we describe a case of its unique presentation as firm papules on the lips of a healthy six-year-old child. These skin-colored papules in the absence of vesicles with lymphatic and/or hemorrhagic fluid may not be clinically indicative of MiLM. This case represents a diagnostic challenge due to the unique morphology of pink, fleshy papules as opposed to the clear or hemorrhagic vesicles typically observed in MiLM.

Objective Research suggests abnormalities in reward-based processes in anorexia nervosa (AN). However, few studies have explored if such alterations might be associated with different temporal activation patterns. This study aims to characterize alterations in time-dependent processes in the ventral striatum (VS) during social feedback in AN using functional magnetic resonance imaging (fMRI). Method Twenty women with restrictive-subtype AN and 20 age-matched healthy controls (HC) underwent a social judgment experimental fMRI task. Temporal VS hemodynamic responses were extracted in SPM for each participant and each social condition (acceptance/rejection). Results Compared with age-matched HC, patients with AN showed a significant time by group interaction of peak VS response throughout the task, with a progressive blunting of peak activation responses, accompanied by a progressive increase in baseline activity levels over time. Discussion The results suggest an attenuated response pattern to repetitive social rejection in the VS in patients with AN, together with a difficulty in returning to baseline. The information obtained from this study will guide future, design-specific studies to further explore alterations temporal dynamics.

Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = −0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.

Objective To develop prediction models for intensive care unit (ICU) vs non-ICU level-of-care need within 24 hours of inpatient admission for emergency department (ED) patients using electronic health record data. Materials and Methods Using records of 41 654 ED visits to a tertiary academic center from 2015 to 2019, we tested 4 algorithms—feed-forward neural networks, regularized regression, random forests, and gradient-boosted trees—to predict ICU vs non-ICU level-of-care within 24 hours and at the 24th hour following admission. Simple-feature models included patient demographics, Emergency Severity Index (ESI), and vital sign summary. Complex-feature models added all vital signs, lab results, and counts of diagnosis, imaging, procedures, medications, and lab orders. Results The best-performing model, a gradient-boosted tree using a full feature set, achieved an AUROC of 0.88 (95%CI: 0.87–0.89) and AUPRC of 0.65 (95%CI: 0.63–0.68) for predicting ICU care need within 24 hours of admission. The logistic regression model using ESI achieved an AUROC of 0.67 (95%CI: 0.65–0.70) and AUPRC of 0.37 (95%CI: 0.35–0.40). Using a discrimination threshold, such as 0.6, the positive predictive value, negative predictive value, sensitivity, and specificity were 85%, 89%, 30%, and 99%, respectively. Vital signs were the most important predictors. Discussion and Conclusions Undertriaging admitted ED patients who subsequently require ICU care is common and associated with poorer outcomes. Machine learning models using readily available electronic health record data predict subsequent need for ICU admission with good discrimination, substantially better than the benchmarking ESI system. The results could be used in a multitiered clinical decision-support system to improve ED triage.

Background: The number of people living with dementia is rising globally due to population aging. Mass media campaigns which aim to reduce the risk of people developing dementia have been conducted across many countries, but few have reported evaluation findings. Objective: The present study investigated the impact of the Your Brain Matters dementia risk reduction campaign in Australia. Methods: The campaign was evaluated by observational cross-sectional surveys of 1000 Australian adults aged 18–75 years before and 24 months after delivery. The national campaign utilized multiple media channels to promote messages about the importance of brain health and reducing the risk of dementia. Dementia risk reduction knowledge, confidence, intentions and actions were measured at baseline and follow-up, and analyzed 2019–2020. Results: Earned television and radio were the most common exposure channels. The proportion of people who understood that it is beneficial to take action to reduce dementia risk before middle age increased (54.1% to 59.4%, OR 1.20 95% CI: 1.01–1.44). There was also an increase (28.5% to 32.8%, OR 1.30, 95% CI: 1.07–1.59) in the proportion who reported taking action to improve brain health. There was no improvement in knowledge about vascular risk factors, or confidence to reduce personal dementia risk. Conclusion: The findings showed some receptivity and positive responses to messages about the benefits of taking action to reduce the risk of dementia. The campaign demonstrated the potential for generating news coverage about this issue, which should highlight the preventive benefits of vascular health behaviors.

The World Health Assembly has adopted the World Health Organization's (WHO) recommended target of achieving a 15% reduction in physical inactivity by 2030. The WHO Global Action Plan on Physical Activity provides a framework for countries to achieve this, using a systems-based approach to address the social and environmental determinants of physical inactivity. Lack of progress in many countries indicates a need to identify new ways of addressing this public health priority. WHO continues to highlight the importance of legislative and regulatory measures within the multicomponent and multisectoral action needed to reduce physical inactivity. Yet research into the role of law for addressing physical inactivity has been limited, in contrast to the legal approaches to other major noncommunicable disease risk factors such as smoking and alcohol use. Conceptual frameworks for public health law offer a method for mapping and understanding the determinants, mechanisms and outcomes of law-making for the promotion of physical activity within populations. We describe the development and application of a framework that aligns legal strategies with the WHO Global Plan policy objectives. This new framework - the Regulatory Approaches to Movement, Physical Activity, Recreation, Transport and Sport - can help policy-makers to use the untapped potential of legal interventions to support or strengthen a whole-system response for promoting physical activity. The framework illustrates the role of legal interventions to improve physical activity and identifies opportunities for research to advance understanding, implementation and evaluation of legal responses to this issue.L'Assemblée mondiale de la Santé a adopté l'objectif recommandé par l'Organisation mondiale de la Santé (OMS) visant à réduire l'inactivité physique de 15% d'ici 2030. L'OMS a élaboré un Plan d'action mondial pour l'activité physique, qui propose aux pays des orientations leur permettant d'atteindre cet objectif, grâce à une approche systémique qui aborde les déterminants sociaux et environnementaux à l'origine de l'inactivité physique. L'absence de progrès dans de nombreux pays indique un besoin d'identifier de nouveaux moyens de faire de cet enjeu de santé publique une priorité. L'OMS continue à souligner l'importance des mesures législatives et réglementaires au cœur de l'action multisectorielle à composantes multiples nécessaire à la promotion de l'exercice physique. Pourtant, les recherches sur la capacité de la loi à lutter contre l'inactivité physique sont limitées, contrairement aux démarches juridiques entamées vis-à-vis d'autres grands facteurs de risque de maladies non transmissibles, comme la consommation de tabac ou d'alcool. Les cadres théoriques régissant le droit sanitaire offrent des méthodes d'analyse et de compréhension des déterminants, mécanismes et impacts du travail législatif sur la promotion de l'activité physique au sein des populations. Dans cet article, nous décrivons le développement et l'application d'un cadre qui aligne les stratégies juridiques sur les objectifs politiques du Plan mondial de l'OMS. Ce cadre inédit – les réglementations relatives au mouvement, à l'activité physique, aux loisirs, au transport et au sport – peut aider les législateurs à utiliser le potentiel inexploité des interventions légales pour soutenir ou renforcer une réponse globale destinée à encourager l'exercice physique. Il illustre le rôle des interventions légales visant à améliorer l'activité physique et identifie les possibilités de recherche en vue de faire progresser la compréhension, la mise en œuvre et l'évaluation des solutions juridiques apportées à ce problème.La Asamblea Mundial de la Salud ha adoptado el objetivo recomendado por la Organización Mundial de la Salud (OMS) de lograr una reducción del 15% de la inactividad física para 2030. El Plan de Acción Mundial de la OMS sobre la Actividad Física proporciona un marco para que los países lo logren, utilizando un enfoque basado en sistemas para abordar los determinantes sociales y ambientales de la inactividad física. La falta de progreso en muchos países indica la necesidad de identificar nuevas formas de abordar esta prioridad de salud pública. La OMS sigue destacando la importancia de las medidas legislativas y reglamentarias dentro de la acción multicomponente y multisectorial necesaria para reducir la inactividad física. Sin embargo, la investigación sobre el papel de la ley para abordar la inactividad física ha sido limitada, en contraste con los enfoques legales de otros factores de riesgo de enfermedades no transmisibles importantes, como el tabaquismo y el consumo de alcohol. Los marcos conceptuales del derecho de la salud pública ofrecen un método para trazar y comprender los determinantes, mecanismos y resultados de la elaboración de leyes para la promoción de la actividad física en las poblaciones. Describimos el desarrollo y la aplicación de un marco que alinea las estrategias legales con los objetivos políticos del Plan Global de la OMS. Este nuevo marco –enfoques normativos del movimiento, la actividad física, el ocio, el transporte y el deporte– puede ayudar a los responsables políticos a utilizar el potencial sin explotar de las intervenciones legales para apoyar o reforzar una respuesta de todo el sistema para promover la actividad física. El marco ilustra el papel de las intervenciones legales para mejorar la actividad física e identifica las oportunidades de investigación para avanzar en la comprensión, implementación y evaluación de las respuestas legales a este tema.اعتمدت جمعية الصحة العالمية الهدف الذي أوصت به منظمة الصحة العالمية (WHO)، والذي يتمثل في تحقيق خفض بنسبة 15% في الخمول البدني بحلول عام 2030. إن خطة العمل العالمية لمنظمة الصحة العالمية بشأن النشاط البدني، توفر إطار عمل للدول لتحقيق هذا الهدف، وذلك باستخدام نهج قائم على النظم للتعامل مع المحددات الاجتماعية والبيئية للخمول البدني. يشير عدم إحراز تقدم في العديد من الدول إلى الحاجة إلى تحديد طرق جديدة للتعامل مع هذه الأولوية الصحية للعامة. تواصل منظمة الصحة العالمية التركيز على أهمية التدابير التشريعية والتنظيمية ضمن الإجراءات متعددة المكونات ومتعددة القطاعات، اللازمة للحد من الخمول البدني. ورغم ذلك، فإن الأبحاث الخاصة بدور القانون في التعامل مع الخمول البدني كانت محدودة، على العكس من أساليب التعامل القانونية مع عوامل خطر الأمراض غير المعدية الرئيسية الأخرى، مثل التدخين وتعاطي الكحول. توفر أطر العمل المفاهيمية لقانون الصحة العامة طريقة لتخطيط وفهم محددات وآليات ونتائج وضع القوانين الساعية للارتقاء بالنشاط البدني بين السكان. نحن نقوم بوصف تطوير وتطبيق إطار عمل يتولى التنسيق بين الاستراتيجيات القانونية وأهداف سياسة الخطة العالمية لمنظمة الصحة العالمية. إن إطار العمل الجديد هذا (وهو الأساليب التنظيمية للحركة والنشاط البدني والترفيه والنقل والرياضة)، يمكنه أن يساعد واضعي السياسات على استخدام الإمكانات غير المستغلة للتدخلات القانونية لدعم أو تقوية استجابة النظام بأكمله للارتقاء بالنشاط البدني. يوضح إطار العمل دور التدخلات القانونية لتحسين النشاط البدني، ويحدد فرص الأبحاث لتعزيز فهم وتنفيذ وتقييم الاستجابات القانونية لهذه القضية.世界卫生大会通过了了世界卫生组织 (WHO) 建议的目标，即到 2030 年不参加体育活动的人数减少 15%。WHO《体育活动全球行动计划》为各国实现该目标提供了框架，以使用系统方法解决缺乏运动的社会和环境决定因素。多个国家没有取得进展表明需要找到解决该公共卫生重点问题的新方法。WHO 不断强调立法和监管措施在减少缺乏运动所需的多组分和多部门行动中的重要性。然而，与其它重大非传染性疾病风险因素（如吸烟和饮酒）的法律措施相比，关于法律在解决缺乏运动中作用的研究比较有限。公共卫生法律的概念性框架提供绘制和了解提高人口体育活动的立法决定因素、机制和成果的方法。我们描述了符合 WHO 全球计划政策目标法律策略的框架制定和应用过程。该新框架——运动、体育活动、娱乐、交通与体育活动监管办法——可帮助政策制定者使用法律干预的未开发潜力支持或加强促进体育活动的全系统响应。框架介绍了法律干预对促进体育活动的作用，并确定了提高对该问题法律响应的了解、实施和评估的研究机会。.Всемирная ассамблея здравоохранения приняла цель, рекомендованную Всемирной организацией здравоохранения (ВОЗ), — добиться сокращения физической неактивности среди населения на 15% к 2030 году. Глобальный план действий ВОЗ по повышению уровня физической активности обеспечивает странам основу для достижения этой цели с использованием системного подхода для определения социальных и экологических детерминант недостаточной физической активности. Отсутствие прогресса во многих странах указывает на необходимость определения новых способов решения этой приоритетной задачи общественного здравоохранения. ВОЗ по-прежнему подчеркивает важность законодательных и нормативных мер в рамках многокомпонентных и многосекторальных действий, необходимых для снижения уровня физической неактивности. Однако исследований роли закона в решении проблемы недостаточной физической активности проводилось ограниченное количество, в отличие от правовых подходов к другим основным факторам риска развития неинфекционных заболеваний, таким как курение и употребление алкоголя. Концептуальные основы законодательства в области общественного здравоохранения предлагают метод для картирования и понимания детерминант, механизмов и результатов законотворческого процесса, направленного на повышение уровня физической активности среди населения. Авторы описывают разработку и применение механизма, который приводит правовые стратегии в соответствие с концептуальными целями Глобального плана ВОЗ. Этот новый механизм, включающий подходы к регулированию передвижения, физической активности, отдыха, транспорта и спорта, может помочь представителям правительственных структур использовать нереализованный потенциал правовых действий для поддержки или усиления ответных мер на уровне всей системы, направленных на поощрение физической активности. Механизм иллюстрирует роль правовых действий для повышения уровня физической активности и определяет возможности для исследований, направленных на углубление понимания, реализации и оценки правовых мер реагирования на эту проблему.

New Zealand blackcurrant (NZBC) extract is a rich source of anthocyanins and in order to exert physiological effects, the anthocyanin-derived metabolites need to be bioavailable in vivo. We examined the plasma uptake of selected phenolic acids following NZBC extract supplementation alongside maintaining a habitual diet (i.e. not restricting habitual polyphenol intake). Twenty healthy volunteers (nine females, age: 28 ± 7 years, height 1.73 ± 0.09 m, body mass 73 ± 11 kg) consumed a 300 mg NZBC extract capsule (CurraNZ®; anthocyanin content 105 mg) following an overnight fast. Venous blood samples were taken pre and 1, 1.5, 2, 3, 4, 5, and 6 h post-ingestion of the capsule. Reversed-phase high-performance liquid chromatography (HPLC) was used for analysis of two dihydroxybenzoic acids [i.e. vanillic acid (VA) and protocatechuic acid (PCA)] and one trihydroxybenzoic acid [i.e. gallic acid (GA)] in plasma following NZBC extract supplementation. Habitual anthocyanin intake was 168 (95%CI:68–404) mg⋅day−1 and no associations were observed between this and VA, PCA, and GA plasma uptake by the NZBC extract intake. Plasma time-concentration curves revealed that GA, and PCA were most abundant at 4, and 1.5 h post-ingestion, representing a 261% and 320% increase above baseline, respectively, with VA remaining unchanged. This is the first study to demonstrate that an NZBC extract supplement increases the plasma uptake of phenolic acids GA, and PCA even when a habitual diet is followed in the days preceding the experimental trial, although inter-individual variability is apparent.

ImportanceInappropriate use of antibiotics for diarrheal illness can result in adverse effects and increase in antimicrobial resistance.ObjectiveTo determine whether the diarrheal etiology prediction (DEP) algorithm, which uses patient-specific and location-specific features to estimate the probability that diarrhea etiology is exclusively viral, impacts antibiotic prescriptions in patients with acute diarrhea.Design, Setting, and ParticipantsA randomized crossover study was conducted to evaluate the DEP incorporated into a smartphone-based electronic clinical decision-support (eCDS) tool. The DEP calculated the probability of viral etiology of diarrhea, based on dynamic patient-specific and location-specific features. Physicians were randomized in the first 4-week study period to the intervention arm (eCDS with the DEP) or control arm (eCDS without the DEP), followed by a 1-week washout period before a subsequent 4-week crossover period. The study was conducted at 3 sites in Bangladesh from November 17, 2021, to January 21, 2021, and at 4 sites in Mali from January 6, 2021, to March 5, 2021. Eligible physicians were those who treated children with diarrhea. Eligible patients were children between ages 2 and 59 months with acute diarrhea and household access to a cell phone for follow-up.InterventionsUse of the eCDS with the DEP (intervention arm) vs use of the eCDS without the DEP (control arm).Main Outcomes and MeasuresThe primary outcome was the proportion of children prescribed an antibiotic.ResultsA total of 30 physician participants and 941 patient participants (57.1% male; median [IQR] age, 12 [8-18] months) were enrolled. There was no evidence of a difference in the proportion of children prescribed antibiotics by physicians using the DEP (risk difference [RD], −4.2%; 95% CI, −10.7% to 1.0%). In a post hoc analysis that accounted for the predicted probability of a viral-only etiology, there was a statistically significant difference in risk of antibiotic prescription between the DEP and control arms (RD, −0.056; 95% CI, −0.128 to −0.01). No known adverse effects of the DEP were detected at 10-day postdischarge.Conclusions and RelevanceUse of a tool that provides an estimate of etiological likelihood did not result in a significant change in overall antibiotic prescriptions. Post hoc analysis suggests that a higher predicted probability of viral etiology was linked to reductions in antibiotic use.Trial RegistrationClinicaltrials.gov Identifier: NCT04602676

Seizures are more common in the neonatal period than at any other stage of life. Phenobarbital is the first-line treatment for neonatal seizures and is at best effective in approximately 50% of babies, but may contribute to neuronal injury. Here, we assessed the efficacy of phenobarbital versus the synthetic neurosteroid, ganaxolone, to moderate seizure activity and neuropathology in neonatal lambs exposed to perinatal asphyxia.Asphyxia was induced via umbilical cord occlusion in term lambs at birth. Lambs were treated with ganaxolone (5mg/kg/bolus then 5mg/kg/day for 2 days) or phenobarbital (20mg/kg/bolus then 5mg/kg/day for 2 days) at 6 hours. Abnormal brain activity was classified as stereotypic evolving (SE) seizures, epileptiform discharges (EDs), and epileptiform transients (ETs) using continuous amplitude-integrated electroencephalographic recordings. At 48 hours, lambs were euthanized for brain pathology.Asphyxia caused abnormal brain activity, including SE seizures that peaked at 18 to 20 hours, EDs, and ETs, and induced neuronal degeneration and neuroinflammation. Ganaxolone treatment was associated with an 86.4% reduction in the number of seizures compared to the asphyxia group. The total seizure duration in the asphyxia+ganaxolone group was less than the untreated asphyxia group. There was no difference in the number of SE seizures between the asphyxia and asphyxia+phenobarbital groups or duration of SE seizures. Ganaxolone treatment, but not phenobarbital, reduced neuronal degeneration within hippocampal CA1 and CA3 regions, and cortical neurons, and ganaxolone reduced neuroinflammation within the thalamus.Ganaxolone provided better seizure control than phenobarbital in this perinatal asphyxia model and was neuroprotective for the newborn brain, affording a new therapeutic opportunity for treatment of neonatal seizures. ANN NEUROL 2022;92:1066-1079.

Background Physical activity mass media campaigns can deliver physical activity messages to many people, but it remains unclear whether they offer good value for money. We aimed to investigate the cost-effectiveness, cost-utility, and costs of physical activity mass media campaigns. Methods A search for economic evaluations (trial- or model-based) and costing studies of physical activity mass media campaigns was performed in six electronic databases (June/2021). The authors reviewed studies independently. A GRADE style rating was used to assess the overall certainty of each modelled economic evaluation. Results were summarised via narrative synthesis. Results Twenty-five studies (five model-based economic evaluations and 20 costing studies) were included, and all were conducted in high-income countries except for one costing study that was conducted in a middle-income country. The methods and assumptions used in the model-based analyses were highly heterogeneous and the results varied, ranging from the intervention being more effective and less costly (dominant) in two models to an incremental cost of US$130,740 (2020 base year) per QALY gained. The level of certainty of the models ranged from very low (n = 2) to low (n = 3). Overall, intervention costs were poorly reported. Conclusions There are few economic evaluations of physical activity mass media campaigns available. The level of certainty of the models was judged to be very low to low, indicating that we have very little to little confidence that the results are reliable for decision making. Therefore, it remains unclear to what extent physical activity mass media campaigns offer good value for money. Future economic evaluations should consider selecting appropriate and comprehensive measures of campaign effectiveness, clearly report the assumptions of the models and fully explore the impact of assumptions in the results. Review registration https://bit.ly/3tKSBZ3

Patients with SARS-CoV-2 infection present with different lung compliance and progression of disease differs. Measures of lung mechanics in SARS-CoV-2 patients may unravel different pathophysiologic mechanisms during mechanical ventilation. The objective of this prospective observational study is to describe whether Electrical Impedance Tomography (EIT) guided positive end-expiratory pressure (PEEP) levels unravel changes in EIT-derived parameters over time and whether the changes differ between survivors and non-survivors. Serial EIT-measurements of alveolar overdistension, collapse, and compliance change in ventilated SARS-CoV-2 patients were analysed. In 80 out of 94 patients, we took 283 EIT measurements (93 from day 1–3 after intubation, 66 from day 4–6, and 124 from day 7 and beyond). Fifty-one patients (64%) survived the ICU. At admission mean PaO2/FiO2-ratio was 184.3 (SD 61.4) vs. 151.3 (SD 54.4) mmHg, (p = 0.017) and PEEP was 11.8 (SD 2.8) cmH2O vs. 11.3 (SD 3.4) cmH2O, (p = 0.475), for ICU survivors and non-survivors. At day 1–3, compliance was ~ 55 mL/cmH2O vs. ~ 45 mL/cmH2O in survivors vs. non-survivors. The intersection of overdistension and collapse curves appeared similar at a PEEP of ~ 12–13 cmH2O. At day 4–6 compliance changed to ~ 50 mL/cmH2O vs. ~ 38 mL/cmH2O. At day 7 and beyond, compliance was ~ 38 mL/cmH2O with the intersection at a PEEP of ~ 9 cmH2O vs. ~ 25 mL/cmH2O with overdistension intersecting at collapse curves at a PEEP of ~ 7 cmH2O. Surviving SARS-CoV-2 patients show more favourable EIT-derived parameters and a higher compliance compared to non-survivors over time. This knowledge is valuable for discovering the different groups.

Background Optimising capacity along clinical pathways is essential to avoid severe hospital pressure and help ensure best patient outcomes and financial sustainability. Yet, typical approaches, using only average arrival rate and average lengths of stay, are known to underestimate the number of beds required. This study investigates the extent to which averages-based estimates can be complemented by a robust assessment of additional ‘flex capacity’ requirements, to be used at times of peak demand. Methods The setting was a major one million resident healthcare system in England, moving towards a centralised stroke pathway. A computer simulation was developed for modelling patient flow along the proposed stroke pathway, accounting for variability in patient arrivals, lengths of stay, and the time taken for transfer processes. The primary outcome measure was flex capacity utilisation over the simulation period. Results For the hyper-acute, acute, and rehabilitation units respectively, flex capacities of 45%, 45%, and 36% above the averages-based calculation would be required to ensure that only 1% of stroke presentations find the hyper-acute unit full and have to wait. For each unit some amount of flex capacity would be required approximately 30%, 20%, and 18% of the time respectively. Conclusions This study demonstrates the importance of appropriately capturing variability within capacity plans, and provides a practical and economical approach which can complement commonly-used averages-based methods. Results of this study have directly informed the healthcare system’s new configuration of stroke services.

Die demografische Entwicklung in Deutschland führt zu einem ärztlichen Nachwuchsmangel. Ziel dieser Arbeit ist es, aus den von der Bundesärztekammer (BÄK) veröffentlichten Ärztestatistiken der letzten 25 Jahre die Entwicklung und den aktuellen demografischen Status der Nuklearmedizin in Deutschland darzustellen und deren Konsequenzen aufzuzeigen.Die seit 1996 von der BÄK jährlich veröffentlichten Zahlen der ärztlichen Versorgung in Deutschland wurden systematisch im Hinblick auf die Altersentwicklung und die Geschlechterverteilung in den Fächern Nuklearmedizin, Radiologie und Strahlentherapie zusammengefasst und mit einer deskriptiven Statistik ausgewertet.Die Anzahl der berufstätigen Fachärzt*innen hat sich von 1996–2021 in der Nuklearmedizin um 114% erhöht mit einer deutlichen Verschiebung der Altersstruktur in die älteren Altersgruppen: 2021 lag der Anteil der Ärzt*innen unter 40 Jahren bei 13,0% in der Nuklearmedizin und bei 21,0% in der Radiologie und derjenige Anteil über 60 Jahren bei 27,1% in der Nuklearmedizin und bei 22,3% in der Radiologie. Der Anteil an Frauen lag im Jahr 2021 in der Medizin insgesamt bei 48,5%, in der Nuklearmedizin, Radiologie und Strahlentherapie bei 34,4%, 37,1% bzw. 48,0%.Die Fachärzt*innen in der Nuklearmedizin sind 2021 deutlich älter als diejenigen in der Strahlentherapie und Radiologie, und der Anteil von Frauen ist unterdurchschnittlich. Wenn die Nuklearmedizin als eigenständiges Fach ihrer klinischen Verantwortung gerecht werden will und eigenständig bestehen bleiben möchte, müssen die Bemühungen vor allem um den weiblichen medizinischen Nachwuchs in der nuklearmedizinischen Gemeinschaft eine maximale Priorität bekommen.

[Background]: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life., [Methods]: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed., [Results]: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth., [Conclusions]: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy., This work was supported by the German Research Foundation (DFG Grant Nos. HA7070/2-2, HA7070/3, HA7070/4 [to TH]) and IZKF of the medical faculty of Münster (Grants No. Dan3/012/17 [to UD] and MzH 3/020/20 [to TH]), and NHMRC projects (Grant No. 1064643 [to BJH] and 1024570 [to CGD]). The CIAM study was supported by the University of Cape Town Research Committee, South African National Research Foundation, and the South African Medical Research Council (principal investigator [PI], Fleur M. Howells) and Grant No. R01MH117601 (to NJ). This work was funded by the German Research Foundation (Grant Nos. FOR2107 JA 1890/7-1 and FOR2107 JA 1890/7-2 [to AJ]) and Swinburne University scholarship/Australian Postgraduate Award (to JK). Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation, and the Society of Mental Health Research (to JK). This work was funded by the German Research Foundation (Grant Nos. FOR2107 KI588/14-1 and FOR2107 KI588/14-2 [to TK]). The St. Göran study was supported by grants from the Swedish Research Council (Grant No. 2018-02653 [to ML]), the Swedish foundation for Strategic Research (Grant No. KF10-0039 [to ML]), the Swedish Brain foundation (Grant No. FO2020-0261 [to ML]), and the Swedish Government under the LUA/ALF agreement (Grant Nos. ALF 20170019 and ALFGBG-716801 [to ML]). This work was supported by RFBR (Grant No. 20-013-00748 [to IL, AST]) and funded by the Health Research Board (Grant No. HRA_POR/2011/100 [to CM]). The Australian Schizophrenia Research Bank (ASRB) was supported by the NHMRC (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation, and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. This work was supported by Deutsche Forschungsgemeinschaft (Grant Nos. DFG NE 2254/2-1, NE 2254/3-1, NE2254/4-1 [to IN]), the University Research Priority Program “Integrative Human Physiology” at the University of Zurich (to ROT), an NHMRC Senior Principal Research Fellowship (Grant No. 1105825 [to CPa]), an NHMRC L3 Investigator Grant (Grant No. 1196508 [to CPa]), and NHMRC Program Grant (Grant No. 1150083 [to CPa]). ASRB was supported by the NHMRC (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant (Agreement No. 798181 [to GP]). ASRB was supported by the NHMRC (Enabling Grant, ID 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. The Imaging Genetics in Psychosis study was funded by Project Grants from the NHMRC (Grant Nos. APP630471 and APP1081603 [to YQ]) and the Macquarie University’s Australian Research Council (ARC) Centre of Excellence in Cognition and its Disorders (Grant No. CE110001021 [to YQ]). This work was supported by the Spanish Ministry of Science, Innovation and Universities/Economy and Competitiveness/Instituto de Salud Carlos III (Grant Nos. PI11/01766 and CPII19/00009 [to JR]), co-financed by European Regional Development Fund funds from the European Commission (“A Way of Making Europe”). ASRB was supported by the NHMRC (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation, and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. SR was supported by an NHMRC Senior Fellowship (Grant No. GNT1154651). Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation, and the Society of Mental Health Research (to SR). This work was supported by NIHR; MRC (to KR), NIH (Grant Nos. MH-094268, MH-105660, and MH-107730 [to ASS]). The Neuroimaging of the Children's Attention Project cohort was funded by NHMRC, Australia (Grant No. 1065895). Earlier funding for the cohort as also provided by NHMRC (Grant No. 1008522) and a grant from the Collier Foundation. The ACPU cohort was funded by NHMRC, Australia (Project Grant Nos. 384419 and 569533 [to TS]). This work was supported by research grants from the National Healthcare Group, Singapore (Grant Nos. SIG/05004, SIG/05028, and SIG /1103), and the Singapore Bioimaging Consortium (RP C009/2006 [to KS]), and the Ministry of Health, Czech Republic - conceptual development of research organization (“Institute for Clinical and Experimental Medicine - IKEM, IN 00023001” [to ASk]). This study was supported by the Italian Ministry of Health (Grant No. RC/17-18-19-20-21/A [to GS]) and Ministry of Health of the Czech Republic (Grant No. NU20-04-00393 [to FS]). The Drakenstein Child Health Study (DCHS) cohort is funded by the Bill and Melinda Gates Foundation (Grant No. OPP 1017641) and the South African Medical Research Council. This DCHS contribution was made possible in part by a grant from Carnegie Corporation of New York. The statements made and views expressed are solely the responsibility of the author (DJS). STRADL study was supported and funded by the Wellcome Trust Strategic Award “Stratifying Resilience and Depression Longitudinally” (Grant No. 104036/Z/14/Z), and the Medical Research Council Mental Health Pathfinder Award “Leveraging routinely collected and linked research data to study the causes and consequences of common mental disorders” (MRC, Grant No. MC_PC_17209). Scottish Bipolar Family Study (SBFS) was supported by National Health Service Research Scotland, through the Scottish Mental Health Research Network (www.smhrn.org.uk), who provided assistance with subject recruitment and assessments. SBFS was conducted at the Brain Research Imaging Centre (http://www.bric.ed.ac.uk), which is supported by SINAPSE (Scottish Imaging Network, a Platform for Scientific Excellence, http://www.sinapse.ac.uk). Processing of the datasets used the resources provided by the Edinburgh Compute and Data Facility (http://www.ecdf.ed.ac.uk/) (ASt). TVR was supported by an NHMRC Early Career Fellowship (Grant No. GNT1088785). Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation, and the Society of Mental Health Research (to TVR). EV was supported by the Spanish Ministry of Science and Innovation (PI18/00805) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the FEDER; the Instituto de Salud Carlos III; the CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental); by the CERCA Programme/Generalitat de Catalunya and the Secretaria d’Universitats i Recerca del Departament d’Economia I Coneixement (Grant No. 2017SGR1355). This study was also supported by the Departament de Salut de la Generalitat de Catalunya, Pla Estratègic de Recerca i Innovació en Salut (PERIS) 2016-2020 (Grant No. SLT006/17/00345) and the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant Nos. 754907 and EU.3.1.3 [to EB]; Treating and managing disease: Grant No. 945151 [to EV]). This study was supported by the National Center for Complementary and Integrative Health (Grant Nos. R21AT009173 and R61AT009864 [to TTY]); by the National Center for Advancing Translational Sciences (CTSI), National Institutes of Health, through UCSF-CTSI (Grant No. UL1TR001872 [to TTY]); by the American Foundation for Suicide Prevention (Grant No. SRG-1-141-18 [to TTY]); by UCSF Research Evaluation and Allocation Committee (REAC) and J. Jacobson Fund (to TTY); by the NIMH (Grant No. R01MH085734 [to TTY]); and by the Brain and Behavior Research Foundation (formerly NARSAD) (to TTY). This work was supported by a personal Veni grant to MH from the Netherlands Organization for Scientific Research (NWO, Grant No. 91619115 [to MH]) and European Community’s Horizon 2020 Programme (H2020/2014 – 2020) (Grant Agreements Nos. 667302 [CoCA], 728018 [Eat2beNICE], and 847879 [PRIME] [to BF]). JBu has been supported by the EU-AIMS (European Autism Interventions) and AIMS-2-TRIALS programmes, which receive support from Innovative Medicines Initiative Joint Undertaking Grant Nos. 115300 and 777394, the resources of which are composed of financial contributions from the European Union’s FP7 and Horizon 2020 Programmes, and from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions, and AUTISM SPEAKS, Autistica and SFARI; and by the Horizon 2020–supported programme CANDY (Grant No. 847818 [to JBu]). This work is supported by Grant No. NIA T32AG058507 and NIH Grant No. U54EB020403 from the Big Data to Knowledge (BD2K) Program (to CRKC). ENIGMA MDD work is supported by NIH (Grant Nos. U54 EB020403 [to PT], R01 MH116147 [to PT], and R01 MH117601 [to NJ and LS]). LS was supported by an NHMRC Career Development Fellowship (Grant No. 1140764). This work was supported by the National Center for Research Resources at the NIH (Grant Nos. NIH 1 U24 RR021992 [Function Biomedical Informatics Research Network], NIH 1 U24 RR025736-01 [Biomedical Informatics Research Network Coordinating Center; http://www.birncommunity.org]). TGMvE is supported by ENIGMA’s NIH BD2K initiative (Grant No. U54 EB020403), ENIGMA Sex Differences (Grant No. R01MH116147), and ENIGMA-COINSTAC: Advanced Worldwide Transdiagnostic Analysis of Valence System Brain Circuits (Grant No. R01MH121246). This work was supported by the NIH (Grant No. R01MH121246 [to JT, Calhoun, and TGMvE]). This work was supported in part by NIH (Grant No. U54 EB020403 [to PT]).

Background: The use of cognitive-enhancing medications and supplements among healthy adults continues to rise. Limited data exists on their use among resident physicians. Given their highly competitive and stressful lifestyle, we sought to evaluate the prevalence, motivations, and side effects of using cognitive-enhancing supplements and medications among resident physicians at a large United States academic institution. Methods: An anonymous web-based survey was circulated to resident physicians inquiring about using cognitive-enhancing supplements and medications, as well as personal characteristics such as gender, marital and parental status, medical diagnoses, and medical specialty. Before circulation, we performed a pilot study. Weighted logistic regression analyses estimated the impact of personal characteristics on the probability of using both supplements and medications. Results: Survey response rate was 46.4%. Of respondents, 48.6% were female, 45.9% were married, 70.9% were without children, and 67.2% were in a non-surgical medical specialty. Few respondents had a related medical diagnosis, with attention deficit hyperactivity disorder being the most common (7.1%). Male, non-married, surgical residents were more likely to take supplements (odds ratio (OR) = 1.06, 1.05, and 1.05). Males, without children, and those who felt pressure to perform well, were afraid of being left behind, felt pressure because colleagues take them, or felt they could not reach their current level of training without medications were more likely to take medications (OR = 1.11, 1.04, 1.05, and 1.08). Adverse effects with medications were common. Conclusion: Supplement and medication use for cognitive enhancement was high among resident physicians at a single institution despite few having a related medical diagnosis. This study raises awareness of the growing pressure in competitive residency environments to use cognitive enhancement regardless of the potential side effects.

Stereotactic ablative radiotherapy (SABR) is a well-established treatment for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) and pulmonary oligometastases. The use of single-fraction SABR in this setting is supported by excellent local control and safety profiles which appear equivalent to multi-fraction SABR based on the available data. The resource efficiency and reduction in hospital outpatient visits associated with single-fraction SABR have been particularly advantageous during the COVID-19 pandemic. Despite the increased interest, single-fraction SABR in subgroups of patients remains controversial, including those with centrally located tumours, synchronous targets, proximity to dose-limiting organs at risk, and concomitant severe respiratory illness. This review provides an overview of the published randomised evidence evaluating single-fraction SABR in primary lung cancer and pulmonary oligometastases, the common clinical challenges faced, immunogenic effect of SABR, as well as technical and cost-utility considerations.

Introduction The past decade has increasingly seen systems approaches as a featured theme in public health studies and policy documents. This trend is evident in the area of physical activity, which is a significant global health risk factor that is addressed in WHO’s Global Action Plan on Physical Activity. We undertook a comprehensive scoping review to characterize the application of systems approaches to physical activity, to develop a typology of the objectives, themes and methods of research papers that purported to apply systems thinking to this issue. Methods We searched electronic databases (PubMed, Web of Science, Scopus and PsycINFO) for studies published during the period 2010–2021 that explicitly applied systems approaches or methods to investigate and/or address population physical activity. A framework using systems-based methodological approaches was adapted to classify physical activity studies according to their predominant approach, covering basic descriptive, complex analytical and advanced forms of practice. We selected case studies from retained studies to depict the current “state of the art”. Results We included 155 articles in our narrative account. Literature reporting the application of systems approaches to physical activity is skewed towards basic methods and frameworks, with most attention devoted to conceptual framing and predictive modelling. There are few well-described examples of physical activity interventions which have been planned, implemented and evaluated using a systems perspective. There is some evidence of “retrofitted” complex system framing to describe programmes and interventions which were not designed as such. Discussion We propose a classification of systems-based approaches to physical activity promotion together with an explanation of the strategies encompassed. The classification is designed to stimulate debate amongst policy-makers, practitioners and researchers to inform the further implementation and evaluation of systems approaches to physical activity. Conclusion The use of systems approaches within the field of physical activity is at an early stage of development, with a preponderance of descriptive approaches and a dearth of more complex analyses. We need to see movement towards a more sophisticated research agenda spanning the development, implementation and evaluation of systems-level interventions.

Introduction Assaults inflicting penetrating head and neck trauma have potential for serious morbidity or mortality. This paper studies in-depth all cases treated at a level one trauma centre in the North East of England over 10 years. Methods All patients assaulted with sharp implements to the head and neck treated from 2010 to 2019 were identified using clinical codes. Results Retrospective data collection were as follows: 214 patients identified (189 male, 25 female). Average age was 31.5 years (range 3–80). The majority presented between 20:00 and 05:00. Knives were the commonest weapon. Fifty-two had scalp, 137 face and 69 neck injuries. Forty-eight percent had additional non-head and neck injuries. Eighty-six percent required admission, 16.6% to intensive care. Oral and maxillofacial and plastic surgeons provided most treatment. One hundred two required treatment under general and 96 local anaesthetic. Sixteen patients had significant vascular injury, 1 brachial plexus injury, 4 facial nerve injuries (of which 3 repaired) and one required parotid duct repair. Mean length of stay was 3.7 days. No mortality was recorded. Incidence significantly increased from 2010 to 2019. Conclusions Head and neck penetrating injuries occur frequently, often with other injuries and mainly in young males. Incidence of significant vascular or nerve injury was low. This study provides important data for those planning trauma services.

Aims Following cast removal for nonoperatively treated distal radius fractures, rehabilitation facilitated by advice leaflet and advice video were compared to a course of face-to-face therapy. Methods Adults with an isolated, nonoperatively treated distal radius fracture were included at six weeks post-cast removal. Participants were randomized to delivery of rehabilitation interventions in one of three ways: an advice leaflet; an advice video; or face-to-face therapy session(s). The primary outcome measure was the Disabilities of the Arm, Shoulder and Hand (DASH) score at six weeks post intervention and secondary outcome measures included DASH at one year, DASH work subscale, grip strength, and range of motion at six weeks and one year. Results A total of 116 (97%) of 120 enrolled participants commenced treatment. Of those, 21 were lost to follow-up, resulting in 30 participants in the advice leaflet, 32 in the advice video, and 33 face-to-face therapy arms, respectively at six weeks of follow-up. There was no significant difference between the treatment groups in the DASH at six weeks (advice leaflet vs face-to-face therapy, p = 0.69; advice video vs face-to-face therapy, p = 0.56; advice leaflet vs advice video, p = 0.37; advice leaflet vs advice video vs face-to-face therapy, p = 0.63). At six weeks, there were no differences in any secondary outcome measures except for the DASH work subscale, where face-to-face therapy conferred benefit over advice leaflet (p = 0.01). Conclusion Following cast removal for nonoperatively treated distal radius fractures, offering an advice leaflet or advice video for rehabilitation gives equivalent patient-reported outcomes to a course of face-to-face therapy. Cite this article: Bone Joint J 2021;103-B(6):1033–1039.