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Abstract: In the April 1930 issue of the journal, Founding Editor-in-Chief William Rush Dunton, Jr, MD, initiated a new series: Museum Meanderings. Eleven installments of the series ran intermittently until December 1931. Here, a 12th installment, an e-museum "tour" of paintings by the great American artist Jacob Lawrence (1917-2000) relevant to rehabilitation medicine, is offered. In particular, his Occupational Therapy No. 1 (1949) is a most thought-provoking and inspiring masterpiece. The painting depicts five women performing various sewing activities with space in the painting brilliantly divided. The painting has been discussed by art critics, but it has not been appreciated that all the women appear actually to be the same person! Thus, the painting shows the stages or cycle of rehabilitation. Echoing Rush Dunton's thoughts in 1930, we invite further contributions to the series., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract The quantitative nature of fusarium head blight (FHB) resistance requires further exploration of the wheat genome to identify regions conferring resistance. In this study, we explored the application of hyperspectral imaging of Fusarium-infected wheat kernels and identified regions of the wheat genome contributing significantly to the accumulation of Deoxynivalenol (DON) mycotoxin. Strong correlations were identified between hyperspectral reflectance values for 204 wavebands in the 397–673 nm range and DON mycotoxin. Dimensionality reduction using principal components was performed for all 204 wavebands and 38 sliding windows across the range of wavebands. The first principal component (PC1) of all 204 wavebands explained 70% of the total variation in waveband reflectance values and was highly correlated with DON mycotoxin. PC1 was used as a phenotype in a genome wide association study and a large effect QTL on chromosome 2D was identified for PC1 of all wavebands as well as nearly all 38 sliding windows. The allele contributing variation in PC1 values also led to a substantial reduction in DON. The 2D polymorphism affecting DON levels localized to the exon of TraesCS2D02G524600 which is upregulated in wheat spike and rachis tissues during FHB infection. This work demonstrates the value of hyperspectral imaging as a correlated trait for investigating the genetic basis of resistance and developing wheat varieties with enhanced resistance to FHB.

Abstract Central nervous system tumors have resisted effective chemotherapy because most therapeutics do not penetrate the blood-tumor-brain-barrier. Nanomedicines between ~ 10 and 100 nm accumulate in many solid tumors by the enhanced permeability and retention effect, but it is controversial whether the effect can be exploited for treatment of brain tumors. PLX038A is a long-acting prodrug of the topoisomerase 1 inhibitor SN-38. It is composed of a 15 nm 4-arm 40 kDa PEG tethered to four SN-38 moieties by linkers that slowly cleave to release the SN-38. The prodrug was remarkably effective at suppressing growth of intracranial breast cancer and glioblastoma (GBM), significantly increasing the life span of mice harboring them. We addressed the important issue of whether the prodrug releases SN-38 systemically and then penetrates the brain to exert anti-tumor effects, or whether it directly penetrates the blood-tumor-brain-barrier and releases the SN-38 cargo within the tumor. We argue that the amount of SN-38 formed systemically is insufficient to inhibit the tumors, and show by PET imaging that a close surrogate of the 40 kDa PEG carrier in PLX038A accumulates and is retained in the GBM. We conclude that the prodrug penetrates the blood-tumor-brain-barrier, accumulates in the tumor microenvironment and releases its SN-38 cargo from within. Based on our results, we pose the provocative question as to whether the 40 kDa nanomolecule PEG carrier might serve as a “Trojan horse” to carry other drugs past the blood-tumor-brain-barrier and release them into brain tumors.

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), and shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here, we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8–92 years old, using a non-invasive diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60 s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders.

IntroductionMolecular chaperones and co-chaperones are highly conserved cellular components that perform a variety of duties related to the proper three-dimensional folding of the proteome. The web of factors that carries out this essential task is called the proteostasis network (PN). Ribonucleoproteins (RNPs) represent an underexplored area in terms of the connections they make with the PN. The Survival Motor Neuron (SMN) complex is an assembly chaperone and serves as a paradigm for studying how specific RNAs are identified and paired with their client substrate proteins to form RNPs. SMN is the eponymous component of a large complex, required for the biogenesis of uridine-rich small nuclear ribonucleoproteins (U-snRNPs), that localizes to distinct membraneless organelles in both the nucleus and cytoplasm of animal cells. SMN protein forms the oligomeric core of this complex, and missense mutations in the human SMN1 gene are known to cause Spinal Muscular Atrophy (SMA). The basic framework for understanding how snRNAs are assembled into U-snRNPs is known. However, the pathways and mechanisms used by cells to regulate their biogenesis are poorly understood.MethodsGiven the importance of these processes to normal development as well as neurodegenerative disease, we set out to identify and characterize novel SMN binding partners. We carried out affinity purification mass spectrometry (AP-MS) of Drosophila SMN complexes using fly lines exclusively expressing either wildtype or SMA-causing missense alleles.ResultsBioinformatic analyses of the pulldown data, along with comparisons to proximity labeling studies carried out in human cells, revealed conserved connections to at least two other major chaperone systems including heat shock folding chaperones (HSPs) and histone/nucleosome assembly chaperones. Notably, we found that heat shock cognate protein Hsc70-4 and other HspA family members preferentially associated with SMA-causing alleles of SMN.DiscussionHsc70-4 is particularly interesting because its mRNA is aberrantly sequestered by a mutant form of TDP-43 in mouse and Drosophila ALS (Amyotrophic Lateral Sclerosis) disease models. Most important, a missense allele of Hsc70-4 (HspA8 in mammals) was recently identified as a bypass suppressor of the SMA phenotype in mice. Collectively, these findings suggest that chaperone-related dysfunction lies at the etiological root of both ALS and SMA.

Abstract We present a rigorous validation strategy to evaluate the performance of Ultivue multiplex immunofluorescence panels. We have quantified the accuracy and precision of four different multiplex panels (three human and one mouse) in tumor specimens with varying levels of T cell density. Our results show that Ultivue panels are typically accurate wherein the relative difference in cell proportion between a multiplex image and a 1-plex image is less than 20% for a given biomarker. Ultivue panels exhibited relatively high intra-run precision (CV ≤ 25%) and relatively low inter-run precision (CV >> 25%) which can be remedied by using local intensity thresholding to gate biomarker positivity. We also evaluated the reproducibility of cell–cell distance estimates measured from multiplex images which show high intra- and inter-run precision. We introduce a new metric, multiplex labeling efficiency, which can be used to benchmark the overall fidelity of the multiplex data across multiple batch runs. Taken together our results provide a comprehensive characterization of Ultivue panels and offer practical guidelines for analyzing multiplex images.

Introduction Medications for opioid use disorder (MOUD) are the most effective interventions for this condition, yet many patients discontinue treatment. Though adjunct psychosocial treatments are recommended to increase retention and reduce relapse, the scarcity of trained providers hinders access to and utilization of evidence-based interventions. We conducted a Phase 1 study to assess the feasibility of a virtual reality-delivered Mindfulness-Oriented Recovery Enhancement (MORE-VR) intervention for patients receiving MOUD.Patients and Methods Patients receiving buprenorphine or methadone for OUD (N = 34) were scheduled for 8 weekly sessions of MORE-VR. Enrollment and retention rates were analyzed. Participants reported on the usability and acceptability of MORE-VR, opioid use, and craving and affect before and after each VR session. Heart rate was monitored during one session of MORE-VR.Results Twenty-three participants completed four or more MORE-VR sessions (minimum recommended intervention dose). Participants reported high usability and acceptability of MORE-VR, which had an excellent safety profile. Illicit opioid use decreased significantly from pre- to post-treatment (F = 4.44, p=.04). We observed a significant within-session decrease in opioid craving (F = 39.3, p

Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval of covalent inhibitors of KRASG12C such as sotorasib or adagrasib, KRAS oncoproteins are important pharmacological targets in non-small cell lung cancer (NSCLC). However, not all KRASG12C-driven NSCLCs respond to these inhibitors, and the emergence of drug resistance in those patients who do respond can be rapid and pleiotropic. Hence, based on a backbone of covalent inhibition of KRASG12C, efforts are underway to develop effective combination therapies. Here, we report that the inhibition of KRASG12C signaling increases autophagy in KRASG12C-expressing lung cancer cells. Moreover, the combination of DCC-3116, a selective ULK1/2 inhibitor, plus sotorasib displays cooperative/synergistic suppression of human KRASG12C-driven lung cancer cell proliferation in vitro and superior tumor control in vivo. Additionally, in genetically engineered mouse models of KRASG12C-driven NSCLC, inhibition of either KRASG12C or ULK1/2 decreases tumor burden and increases mouse survival. Consequently, these data suggest that ULK1/2-mediated autophagy is a pharmacologically actionable cytoprotective stress response to inhibition of KRASG12C in lung cancer.

Introduction Many individuals receiving outpatient physical therapy have musculoskeletal pain and up to one-third use prescription opioids. The impact of physical therapist-led mindfulness-based interventions integrated with evidence-based physical therapy (I-EPT) to manage patients with chronic musculoskeletal pain and long-term opioid treatment has not been elucidated. This project evaluates the feasibility of conducting a cluster randomised trial to test the effectiveness of I-EPT.Methods and analysis Study 1 aim: Refine and manualise the I-EPT treatment protocol. Our approach will use semistructured interviews of patients and physical therapists to refine an I-EPT training manual. Study 2 aim: Evaluate different intensities of physical therapist training programmes for the refined I-EPT treatment protocol. Physical therapists will be randomised 1:1:1 to high-intensity training (HighIT), low-IT (LowIT) training and no training arms. Following training, competency in the provision of I-EPT (LowIT and HighIT groups) will be assessed using standardised patient simulations. Study 3 aim: Evaluate the feasibility of the I-EPT intervention across domains of the Reach, Effectiveness, Adoption, Implementation, Maintenance implementation framework. The refined I-EPT treatment protocol will be tested in two different health systems with 90 patients managed by the randomised physical therapists. The coprimary endpoints for study 3 are the proportions of the Pain, Enjoyment of Life and General Activity Scale and the Timeline Followback for opioid use/dose collected at 12 weeks.Ethics and dissemination Ethics approval for the study was obtained from the University of Utah, University of Florida and Florida State University Institutional Review Boards. Informed consent is required for participant enrolment in all phases of this project. On completion, study data will be made available in compliance with NIH data sharing policies.Trial registration number NCT05875207.

Hippocampal replay – the time-compressed, sequential reactivation of ensembles of neurons related to past experience – is a key neural mechanism of memory consolidation. Replay typically coincides with a characteristic pattern of local field potential activity, the sharp-wave ripple (SWR). Reduced SWR rates are associated with cognitive impairment in multiple models of neurodegenerative disease, suggesting that a clinically viable intervention to promote SWRs and replay would prove beneficial. We therefore developed a neurofeedback paradigm for rat subjects in which SWR detection triggered rapid positive feedback in the context of a memory-dependent task. This training protocol increased the prevalence of task-relevant replay during the targeted neurofeedback period by changing the temporal dynamics of SWR occurrence. This increase was also associated with neural and behavioral forms of compensation after the targeted period. These findings reveal short-timescale regulation of SWR generation and demonstrate that neurofeedback is an effective strategy for modulating hippocampal replay.

BackgroundFew cost-effective strategies to shift dietary habits of populations in a healthier direction have been identified. We examined if participating in a chatbot health education program transmitted by Short Messages Service ("SMS-program") could improve adolescent dietary behaviors and body weight trajectories. We also explored possible added effects of maternal or peer involvement.Methods and findingsWe conducted a randomized controlled trial (RCT) among adolescents from the Danish National Birth Cohort (DNBC). Eligible were adolescents who during 2015 to 2016 at age 14 years had completed a questionnaire assessing height, weight, and dietary habits. Two thirds were offered participation in an SMS-program, whereas 1/3 ("non-SMS group") received no offer. The SMS program aimed to improve 3 key dietary intake behaviors: sugar-sweetened beverages (SSBs), fruit and vegetables (FV), and fish. The offered programs had 3 factorially randomized schemes; the aims of these were to test effect of asking the mother or a friend to also participate in the health promotion program, and to test the effect of a 4-week individually tailored SMS program against the full 12-week SMS program targeting all 3 dietary factors. Height and weight and intakes of SSB, FV, and fish were assessed twice by a smartphone-based abbreviated dietary questionnaire completed at 6 months (m) and 18 m follow-up. Main outcome measures were (1) body mass index (BMI) z-score; and (2) an abbreviated Healthy Eating Index (mini-HEI, 1 m window, as mean of z-scores for SSB, FV, and fish). Among the 7,890 randomized adolescents, 5,260 were assigned to any SMS program; 63% (3,338) joined the offered program. Among the 7,890 randomized, 74% (5,853) and 68% (5,370) responded to follow-ups at 6 m and 18 m, respectively. Effects were estimated by intention-to-treat (ITT) analyses and inverse probability weighted per-protocol (IPW-PP) analyses excluding adolescents who did not join the program. Mean (standard deviation (SD)) mini-HEI at baseline, 6 m and 18 m was -0.01 (0.64), 0.01 (0.59), and -0.01 (0.59), respectively. In ITT-analyses, no effects were observed, at any time point, in those who had received any SMS program compared to the non-SMS group, on BMI z-score (6 m: -0.010 [95% confidence interval (CI) -0.035, 0.015]; p = 0.442, 18 m: 0.002 [95% CI -0.029, 0.033]; p = 0.901) or mini-HEI (6 m: 0.016 [95% CI -0.011, 0.043]; p = 0.253, 18m: -0.016 [95% CI -0.045, 0.013]; p = 0.286). In IPW-PP analyses, at 6 m, a small decrease in BMI z-score (-0.030 [95% CI -0.057, -0.003]; p = 0.032) was observed, whereas no significant effect was observed in mini-HEI (0.027 [95% CI -0.002, 0.056]; p = 0.072), among those who had received any SMS program compared to the non-SMS group. At 18 m, no associations were observed (BMI z-score: -0.006 [95% CI -0.039, 0.027]; p = 0.724, and mini-HEI: -0.005 [95% CI -0.036, 0.026]; p = 0.755). The main limitations of the study were that DNBC participants, though derived from the general population, tend to have higher socioeconomic status than average, and that outcome measures were self-reported.ConclusionsIn this study, a chatbot health education program delivered through an SMS program had no effect on dietary habits or weight trajectories in ITT analyses. However, IPW-PP-analyses, based on those 63% who had joined the offered SMS program, suggested modest improvements in weight development at 6 m, which had faded at 18 m. Future research should focus on developing gender-specific messaging programs including "booster" messages to obtain sustained engagement.Clinical trial registrationClinicalTrials.gov Identifier: NCT02809196 https://clinicaltrials.gov/study/NCT02809196.

The Cartesian medical model is leading to overmedicalization all over the world. Modern palliative care, derived from a reflection on the Cartesian medical model, aims to relieve the suffering of critically ill patients and their caregivers. It also focuses on the unnecessary harm of medical technology itself. This paper presents some issues from a case and inspires further thinking and profound understanding of China's palliative care by reviewing the history of relieving suffering, the views and shortcomings of the Cartesian medical model, and the application of life-sustaining treatment and good death.

Abstract The consequences of returning infectious pathogen test results identified incidentally in research studies have not been well-studied. Concerns include identification of an important health issue for individuals, accuracy of research test results, public health impact, potential emotional distress for participants, and need for IRB permissions. Blood RNA-sequencing analysis for non-human RNA in 3984 participants from the COPDGene study identified 228 participants with evidence suggestive for hepatitis C virus (HCV) infection. We hypothesized that incidentally discovered HCV results could be effectively returned to COPDGene participants with attention to the identified concerns. In conjunction with a COPDGene Participant Advisory Panel, we developed and obtained IRB approval for a process of returning HCV research results and an HCV Follow-Up Study questionnaire to capture information about previous HCV diagnosis and treatment information and participant reactions to return of HCV results. During phone calls following the initial HCV notification letter, 84 of 124 participants who could be contacted (67.7%) volunteered that they had been previously diagnosed with HCV infection. Thirty-one of these 124 COPDGene participants were enrolled in the HCV Follow-Up Study. Five of the 31 HCV Follow-Up Study participants did not report a previous diagnosis of HCV. For four of these participants, subsequent clinical HCV testing confirmed HCV infection. Thus, 30/31 Follow-Up Study participants had confirmed HCV diagnoses, supporting the accuracy of the HCV research test results. However, the limited number of participants in the Follow-Up Study precludes an accurate assessment of the false-positive and false-negative rates of the research RNA sequencing evidence for HCV. Most HCV Follow-Up Study participants (29/31) were supportive of returning HCV research results, and most participants found the process for returning HCV results to be informative and not upsetting. Newly diagnosed participants were more likely to be pleased to learn about a potentially curable infection (p = 0.027) and showed a trend toward being more frightened by the potential health risks of HCV (p = 0.11). We conclude that HCV results identified incidentally during transcriptomic research studies can be successfully returned to research study participants with a carefully designed process.

Abstract Lung adenocarcinoma (LUAD) is the predominant type of lung cancer in the U.S. and exhibits a broad variety of behaviors ranging from indolent to aggressive. Identification of the biological determinants of LUAD behavior at early stages can improve existing diagnostic and treatment strategies. Extracellular matrix (ECM) remodeling and cancer-associated fibroblasts play a crucial role in the regulation of cancer aggressiveness and there is a growing need to investigate their role in the determination of LUAD behavior at early stages. We analyzed tissue samples isolated from patients with LUAD at early stages and used imaging-based biomarkers to predict LUAD behavior. Single-cell RNA sequencing and histological assessment showed that aggressive LUADs are characterized by a decreased number of ADH1B+ CAFs in comparison to indolent tumors. ADH1B+ CAF enrichment is associated with distinct ECM and immune cell signatures in early-stage LUADs. Also, we found a positive correlation between the gene expression of ADH1B+ CAF markers in early-stage LUADs and better survival. We performed TCGA dataset analysis to validate our findings. Identified associations can be used for the development of the predictive model of LUAD aggressiveness and novel therapeutic approaches.

Abstract Glasses with high antimicrobial efficacy were developed in the Fe2O3-CuO-P2O5 ternary system to mitigate fomite-mediated transmission of infectious diseases in high-risk settings such as hospitals, daycares, and nursing homes. Binary CuO-P2O5 glasses were not durable enough for use as high touch point articles, so Fe2O3 was added to the compositions to increase the chemical durability. The amount of Cu leachate decreased by at least 3 orders of magnitude when Fe2O3 was increased from 0 to 13.1 mol%. At the highest Fe2O3 contents and corresponding highest durability, the glass was no longer able to pass a test of antimicrobial efficacy with 5 log kill for all other compositions. Ab-initio molecular dynamics simulations showed increasing bridging oxygen species at the expense of non-bridging oxygen species with the increase in Fe2O3 content, showing that the glasses exhibited increased chemical durability because they were more interconnected and structurally bound. Experimental results with glasses at fixed CuO and decreasing Fe2O3 confirmed that Fe2O3 content (not CuO) controlled the Cu release rate and, thus, the antimicrobial efficacy of the glasses. The significance of the oxidation state of the leached Cu was overwhelmed by the importance of the amount of Cu leachate.

In image-guided surgery, imaging systems such as (stereo-)endoscopes allow intra-operative 3D reconstructions in form of point clouds. However, endoscopes provide only a narrow field of view, resulting in a confined point cloud. In this paper, we present an analysis and registration pipeline for confined point clouds acquired by stereo endoscopes into a fused representation. For a coarse registration, TEASER is applied, while a refinement is conducted utilizing point-to-plane ICP. The pipeline is tested on two datasets: acquired point clouds of a head phantom using a EinsteinVision® 3.0 endoscope and point clouds from the Stereo Correspondence And Reconstruction of Endoscopic Data challenge. The results for both datasets show that 3D reconstructions of anatomical structures by utilizing stereo-endoscopes and point cloud registration is a promising contactless and radiation-free method. However, non-rigid deformations are not yet incorporated and evaluation of the method compared to reference data is challenging.

Surgical phase recognition is an important aspect of surgical workflow analysis, as it allows an automatic analysis of the performance and efficiency of surgical procedures. A big challenge for training a neural network for surgical phase recognition is the availability of training data and the large (visual) variability in procedures of different surgeons. Hence, a network must be able to generalize to new data. In this paper, we present an adaptation of a Temporal Convolutional Network for surgical phase recognition in order to ensure the generalization of the network to new scenes with different conditions on the example of cholecystectomy. We used publicly available datasets of 104 surgeries from four different centers for training. The results showed that the network was able to generalize to new scenes and we obtained recognition results with accuracy up to 82% on our own six captured surgeries, performed in a different hospital. This performance is similar for test data from the hospitals of the training data, suggesting that the network can well generalize to new surgical rooms and surgeons. The findings have important implications for the development of automated surgical decision support systems that can be applied in a variety of real-world surgical settings.

Hyperspectral imaging is an emerging technology that has gained significant attention in the medical field due to its ability to provide precise and accurate imaging of biological tissues. The current methods of hyperspectral imaging, such as filter-wheel, snapshot, line-scanning, and push-broom cameras have limitations such as low spatial and spectral resolution, slow acquisition time. New developments on the field of light field cameras show the potential to overcome these limitations. In this paper, we use a novel hyperspectral lightfield camera and try to combine the capability of hyperspectral and 3D analysis. For this purpose we calibrate our system and test it during two ENT-surgeries to show its potential for improving surgical outcomes. The micro-lenses of the camera map 66 spectral sub-images onto the sensor allowing to reconstruct the spectral behavior of the captured scene in the spectral range of 350-1000nm. In addition, we use the sensor data to apply a 3D camera calibration pipeline to allow 3D surface reconstruction. We captured 26 calibration images and achieved calibration results in accordance to stated company data. The best calibration showed a re-projection error of 0.55 px. Further, we tested the camera during a parotidectomy and a neck-dissection. The extracted reflectance spectra of the selected venal and arterial regions correspond perfectly to the spectrum of oxygenated and deoxygenated hemoglobin. For the first time, up to our knowledge, a hyperspectral lightfield camera has been used during a surgery. We were able to continuously capture images and analyze the reconstructed spectra of specific tissue types. Further, we are able to use the sensor data of the micro-lens projections to calibrate the multilens camera system for later intraoperative measurement tasks.

Spectral imaging allows to analyze optical tissue properties that are invisible to the naked eye. Different spectral setups have been introduced in the last years to allow intraoperative image-guidance. All systems suffer from different disadvantages, such as lack of real-time capability, limited spectral coverage or low resolution. We present a novel approach using two multispectral snapshot cameras covering different spectral ranges as a stereo-system. The proposed method allows for continuous hyperspectral imaging of the surgical scene, while also enabling 3D scene reconstruction. The study demonstrates the feasibility of this approach and its potential applications in real-time monitoring and tissue identification of surgical interventions. The paper also discusses the technical challenges and future directions for improving the imaging system.

The modified Allen test (MAT) is a widely used tool to examine the perfusion capacities of the arteries (ulnar or radial) of the hand. In clinical practice, MAT is utilized to ensure that in the event of occlusion, remaining vessels guarantee sufficient hand perfusion. This work shows that perfusion assessment via imaging photoplethysmography (iPPG) can be used to assess MAT. We captured the hands of seven subjects with a standard RGB camera while performing a MAT. Out of these captured video recordings, the iPPG signal was extracted via plane-orthogonal-to-skin transformation. Based on these extracted signals, we derive the heart rate, signal-to-noise ratio, DC parameter, and correlation with a reference iPPG signal to determine if an Allen test was pathological or inconspicuous. For all seven subjects, the results of our MAT assessment were identical to the medical expert’s assessment. This paper presents a procedure and initial thresholds for objectively evaluating and quantifying MAT.We show how globally and locally calculated parameters can be used to assess the perfusion of the investigated hand. This analysis makes it possible to quantify the exact point in time when the perfusion is again sufficient. If a reperfusion problem occurs, we are able to localize the spatial regions of occurrence. The presented hardware setup is affordable and can be easily installed and used in every doctor’s office.

Abstract A bidirectional communication exists between the brain and the gut, in which the gut microbiota influences cognitive function and vice-versa. Gut dysbiosis has been linked to several diseases, including Alzheimer's disease and related dementias (ADRD). However, the relationship between gut dysbiosis and markers of cerebral small vessel disease (cSVD), a major contributor to ADRD, is unknown. In this cross-sectional study, we examined the connection between the gut microbiome, cognitive, and neuroimaging markers of cSVD in the Framingham Heart Study (FHS). Markers of cSVD included white matter hyperintensities (WMH), peak width of skeletonized mean diffusivity (PSMD), and executive function (EF), estimated as the difference between the trail-making tests B and A. We included 972 FHS participants with MRI scans, neurocognitive measures, and stool samples and quantified the gut microbiota composition using 16S rRNA sequencing. We used multivariable association and differential abundance analyses adjusting for age, sex, BMI, and education level to estimate the association between gut microbiota and WMH, PSMD, and EF measures. Our results suggest an increased abundance of Pseudobutyrivibrio and Ruminococcus genera was associated with lower WMH and PSMD (p values

This prospective, community-based, active surveillance study aimed to report the incidence of moderate, severe, and serious adverse events (AEs) after chiropractic (n = 100) / physiotherapist (n = 50) visit in offices throughout North America between October-2015 and December-2017. Three content-validated questionnaires were used to collect AE information: two completed by the patient (pre-treatment [T0] and 2-7 days post-treatment [T2]) and one completed by the provider immediately post-treatment [T1]. Any new or worsened symptom was considered an AE and further classified as mild, moderate, severe or serious. From the 42 participating providers (31 chiropractors; 11 physiotherapists), 3819 patient visits had complete T0 and T1 assessments. The patients were on average 50±18 years of age and 62.5% females. Neck/back pain was the most common presenting condition (70.0%) with 24.3% of patients reporting no condition/preventative care. From the patients visits with a complete T2 assessment (n = 2136 patient visits, 55.9%), 21.3% reported an AE, of which: 7.9% were mild, 6.2% moderate, 3.7% severe, 1.5% serious, and 2.0% had missing severity rating. The most common symptoms reported with moderate or higher severity were discomfort/pain, stiffness, difficulty walking and headache. This study provides valuable information for patients and providers regarding incidence and severity of AEs following patient visits in multiple community-based professions. These findings can be used to inform patients of what AEs may occur and future research opportunities can focus on mitigating common AEs.

[This corrects the article DOI: 10.1371/journal.pone.0293848.].

Abstract Introduction: The value of Source Data Verification (SDV) has been a common theme in the applied Clinical Translational Science literature. Yet, few published assessments of SDV quality exist even though they are needed to design risk-based and reduced monitoring schemes. This review was conducted to identify reports of SDV quality, with a specific focus on accuracy. Methods: A scoping review was conducted of the SDV and clinical trial monitoring literature to identify articles addressing SDV quality. Articles were systematically screened and summarized in terms of research design, SDV context, and reported measures. Results: The review found significant heterogeneity in underlying SDV methods, domains of SDV quality measured, the outcomes assessed, and the levels at which they were reported. This variability precluded comparison or pooling of results across the articles. No absolute measures of SDV accuracy were identified. Conclusions: A definitive and comprehensive characterization of SDV process accuracy was not found. Reducing the SDV without understanding the risk of critical findings going undetected, i.e., SDV sensitivity, is counter to recommendations in Good Clinical Practice and the principles of Quality by Design. Reference estimates (or methods to obtain estimates) of SDV accuracy are needed to confidently design risk-based, reduced SDV processes for clinical studies.

The agrochemical industry has launched several new synthetic auxin herbicides in rice to combat increasing numbers of herbicide resistant weeds to other modes of action. Excessive or inappropriate use of these herbicides has resulted in unintended consequences near the sites of application, such as herbicide drift. This study was conducted to determine the impact of drift of quinclorac and florpyrauxifen-benzyl+penoxsulam (FBP) on the yield and yield components of two sunflower cultivars. In a growth chamber experiment, quinclorac and FBP were applied to 2–4 true leaf stages at rates ranging from 2.93 to 93.75 and from 0.51 to 16.25 g ai ha−1, respectively. Nonlinear regression analyses indicated that the cultivar Bosfora was more sensitive to quinclorac and FBP than the cultivar Tunca. In field experiments, these sunflower cultivars were treated with drift rates of quinclorac (

Family medicine has existed as a training pathway through a private university in Tanzania since 2004. As global calls have increased to embrace primary health care as a pathway to ensuring universal health coverage, so has Tanzania recently turned to explore family medicine as a specialty to improve access to comprehensive, high-quality healthcare for her entire population. This article outlines ongoing efforts to define competencies and skills of a family medicine physician in Tanzania, engage government support and open the first public university training programme for family medicine postgraduate education.

Abstract A deep learning model (LCP CNN) for the stratification of indeterminate pulmonary nodules (IPNs) demonstrated better discrimination than commonly used clinical prediction models. However, the LCP CNN score is based on a single timepoint that ignores longitudinal information when prior imaging studies are available. Clinically, IPNs are often followed over time and temporal trends in nodule size or morphology inform management. In this study we investigated whether the change in LCP CNN scores over time was different between benign and malignant nodules. This study used a prospective-specimen collection, retrospective-blinded-evaluation (PRoBE) design. Subjects with incidentally or screening detected IPNs 6–30 mm in diameter with at least 3 consecutive CT scans prior to diagnosis (slice thickness ≤ 1.5 mm) with the same nodule present were included. Disease outcome was adjudicated by biopsy-proven malignancy, biopsy-proven benign disease and absence of growth on at least 2-year imaging follow-up. Lung nodules were analyzed using the Optellum LCP CNN model. Investigators performing image analysis were blinded to all clinical data. The LCP CNN score was determined for 48 benign and 32 malignant nodules. There was no significant difference in the initial LCP CNN score between benign and malignant nodules. Overall, the LCP CNN scores of benign nodules remained relatively stable over time while that of malignant nodules continued to increase over time. The difference in these two trends was statistically significant. We also developed a joint model that incorporates longitudinal LCP CNN scores to predict future probability of cancer. Malignant and benign nodules appear to have distinctive trends in LCP CNN score over time. This suggests that longitudinal modeling may improve radiomic prediction of lung cancer over current models. Additional studies are needed to validate these early findings.

Introduction The increasing prevalence of coexisting health conditions poses a challenge to healthcare providers and healthcare systems. Spinal pain (eg, neck and back pain) and spinal pathologies (eg, osteoporotic fractures and degenerative spinal disease) exist concurrently with other non-spinal health conditions (NSHC). However, the scope of what associations may exist among these co-occurring conditions is unclear. Therefore, this scoping review aims to map the epidemiological literature that reports associations between spine-related pain and pathologies (SPPs) and NSHCs.Methods and analysis This scoping review will follow the JBI protocol and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. We will systematically search the literature using key words and MeSH terms for SPPs and NSHCs. Terminology/vocabulary for NSHCs will include those for communicable and non-communicable diseases as reported by WHO Global Burden of Disease reports. Five databases will be searched from inception: MEDLINE, EMBASE, APA PsycInfo, Scopus and Web of Science Core Collection. Papers published in English, in peer-reviewed journals, including measures of association between SPPs and NSHCs and using observational epidemiologic study designs will be included. Excluded will be studies of cadaveric, animal or health behaviours; studies with no measures of association and non-observational epidemiologic studies. Results will include the number of studies, the studies that have evaluated the measures of association and the frequency of the studied associations between SPPs and NSHCs. Results will be reported in tables and diagrams. Themes of comorbidities will be synthesised into a descriptive report.Ethics and dissemination This scoping review was deemed exempt from ethics review. This review will provide a comprehensive overview of the literature that reports associations between SPPs and NSHCs to inform future research initiatives and practices. Results will be disseminated through publication in peer-reviewed journals and research conferences.Registration details https://osf.io/w49u3.

Abstract Flap loss through limited perfusion remains a major complication in reconstructive surgery. Continuous monitoring of perfusion will facilitate early detection of insufficient perfusion. Remote or imaging photoplethysmography (rPPG/iPPG) as a non-contact, non-ionizing, and non-invasive monitoring technique provides objective and reproducible information on physiological parameters. The aim of this study is to establish rPPG for intra- and postoperative monitoring of flap perfusion in patients undergoing reconstruction with free fasciocutaneous flaps (FFCF). We developed a monitoring algorithm for flap perfusion, which was evaluated in 15 patients. For 14 patients, ischemia of the FFCF in the forearm and successful reperfusion of the implanted FFCF was quantified based on the local signal. One FFCF showed no perfusion after reperfusion and devitalized in the course. Intraoperative monitoring of perfusion with rPPG provides objective and reproducible results. Therefore, rPPG is a promising technology for standard flap perfusion monitoring on low costs without the need for additional monitoring devices.

Objective Interstitial lung disease (ILD) is an important cause of mortality in some patients with rheumatoid arthritis (RA). Patient-level factors may predict which patients with RA are at the highest risk of developing ILD and are therefore candidates for screening for this complication of the underlying disease.Methods A systematic literature review was performed using PubMed, Embase and Scopus over a 10-year period up to July 2021. Publications reporting patient-level factors in patients with RA with and without ILD that were assessed before development of ILD (or were unchanged over time and therefore could be extrapolated to before development of ILD) were retrieved for assessment of evidence. Genetic variation in MUC5B and treatment with methotrexate were not included in the assessment of evidence because these factors have already been widely investigated for association with ILD.Results We found consistent associations of age, sex, smoking status and autoantibodies with development of ILD. For biomarkers such as Krebs von den Lungen 6, which have been shown to be diagnostic for ILD, there were no publications meeting criteria for this study.Conclusions This analysis provides an initial step in the identification of patient-level factors for potential development of a risk algorithm to identify patients with RA who may be candidates for screening for ILD. The findings represent a useful basis for future research leading to an improved understanding of the disease course and improved care for patients with RA at risk of development and progression of ILD.

Background Fungal lung diseases are global in distribution and require specific tests for diagnosis. We report a survey of diagnostic service provision in Africa. Methods A written questionnaire was followed by a video conference call with each respondent(s) and external validation. To disseminate the questionnaire, a snowball sample was used. Results Data were successfully collected from 50 of 51 African countries with populations >1 million. The questionnaire was completed by respondents affiliated with 72 health facilities. Of these 72 respondents, 33 (45.8%) reported data for the whole country while others reported data for a specific region/province within their country. In the public sector, chest X-ray and computed tomography are performed often in 49 countries (98%) and occasionally in 37 countries (74%), and less often in the private sector. Bronchoscopy and spirometry were done often in 28 countries (56%) and occasionally in 18 countries (36%) in the tertiary health facilities of public sector. The most conducted laboratory diagnostic assay was fungal culture (often or occasionally) in 29 countries (58%). In collaboration with the Africa Centre for Disease Control and Prevention, regional webinars and individual country profiles provided further data validation. Conclusion This survey has found a huge disparity of diagnostic test capability across the African continent. Some good examples of good diagnostic provision and very high-quality care were seen, but this was unusual. The unavailability of essential testing such as spirometry was noted, which has a high impact in the diagnosis of lung diseases. It is important for countries to implement tests based on the World Health Organization Essential Diagnostics List.

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic caused significant disruption to in-office and surgical procedures in the field of ophthalmology. The magnitude of the impact of the pandemic on surgical training among ophthalmology residents is not known. This study aims to quantify changes in average case logs among United States (U.S.) ophthalmology residency graduates prior to and during the COVID-19 pandemic. Methods Retrospective, cross-sectional analysis of aggregate, national data on case logs of U.S. ophthalmology residency graduates from 2012 to 2020. The yearly percent change in the average number of procedures performed in the Accreditation Council for Graduate Medical Education (ACGME) ophthalmology resident case logs were analyzed using linear regression on log-transformed dependent variables. The average percent change from 2019 to 2020 was compared to the average yearly percent change from 2012 to 2019 for procedures performed as the primary surgeon, and primary surgeon and surgical assistant (S + A), as well as procedures for which there are ACGME minimum graduating numbers. Results Across all procedures and roles, average case logs in 2020 were lower than the averages in 2019. While average total cases logged as primary surgeon increased yearly by 3.2% (95% CI: 2.7, 3.8%, p

Abstract The Grade of meningioma has significant implications for selecting treatment regimens ranging from observation to surgical resection with adjuvant radiation. For most patients, meningiomas are diagnosed radiologically, and Grade is not determined unless a surgical procedure is performed. The goal of this study is to train a novel auto-classification network to determine Grade I and II meningiomas using T1-contrast enhancing (T1-CE) and T2-Fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) images. Ninety-six consecutive treatment naïve patients with pre-operative T1-CE and T2-FLAIR MR images and subsequent pathologically diagnosed intracranial meningiomas were evaluated. Delineation of meningiomas was completed on both MR images. A novel asymmetric 3D convolutional neural network (CNN) architecture was constructed with two encoding paths based on T1-CE and T2-FLAIR. Each path used the same 3 × 3 × 3 kernel with different filters to weigh the spatial features of each sequence separately. Final model performance was assessed by tenfold cross-validation. Of the 96 patients, 55 (57%) were pathologically classified as Grade I and 41 (43%) as Grade II meningiomas. Optimization of our model led to a filter weighting of 18:2 between the T1-CE and T2-FLAIR MR image paths. 86 (90%) patients were classified correctly, and 10 (10%) were misclassified based on their pre-operative MRs with a model sensitivity of 0.85 and specificity of 0.93. Among the misclassified, 4 were Grade I, and 6 were Grade II. The model is robust to tumor locations and sizes. A novel asymmetric CNN with two differently weighted encoding paths was developed for successful automated meningioma grade classification. Our model outperforms CNN using a single path for single or multimodal MR-based classification.

Reservoir host associations have been observed among and within Borrelia genospecies, and host complement-mediated killing is a major determinant in these interactions. In North America, only a subset of Borrelia burgdorferi lineages cause the majority of disseminated infections in humans. We hypothesize that differential resistance to human complement-mediated killing may be a major phenotypic determinant of whether a lineage can establish systemic infection. As a corollary, we hypothesize that borreliacidal action may differ among human subjects. To test these hypotheses, we isolated primary B. burgdorferi clones from field-collected ticks and determined whether the killing effects of human serum differed among those clones in vitro and/or whether these effects were consistent among human sera. Clones associated with human invasiveness did not show higher survival in human serum compared to noninvasive clones. These results indicate that differential complement-mediated killing of B. burgdorferi lineages is not a determinant of invasiveness in humans. Only one significant difference in the survivorship of individual clones incubated in different human sera was detected, suggesting that complement-mediated killing of B. burgdorferi is usually similar among humans. Mechanisms other than differential human complement-mediated killing of B. burgdorferi lineages likely explain why only certain lineages cause the majority of disseminated human infections.

Abstract Deposits from explosive submarine eruptions have been found in the deep sea, 1–4 km below the surface, with both flow and fall deposits extending several km’s over the seafloor. A model of a turbulent fountain suggests that after rising 10–20 m above the vent, the erupting particle-laden mixture entrains and mixes with sufficient seawater that it becomes denser than seawater. The momentum of the resulting negatively buoyant fountain is only sufficient to carry the material 50–200 m above the seafloor and much of the solid material then collapses to the seafloor; this will not produce the far-reaching fall deposits observed on the seabed. However, new laboratory experiments show that particle sedimentation at the top of the fountain enables some of the hot, buoyant water in the fountain to separate from the collapsing flow and continue rising as a buoyant plume until it forms a radially spreading intrusion higher in the water column. With eruption rates of 10 $$^6$$ 6 –10 $$^7$$ 7 $$\hbox {kg s}^{-1}$$ kg s - 1 , we estimate that this warm water may rise a few 100’s m above the fountain. Some of the finer grained pyroclasts can be carried upwards by this flow and as they spread out in the radial intrusion, they gradually sediment to form a fall deposit which may extend 1000’s m from the source. Meanwhile, material collapsing from the dense fountain forms aqueous pyroclastic flows which may also spread 1000’s m from the vent forming a flow deposit on the seabed. Quantification of the controls on the concurrent fall and flow deposits, and comparison with field observations, including from the 2012 eruption of Havre Volcano in the South Pacific, open the way to new understanding of submarine eruptions.

Previous studies on the relationship between dairy consumption and hip fracture risk have reported inconsistent findings. Therefore, we aimed to conduct an algorithmically driven non-linear dose-response meta-analysis of studies assessing dairy intake and risk of developing incident hip fracture. Meta-analysis from PubMed and Google Scholar searches for articles of prospective studies of dairy intake and risk of hip fracture, supplemented by additional detailed data provided by authors. Meta-regression derived dose-response relative risks, with comprehensive algorithm-driven dose assessment across the entire dairy consumption spectrum for non-linear associations. Review of studies published in English from 1946 through December 2021. A search yielded 13 studies, with 486 950 adults and 15 320 fractures. Non-linear dose models were found to be empirically superior to a linear explanation for the effects of milk. Milk consumption was associated with incrementally higher risk of hip fractures up to an intake of 400 g/d, with a 7 % higher risk of hip fracture per 200 g/d of milk (RR 1⋅07, 95 % CI 1⋅05, 1⋅10; P < 0⋅0001), peaking with 15 % higher risk (RR 1⋅15, 95 % CI 1⋅09, 1⋅21, P < 0⋅0001) at 400 g/d versus 0 g/d. Although there is a dose-risk attenuation above 400 g/d, milk consumption nevertheless continued to exhibit elevated risk of hip fracture, compared to zero intake, up to 750 g/d. Meanwhile, the analysis of five cohort studies of yoghurt intake per 250 g/d found a linear inverse association with fracture risk (RR 0⋅85, 95 % CI 0⋅82, 0⋅89), as did the five studies of cheese intake per 43 g/d (~1 serving/day) (RR 0⋅81, 95 % CI 0⋅72, 0⋅92); these studies did not control for socioeconomic status. However, no apparent association between total dairy intake and hip fracture (RR per 250 g/d of total dairy = 0⋅97, 95 % CI 0⋅93, 1⋅004; P = 0⋅079). There were both non-linear effects and overall elevated risk of hip fracture associated with greater milk intake, while lower risks of hip fracture were reported for higher yoghurt and cheese intakes.

We present a stereo-multispectral microscope equipped with an additional illumination unit allowing further narrow-band illumination in the spectral range of 400n.m up to 800nm. The combination of the normal microscope illumination with the multispectral light unit allows different illumination modalities to be realized, which enables intraoperative spectral tissue analysis with direct visualization. Two illumination methods were tested in two cholesteatoma surgeries. In addition, two cholesteatom samples were illuminated and analyzed ex vivo. Cholesteatoma showed :fluorescent characteristics in our ex vivo analysis. This behavior could be used intraoperatively using a combination of white light and strong near-UV to blue illumination to highlight cholesteatoma tissue in the microscopic image. Thus, the visual differentiability of different tissue types can be improved and the clinical decision-making process can be accelerated.

Existing challenges in surgical education (See one, do one, teach one) as well as the Covid-19 pandemic make it necessary to develop new ways for surgical training. This is also crucial for the dissemination of new technological developments. As today’s live transmissions of surgeries to remote locations always come with high information loss, e.g. stereoscopic depth perception, and limited communication channels. This work describes the implementation of a scalable remote solution for surgical training, called TeleSTAR (Telepresence for Surgical Assistance and Training using Augmented Reality), using immersive, interactive and augmented reality elements with a bi-lateral audio pipeline to foster direct communication. The system uses a full digital surgical microscope with a modular software-based AR interface, which consists of an interactive annotation mode to mark anatomical landmarks using an integrated touch panel as well as an intraoperative image-based stereo-spectral algorithm unit to measure anatomical details and highlight tissue characteristics.We broadcasted three cochlea implant surgeries in the context of otorhinolaryngology. The intervention scaled to five different remote locations in Germany and the Netherlands with lowlatency. In total, more than 150 persons could be reached and included an evaluation of a participant’s questionnaire indicating that annotated AR-based 3D live transmissions add an extra level of surgical transparency and improve the learning outcome.

Abstract Background Genetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase the risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies. Methods We characterised the genetic architecture of the human blood lipidome in 5662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci. Results We identified 253 genetic associations with 181 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 502 genetic associations with 244 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci. Conclusions Our findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci.

Background: Collagenase Clostridium histolyticum (CCH), which was approved by the FDA for the treatment of Peyronie's disease (PD) in 2013, may obviate the need for surgery but its historically high cost must be considered when offering CCH vs surgical intervention to affected patients. Aim: To compare trends of intralesional injections vs surgical treatment for PD and assess the contemporary cost of treatment with CCH vs surgical intervention. Methods: We reviewed 2009–2019 MarketScan Commercial Claims data to identify all men 18 years and older with PD. CPT and HCPCS codes were used to identify PD treatments for each patient. Associated insurance claims in USD were summed for each treatment type. Outcomes: Total and out-of-pocket costs, as well as frequencies, for treatments were calculated on a yearly basis and the Cochran-Armitage test was used to compare frequencies before and after FDA approval of CCH. Results: Of 89,205 men diagnosed with PD, 21,605 (24.2%) underwent treatment; most required only intralesional injections, however 1,519 (7.0%) received only surgical therapy and 1,951 (9.0%) required medical and surgical therapy. Intralesional CCH use sharply increased after its FDA-approval in 2013 with a concomitant fall of intralesional verapamil use. The use of both surgical plication and plaque grafting decreased steadily from 2009 to 2019. The median cost per patient for all 3 treatments increased over the study time-period: $1,856 to $3,196 for plication, $2,233 to $3,631 for plaque grafting, and $6,940 to $8,895 per cycle for CCH. Out-of-pocket median patient contribution for plication, plaque grafting, and per cycle intralesional CCH injection were similar over the study period and never exceeded $300. Clinical Implications: CCH is significantly more expensive than any surgical treatment option, however, the out-of-pocket patient contribution for surgery and CCH are similar. Strengths & Limitations: This study incorporated all procedure costs and is the most contemporary, comprehensive, and accurate reflection of overall and out-of-pocket costs to patients for surgical and intralesional PD therapies. We anticipate these data to allow for a more complete discussion between patients and providers regarding their care. The use of a commercial claims database prohibited assessment of post-procedural costs and treatment outcomes. Conclusion: CCH use has increased significantly since its FDA approval in 2013 with out-of-pocket patient contribution comparable to surgical therapy despite significantly higher total treatment costs.Walton EL, Quinn TP, Mulloy E, et al. Cost of Intralesional Collagenase Clostridium Histiolyticum Therapy Versus Surgery for the Management of Peyronie's Disease: A Claims-Based Analysis (2009–2019). Sex Med 2022;10:100517.

Abstract Background Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive neoplasm arising from the synovium of joints, bursae, and tendon sheaths affecting small and large joints. It represents a wide spectrum ranging from minimally symptomatic to massively debilitating. Most findings to date are mainly from small, retrospective case series, and thus the morbidity and actual impact of this rare disease remain to be elucidated. This study prospectively explores the management of TGCT in tertiary sarcoma centers. Methods The TGCT Observational Platform Project registry was a multinational, multicenter, prospective observational study involving 12 tertiary sarcoma centers in 7 European countries, and 2 US sites. This study enrolled for 2 years all consecutive ≥ 18 years old patients, with histologically diagnosed primary or recurrent cases of diffuse-type TGCT. Patient demographic and clinical characteristics were collected at baseline and every 6 months for 24 months. Quality of life questionnaires (PROMIS-PF and EQ-5D) were also administered at the same time-points. Here we report baseline patient characteristics. Results 166 patients were enrolled between November 2016 and March 2019. Baseline characteristics were: mean age 44 years (mean age at disease onset: 39 years), 139/166 (83.7%) had prior treatment, 71/166 patients (42.8%) had ≥ 1 recurrence after treatment of their primary tumor, 76/136 (55.9%) visited a medical specialist ≥ 5 times, 66/116 (56.9%) missed work in the 24 months prior to baseline, and 17/166 (11.6%) changed employment status or retired prematurely due to disease burden. Prior treatment consisted of surgery (i.e., arthroscopic, open synovectomy) (128/166; 77.1%) and systemic treatments (52/166; 31.3%) with imatinib (19/52; 36.5%) or pexidartinib (27/52; 51.9%). Treatment strategies at baseline visits consisted mainly of watchful waiting (81/166; 48.8%), surgery (41/166; 24.7%), or targeted systemic therapy (37/166; 22.3%). Patients indicated for treatment reported more impairment compared to patients indicated for watchful waiting: worst stiffness NRS 5.16/3.44, worst pain NRS 6.13/5.03, PROMIS-PF 39.48/43.85, and EQ-5D VAS 66.54/71.85. Conclusion This study confirms that diffuse-type TGCT can highly impact quality of life. A prospective observational registry in rare disease is feasible and can be a tool to collect curated-population reflective data in orphan diseases. Name of registry: Tenosynovial Giant Cell Tumors (TGCT) Observational Platform Project (TOPP). Trial registration number: NCT02948088. Date of registration: 10 October 2016. URL of Trial registry record: https://clinicaltrials.gov/ct2/show/NCT02948088?term=NCT02948088&draw=2 .

Abstract Human machine interfaces that can track head motion will result in advances in physical rehabilitation, improved augmented reality/virtual reality systems, and aid in the study of human behavior. This paper presents a head position monitoring and classification system using thin flexible strain sensing threads placed on the neck of an individual. A wireless circuit module consisting of impedance readout circuitry and a Bluetooth module records and transmits strain information to a computer. A data processing algorithm for motion recognition provides near real-time quantification of head position. Incoming data is filtered, normalized and divided into data segments. A set of features is extracted from each data segment and employed as input to nine classifiers including Support Vector Machine, Naive Bayes and KNN for position prediction. A testing accuracy of around 92% was achieved for a set of nine head orientations. Results indicate that this human machine interface platform is accurate, flexible, easy to use, and cost effective.

Introduction Rheumatoid arthritis (RA) affects approximately 0.5%–1% of the general population. Clinically significant interstitial lung diseases (ILD) develops in just under 10% of people with RA, and subclinical disease is more common. Little is known about RA-ILD in New Zealand (NZ), or the number of persons with RA in Canterbury, NZ. This study aims to determine: (1) incidence and prevalence of RA, (2) incidence and prevalence of RA-ILD, (3) clinical characteristics and risk factors for the development of RA-ILD, (4) long-term outcomes of RA-ILD, in the population resident within the Canterbury District Health Board (CDHB) catchment area.Methods and analysis Persons aged 18 years of age and older, and resident in the region covered by the CDHB with RA as well as RA-ILD will be identified by retrospective review of medical records. Prevalent as well as incident cases of RA between 1 January 2006 and 31 December 2008 and between 1 January 2011 and 31 December 2013 will be identified, and followed until 30 June 2019. Existing as well as incident cases of RA-ILD during this time will be identified. The association between the development of ILD and clinical characteristics and environmental exposures will be examined using Cox-proportional hazard models. Kaplan-Meier methods will be used to estimate survival rates for patients with RA-ILD. Mortality for people with RA and RA-ILD will also be compared with the general population of the CDHB.Ethics and dissemination Data will be obtained by retrospective review of medical records. Deidentified patient data will be stored in a secure online database. Data on individual patients will not be released, and all results will only be published in aggregate. Ethical approval has been obtained from the University of Otago Human Research Ethics Committee (REF HD18/079). Results will be published in peer-reviewed medical journals and presented at conferences.Trial registration number ACTRN12619001310156; Pre-results.

We present a stereo-multispectral endoscopic prototype using a filter-wheel to guide the removal of cholesteatoma tissue in the middle ear. An image-based method is used that combines multispectral tissue classification for the detection of tissue to be removed and 3Dreconstruction to determine its metric dimensions. The multispectral illumination used for tissue classification ranges from λ = 400 nm to λ = 500 nm with step-size of 20 nm, which results in six different narrow-band illumination modes. For classical RGB imaging and metric calculations, a broadband illumination mode is applied before and after the narrow-band illumination. The spectral information is augmented into the broadband mode using an overlay technique. The combination of multispectral imaging with stereoscopic 3D-reconstruction results in new valuable visualization of intraoperative data. This allows to generate a 3D-model of the patients anatomy highlighting the identified malicious tissue and compare the anatomical dimensions with pre-operative CT data.

Cross-discipline collaboration among state and local health departments improved foodborne illness surveillance for a 2018 Salmonella enterica serovar Enteritidis outbreak in Massachusetts, USA. Prompt linking of epidemiologic and laboratory data and implementation of in-state whole-genome sequencing and analysis improved public health surveillance capacity for outbreak detection and control.

Repellents serve an important role in bite protection. Tick repellents largely rely on biomechanisms that induce responses with direct contact, but synthetic pyrethroids used as spatial repellents against insects have received recent attention for potential use in tick protection systems. An in vitro vertical climb assay was designed to assess spatial repellency against Dermacentor variabilis, Amblyomma americanum, and Ixodes scapularis adult, female ticks. Climbing behavior was assessed with and without the presence of two spatial repellents, transfluthrin and metofluthrin. Repellency parameters were defined to simulate the natural questing behavior of ambushing ticks, including measures of detachment, pseudo-questing duration, climbing deterrence, and activity. Significant effects were observed within each parameter. D. variabilis showed the greatest general susceptibility to each repellent, followed by A. americanum, and I. scapularis. The most important and integrative measure of repellency was climbing deterrence-a measure of the spatial repellent's ability to disrupt a tick's natural propensity to climb. Transfluthrin deterred 75% of D. variabilis, 67% of A. americanum, and 50% of I. scapularis. Metofluthrin was slightly more effective, deterring 81% of D. variabilis, 73% of A. americanum, and 72% of I. scapularis. The present study poses a novel paradigm for repellency and reports a preliminary assessment of spatial repellent effect on tick behavior. Further research will assess spatial repellency in a more natural setting, scale exposure conditions, and incorporate host cues.

Mangrove forests are the most important ecosystems on Pohnpei Island, Federated States of Micronesia, as the island communities of the central Pacific rely on the forests for many essential services including protection from sea-level rise that is occurring at a greater pace than the global average. As part of a multi-component assessment to evaluate vulnerabilities of mangrove forests on Pohnpei, mangrove forests were mapped at two points in time: 1983 and 2018. In 2018, the island had 6,426 ha of mangrove forest. Change analysis indicated a slight (0.76%) increase of mangrove area between 1983 and 2018, contrasting with global mangrove area declines. Forest structure and aboveground carbon (AGC) stocks were inventoried using a systematic sampling of field survey plots and extrapolated to the island using k-nearest neighbor and random forest species models. A gridded or wall to wall approach is suggested when possible for defining carbon stocks of a large area due to high variability seen in our data. The k-nearest neighbor model performed better than random forest models to map species dominance in these forests. Mean AGC was 167 ± 11 MgC ha-1, which is greater than the global average of mangroves (115 ± 7 MgC ha-1) but within their global range (37-255 MgC ha-1) Kauffman et al. (2020). In 2018, Pohnpei mangroves contained over 1.07 million MgC in AGC pools. By assigning the mean AGC stock per species per area to the map, carbon stock distributions were visualized spatially, allowing future conservation efforts to be directed to carbon dense stands.

Background 18F-fluorodeoxyglucose (FDG) PET/CT is recommended for evaluation of intermediate-risk indeterminate pulmonary nodules (IPNs). While highly sensitive, the specificity of FDG remains suboptimal for differentiating malignant from benign nodules, particularly in areas where fungal lung diseases are prevalent. Thus, a cancer-specific imaging probe is greatly needed. In this study, we tested the hypothesis that a PET radiotracer (S)-4-(3-[18F]-fluoropropyl)-L-glutamic acid (FSPG) improves the diagnostic accuracy of IPNs compared to 18F-FDG PET/CT. Methods This study was conducted at a major academic medical center and an affiliated VA medical center. Twenty-six patients with newly discovered IPNs 7-30mm diameter or newly diagnosed lung cancer completed serial PET/CT scans utilizing 18F-FDG and 18F-FSPG, without intervening treatment of the lesion. The scans were independently reviewed by two dual-trained diagnostic radiology and nuclear medicine physicians. Characteristics evaluated included quantitative SUVmax values of the pulmonary nodules and metastases. Results A total of 17 out of 26 patients had cancer and 9 had benign lesions. 18F-FSPG was negative in 6 of 9 benign lesions compared to 7 of 9 with 18F-FDG. 18F-FSPG and 18F-FDG were positive in 14 of 17 and 12 of 17 malignant lesions, respectively. 18F-FSPG detected brain and intracardiac metastases missed by 18F-FDG PET in one case, while 18F-FDG detected a metastasis to the kidney missed by 18F-FSPG. Conclusion In this pilot study, there was no significant difference in overall diagnostic accuracy between 18F-FSPG and 18F-FDG for the evaluation of IPNs and staging of lung cancer. Additional studies will be needed to determine the clinical utility of this tracer in the management of IPNs and lung cancer.