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Abstract Wildlife in cities divides people, with some animals bringing positive benefits and others causing conflict, for example due to property damage. Urban wildlife professionals from municipal administration, nature conservation, and hunting associations have a crucial role in shaping human‐wildlife relationships in cities and fostering conflict‐free coexistence. While many studies on urban wildlife have focused on the views of citizens, few have investigated the perspectives of experts to date. To address this knowledge gap, we interviewed 36 urban wildlife professionals giving guidance in the context of urban wildlife management, either in one of the four largest German cities by population (Berlin, Hamburg, Munich and Cologne) or at the national level. Red foxes, wild boars, raccoons, stone martens and Eurasian beavers were the five mammal species most frequently highlighted in interviews to cause human‐wildlife conflicts. The interviewees saw wild boars and raccoons as the most controversial urban wild mammals but emphasized the need to create refuges for beavers and better inform the public about foxes. Management in terms of public outreach, urban planning and population control, as well as establishing official contact points and stricter fines of activities violating regulations were highlighted as important elements of a toolkit to manage urban wildlife conflicts. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Plasma biomarkers of dementia, including phosphorylated tau (p-tau217), offer promise as tools for diagnosis, stratification for clinical trials, monitoring disease progression, and assessing the success of interventions in those living with Alzheimer’s disease. However, currently, it is unknown whether these dementia biomarker levels vary with the time of day, which could have implications for their clinical value. In two protocols, we studied 38 participants (70.8 ± 7.6 years; mean ± SD) in a 27-h laboratory protocol with either two samples taken 12 h apart or 3-hourly blood sampling for 24 h in the presence of a sleep–wake cycle. The study population comprised people living with mild Alzheimer’s disease (PLWA, n = 8), partners/caregivers of PLWA (n = 6) and cognitively intact older adults (n = 24). Single-molecule array technology was used to measure phosphorylated tau (p-tau217) (ALZpath), amyloid-beta 40 (Aβ40), amyloid-beta 42 (Aβ42), glial fibrillary acidic protein, and neurofilament light (NfL) (Neuro 4-Plex E). Analysis with a linear mixed model (SAS, PROC MIXED) revealed a significant effect of time of day for p-tau217, Aβ40, Aβ42, and NfL, and a significant effect of participant group for p-tau217. For p-tau217, the lowest levels were observed in the morning upon waking and the highest values in the afternoon/early evening. The magnitude of the diurnal variation for p-tau217 was similar to the reported increase in p-tau217 over one year in amyloid-β-positive mild cognitively impaired people. Currently, the factors driving this diurnal variation are unknown and could be related to sleep, circadian mechanisms, activity, posture, or meals. Overall, this work implies that the time of day of sample collection may be relevant in the implementation and interpretation of plasma biomarkers in dementia research and care.

Future cities have the potential to be biodiverse areas in which humans and wildlife can coexist. However, the success of creating or maintaining wildlife-inclusive future cities can be challenged by management actions that are solely based on ecological research, while overlooking research on human perspectives. Despite the growth of literature on human-wildlife interactions, which complements the breadth of urban ecology research, the overlap between these two research areas is still uncommon. In this study, we reviewed the literature of wild mammals in urban areas to identify patterns and gaps in the literature. We found 848 published journal articles, of which 480 articles focused on wildlife ecology, 269 articles focused on human dimensions and 99 articles had interdisciplinary combinations of both. Ecology-centered publications tended to be about habitat, rather than behavior, diet, health, reproduction and inter-species-relations, and literature on human dimensions was more evenly divided into management, perception, conflict and coexistence. Most ecology studies reported on specific taxonomic families, mainly canids and murids, but in human-dimension studies, “wildlife” was considered more as a general community of species. The most studied interdisciplinary combination of research themes was wildlife habitat and human-wildlife conflicts (n = 22), while only nine studies incorporated perception with ecological research. Even though studies on human dimensions of wildlife in cities are increasing, interdisciplinary research is lacking, which limits the knowledge on how to manage and shape urban areas to achieve coexistence of humans and wild mammals. For future cities to successfully become biophilic and support human-wildlife coexistence, we outlined five key elements for a research agenda: 1) Investigate urban mammal research through an interdisciplinary lens; 2) Explore ecological dynamics beyond habitat selection; 3) Conduct research for coexistence; 4) Disentangle what is “urban wildlife”; 5) Study a diverse array of urban wild mammals.

Abstract Background We evaluated the role of dual-energy computed tomography (DECT)-based collagen maps in assessing thoracic disc degeneration. Methods We performed a retrospective analysis of patients who underwent DECT and magnetic resonance imaging (MRI) of the thoracic spine within a 2-week period from July 2019 to October 2022. Thoracic disc degeneration was classified by three blinded radiologists into three Pfirrmann categories: no/mild (grade 1–2), moderate (grade 3–4), and severe (grade 5). The DECT performance was determined using MRI as a reference standard. Interreader reliability was assessed using intraclass correlation coefficient (ICC). Five-point Likert scales were used to assess diagnostic confidence and image quality. Results In total, 612 intervertebral discs across 51 patients aged 68 ± 16 years (mean ± standard deviation), 28 males and 23 females, were assessed. MRI revealed 135 no/mildly degenerated discs (22.1%), 470 moderately degenerated discs (76.8%), and 7 severely degenerated discs (1.1%). DECT collagen maps achieved an overall accuracy of 1,483/1,838 (80.8%) for thoracic disc degeneration. Overall recall (sensitivity) was 331/405 (81.7%) for detecting no/mild degeneration, 1,134/1,410 (80.4%) for moderate degeneration, and 18/21 (85.7%) for severe degeneration. Interrater agreement was good (ICC = 0.89). Assessment of DECT-based collagen maps demonstrated high diagnostic confidence (median 4; interquartile range 3–4) and good image quality (median 4; interquartile range 4–4). Conclusion DECT showed an overall 81% accuracy for disc degeneration by visualizing differences in the collagen content of thoracic discs. Relevance statement Utilizing DECT-based collagen maps to distinguish various stages of thoracic disc degeneration could be clinically relevant for early detection of disc-related conditions. This approach may be particularly beneficial when MRI is contraindicated. Key Points A total of 612 intervertebral discs across 51 patients were retrospectively assessed with DECT, using MRI as a reference standard. DECT-based collagen maps allowed thoracic disc degeneration assessment achieving an overall 81% accuracy with good interrater agreement (ICC = 0.89). DECT-based collagen maps could be a good alternative in the case of contraindications to MRI. Graphical Abstract

Abstract Background Endoscopic ultrasound (EUS) is a unique example of POCUS, which allows the gastroenterologist to discuss subepithelial pathology immediately after an endoscopy. The challenges that are encountered to create an acoustic interface by adding free water during the endoscopy may be curtailing the full utilization of EUS during endoscopic procedures. Eosinophilic esophagitis (EoE) is a progressive inflammatory condition whose morbidity is related to esophageal wall remodeling. However, in clinical practice, in clinical guidelines, and in many trials, EoE outcomes are based on esophageal eosinophilia and symptoms. Hence, a method to identify and quantitate the thickening of the esophageal wall, could contribute to the management of this disease. Results A modification of the approach employed to perform EUS during bronchoscopy was developed. An EUS miniprobe was positioned inside of a water filled balloon sheath. This technique permitted rapid and reproducible images acquisition of the total esophageal wall and its sublayers (mucosa, and submucosa + submucosa, which permitted derivation of the muscle layer). The presented series describes the results from 22 consecutive EoE patients. A full set of measurements from both the mid and distal esophagus were achieved in all EoE patients in an average time of less than 10 minutes. Conclusions This pilot study supports further investigations evaluating this economical, convenient, and safe technique to follow EoE patients. In addition, this approach could be potentially employed in all patients who are found to have subepithelial gastrointestinal pathology during routine endoscopic procedures.

Abstract While reintroductions of regionally extinct native species usually benefit ecosystems, reintroduced animals often struggle to locate appropriate habitats where they can establish themselves without conflict with humans. European beavers (Castor fiber) were successfully reintroduced to Germany almost 60 years ago and have reached high abundances again. As beavers can damage trees and change landscapes, they are increasingly in conflict with humans. We investigated human perceptions of beavers in Germany using an online survey, as they are an example of a reintroduced species with an expanding population and potential conflicts with humans. We asked participants about their emotions (anger, fear, interest, joy) towards beavers and what they consider to be acceptable beaver habitats. Of nearly 1500 survey participants, 803 (53%) were from the general public, 475 (32%) from the agricultural sector and 219 (15%) from forestry. People in these sectors had very different perspectives: beavers were positively perceived by the general public, but negatively by stakeholders working in agriculture and forestry. Independently of stakeholder groups, we also found regional differences, as participants from Bavaria—the German state with the highest beaver densities—viewed beavers more negatively than those from the rest of Germany. Zoos and wildlife parks, as well as urban and nature conservation areas, were considered to be the most acceptable habitats for beavers, whereas survey participants did not accept private gardens and cultivated areas as beaver habitats. We discuss the sources of negative emotions towards beavers and how ecologically suitable habitats differ from those that appear acceptable by humans. Even 60 years after their reintroduction, beavers in Germany are still being recognized as both a novelty and a nuisance. Our findings highlight the need for active beaver management and increased public engagement to enable positive coexistence between beavers and humans in Germany. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Chimeric antigen receptor T-cell (CAR-T) therapies are a paradigm-shifting therapeutic in patients with hematological malignancies. However, some concerns remain that they may cause serious cardiovascular adverse events (AEs), for which data are scarce. In this study, gradient boosting machine algorithm-based model was fitted to identify safety signals of serious cardiovascular AEs reported for tisagenlecleucel in the World Health Organization Vigibase up until February 2024. Input dataset, comprised of positive and negative controls of tisagenlecleucel based on its labeling information and literature search, was used to train the model. Then, we implemented the model to calculate the predicted probability of serious cardiovascular AEs defined by preferred terms included in the important medical event list from European Medicine Agency. There were 467 distinct AEs from 3,280 safety cases reports for tisagenlecleucel, of which 363 (77.7%) were classified as positive controls, 66 (14.2%) as negative controls, and 37 (7.9%) as unknown AEs. The prediction model had area under the receiver operating characteristic curve of 0.76 in the test dataset application. Of the unknown AEs, six cardiovascular AEs were predicted as the safety signals: bradycardia (predicted probability 0.99), pleural effusion (0.98), pulseless electrical activity (0.89), cardiotoxicity (0.83), cardio-respiratory arrest (0.69), and acute myocardial infarction (0.58). Our findings underscore vigilant monitoring of acute cardiotoxicities with tisagenlecleucel therapy.

Abstract Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is considered a growing health concern. The majority of NTM-PD cases in Europe are caused by slow-growing mycobacteria (SGM). However, distinct radiological features of different SGM remain largely uninvestigated. We applied a previously described radiological score to a patient cohort consisting of individuals with isolation of different SGM. Correlations between clinical data, species and computed tomography (CT) features were examined by logistic and linear regression analyses, as well as over the course of time. Overall, 135 pulmonary CT scans from 84 patients were included. The isolated NTM-species were mainly Mycobacterium avium complex (MAC, n = 49), as well as 35 patients with non-MAC-species. Patients with isolation of M. intracellulare had more extensive CT findings compared to all other SGM species (coefficient 3.53, 95% Cl − 0.37 to 7.52, p = 0.075) while patients meeting the ATS criteria and not undergoing therapy exhibited an increase in CT scores over time. This study provides insights into differential radiological features of slow-growing NTM. While M. intracellulare exhibited a tendency towards higher overall CT scores, the radiological features were similar across different SGM. The applied CT score might be a useful instrument for monitoring patients and could help to guide antimycobacterial therapy.

Complex endovascular aortic repair (EVAR) requires the use of multiple small sheath cannulation inside a large sheath. Because the large sheath is not designed for multiple small sheath cannulation, large amounts of blood loss can be encountered in complex EVARs. Cell Saver can be used effectively in complex EVARs using a modified draping technique, allowing for increased cell salvage and autogenous transfusions as needed.

ObjectivesTo investigate the effects of a mindfulness-based family psychoeducation (MBFPE) intervention on caregivers and the young adults with first-episode psychosis in mental health care.MethodsSixty-five caregivers were randomly assigned to the MBFPE program (n = 33) or an ordinary family psychoeducation (FPE) program (n = 32). Eighteen young adults in recovery (YAIR) also participated in the study. All of the participants completed the assessments before participating in the intervention (T1), after the intervention (T2), and at 9-month follow-up (T3).ResultsIntention-to-treat analyses were conducted. The caregivers reported a significant and large effect size on positive caregiving experiences based on a Time × Group analysis (g = 0.862, p = 0.006). Among the YAIR participants, between-group differences were significant in their perceptions of caregivers’ expressed emotions, including large effect sizes of perceived criticism (g = 1.396, p = 0.049) and hostility (g = 1.444, p = 0.043). Caregiver demographics, including age, education level, socioeconomic status, and number of family members, were found to moderate the effect sizes of the variables studied.ConclusionThis study provides evidence of the effects of MBFPE programs on the outcomes of caregivers and the young adults with first-episode psychosis in their care. Specifically, the MBFPE program in this study played a greater role in promoting positive caregiving experiences and changing caregivers’ expressed emotions, especially their expressed criticism of YAIR, compared with the regular FPE program. Therefore, the application of mindfulness training to promote family care and YAIR recovery should be encouraged.Clinical trial registrationClinicalTrials.gov, identifier NCT03688009.

Summary: Background: Timely and economic provision of revascularisation procedures is a major healthcare need. We aimed to examine the safety and efficacy of daycase-based lower extremity endovascular revascularisation procedures in patients with peripheral artery disease. Methods: In this systematic review and meta-analysis, we searched MEDLINE and Embase for studies from Jan 01, 2000 through Apr 01, 2024 reporting complications of lower limb endovascular revascularisation procedures with same-day discharge. Eligibility-criteria, complications, and patient characteristics were extracted, methodological quality assessed (adapted Newcastle–Ottawa Scale), and meta-analyses of complications and technical success performed to provide pooled estimates. This study is registered with PROSPERO, CRD42022316466. Findings: Thirty observational studies (17 retrospective, 13 prospective) and 1 RCT reported 2427 minor and 653 major complications after 99,600 daycase procedures (93,344 patients). Eighteen studies reported daycase eligibility-criteria including ‘responsible adult companion’ (78%), ‘proximity to hospital’, and ‘telephone availability’ and excluding unstable and severe co-morbidities, offset coagulation, and severe chronic kidney disease. Pooled incidences of minor (4.7% [95% CI 3.8–5.6%], I2 = 96%) and major (0.64% [95% CI 0.48–0.79%], I2 = 46%) complications were low and technical success high (93% [95% CI 91–96%], I2 = 97%). Most complications were related to the puncture site. Pooled conversion-to-hospitalisation rates and re-admission after discharge were 1.6% (95% CI 1.1–2.2%, I2 = 82%) and 0.11% (95% CI 0.095–0.23%, I2 = 97%), respectively. Meta-regression identified that minor complications decreased since 2000. Male sex and coronary artery disease were associated with more frequent, and higher age and closure device use with less minor complications. Diabetes mellitus and chronic kidney disease were associated with less major complications. Six studies reported complication rates both in daycases and inpatients and there was no significant difference (−0.8% [95% CI −1.9 to 0.3%]). Interpretation: After careful evaluation of eligibility, lower limb angioplasty can be performed safely with high technical success in a daycase setting. Most complications arise from the puncture site and not the procedure itself highlighting the importance of optimal access site management. The heterogeneity between studies warrants standardised monitoring of complications and outcomes. Funding: European Partnership on Metrology, co-financed from European Union’s Horizon Europe Research and Innovation Programme and UK Research and Innovation, and Medical Research Council.

Anxiety is the most common form of mental health disorder, affecting millions of people worldwide. Psychosocial interventions such as mindfulness and cognitive behavioral therapy (CBT) have been suggested as an effective treatment in the management of general anxiety and anxiety disorders, with emerging evidence also suggesting the effectiveness of hypnosis. Moreover, anxiety has shown to be linked to the onset and development of several cardiovascular diseases (CVD), which are the leading cause of global death. In this paper, we review the current literature to examine the role that anxiety has on the onset and development of CVD and summarize the current knowledge on the role that hypnosis and hypnotherapy have in reducing anxiety, also explaining how this can impact the cardiovascular system and the prevention of CVD. Review of the evidence suggests that hypnosis and hypnotherapy are effective in treating anxiety and may positively affect the heart and the cardiovascular system, reducing sympathetic activation and increasing parasympathetic tone, potentially preventing the onset of CVD related to increased sympathetic activation. However, further studies are required to further understand how hypnosis and hypnotherapy affect the cardiovascular system through investigation of the neurophysiological components of the hypnotic state and of the mind-body relationship. Healthcare systems should embed mental health screening in patients at risk of developing CVD as part of the clinical pathway and consider the role that hypnosis and hypnotherapy may play in the management of CVD.

Purpose: Nascent geographic atrophy (nGA) refers to specific features seen on OCT B-scans, which are strongly associated with the future development of geographic atrophy (GA). This study sought to develop a deep learning model to screen OCT B-scans for nGA that warrant further manual review (an artificial intelligence [AI]-assisted approach), and to determine the extent of reduction in OCT B-scan load requiring manual review while maintaining near-perfect nGA detection performance. Design: Development and evaluation of a deep learning model. Participants: One thousand eight hundred and eighty four OCT volume scans (49 B-scans per volume) without neovascular age-related macular degeneration from 280 eyes of 140 participants with bilateral large drusen at baseline, seen at 6-monthly intervals up to a 36-month period (from which 40 eyes developed nGA). Methods: OCT volume and B-scans were labeled for the presence of nGA. Their presence at the volume scan level provided the ground truth for training a deep learning model to identify OCT B-scans that potentially showed nGA requiring manual review. Using a threshold that provided a sensitivity of 0.99, the B-scans identified were assigned the ground truth label with the AI-assisted approach. The performance of this approach for detecting nGA across all visits, or at the visit of nGA onset, was evaluated using fivefold cross-validation. Main Outcome Measures: Sensitivity for detecting nGA, and proportion of OCT B-scans requiring manual review. Results: The AI-assisted approach (utilizing outputs from the deep learning model to guide manual review) had a sensitivity of 0.97 (95% confidence interval [CI] = 0.93–1.00) and 0.95 (95% CI = 0.87–1.00) for detecting nGA across all visits and at the visit of nGA onset, respectively, when requiring manual review of only 2.7% and 1.9% of selected OCT B-scans, respectively. Conclusions: A deep learning model could be used to enable near-perfect detection of nGA onset while reducing the number of OCT B-scans requiring manual review by over 50-fold. This AI-assisted approach shows promise for substantially reducing the current burden of manual review of OCT B-scans to detect this crucial feature that portends future development of GA. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Abstract Background Use of bystander video livestreaming from scene to Emergency Medical Services (EMS) is becoming increasingly common to aid decision making about the resources required. Possible benefits include earlier, more appropriate dispatch and clinical and financial gains, but evidence is sparse. Methods A feasibility randomised controlled trial with an embedded process evaluation and exploratory economic evaluation where working shifts during six trial weeks were randomised 1:1 to use video livestreaming during eligible trauma incidents (using GoodSAM Instant-On-Scene) or standard care only. Pre-defined progression criteria were: (1) ≥ 70% callers (bystanders) with smartphones agreeing and able to activate live stream; (2) ≥ 50% requests to activate resulting in footage being viewed; (3) Helicopter Emergency Medical Services (HEMS) stand-down rate reducing by ≥ 10% as a result of live footage; (4) no evidence of psychological harm in callers or staff/dispatchers. Observational sub-studies included (i) an inner-city EMS who routinely use video livestreaming to explore acceptability in a diverse population; and (ii) staff wellbeing in an EMS not using video livestreaming for comparison to the trial site. Results Sixty-two shifts were randomised, including 240 incidents (132 control; 108 intervention). Livestreaming was successful in 53 incidents in the intervention arm. Patient recruitment (to determine appropriateness of dispatch), and caller recruitment (to measure potential harm) were low (58/269, 22% of patients; 4/244, 2% of callers). Two progression criteria were met: (1) 86% of callers with smartphones agreed and were able to activate livestreaming; (2) 85% of requests to activate livestreaming resulted in footage being obtained; and two were indeterminate due to insufficient data: (3) 2/6 (33%) HEMS stand down due to livestreaming; (4) no evidence of psychological harm from survey, observations or interviews, but insufficient survey data from callers or comparison EMS site to be confident. Language barriers and older age were reported in interviews as potential challenges to video livestreaming by dispatchers in the inner-city EMS. Conclusions Progression to a definitive RCT is supported by these findings. Bystander video livestreaming from scene is feasible to implement, acceptable to both 999 callers and dispatchers, and may aid dispatch decision-making. Further assessment of unintended consequences, benefits and harm is required. Trial registration. ISRCTN 11449333 (22 March 2022). https://www.isrctn.com/ISRCTN11449333

Abstract Previous studies on putative neural mechanisms of negative symptoms in schizophrenia mainly used single modal imaging data, and seldom utilized schizophrenia patients with prominent negative symptoms (PNS).This study adopted the multimodal fusion method and recruited a homogeneous sample with PNS. We aimed to identify negative symptoms-related structural and functional neural correlates of schizophrenia. Structural magnetic resonance imaging (sMRI) and resting-state functional MRI (rs-fMRI) were performed in 31 schizophrenia patients with PNS and 33 demographically matched healthy controls.Compared to healthy controls, schizophrenia patients with PNS exhibited significantly altered functional activations in the default mode network (DMN) and had structural gray matter volume (GMV) alterations in the cerebello-thalamo-cortical network. Correlational analyses showed that negative symptoms severity was significantly correlated with the cerebello-thalamo-cortical structural network, but not with the DMN network in schizophrenia patients with PNS.Our findings highlight the important role of the cerebello-thalamo-cortical structural network underpinning the neuropathology of negative symptoms in schizophrenia. Future research should recruit a large sample and schizophrenia patients without PNS, and apply adjustments for multiple comparison, to verify our preliminary findings.

Abstract Kaplan–Meier (KM) survival analyses based on complex patient categorization due to the burgeoning volumes of genomic, molecular and phenotypic data, are an increasingly important aspect of the biomedical researcher’s toolkit. Commercial statistics and graphing packages for such analyses are functionally limited, whereas open-source tools have a high barrier-to-entry in terms of understanding of methodologies and computational expertise. We developed surviveR to address this unmet need for a survival analysis tool that can enable users with limited computational expertise to conduct routine but complex analyses. surviveR is a cloud-based Shiny application, that addresses our identified unmet need for an easy-to-use web-based tool that can plot and analyse survival based datasets. Integrated customization options allows a user with limited computational expertise to easily filter patients to enable custom cohort generation, automatically calculate log-rank test and Cox hazard ratios. Continuous datasets can be integrated, such as RNA or protein expression measurements which can be then used as categories for survival plotting. We further demonstrate the utility through exemplifying its application to a clinically relevant colorectal cancer patient dataset. surviveR is a cloud-based web application available at https://generatr.qub.ac.uk/app/surviveR , that can be used by non-experts users to perform complex custom survival analysis.

Abstract The USP19 deubiquitinase is found in a locus associated with Parkinson’s Disease (PD), interacts with chaperonins, and promotes secretion of α-synuclein (α-syn) through the misfolding-associated protein secretion (MAPS) pathway. Since these processes might modulate the processing of α-syn aggregates in PD, we inactivated USP19 (KO) in mice expressing the A53T mutation of α-syn and in whom α-syn preformed fibrils (PFF) had been injected in the striatum. Compared to WT, KO brains showed decreased accumulation of phospho-synuclein (pSyn) positive aggregates. This improvement was associated with less activation of microglia and improved performance in a tail-suspension test. Exposure of primary neurons from WT and KO mice to PFF in vitro also led to decreased accumulation of pSyn aggregates. KO did not affect uptake of PFF nor propagation of aggregates in the cultured neurons. We conclude that USP19 instead modulates intracellular dynamics of aggregates. At an early time following PFF injection when the number of pSyn-positive neurons were similar in WT and KO brains, the KO neurons contained less aggregates. KO brain aggregates stained more intensely with anti-ubiquitin antibodies. Immunoprecipitation of soluble proteins from WT and KO brains with antibodies to pSyn showed higher levels of ubiquitinated oligomeric species in the KO samples. We propose that the improved pathology in USP19 KO brains may arise from decreased formation or enhanced clearance of the more ubiquitinated aggregates and/or enhanced disassembly towards more soluble oligomeric species. USP19 inhibition may represent a novel therapeutic approach that targets the intracellular dynamics of α-syn complexes.

As natural habitats decline and wildlife adapts to increasing anthropogenic disturbance, it is crucial to understand human-wildlife relationships in residential areas. However, relevant studies are limited and mostly focused on single cities. To address this knowledge gap, we investigated people’s preferences for seeing wild mammals in residential areas by conducting and analyzing an online survey distributed across Germany (n = 2997 participants). Our results revealed that preferred species (squirrels, hedgehogs, hares, roe deer) were frequently encountered, whereas unpreferred species were those encountered frequently (rats, martens), as well as those encountered rarely (wild boar, coypus, raccoons). We also found a moderately positive correlation between the number of encounters with mammals and them being preferred by humans. Finally, some socio-demographic variables, particularly gender, garden access, and urbanity, are significantly related to human preferences. Based on our results, we propose tailoring wildlife management in residential areas to promote the positive attributes of preferred wildlife as biodiversity ambassadors, while also addressing ways to mitigate encounters and negative perceptions associated with unpreferred species.

Radiotherapy is the dominant treatment modality for painful spine and non-spine bone metastases (NSBM). Historically, this was achieved with conventional low dose external beam radiotherapy, however, stereotactic body radiotherapy (SBRT) is increasingly applied for these indications. Meta-analyses and randomized clinical trials have demonstrated improved pain response and more durable tumor control with SBRT for spine metastases. However, in the setting of NSBM, there is limited evidence supporting global adoption and large scale randomized clinical trials are in need. SBRT is technically demanding requiring careful consideration of organ at risk tolerance, and strict adherence to technical requirements including immobilization, simulation, contouring and image-guidance procedures. Additional considerations include follow up practices after SBRT, with appropriate imaging playing a critical role in response assessment. Finally, there is renewed research into promising new technologies that may further refine the use of SBRT in both spinal and NSBM in the years to come.

Background: Road trauma is a leading cause of death and disability for young Australians (15–24 years). Young adults are overrepresented in crashes due to sleepiness, with two-thirds of their fatal crashes attributed to sleepy driving. This trial aims to examine the effectiveness of a sleep extension and education program for improved road safety in young adults. Methods: Young adults aged 18–24 years (n = 210) will be recruited for a pragmatic randomised controlled trial employing a placebo-controlled, parallel-groups design. The intervention group will undergo sleep extension and receive education on sleep, whereas the placebo control group will be provided with information about diet and nutrition. The primary outcomes of habitual sleep and on-road driving performance will be assessed via actigraphy and in-vehicle accelerometery. A range of secondary outcomes including driving behaviours (driving simulator), sleep (diaries and questionnaire) and socio-emotional measures will be assessed. Discussion: Sleep is a modifiable factor that may reduce the risk of sleepiness-related crashes. Modifying sleep behaviour could potentially help to reduce the risk of young driver sleepiness-related crashes. This randomised control trial will objectively assess the efficacy of implementing sleep behaviour manipulation and education on reducing crash risk in young adult drivers.

Purpose: Brain metastases are common among adult patients with solid malignancies and are increasingly being treated with stereotactic radiosurgery (SRS). As more patients with brain metastases are becoming eligible for SRS, there is a need for practical review of patient selection and treatment considerations. Methods and Materials: Two patient cases were identified to use as the foundation for a discussion of a wide and representative range of management principles: (A) SRS alone for 5 to 15 lesions and (B) a large single metastasis to be treated with pre- or postoperative SRS. Patient selection, fractionation, prescription dose, treatment technique, and dose constraints are discussed. Literature relevant to these cases is summarized to provide a framework for treatment of similar patients. Results: Treatment of brain metastases with SRS requires many considerations including optimal patient selection, fractionation selection, and plan optimization. Conclusions: Case-based practice guidelines developed by the Radiosurgery Society provide a practical guide to the common scenarios noted above affecting patients with metastatic brain tumors.

Vernal keratoconjunctivitis (VKC) is a chronic, progressive, allergic ocular surface disorder that can lead to sight-threatening complications. VKC occurs primarily in children and generally resolves about the time of puberty; however, case series and retrospective analyses indicate that approximately 10% of patients with VKC are adults, and that a subset of adult cases develop after puberty. Consequently, two age-related variants of VKC have recently been described: early-onset VKC—which manifests during childhood and persists into adult life—and late-onset disease, which emerges de novo after puberty. Although the signs and symptoms of adult and childhood VKC are similar, adult VKC is a long-lasting disease characterized by severe inflammation and increased risk of conjunctival fibrosis, which may place adult patients at higher risk for sight-threatening complications and adverse impacts on daily life. This review discusses the epidemiology, signs, symptoms, immunopathogenesis of adult VKC variants, and highlights current gaps in research and management of patients with this condition.

Summary: Background: Ankle brachial pressure index can be estimated (eABPI) using cuffless ankle Doppler ultrasound. We evaluated the prognostic value of eABPI measured during pre- and post-procedural ultrasound exams to predict the clinical outcome after endovascular revascularisations. Methods: In this prospective, single-centre, service evaluation, consecutive patients with symptomatic peripheral artery disease undergoing lower limb endovascular revascularisations between July, 26 2018 and January, 13 2022 at Surrey and Sussex Healthcare NHS Trust (Redhill, UK) were analysed. eABPI was determined using the higher acceleration index measured with angle-corrected duplex ultrasound in ankle arteries before and ≤1 month post-procedure. Clinical outcomes (mortality, major amputations, amputation-free survival [AFS], clinically driven target lesion revascularization [cdTLR], major adverse limb events [MALE; cdTLR and major amputation], wound healing) were assessed over 1 year. Findings: Of 246 patients treated, for 219 patients (median 75 [IQR 66–83] years) pre- and post-procedural eABPI (0.50 [0.33–0.59] and 0.90 [0.69–1.0], p

Abstract Background Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC‐specific survival (BCSS) compared to non‐carriers. Aim To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow‐up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi‐state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi‐state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non‐carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09–1.56)]. Conclusion Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.

Abstract Background Genome-wide studies of gene–environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene–environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 × 10–5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability

Microscopic colitis (MC) and coeliac disease (CD) are common associated gastrointestinal conditions. We present the largest study assessing hospitalisation in patients with MC and the effect of a concomitant diagnosis of CD. Data were retrospectively collected between January 2007 and December 2021 from all patients diagnosed with MC and compared to a database of patients with only CD. In total, 892 patients with MC (65% female, median age 65 years (IQR: 54–74 years) were identified, with 6.4% admitted to hospital due to a flare of MC. Patients admitted were older (76 vs. 65 years, p < 0.001) and presented with diarrhoea (87.7%), abdominal pain (26.3%), and acute kidney injury (17.5%). Treatment was given in 75.9% of patients, including intravenous fluids (39.5%), steroids (20.9%), and loperamide (16.3%). Concomitant CD was diagnosed in 3.3% of patients and diagnosed before MC (57 versus 64 years, p < 0.001). Patients with both conditions were diagnosed with CD later than patients with only CD (57 years versus 44 years, p < 0.001). In conclusion, older patients are at a higher risk of hospitalisation due to MC, and this is seen in patients with a concomitant diagnosis of CD too. Patients with MC are diagnosed with CD later than those without.

Abstract Elevated aggression in individuals with psychiatric disorders is frequently reported yet aggressive acts among people with mental illness are often intertwined with proneness to aggression and other risk factors. Evidence has suggested that both general psychopathology and proneness to aggression may share common psychological characteristics. This study aims to investigate the complex relationship between general psychopathology, proneness to aggression, and their contributing factors in community youth. Here, we first examined the association between proneness to aggression and the level of general psychopathology in 2184 community youths (male: 41.2%). To identify common characteristics, we trained machine learning models using LASSO based on 230 features covering sociodemographic, cognitive functions, lifestyle, well-being, and psychological characteristics to predict levels of general psychopathology and proneness to aggression. A subsequent Gaussian Graph Model (GGM) was fitted to understand the relationships between the general psychopathology, proneness to aggression, and selected features. We showed that proneness to aggression was associated with a higher level of general psychopathology (discovery: r = 0.56, 95% CI: [0.52–0.59]; holdout: r = 0.60, 95% CI: [0.54–0.65]). The LASSO model trained on the discovery dataset for general psychopathology was able to predict proneness to aggression in the holdout dataset with a moderate correlation coefficient of 0.606. Similarly, the model trained on the proneness to aggression in the discovery dataset was able to predict general psychopathology in the holdout dataset with a correlation coefficient of 0.717. These results suggest that there is substantial shared information between the two outcomes. The GGM model revealed that isolation and impulsivity factors were directly associated with both general psychopathology and proneness to aggression. These results revealed shared psychological characteristics of general psychopathology and proneness to aggression in a community sample of youths.

Abstract Background Treatment plans for squamous cell carcinoma of the head and neck (SCCHN) are individually decided in tumor board meetings but some treatment decision-steps lack objective prognostic estimates. Our purpose was to explore the potential of radiomics for SCCHN therapy-specific survival prognostication and to increase the models’ interpretability by ranking the features based on their predictive importance. Methods We included 157 SCCHN patients (male, 119; female, 38; mean age, 64.39 ± 10.71 years) with baseline head and neck CT between 09/2014 and 08/2020 in this retrospective study. Patients were stratified according to their treatment. Using independent training and test datasets with cross-validation and 100 iterations, we identified, ranked and inter-correlated prognostic signatures using elastic net (EN) and random survival forest (RSF). We benchmarked the models against clinical parameters. Inter-reader variation was analyzed using intraclass-correlation coefficients (ICC). Results EN and RSF achieved top prognostication performances of AUC = 0.795 (95% CI 0.767–0.822) and AUC = 0.811 (95% CI 0.782–0.839). RSF prognostication slightly outperformed the EN for the complete (ΔAUC 0.035, p = 0.002) and radiochemotherapy (ΔAUC 0.092, p

Purpose: To assess different microperimetry (MP) macular sensitivity outcome measures capturing functional deterioration in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Design: Patients were included from 2 identically designed, phase III, double-masked, randomized controlled clinical trials, Chroma (NCT02247479) and Spectri (NCT02247531). Participants: Patients enrolled were aged ≥ 50 years with bilateral GA and no evidence of previous or active neovascular AMD. Methods: Patients were randomized 2:1:2:1 to receive through 96 weeks intravitreal lampalizumab 10 mg every 4 weeks (LQ4W), every 6 weeks (LQ6W), or corresponding sham procedures. For this study, mesopic macular sensitivity of the central 20° was assessed using MP-1 microperimeter at selected sites. Main Outcome Measures: Two exploratory endpoints were developed, namely perilesional sensitivity (average of points adjacent to absolute scotomatous points) and responding sensitivity (average of all nonscotomatous points; > 0 dB at baseline) by using customized masks for each patient. These were compared with conventional MP endpoints (mean macular sensitivity and number of absolute scotomatous points). Results: Of 1881 Chroma and Spectri participants, 277 agreed to participate in the present study. Of these, 197 (LQ4W, n = 63; LQ6W, n = 68; pooled sham, n = 66) had reliable MP results. Enlargement of GA lesion area by approximately 2 mm2/year across treatment groups was accompanied by deterioration in all MP parameters. There was no difference in worsening of macular sensitivity or absolute scotomatous points among treatment groups. Perilesional and responding sensitivities showed greater decline over time than mean macular sensitivity. Change in GA lesion area at week 48 showed better correlation with perilesional sensitivity (r = −0.17) and responding sensitivity (r = −0.20) than mean macular sensitivity (r = −0.03), while the correlation was highest with the number of absolute scotomatous points (r = 0.37). Conclusions: Perilesional or responding macular sensitivity measured by MP should be considered more sensitive endpoints than mean macular sensitivity for monitoring functional decline over time in GA. Although perilesional, responding, and mean macular sensitivity had weak correlation with GA lesion area, the number of absolute scotomatous points may provide additional information on the anatomic/functional correlation. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Background: Current evidence suggests that precarious employment is a risk factor for poor mental health. Although the mechanisms underpinning this relationship are unclear, poor sleep has been proposed to have a role in this relationship. This study explored the mediating effects of poor sleep quality and duration on the relationship between precarious employment and mental health. Methods: Data were obtained from wave 17 of the Household, Income and Labour Dynamics in Australia survey. A novel precarious employment score (PES) was developed using exploratory and confirmatory factor analyses (CFA) in 8127 workers (4195 female, aged 18–65). Structural equation modelling (SEM) was used to evaluate the mediating effect of sleep quality and duration on the relationship between precarious employment and mental health (SF-36 mental health subscale). Results: The PES identified 650 workers with a high level of precariousness, 2417 with a moderate level of precariousness, and 5060 workers with a low level of precariousness out of 8127 in total. There was a significant direct association between precarious employment and mental health; with higher precarity increasing the likelihood of poor mental health. The SEM results revealed that sleep quality partially mediated the association between precarious employment and mental health (Coefficient = 0.025, 95 % CI [0.015, 0.034], P ≤ 0.001). However, a mediation effect was not found for sleep duration. Conclusion: Encouraging precarious employees to improve sleep quality may mitigate the adverse effects of precarious work on their mental health. Further objective measurement of sleep duration warrants a more accurate insight into this mediating effect in this group.

External beam radiation therapy (EBRT) has increasingly been utilized in the treatment of hepatocellular carcinoma (HCC) due to technological advances with positive clinical outcomes. Innovations in EBRT include improved image guidance, motion management, treatment planning, and highly conformal techniques such as intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT). Moreover, proton beam therapy (PBT) and magnetic resonance image-guided radiation therapy (MRgRT) have expanded the capabilities of EBRT. PBT offers the advantage of minimizing low- and moderate-dose radiation to the surrounding normal tissue, thereby preserving uninvolved liver and allowing for dose escalation. MRgRT provides the advantage of improved soft tissue delineation compared to computerized tomography (CT) guidance. Additionally, MRgRT with online adaptive therapy is particularly useful for addressing motion not otherwise managed and reducing high-dose radiation to the normal tissue such as the stomach and bowel. PBT and online adaptive MRgRT are emerging technological advancements in EBRT that may provide a significant clinical benefit for patients with HCC.

Abstract Background The advent of next-generation computed tomography (CT)- and magnetic resonance imaging (MRI) opened many new perspectives in the evaluation of tumor characteristics. An increasing body of evidence suggests the incorporation of quantitative imaging biomarkers into clinical decision-making to provide mineable tissue information. The present study sought to evaluate the diagnostic and predictive value of a multiparametric approach involving radiomics texture analysis, dual-energy CT-derived iodine concentration (DECT-IC), and diffusion-weighted MRI (DWI) in participants with histologically proven pancreatic cancer. Methods In this study, a total of 143 participants (63 years ± 13, 48 females) who underwent third-generation dual-source DECT and DWI between November 2014 and October 2022 were included. Among these, 83 received a final diagnosis of pancreatic cancer, 20 had pancreatitis, and 40 had no evidence of pancreatic pathologies. Data comparisons were performed using chi-square statistic tests, one-way ANOVA, or two-tailed Student’s t-test. For the assessment of the association of texture features with overall survival, receiver operating characteristics analysis and Cox regression tests were used. Results Malignant pancreatic tissue differed significantly from normal or inflamed tissue regarding radiomics features (overall P

Abstract We performed a prospective study of circulating immune cell changes after stereotactic body radiotherapy (SBRT) in 50 early-stage NSCLC patients. We found no significant increase in CD8+ cytotoxic T lymphocytes at first follow-up (the primary endpoint) but detected a significant increase in expanding Ki-67+CD8+ and Ki-67+CD4+ T-cell fractions in patients treated with 10 Gy or less per fraction. SBRT can induce significant expansion in circulating effector T-cells immediately post-treatment.

Chang et al. classify people with Temporal Lobe Epilepsy (TLE), Alzheimer’s disease and healthy controls using a convolutional neural network algorithm applied to magnetic resonance imaging (MRI) scans. People with TLE can be distinguished, including those without easily identifiable TLE-associated MRI features.

(1) Background: Low bone mineral density (BMD) is a significant risk factor for complicated surgery and leads to the increased use of bone substitutes in patients with distal radius fractures (DRFs). No accepted model has yet been established to predict the use of bone substitutes to facilitate preoperative planning. (2) Methods: Unenhanced dual-energy CT (DECT) images of DRFs were retrospectively acquired between March 2016 and September 2020 using the internal PACS system. Available follow-up imaging and medical health records were reviewed to determine the use of bone substitutes. DECT-based BMD, trabecular Hounsfield units (HU), cortical HU, and cortical thickness ratio were measured in non-fractured segments of the distal radius. Diagnostic accuracy parameters were calculated for all metrics using receiver-operating characteristic (ROC) curves and associations of all metrics with the use of bone substitutes were evaluated using logistic regression models. (3) The final study population comprised 262 patients (median age 55 years [IQR 43–67 years]; 159 females, 103 males). According to logistic regression analysis, DECT-based BMD was the only metric significantly associated with the use of bone substitutes (odds ratio 0.96, p = 0.003). However, no significant associations were found for cortical HU (p = 0.06), trabecular HU (p = 0.33), or cortical thickness ratio (p = 0.21). ROC-curve analysis revealed that a combined model of all four metrics had the highest diagnostic accuracy with an area under the curve (AUC) of 0.76. (4) Conclusions: DECT-based BMD measurements performed better than HU-based measurements and cortical thickness ratio. The diagnostic performance of all four metrics combined was superior to that of the individual parameters.

The disaster-resilient village programme, which aims to develop settlements with the autonomy to adapt and deal with disasters aims to promote disaster awareness. Several questions arise regarding the contribution of the programme to the development of the adaptive capacity of village communities, including: what types of adaptive capacity emerge as a result of the programme’s implementation, and what factors promote and inhibit the development of adaptive capacity? This study employs a comprehensive literature review. The initial step is to do a keyword search using Publish or Perish 8.2.3944.8118. This study includes a range of search phrases, including the phrase ‘disaster-resilience’ and keywords: community resiliency, disaster preparedness and disaster policy. The type of adaptive capacity that emerges from the implementation of the disaster response village programme incorporates the topic of flexibility predominantly, showing that this programme raises a diversity of adaption practices and possibilities in the community. This approach is influenced by the disaster-prone geographical characteristics of Indonesia. Practical gaps exist in the form of evaluating values in the development of similar disaster programmes, while theoretical gaps exist in the form of conceptual identification of cultural characteristics that may occur as a result of efforts to build adaptive ability through the programme. This article examines societal values that are affected by programmes. Contribution: This manuscript aims to add to the variety of disaster programme design initiatives requiring community resilience and sustainability. This sociocultural and disaster-related field is pertinent to the scope of this publication.

Conventional polymeric 3D printing offers efficient ways to produce 3D structures. To provide the functional capability of 3D structures, we have incorporated conductive additives such as multi-walled carbon nanotubes (MWCNTs) within the 3D printed structures by utilizing a pellet-based extrusion system. The inclusion of MWCNTs in the nanocomposites allows the creation of semiconductive structures that can detect force or strain due to piezoresistive properties. During the printing process, the shear forces can cause the MWCNTs to partially align, and this alignment is influenced by the chosen path scanning strategies. Our study aimed to determine how the alignment of MWCNTs affects the mechanical, electrical, and thermal properties of 3D-printed nanocomposite objects. We employed various characterization techniques including scanning electron microscopy (SEM), resistivity measurements, dynamic mechanical analysis (DMA), three-point bending, and cyclic bending tests at different raster angles (0°, 45°, and 90°) of 3D printed parts. A 3D Random Walk model was developed to simulate the influence of MWCNTs alignment on the piezoresistive behavior. The experimental results showed low electrical resistivity and high flexural strength in 3D printed samples, especially when printed in a longitudinal direction (0°). The highest sensing gauge factor was achieved when printing laterally (90°). To demonstrate the real-world applicability, we designed a self-sensing claw system for grippers with an integrated feedback mechanism using the 3D-printed nanocomposite. This study highlights the potential of pellet-fed polymeric nanocomposite 3D printing for generating semiconductive structures with sensing capabilities in diverse applications.

Feature learning is a widely used method for large-scale face recognition tasks. Recently, large-margin softmax loss methods have demonstrated significant improvements in deep face recognition. However, these methods typically propose fixed positive margins to enforce intra-class compactness and inter-class diversity, without considering imbalanced learning issues that arise due to different learning difficulties or the number of training samples available in each class. This overlook not only compromises the efficiency of the learning process but, more critically, the generalization capability of the resultant models. To address this problem, we introduce a novel adaptive strategy called KappaFace, which modulates the relative importance of each class based on its learning difficulty and imbalance. Drawing inspiration from the von Mises-Fisher distribution, KappaFace increases the margin values for the challenging or underrepresented classes and decreases that of more well-represented classes. Comprehensive experiments across eight cutting-edge baselines and nine well-established facial benchmark datasets strongly confirm the advantage of our method. Notably, we observed an enhancement of up to 0.5% on the verification task when evaluated on the IJB-B/C datasets. In conclusion, KappaFace offers a novel solution that effectively tackles imbalanced learning in deep face recognition tasks and establishes a new baseline.

Contrastive learning methods have been widely adopted in numerous unsupervised and self-supervised visual representation learning methods. Such algorithms aim to maximize the cosine similarity between two positive samples while minimizing that of the negative samples. Recently, Grill et al. propose an algorithm, BYOL, to utilize only positive samples, completely giving up on negative ones, by introducing a Siamese-like asymmetric architecture. Although many recent state-of-the-art (SOTA) methods adopt the architecture, most of them simply introduce the additional neural network, the predictor, without much exploration of the asymmetrical architecture. In contrast, He et al. propose SimSiam, a simple Siamese architecture relying on the stop-gradient operation instead of the momentum encoder and describe the framework from the perspective of Expectation-Maximization. We argue that BYOL-like algorithms attain suboptimal performance due to representation inconsistency during training. In this work, we explain and propose a novel self-supervised objective, Expectation-Maximization via Pretext-Invariant Representations (EMPIR), which enhances Expectation-Maximization-based optimization in BYOL-like algorithms by enforcing augmentation invariance within a local region of k nearest neighbors, resulting in consistent representation learning. In other words, we propose Expectation-Maximization as a core task of asymmetric architectures. We show that it consistently outperforms other (SOTA) algorithms by a decent margin. We also demonstrate its transfer learning capabilities on downstream image recognition tasks.

Abstract We aimed to identify hepatocellular carcinoma (HCC) patients who will respond to repetitive transarterial chemoembolization (TACE) to improve the treatment algorithm. Retrospectively, 61 patients (mean age, 65.3 years ± 10.0 [SD]; 49 men) with 94 HCC mRECIST target-lesions who had three consecutive TACE between 01/2012 and 01/2020 were included. Robust and non-redundant radiomics features were extracted from the 24 h post-embolization CT. Five different clinical TACE-scores were assessed. Seven different feature selection methods and machine learning models were used. Radiomics, clinical and combined models were built to predict response to TACE on a lesion-wise and patient-wise level as well as its impact on overall-survival prognostication. 29 target-lesions of 19 patients were evaluated in the test set. Response rates were 37.9% (11/29) on the lesion-level and 42.1% (8/19) on the patient-level. Radiomics top lesion-wise response prognostications was AUC 0.55–0.67. Clinical scores revealed top AUCs of 0.65–0.69. The best working model combined the radiomic feature LargeDependenceHighGrayLevelEmphasis and the clinical score mHAP_II_score_group with AUC = 0.70, accuracy = 0.72. We transferred this model on a patient-level to achieve AUC = 0.62, CI = 0.41–0.83. The two radiomics-clinical features revealed overall-survival prognostication of C-index = 0.67. In conclusion, a random forest model using the radiomic feature LargeDependenceHighGrayLevelEmphasis and the clinical mHAP-II-score-group seems promising for TACE response prognostication.

Abstract The accurate assessment of cerebrospinal fluid opening pressure during spinal puncture provides important medical information in diagnosis, prognosis and therapy of several neurological conditions. However, purpose-specific spinal needle choice is debated. While atraumatic needles are associated with lower incidence of post-puncture headache and re-hospitalisation, some clinicians believe that they lack in accuracy of CSF opening pressure assessment. Our primary objective was to investigate different needle types on correctly assessing CSF opening pressure. We compared typical clinically utilised traumatic (0.9 mm outer diameter) and atraumatic (0.7 mm; 0.45 mm) spinal needles with regards to the assessment of the opening pressure in an experimental spinal puncture model testing experimental and cerebrospinal fluids in predefined pressures. Our goal was to measure the time until indicated pressure levels were correctly shown. Atraumatic needles of at least 0.7 mm diameter had a similar accuracy as traumatic needles without significant differences in time-to-equilibrium. These results were independent of protein and glucose concentration and the presence of haemoglobin. This study demonstrates that atraumatic needles can be used to accurately measure CSF opening pressure. This knowledge might guide clinicians in their choice of needle and help to reduce post-puncture headaches and re-hospitalisation.

Abstract Background and purpose Tumor-infiltrating lymphocytes (TILs) are associated with locoregional control (LRC) in head-and-neck squamous cell carcinoma (HNSCC) patients undergoing (chemo)radiotherapy. As immunosenescence results in reduced immune activity, the role of TILs in elderly HNSCC patients may differ compared to younger patients, providing a rationale to study the prognostic role of TILs and immune checkpoints (ICs) in this population. Material and methods Sixty-three HNSCC patients aged ≥ 65 years undergoing definitive (chemo)radiotherapy between 2010 and 2019 with sufficient material from pre-treatment biopsies were included in the analysis. Immunohistochemical stainings of CD3, CD4, CD8, PD-L1, TIM3, LAG3, TIGIT and CD96, and of osteopontin as an immunosenescence-associated protein were performed. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan–Meier method, and Fine-Gray's models were used for locoregional failure (LRF) analyses. Results While there was no correlation between patient age and IC expression, osteopontin levels correlated with increasing age (r = 0.322, p

Abstract Objectives Oral rehabilitation can be a challenge in patients on high‐dose antiresorptive medication (HDAR), especially if the alveolar anatomy has changed due to previous medication‐related osteonecrosis of the jaw (MRONJ) resection. In healthy patients, dental implant treatment has found wide acceptance in prosthetic rehabilitation as it increases the patient's oral health‐related quality of life. However, it is considered contraindicated in patients on HDAR due to the risk of MRONJ, although a recent feasibility study indicates that implant treatment may indeed be an option in these patients. The aim of the present case report is to illustrate the risk of MRONJ in a patient with cancer on HDAR and to discuss the reasons behind the outcomes of the implant treatment. Materials and Methods A patient with prostate cancer with bone metastases on high‐dose denosumab therapy with previous MRONJ had four implants inserted bilaterally in the maxilla (14, 13, 23, 24). Two identical implant‐supported screw‐retained cantilever bridges were fabricated. The patient was followed for more than 1 year. Results and Conclusion Peri‐implantitis, and/or MRONJ, was diagnosed around two of the implants (23, 24), probably induced by crestal bone trauma from a healing abutment and/or a misfitting prosthetic reconstruction. A peri‐implantitis operation was performed, but without the desired response, and the two implants (23, 24) were later removed in an MRONJ resection. The implants on the other side of the maxilla (14, 13) remained without complications. Dental implant treatment is feasible in patients on HDAR, but comorbidities (e.g., diabetes mellitus) and polypharmacy (e.g., chemotherapy and steroids) may add to the risk of implant failure. Minimal trauma surgery and prosthodontics are crucial to increase the chance of successful healing in an HDAR patient.

AimsDespite multiple trials and case series on hip hemiarthroplasty designs, guidance is still lacking on which implant to use. One particularly deficient area is long-term outcomes. We present over 1,000 consecutive cemented Thompson’s hemiarthroplasties over a ten-year period, recording all accessible patient and implant outcomes.MethodsPatient identifiers for a consecutive cohort treated between 1 January 2003 and 31 December 2011 were linked to radiographs, surgical notes, clinic letters, and mortality data from a national dataset. This allowed charting of their postoperative course, complications, readmissions, returns to theatre, revisions, and deaths. We also identified all postoperative attendances at the Emergency and Outpatient Departments, and recorded any subsequent skeletal injuries.ResultsIn total, 1,312 Thompson’s hemiarthroplasties were analyzed (mean age at surgery 82.8 years); 125 complications were recorded, necessitating 82 returns to theatre. These included 14 patients undergoing aspiration or manipulation under anaesthesia, 68 reoperations (5.2%) for debridement and implant retention (n = 12), haematoma evacuation (n = 2), open reduction for dislocation (n = 1), fixation of periprosthetic fracture (n = 5), and 48 revised stems (3.7%), for infection (n = 13), dislocation (n = 12), aseptic loosening (n = 9), persistent pain (n = 6), periprosthetic fracture (n = 4), acetabular erosion (n = 3), and metastatic bone disease (n = 1). Their status at ten years is summarized as follows: 1,180 (89.9%) dead without revision, 34 (2.6%) dead having had revision, 84 (6.6%) alive with the stem unrevised, and 14 (1.1%) alive having had revision. Cumulative implant survivorship was 90.3% at ten years; patient survivorship was 7.4%.ConclusionThe Thompson’s stem demonstrates very low rates of complications requiring reoperation and revision, up to ten years after the index procedure. Fewer than one in ten patients live for ten years after fracture. This study supports the use of a cemented Thompson’s implant as a cost-effective option for frail hip fracture patients.Cite this article: Bone Jt Open 2022;3(9):710–715.

Schizophrenia is a heritable neurocognitive disorder affecting about 1% of the population, and usually has an onset age at around 21–25 in males and 25–30 in females. Recent advances in genetics have helped to identify many common and rare variants for the liability to schizophrenia. Earlier evidence appeared to suggest that younger onset age is associated with higher genetic liability to schizophrenia. Clinical longitudinal research also found that early and very-early onset schizophrenia are associated with poor clinical, neurocognitive, and functional profiles. A recent study reported a heritability of 0.33 for schizophrenia onset age, but the genetic basis of this trait in schizophrenia remains elusive. In the pre-Genome-Wide Association Study (GWAS) era, genetic loci found to be associated with onset age were seldom replicated. In the post-Genome-Wide Association Study era, new conceptual frameworks are needed to clarify the role of onset age in genetic research in schizophrenia, and to identify its genetic basis. In this review, we first discussed the potential of onset age as a characterizing/subtyping feature for psychosis, and as an important phenotypic dimension of schizophrenia. Second, we reviewed the methods, samples, findings and limitations of previous genetic research on onset age in schizophrenia. Third, we discussed a potential conceptual framework for studying the genetic basis of onset age, as well as the concepts of susceptibility, modifier, and “mixed” genes. Fourth, we discussed the limitations of this review. Lastly, we discussed the potential clinical implications for genetic research of onset age of schizophrenia, and how future research can unveil the potential mechanisms for this trait.

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia, affecting 2%–3% of the world's population. Mental and emotional stress, as well as some mental health conditions (e.g., depression) have been shown to significantly impact the heart and have been suggested to act both as independent risk factors and triggers in the onset of AF. In this paper, we review the current literature to examine the role that mental and emotional stress have in the onset of AF and summarise the current knowledge on the interaction between the brain and heart, and the cortical and subcortical pathways involved in the response to stress. Review of the evidence suggests that mental and emotional stress negatively affect the cardiac system, potentially increasing the risk for developing and/or triggering AF. Further studies are required to further understand the cortical and sub-cortical structures involved in the mental stress response and how these interact with the cardiac system, which may help in defining new strategies and interventions to prevent the development of, and improve the management of AF.

ObjectivesThis study aims to assess the attenuation of pericoronary adipose tissue (PCAT) surrounding the proximal right coronary artery (RCA) in patients with aortic stenosis (AS) and undergoing transcatheter aortic valve replacement (TAVR). RCA PCAT attenuation is a novel computed tomography (CT)–based marker for evaluating coronary inflammation. Coronary artery disease (CAD) in TAVR patients is common and usually evaluated prior to intervention. The most sensible screening method and consequential treatment approach are unclear and remain a matter of ceaseless discussion. Thus, interest remains for safe and low-demand predictive markers to identify patients at risk for adverse outcomes postaortic valve replacement.MethodsThis single-center retrospective study included patients receiving a standard planning CT scan prior to TAVR. Conventional CAD diagnostic tools, such as coronary artery calcium score and significant stenosis via invasive coronary angiography and coronary computed tomography angiography, were determined in addition to RCA PCAT attenuation using semiautomated software. These were assessed for their relationship with major adverse cardiovascular events (MACE) during a 24-month follow-up period.ResultsFrom a total of 62 patients (mean age: 82 ± 6.7 years), 15 (24.2%) patients experienced an event within the observation period, 10 of which were attributed to cardiovascular death. The mean RCA PCAT attenuation was higher in patients enduring MACE than that in those without an endpoint (−69.8 ± 7.5 vs. −74.6 ± 6.2, P = 0.02). Using a predefined cutoff of >−70.5 HU, 20 patients (32.3%) with high RCA PCAT attenuation were identified, nine (45%) of which met the endpoint within 2 years after TAVR. In a multivariate Cox regression model including conventional CAD diagnostic tools, RCA PCAT attenuation prevailed as the only marker with significant association with MACE (P = 0.02). After dichotomization of patients into high- and low-RCA PCAT attenuation groups, high attenuation was related to greater risk of MACE (hazard ration: 3.82, P = 0.011).ConclusionRCA PCAT attenuation appears to have predictive value also in a setting of concomitant AS in patients receiving TAVR. RCA PCAT attenuation was more reliable than conventional CAD diagnostic tools in identifying patients at risk for MACE .

In 2020, the invasive Thrips parvispinus (Karny) was first detected in Florida, United States. In response to the implemented regulatory restrictions, we conducted laboratory experiments under containment conditions. Thrips larvae and adults were exposed to 32 products (conventional and biorational insecticides) either directly or indirectly. Direct exposure was performed using a Spray Potter Tower, while indirect exposure was conducted by evaluating residue toxicity against the thrips. Water served as a control. We assessed mortality and leaf-feeding damage 48 h post-treatment. Among the conventional insecticides, chlorfenapyr, sulfoxaflor-spinetoram, and spinosad caused high mortality across all stages in both direct and residue toxicity assays. Pyridalyl, acetamiprid, tolfenpyrad, cyclaniliprole-flonicamid, acephate, novaluron, abamectin, cyantraniliprole, imidacloprid, cyclaniliprole, spirotetramat, and carbaryl displayed moderate toxicity, affecting at least two stages in either exposure route. Additionally, chlorfenapyr, spinosad, sulfoxaflor-spinetoram, pyridalyl, acetamiprid, cyclaniliprole, cyclaniliprole-flonicamid, abamectin, and acephate inhibited larvae and adult’s leaf-feeding damage in both direct and residue toxicity assays. Regarding biorational insecticides, mineral oil (3%) and sesame oil caused the highest mortality and lowest leaf-feeding damage. Greenhouse evaluations of spinosad, chlorfenapyr, sulfoxaflor-spinetoram, and pyridalyl are recommended. Also, a rotation program incorporating these products, while considering different modes of action, is advised for ornamental growers to avoid resistance and to comply with regulations.

Given the importance of young children’s postures and movements to health and development, robust objective measures are required to provide high-quality evidence. This study aimed to systematically review the available evidence for objective measurement of young (0–5 years) children’s posture and movement using machine learning and other algorithm methods on accelerometer data. From 1663 papers, a total of 20 papers reporting on 18 studies met the inclusion criteria. Papers were quality-assessed and data extracted and synthesised on sample, postures and movements identified, sensors used, model development, and accuracy. A common limitation of studies was a poor description of their sample data, yet over half scored adequate/good on their overall study design quality assessment. There was great diversity in all aspects examined, with evidence of increasing sophistication in approaches used over time. Model accuracy varied greatly, but for a range of postures and movements, models developed on a reasonable-sized (n > 25) sample were able to achieve an accuracy of >80%. Issues related to model development are discussed and implications for future research outlined. The current evidence suggests the rapidly developing field of machine learning has clear potential to enable the collection of high-quality evidence on the postures and movements of young children.