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Competent authorities of many countries, including Belgium, impose control measures (preventing wild bird access to feeders and water facilities, indoor confinement of captive birds, or fencing off outdoor ranges with nets) on professional and non-professional keepers of birds to prevent the spread of avian influenza (AI). Flemish laying hen farmers (FAR, n = 33) and private keepers of captive birds (PRI, n = 263) were surveyed about their opinion on and compliance with AI measures legally imposed during the most recent high-risk period before this survey in 2021. Participants answered questions on a 5-point Likert scale (1 = the worst, 3 = neutral, and 5 = the best). FAR indicated better compliance with the AI measures than PRI, except for net confinement. FAR indicated that they and other poultry farmers complied better with AI measures than PRI. Additionally, PRI indicated that they better complied than other PRI keepers. FAR regarded the AI measures as more effective than PRI. To prevent the spread of AI more effectively, national authorities could focus on information campaigns explaining to private bird keepers the need for the various control measures that they impose. If these campaigns fail, local authorities may need stricter enforcement or alternative ways to increase compliance.

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Abstract The limited sensitivity of circulating tumor cell (CTC) detection in pancreatic adenocarcinoma (PDAC) stems from their extremely low concentration in the whole circulating blood, necessitating enhanced detection methodologies. This study sought to amplify assay-sensitivity by employing diagnostic leukapheresis (DLA) to screen large blood volumes. Sixty patients were subjected to DLA, with a median processed blood volume of ~ 2.8 L and approximately 5% of the resulting DLA-product analyzed using CellSearch (CS). Notably, DLA significantly increased CS-CTC detection to 44% in M0-patients and 74% in M1-patients, yielding a 60-fold increase in CS-CTC enumeration. DLA also provided sufficient CS-CTCs for genomic profiling, thereby delivering additional genomic information compared to tissue biopsy samples. DLA CS-CTCs exhibited a pronounced negative prognostic impact on overall survival (OS), evidenced by a reduction in OS from 28.6 to 8.5 months (univariate: p = 0.002; multivariable: p = 0.043). Additionally, a marked enhancement in sensitivity was achieved (by around 3-4-times) compared to peripheral blood (PB) samples, with positive predictive values for OS being preserved at around 90%. Prognostic relevance of CS-CTCs in PDAC was further validated in PB-samples from 228 PDAC patients, consolidating the established association between CTC-presence and reduced OS (8.5 vs. 19.0 months, p

Abstract Background The gut microbiome is a salient contributor to the development of obesity, and diet is the greatest modifier of the gut microbiome, which highlights the need to better understand how specific diets alter the gut microbiota to impact metabolic disease. Increased dietary fiber intake shifts the gut microbiome and improves energy and glucose homeostasis. Dietary fibers are found in various plant-based flours which vary in fiber composition. However, the comparative efficacy of specific plant-based flours to improve energy homeostasis and the mechanism by which this occurs is not well characterized. Methods In experiment 1, obese rats were fed a high fat diet (HFD) supplemented with four different plant-based flours for 12 weeks. Barley flour (BF), oat bran (OB), wheat bran (WB), and Hi-maize amylose (HMA) were incorporated into the HFD at 5% or 10% total fiber content and were compared to a HFD control. For experiment 2, lean, chow-fed rats were switched to HFD supplemented with 10% WB or BF to determine the preventative efficacy of flour supplementation. Results In experiment 1, 10% BF and 10% WB reduced body weight and adiposity gain and increased cecal butyrate. Gut microbiota analysis of WB and BF treated rats revealed increases in relative abundance of SCFA-producing bacteria. 10% WB and BF were also efficacious in preventing HFD-induced obesity; 10% WB and BF decreased body weight and adiposity, improved glucose tolerance, and reduced inflammatory markers and lipogenic enzyme expression in liver and adipose tissue. These effects were accompanied by alterations in the gut microbiota including increased relative abundance of Lactobacillus and LachnospiraceaeUCG001, along with increased portal taurodeoxycholic acid (TDCA) in 10% WB and BF rats compared to HFD rats. Conclusions Therapeutic and preventative supplementation with 10%, but not 5%, WB or BF improves metabolic homeostasis, which is possibly due to gut microbiome-induced alterations. Specifically, these effects are proposed to be due to increased concentrations of intestinal butyrate and circulating TDCA.

Background and objectivesThis study investigates geographic disparities in aneurysmal subarachnoid hemorrhage (aSAH) care for Black patients and aims to explore the association with segregation in treatment facilities. Understanding these dynamics can guide efforts to improve healthcare outcomes for marginalized populations.MethodsThis cohort study evaluated regional differences in segregation for Black patients with aSAH and the association with geographic variations in disparities from 2016 to 2020. The National Inpatient Sample (NIS) database was queried for admission data on aSAH. Black patients were compared to White patients. Segregation in treatment facilities was calculated using the dissimilarity (D) index. Using multivariable logistic regression models, the regional disparities in aSAH treatment, functional outcomes, mortality, and end-of-life care between Black and White patients and the association of geographical segregation in treatment facilities was assessed.Results142,285 Black and White patients were diagnosed with aSAH from 2016 to 2020. The Pacific division (D index = 0.55) had the greatest degree of segregation in treatment facilities, while the South Atlantic (D index = 0.39) had the lowest. Compared to lower segregation, regions with higher levels of segregation (global F test p

IntroductionOsteomyelitis (OMS) is a bone infection causing bone pain and severe complications. A balanced immune response is critical to eradicate infection without harming the host, yet pathogens manipulate immunity to establish a chronic infection. Understanding OMS-driven inflammation is essential for disease management, but comprehensive data on immune profiles and immune cell activation during OMS are lacking.MethodsUsing high-dimensional flow cytometry, we investigated the detailed innate and adaptive systemic immune cell populations in OMS and age- and sex-matched controls.ResultsOur study revealed that OMS is associated with increased levels of immune regulatory cells, namely T regulatory cells, B regulatory cells, and T follicular regulatory cells. In addition, the expression of immune activation markers HLA-DR and CD86 was decreased in OMS, while the expression of immune exhaustion markers TIM-3, PD-1, PD-L1, and VISTA was increased. Members of the T follicular helper (Tfh) cell family as well as classical and typical memory B cells were significantly increased in OMS individuals. We also found a strong correlation between memory B cells and Tfh cells.DiscussionWe conclude that OMS skews the host immune system towards the immunomodulatory arm and that the Tfh memory B cell axis is evident in OMS. Therefore, immune-directed therapies may be a promising alternative for eradication and recurrence of infection in OMS, particularly in individuals and areas where antibiotic resistance is a major concern.

Purpose: To determine the rate of reporting for sociodemographic variables in randomized controlled trials (RCTs) investigating femoral acetabular impingement (FAI) and hip arthroscopy. Methods: PubMed, Scopus, and Web of Science were queried for articles relating to FAI and hip arthroscopy. Articles included in final analysis were RCTs investigating operative management of FAI. Included RCTs were analyzed for reporting of age and sex or gender as well as the following sociodemographic variables: race, ethnicity, insurance status, income, housing status, work status, and education level in the results section or any section of the paper. Data was analyzed using χ2 and Fisher exact tests with significance defined as P < .05. Results: Forty-eight RCTs were identified from 2011 to 2023. Age was reported in 48 of 48 (100%) of included papers; sex or gender was reported in 47 of 48 (97.9%). Reporting of sociodemographic variables in any section respectively was: race (7/48, 14.6%), ethnicity (4/48, 8.33%), insurance status (0/48, 0%), income (1/48, 2.08%), housing status (0/48, 0%), work status (3/48, 6.25%), and education (2/48, 4.17%). There was no significant difference for reporting demographic variables with respect to journal or year of publication (P = .666 and P = .761, respectively). Sociodemographic variables (9/48) were reported significantly less frequently than age and sex or gender (48/48) (P < .001). Conclusions: This study found that sociodemographic variables in FAI and hip arthroscopy RCTs are reported with much lower frequency than age and sex or gender. These findings may demonstrate the need to include patient sociodemographic data in RCTs so that their results can be better generalized and applied to the appropriate patient population. Level of Evidence: Level II, systematic review of level I and II evidence.

Summary: Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with the enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45+ cells obtained from the gastric tissue of 20 subjects. We demonstrate 11 immune cell clusters with T cells being most abundant followed by myeloid cells. The proportions of cells belonging to the 11 clusters were similar between IG and controls. However, 9/11 clusters showed 578-11,429 differentially expressed genes. In IG, MM had decreased expression of tissue-protective and microglial genes and increased the expression of monocyte trafficking and stromal activating genes. Furthermore, in IG, IL12 mediated JAK-STAT signaling involved in the activation of tissue-resident macrophages and Eph-ephrin signaling involved in monocyte chemotaxis were upregulated. Patients with IG had a greater abundance of monocyte-like cells. These data further link immune dysregulation to the pathophysiology of gastroparesis.

Abstract The effect of the blade inlet angle on the pump‐as‐turbine (PAT) has not been adequately investigated. The hydraulic performance of PAT was analyzed using an available test rig. The accuracy of the numerical data was established by the comparative analysis of the experimental data. The study demonstrated that as the blade inlet angle increases, so does hydraulic performance, but only to a certain degree. The required pressure head and the shaft power increased with the increase in blade inlet angle. As compared to the volute and outlet pipe, the hydraulic power loss within the impeller accounts for a large portion of the total power loss. The impeller power loss decreases and increases at low and high flow rates, respectively, as the blade inlet angle increases. The fluid angle of attack decreases as the blade inlet angle increases at high flow, allowing the impeller power loss to drop and performance to increase. To visualize PAT internal energy loss, the distribution of the variable of pressure, velocity, and entropy dissipation theory was applied. The impeller had the highest energy loss of the PAT geometrical parameters. The shock loss, flow separation, and asymmetric volute structure are the primary causes of impeller loss. The unsteady simulation results showed that rotor–stator interaction greatly influences the gap between the volute tongue and the impeller tip. The research results provide a reference for the design of the PAT.

Background: Total ankle arthroplasty (TAA), first developed as an alternative to ankle arthrodesis, has become an increasingly popular management option for end-stage ankle arthritis. Prior studies have shown commercial insurance payers base their coverage criteria on limited and low level of evidence research. This study aims to quantify and describe the evidence insurance companies use to support TAA coverage policies. Methods: The top 11 national commercial health insurance payers for TAA were identified. A google search was performed to identify payer coverage policies. Policy documents were examined and cited references were classified by type of reference as well as reviewed for level of evidence (LOE). Specific coverage criteria for each individual payer were then extracted. Criteria were compared to assess for similarities among commercial payers. Finally, all references cited by each payer were examined to determine whether they mentioned the specific payer criteria. Results: Six of the 11 payers had accessible coverage policies. The majority of cited references were primary journal articles (145, 60.9%) and the majority of references cited (179, 75.2%) were level III or level IV evidence. We found significant homogeneity in coverage criteria among payers. In addition, cited sources inconsistently mentioned specific payer coverage criteria. Conclusion: This study demonstrates that commercial insurance payers rely on the relatively low level of currently available scientific evidence when formulating coverage policies for TAA use and adopt criteria that have not been thoroughly analyzed in the literature. More high level of evidence research is needed to help clinicians and insurance companies further refine indications for TAA so that patients who might benefit from the procedure are adequately covered. Level of Evidence: Level IV, review.

Abstract. Objectives:. To compare mortality rates between patients treated surgically for periprosthetic fractures (PPF) after total hip arthroplasty (THA), total knee arthroplasty (TKA), peri-implant (PI), and interprosthetic (IP) fractures while identifying risk factors associated with mortality following PPF. Design:. Retrospective. Setting:. Single, Level II Trauma Center. Patients/Participants:. A retrospective review was conducted of 129 consecutive patients treated surgically for fractures around a pre-existing prosthesis or implant from 2013 to 2020. Patients were separated into 4 comparison groups: THA, TKA, PI, and IP fractures. Intervention:. Revision implant or arthroplasty, open reduction and internal fixation (ORIF), intramedullary nailing (IMN), percutaneous screws, or a combination of techniques. Main Outcome Measurements:. Primary outcome measures include mortality rates of different types of PPF, PI, and IP fractures at 1-month, 3-month, 6-month, 1-year, and 2-year postoperative. We analyzed risk factors associated with mortality aimed to determine whether treatment type affects mortality. Results:. One hundred twenty-nine patients were included for final analysis. Average follow-up was similar between all groups. The overall 1-year mortality rate was 1 month (5%), 3 months (12%), 6 months (13%), 1 year (15%), and 2 years (22%). There were no differences in mortality rates between each group at 30 days, 90 days, 6 months, 1 year, and 2 years (P-value = 0.86). A Kaplan–Meier survival curve demonstrated no difference in survivorship up to 2 years. Older than 65 years, history of hypothyroidism and dementia, and discharge to a skilled nursing facility (SNF) led to increased mortality. There was no survival benefit in treating patients with PPFs with either revision, ORIF, IMN, or a combination of techniques. Conclusion:. The overall mortality rates observed were 1 month (5%), 3 months (12%), 6 months (13%), 1 year (15%), and 2 years (22%), and no differences were found between each group at all follow-up time points. Patients aged 65 and older with a history of hypothyroidism and/or dementia discharged to an SNF are at increased risk for mortality. From a mortality perspective, surgeons should not hesitate to choose the surgical treatment they feel most comfortable performing. Level of Evidence:. Level III.

ABSTRACT Pericytes are located around blood vessels, in close contact with endothelial cells. We discovered that pericytes dampen pro-inflammatory endothelial cell responses. Endothelial cells co-cultured with pericytes had markedly reduced expression of adhesion molecules (PECAM-1 and ICAM-1) and proinflammatory cytokines (CCL-2 and IL-6) in response to bacterial stimuli (Brucella ovis, Listeria monocytogenes, or Escherichia coli lipopolysaccharide). Pericyte-depleted mice intraperitoneally inoculated with either B. ovis, a stealthy pathogen that does not trigger detectable inflammation, or Listeria monocytogenes, developed peritonitis. Further, during Citrobacter rodentium infection, pericyte-depleted mice developed severe intestinal inflammation, which was not evident in control mice. The anti-inflammatory effect of pericytes required connexin 43, as either chemical inhibition or silencing of connexin 43 abrogated pericyte-mediated suppression of endothelial inflammatory responses. Our results define a mechanism by which pericytes modulate inflammation during infection, which shifts our understanding of pericyte biology: from a structural cell to a pro-active player in modulating inflammation.IMPORTANCEA previously unknown mechanism by which pericytes modulate inflammation was discovered. The absence of pericytes or blocking interaction between pericytes and endothelium through connexin 43 results in stronger inflammation, which shifts our understanding of pericyte biology, from a structural cell to a player in controlling inflammation.

Abstract Background Upper small intestinal dietary lipids activate a gut-brain axis regulating energy homeostasis. The prebiotic, oligofructose (OFS) improves body weight and adiposity during metabolic dysregulation but the exact mechanisms remain unknown. This study examines whether alterations to the small intestinal microbiota following OFS treatment improve small intestinal lipid-sensing to regulate food intake in high fat (HF)-fed rats. Results In rats fed a HF diet for 4 weeks, OFS supplementation decreased food intake and meal size within 2 days, and reduced body weight and adiposity after 6 weeks. Acute (3 day) OFS treatment restored small intestinal lipid-induced satiation during HF-feeding, and was associated with increased small intestinal CD36 expression, portal GLP-1 levels and hindbrain neuronal activation following a small intestinal lipid infusion. Transplant of the small intestinal microbiota from acute OFS treated donors into HF-fed rats also restored lipid-sensing mechanisms to lower food intake. 16S rRNA gene sequencing revealed that both long and short-term OFS altered the small intestinal microbiota, increasing Bifidobacterium relative abundance. Small intestinal administration of Bifidobacterium pseudolongum to HF-fed rats improved small intestinal lipid-sensing to decrease food intake. Conclusion OFS supplementation rapidly modulates the small intestinal gut microbiota, which mediates improvements in small intestinal lipid sensing mechanisms that control food intake to improve energy homeostasis. Video Abstract

Abstract Orofacial soft tissue wounds caused by surgery for congenital defects, trauma, or disease frequently occur leading to complications affecting patients' quality of life. Scarring and fibrosis prevent proper skin, mucosa and muscle regeneration during wound repair. This may hamper maxillofacial growth and speech development. To promote the regeneration of injured orofacial soft tissue and attenuate scarring and fibrosis, intraoral and extraoral stem cells have been studied for their properties of facilitating maintenance and repair processes. In addition, the administration of stem cell-derived extracellular vesicles (EVs) may prevent fibrosis and promote the regeneration of orofacial soft tissues. Applying stem cells and EVs to treat orofacial defects forms a challenging but promising strategy to optimize treatment. This review provides an overview of the putative pitfalls, promises and the future of stem cells and EV therapy, focused on orofacial soft tissue regeneration.

Abstract In recent years, computer vision has contributed significantly to the study of farm animal behavior. In complex environments such as commercial farms, however, the automated detection of social behavior and specific interactions between animals can be improved. The present study addresses the automated detection of agonistic interactions between caged animals in a complex environment, relying solely on computer vision. An automated pipeline including group-level temporal action segmentation, object detection, object tracking and rule-based action classification for the detection of agonistic interactions was developed and extensively validated at a level unique in the field. Comparing with observations made by human observers, our pipeline reaches 77% precision and 85% recall using a 5-min tolerance interval for the detection of agonistic interactions. Results obtained using this pipeline allow to construct time-dependent socio-matrices of a group of animals and derive metrics on the dominance hierarchy in a semi-automated manner. Group-housed breeding rabbits (does) with their litters in commercial farms are the main use-case in this work, but the idea is probably also applicable to other social farm animals.

Abstract Cities can host significant biological diversity. Yet, urbanisation leads to the loss of habitats, species, and functional groups. Understanding how multiple taxa respond to urbanisation globally is essential to promote and conserve biodiversity in cities. Using a dataset encompassing six terrestrial faunal taxa (amphibians, bats, bees, birds, carabid beetles and reptiles) across 379 cities on 6 continents, we show that urbanisation produces taxon-specific changes in trait composition, with traits related to reproductive strategy showing the strongest response. Our findings suggest that urbanisation results in four trait syndromes (mobile generalists, site specialists, central place foragers, and mobile specialists), with resources associated with reproduction and diet likely driving patterns in traits associated with mobility and body size. Functional diversity measures showed varied responses, leading to shifts in trait space likely driven by critical resource distribution and abundance, and taxon-specific trait syndromes. Maximising opportunities to support taxa with different urban trait syndromes should be pivotal in conservation and management programmes within and among cities. This will reduce the likelihood of biotic homogenisation and helps ensure that urban environments have the capacity to respond to future challenges. These actions are critical to reframe the role of cities in global biodiversity loss.

Abstract Tuberculosis (TB) is a prevalent disease causing an estimated 1.6 million deaths and 10.6 million new cases annually. Discriminating TB disease from differential diagnoses can be complex, particularly in the field. Increased levels of complement component C1q in serum have been identified as a specific and accessible biomarker for TB disease but the source of C1q in circulation has not been identified. Here, data and samples previously collected from human cohorts, a clinical trial and a non-human primate study were used to identify cells producing C1q in circulation. Cell subset frequencies were correlated with serum C1q levels and combined with single cell RNA sequencing and flow cytometry analyses. This identified monocytes as C1q producers in circulation, with a pronounced expression of C1q in classical and intermediate monocytes and variable expression in non-classical monocytes.

Study Design Retrospective cohort. Purpose To assess preoperative arm pain severity influence on postoperative patient-reported outcomes measures (PROMs) and minimal clinically important difference (MCID) achievement following single-level anterior cervical discectomy and fusion (ACDF). Overview of Literature There is evidence that preoperative symptom severity can affect postoperative outcomes. Few have evaluated this association between preoperative arm pain severity and postoperative PROMs and MCID achievement following ACDF. Methods Individuals undergoing single-level ACDF were identified. Patients were grouped by preoperative Visual Analog Scale (VAS) arm ≤8 vs. >8. PROMs collected preoperatively and postoperatively included VAS-arm/VAS-neck/Neck Disability Index (NDI)/12-item Short Form (SF-12) Physical Composite Score (PCS)/SF-12 mental composite score (MCS)/Patient-Reported Outcomes Measurement Information System physical function (PROMIS-PF). Demographics, PROMs, and MCID rates were compared between cohorts. Results A total of 128 patients were included. The VAS arm ≤8 cohort significantly improved for all PROMs excepting VAS arm at 1-year/2-years, SF-12 MCS at 12-weeks/1-year/2-years, and SF-12 PCS/PROMIS-PF at 6-weeks, only (p≤0.021, all). The VAS arm >8 cohort significantly improved for VAS neck at all timepoints, VAS arm from 6-weeks to 1-year, NDI from 6-weeks to 6-months, and SF-12 MCS/PROMIS-PF at 6-months (p≤0.038, all). Postoperatively, the VAS arm >8 cohort had higher VAS-neck (6 weeks/6 months), VAS-arm (12 weeks/6 months), NDI (6 weeks/6 months), lower SF-12 MCS (6 weeks/6 months), SF-12 PCS (6 months), and PROMIS-PF (12 weeks/6 months) (p≤0.038, all). MCID achievement rates were higher among the VAS arm >8 cohort for the VAS-arm at 6-weeks/12-weeks/1-year/overall and NDI at 2 years (p≤0.038, all). Conclusions Significance in PROM score differences between VAS arm ≤8 vs. >8 generally dissipated at the 1-year and 2-year time-point, although higher preoperative arm pain patients suffered from worse pain, disability, and mental/physical function scores. Furthermore, clinically meaningful rates of improvement were similar throughout the vast majority of timepoints for all PROMs studied.

Considering the fact that Toxoplasma is a common parasite of humans and Toxoplasma bradyzoites can reside in skeletal muscle, T. gondii-mediated immune responses may modulate the progression and pathophysiology of another musculoskeletal disorder, osteoporosis. In the current study, we investigated the association of bone health and Toxoplasma gondii infection status. A total of 138 patients living in Germany with either osteopenia or osteoporosis were included in the study, and they were categorized into two groups, T. gondii uninfected (n = 74) and infected (n = 64), based on the presence of T. gondii-specific IgG antibodies. The demographic and clinical details of the study subjects were collected from the medical records. Logistic regression analysis was performed to delineate the association of bone health parameters with the infection status. The prevalence of toxoplasmosis was 46.4% in the study participants. The infected individuals with osteopenia and osteoporosis showed higher levels of mean spine and femoral T score, Z score, and bone mineral density (BMD), indicating improved bone health compared to the uninfected group. Logistic regression analysis showed that subjects with T. gondii infection displayed increased odds of having a higher mean femur T score, femur BMD, and femur Z score even after adjusting for age, creatinine, and urea levels. However, when the duration of drug intake for osteoporosis was taken into account, the association lost statistical significance. In summary, in this study, an improvement in osteopenia and osteoporosis was observed in Toxoplasma-infected patients, which may be partly due to the longer duration of drug intake for osteoporosis in the infected patient group.

Alberta’s electricity system is in transition. From a system dominated by coal generation less than a decade ago, Alberta’s electricity is now largely supplied by natural gas generation with an increasing share of variable wind and solar energy. Falling clean technology costs, federal clean electricity regulations and a rising carbon price will further shift Alberta’s supply mix away from unabated fossil fuels into one more reliant on a mix of renewables and new technologies, such as carbon-captured natural gas, small modular nuclear reactors and hydrogen generation. In this report, we consider future market designs fit for purpose for this changing electricity mix. We assess market design options based on the criteria of reliability, affordability, investor confidence and complexity. At the heart of the matter is the question of which approach is best able to deliver reliable and low emission supply at low cost to Alberta consumers. Importantly, we consider market designs suitable for the changing nature of 21st century grids with more variability on the supply side and more flexibility on the demand side. If the grid of the past involved forecasting demand and dispatching supply, increasingly grids of the future will flip this upside down by forecasting supply and dispatching demand. Alberta’s market design needs to both reflect and enable this new reality.

Purpose: To describe the incidence and types of spin in systematic reviews of platelet-rich plasma (PRP) injections for hip osteoarthritis (OA) and to determine whether patterns in study characteristics could be identified among studies with identifiable spin. Methods: The PubMed, Scopus, and SPORTDiscus databases were queried. Inclusion criteria were systematic reviews or meta-analyses that included an assessment of intra-articular PRP injections as a stand-alone treatment for hip OA. Two authors independently assessed the presence of spin in the included studies and recorded general study characteristics. The prevalence of the 15 different categories of spin was quantified using descriptive statistics. Results: Fifteen studies met inclusion criteria for this study. All studies contained at least two types of spin (range 2-9), with a median of 2. The most common type of spin was type 14 (“Failure to report a wide confidence interval of estimates”), which was observed in 10 studies. The second most common type of spin was type 13 (“Failure to specify the direction of the effect when it favors the control intervention”), found in 6 studies. Conclusions: Spin is highly prevalent in abstracts of systematic reviews of PRP in the treatment of hip OA. Several associations were found between spin types and the study characteristics of AMSTAR 2 rating, Scopus CiteScore, journal impact factor, and PROSPERO preregistration. When present, spin in the abstracts of reviewed studies tended to favor the use of PRP in hip osteoarthritis. Clinical Relevance: It is important to understand the prevalence of spin in published abstracts, especially in areas of great impact or interest, so authors and readers can have a greater awareness of this potential form of bias.

BackgroundChronic systemic inflammation and poverty are both linked to an increased mortality risk. The goal of this study was to determine if there is a synergistic effect of the presence of inflammation and poverty on the 15-year risk of all-cause, heart disease and cancer mortality among US adults.MethodsWe analyzed the nationally representative National Health and Nutrition Examination Survey (NHANES) 1999 to 2002 with linked records to the National Death Index through the date December 31, 2019. Among adults aged 40 and older, 15-year mortality risk associated with inflammation, C-reactive protein (CRP), and poverty was assessed in Cox regressions. All-cause, heart disease and cancer mortality were the outcomes.ResultsIndividuals with elevated CRP at 1.0 mg/dL and poverty were at greater risk of 15-year adjusted, all-cause mortality (HR = 2.45; 95% CI 1.64, 3.67) than individuals with low CRP and were above poverty. For individuals with just one at risk characteristic, low inflammation/poverty (HR = 1.58; 95% CI 1.30, 1.93), inflammation/above poverty (HR = 1.59; 95% CI 1.31, 1.93) the mortality risk was essentially the same and substantially lower than the risk for adults with both. Individuals with both elevated inflammation and living in poverty experience a 15-year heart disease mortality risk elevated by 127% and 15-year cancer mortality elevated by 196%.DiscussionThis study extends the past research showing an increased mortality risk for poverty and systemic inflammation to indicate that there is a potential synergistic effect for increased mortality risk when an adult has both increased inflammation and is living in poverty.

Introduction: The contribution of associated Alzheimer disease to poststroke cognitive impairment has been suggested on clinical grounds. However, the few published studies using amyloid PET have provided a widely ranging prevalence and a questionable relationship with cognitive status.The main objective of the study was to determine the prevalence of amyloid PET positivity among poststroke patients with at least one impaired cognitive score. The secondary objectives were to determine the association between clinical, cognitive, and imaging characteristics at baseline with amyloid status. Methods: The IDEA3 cohort included 91 stroke patients (cerebral infarct: 89%; hemorrhage: 11%). They were assessed at 808 ± 589 days poststroke with a cognitive battery, MRI, and florbetapir PET. Clinical, cognitive, and imaging characteristics at baseline were compared according to amyloid status. Results: Amyloid PET was positive for 14 patients, corresponding to a prevalence of 15.4% (95%CI: 7.97-22.8). Amyloid-positive patients were older (p = 0.0001), did not differ according to the cause of stroke, except for a tendency towards a higher frequency of cerebral amyloid angiopathy in the hemorrhagic subgroup (p = 0.06). Their cognitive performance was lower on both the cognitive screening test (p = 0.023) and battery (p = 0.02), without a specific profile. Discussion: This study supports the mild prevalence of amyloid burden and shows that it contributes to poststroke cognitive impairment.

Type 2 diabetes mellitus (T2DM) patients are at increased risk of infections, such as malignant otitis externa and rhinocerebral mucormycosis, with the urinary tract being the most affected (for example, emphysematous pyelonephritis commonly caused by Escherichia coli). Hence, this study assessed the prevalence of bacteriuria and antibiogram patterns of bacteria isolates among T2DM patients visiting the Ejisu Government Hospital in the Ashanti Region, Ghana. In this cross-sectional study, 58 patients visiting the hospital for routine healthcare were conveniently recruited after obtaining informed consent. Data on sociodemographic characteristics and medical history were obtained using pretested structured questionnaires. Mid-stream urine was collected for bacteria isolation and identification using standard bacterial culture and biochemical tests. Bacteria cultures ≥ 105 CFU/mL were considered significant bacteriuria. The antibiotic sensitivity patterns of the bacteria isolates were evaluated using the Kirby-Bauer disc diffusion method. Bacteriuria was recorded among 15.5% (9/58) of the patients, mainly those with no previous history (77.8%) and no symptoms (55.6%) of urinary tract infections (UTIs). E. coli (55.6%) and Klebsiella spp. (44.6%) were primarily isolated from the T2DM patients. All the bacteria isolates (E. coli and Klebsiella spp.) demonstrated the highest resistance to co-trimoxazole and tetracycline (55.6%) and a complete susceptibility to amikacin and levofloxacin (100%). However, 60% of the E. coli isolates and 25% of the Klebsiella isolates were multidrug resistant (MDR; resistant to at least one antibiotic agent in three or more antimicrobial categories). The study shows that T2DM patients have bacteria in their urine which are resistant to most common antibiotics, even among those with no history of UTIs; hence, routine bacterial culture and antibiotic sensitivity testing among T2DM patients is recommended for better patient management to reduce the co-morbidities of UTIs.

Objective: We aimed to develop two injection testing systems to allow future work to measure the dynamic performance of injections using prefilled syringes across different fluid viscosities. Background: Subcutaneous (SC) injections, delivered into adipose tissue, are a convenient and cost-effective method of administering medications. However, administration via syringes can pose physical ergonomic challenges as the medication viscosity increases. Methods: To investigate the relationship between applied force and fluid viscosity, we constructed two testing systems: a passive system using prefilled syringes containing fluids of different viscosities and an active system that simulates different fluid viscosities by adjusting the cross-sectional area of a tube to modulate fluidic resistance. Both systems record the force exerted on the syringe plunger. Results: Results from data collection using a syringe pump with solutions of 5, 10, 15, and 20 centipoise (cP) revealed a polynomial relationship between viscosity and force, contrary to the expected linear relationship. This unexpected pattern likely resulted from complex fluid dynamics in the 27-gauge needle. Testing of both systems confirmed that fluidic resistance control through viscosity and resistance effectively captured injection profiles. User testing further supported these findings. Conclusion: The test systems provide valuable insights into the complex interplay between fluid viscosity, applied force, and syringe characteristics. Application: These findings can inform future syringe design, needle gauge selection, and help establish upper viscosity limits for SC injectable medications. The presented systems offer valuable tools for future Human Factors studies, enabling quantification of user strength during syringe injections across various groups, including those with hand impairments. Précis: Two novel testing systems mimicking variable viscosity injections through fluidic or mechanical property variation enable the quantification of user strength in Human Factors studies and inform syringe design and viscosity limits.

Purpose: To identify the quantity and types of spin present in systematic reviews and meta-analyses of ulnar collateral ligament reconstruction (UCLR) outcomes and to characterize the studies with spin to determine if any patterns exist. Methods: This study was conducted per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In August 2022, PubMed, Scopus, and SportDiscus databases were searched using the terms “ulnar collateral ligament reconstruction” AND “systematic review” OR “meta-analysis.” Each abstract was assessed for the presence of the 15 most common types of spin derived from a previously established methodology. General data that were extracted included study title, authors, publication year, journal, level of evidence, study design, funding source, reported adherence to PRISMA guidelines, preregistration of the study protocol, and methodologic quality per A Measurement Tool to Assess Systematic Reviews Version 2 (AMSTAR 2). Results: In total, 122 studies were identified during the preliminary search, of which 19 met the inclusion criteria. Each study had at least 1 form of spin. The most common type of spin identified was type 5 (“The conclusion claims the beneficial effect of the experimental treatment despite a high risk of bias in primary studies”) (7/19, 36.8%). AMSTAR type 9 (“Did the review authors use a satisfactory technique for assessing the RoB [risk of bias] in individual studies that were included in the review?”) was associated with both a lower Clarivate Impact Factor (P = .001) and a lower Scopus CiteScore (P = .015). Studies receiving external funding were associated with the failure to satisfy AMSTAR type 3 (“Did the review authors explain their selection of the study designs for inclusion in the review?”) (P = .047). Conclusions: Spin is highly prevalent in the abstracts of systematic reviews and meta-analyses that investigate the outcomes of UCLR. Clinical Relevance: Spin has been identified in peer-reviewed articles published on various topics, including many in orthopaedics. Systematic reviews and meta-analyses contain the most comprehensive evidence regarding a clinical question, so it is important to identify spin that may be included in these reports. Greater efforts are needed to ensure that the abstracts of papers accurately represent the results in the full text.

Background: Normothermic regional perfusion (NRP) has been growing as a novel procurement strategy after circulatory death (donation after circulatory death (DCD)) in the context of heart transplantation. However, the impact of NRP on lung graft viability is largely unknown. We sought to determine lung function after thoraco-abdominal NRP (TA-NRP) in a clinically relevant porcine DCD model. Methods: Donor domestic pigs underwent hypoxic cardiac arrest to simulate DCD procurement and were randomly allocated to either 1-hour resuscitation on TA-NRP (n = 4) or direct lung procurement (direct procurement and perfusion (DPP), n = 4). All lungs were placed on ex-vivo lung perfusion (EVLP) and evaluated for 3 hours to assess functional outcome parameters and suitability for transplantation. Results: After 1 hour of TA-NRP, cardiopulmonary bypass was weaned, and mean systemic PaO2/fraction of inspired oxygen was 418 ± 76 mm Hg, which was comparable to baseline (467 ± 41, p = 0.41). No significant differences were seen between the groups during EVLP, except for a higher pulmonary artery pressure in the TA-NRP group at 3 hours of EVLP (19.7 ± 1.5 vs 14.7 ± 2.1 mm Hg, p = 0.02). Perfusate inflammatory cytokines levels of IL-6 and IL-8 were higher at the first hour of EVLP in the TA-NRP group; however, these differences were not sustained as levels were similar by the last hour of EVLP. There were no differences in histology, cytokines, or metabolic profile of the TA-NRP lungs compared to DPP. Conclusions: TA-NRP porcine lungs met functional criteria to proceed to transplantation and demonstrated no significant histological, cytokine, and metabolic differences when compared to DPP porcine lungs. This study highlights the value of considering TA-NRP lungs for transplant with well-established protocols.

Background: Delirium is a neurocognitive disorder characterized by an abrupt decline in attention, awareness, and cognition after surgical/illness-induced stressors on the brain. There is now an increasing focus on how cardiovascular health interacts with neurocognitive disorders given their overlapping risk factors and links to subsequent dementia and mortality. One common indicator for cardiovascular health is the heart rate response/recovery (HRR) to exercise, but how this relates to future delirium is unknown. Methods: Electrocardiogram data were examined in 38,740 middle- to older-aged UK Biobank participants (mean age = 58.1 years, range: 40–72 years; 47.3% males) who completed a standardized submaximal exercise stress test (15-s baseline, 6-min exercise, and 1-min recovery) and required hospitalization during follow-up. An HRR index was derived as the product of the heart rate (HR) responses during exercise (peak/resting HRs) and recovery (peak/recovery HRs) and categorized into low/average/high groups as the bottom quartile/middle 2 quartiles/top quartile, respectively. Associations between 3 HRR groups and new-onset delirium were investigated using Cox proportional hazards models and a 2-year landmark analysis to minimize reverse causation. Sociodemographic factors, lifestyle factors/physical activity, cardiovascular risk, comorbidities, cognition, and maximal workload achieved were included as covariates. Results: During a median follow-up period of 11 years, 348 participants (9/1000) newly developed delirium. Compared with the high HRR group (16/1000), the risk for delirium was almost doubled in those with low HRR (hazard ratio = 1.90, 95% confidence interval (95%CI): 1.30–2.79, p = 0.001) and average HRR (hazard ratio = 1.54, 95%CI: 1.07–2.22, p = 0.020)). Low HRR was equivalent to being 6 years older, a current smoker, or ≥3 additional cardiovascular disease risks. Results were robust in sensitivity analysis, but the risk appeared larger in those with better cognition and when only postoperative delirium was considered (n = 147; hazard ratio = 2.66, 95%CI: 1.46–4.85, p = 0.001). Conclusion: HRR during submaximal exercise is associated with future risk for delirium. Given that HRR is potentially modifiable, it may prove useful for neurological risk stratification alongside traditional cardiovascular risk factors.

Abstract Background Current recommendations for physical exercise include information about the frequency, intensity, type, and duration of exercise. However, to date, there are no recommendations on what time of day one should exercise. The aim was to perform a systematic review with meta-analysis to investigate if the time of day of exercise training in intervention studies influences the degree of improvements in physical performance or health-related outcomes. Methods The databases EMBASE, PubMed, Cochrane Library, and SPORTDiscus were searched from inception to January 2023. Eligibility criteria were that the studies conducted structured endurance and/or strength training with a minimum of two exercise sessions per week for at least 2 weeks and compared exercise training between at least two different times of the day using a randomized crossover or parallel group design. Results From 14,125 screened articles, 26 articles were included in the systematic review of which seven were also included in the meta-analyses. Both the qualitative synthesis and the quantitative synthesis (i.e., meta-analysis) provide little evidence for or against the hypothesis that training at a specific time of day leads to more improvements in performance-related or health-related outcomes compared to other times. There was some evidence that there is a benefit when training and testing occur at the same time of day, mainly for performance-related outcomes. Overall, the risk of bias in most studies was high. Conclusions The current state of research provides evidence neither for nor against a specific time of the day being more beneficial, but provides evidence for larger effects when there is congruency between training and testing times. This review provides recommendations to improve the design and execution of future studies on this topic. Registration: PROSPERO (CRD42021246468).

Purpose: Breast cancer patients often engage in shared decision-making to select an individualized treatment regimen from multiple options. However, dissatisfaction with treatment outcomes can lead to decision regret. We evaluated decision regret and physical and psychological well-being among breast cancer patients who underwent adjuvant radiotherapy and explored their associations with patient, tumor, treatment, and symptom characteristics. Methods: This cross-sectional study involved retrospectively obtaining clinical data and data collected through interviews carried out as part of regular long-term medical aftercare. Decision regret regarding the radiotherapy was assessed using the Ottawa Decision Regret Scale, physical and psychological well-being were assessed using the PROMIS Global Health-10 questionnaire, and patients were asked about their treatment outcomes and symptoms. The questionnaire was administered 14 months to 4 years after completion of radiotherapy. Results: Of the 172 included breast cancer patients, only 13.9% expressed high decision regret, with most patients expressing little or no decision regret. More decision regret was associated with volumetric modulated arc therapy, chest wall irradiation, use of docetaxel as a chemotherapy agent, lymphangiosis carcinomatosa, new heart disease after radiotherapy, and lower psychological well-being. Conclusion: Although most patients reported little or no decision regret, we identified several patient, treatment, and symptom characteristics associated with more decision regret. Our findings suggest that psychological well-being influences patients’ satisfaction with therapy decisions, implying that practitioners should pay special attention to maintaining psychological well-being during shared decision-making and ensuring that psychological assessment and treatment is provided after cancer therapy to deal with long-term effects of radiotherapy.

Background: Osteoarthritis (OA) of the knee is an inflammatory joint disorder of the cartilage, joint capsule, synovium, and surrounding bone. Intraarticular inflammation induces angiogenesis leading to pain and inflammation. Research suggests a relationship between patients with osteoarthritis of the knee and venous insufficiency or contributing arteriovenous malformations (AVMs). Similar to genicular artery embolization (GAE), transvenous or transmalformation cannulation and embolization offers a minimally invasive treatment modality for patients with mild to moderate osteoarthritis. Case presentations: Here, we present the successful treatment of OA of the knee using direct puncture transmalformation cannulation and embolization in five patients. Direct puncture, a technique used to embolize peripheral AVMs, is a safe, less invasive method for the treatment of osteoarthritis with associated AVMs. Conclusions: For patients with OA-related knee pain and associated AVMs, the advancement of endovascular techniques offers alternative approaches to the treatment of mild to moderate OA. Direct puncture and transmalformation cannulation and embolization reduce the risk of intra- and post-operative complications, improve recovery time, and minimize operating time and operating costs. In review of the literature, this is one of the first published reports describing the use of direct puncture transvenous or transmalformation cannulation and embolization to treat OA-related pain.

Uterine leiomyomas are the most common benign pelvic tumors in premenopausal women, causing significant morbidity. Uterine fibroid embolization is a minimally invasive alternative to traditional open or laparoscopic surgeries for the management of symptomatic uterine leiomyoma. For large fibroids, hospitalization after treatment is often required. However, there are limited data on patients with large, complex uterine leiomyomas treated by embolization. This report of 2 cases describes 2 females with large, complex fibroids causing pain and decreased quality of life who were evaluated and treated with embolization in the outpatient setting. Each patient underwent transradial cannulation and uterine artery embolization under local anesthesia or conscious sedation and returned home without complication. For women wishing to preserve their uterus, uterine fibroid embolization is an effective nonsurgical alternative to hysterectomy and myomectomy in an outpatient setting. If standard protocols are followed, embolization by way of transradial artery catheterization is safe for the treatment of large, complex, symptomatic fibroids in the outpatient setting; however, additional studies with larger cohorts are warranted. Accessing the uterine arteries transradially reduces the risk of intra- and post-operative complications for patients, reduces their time spent in a hospital, and minimizes operating costs.

Abstract Background Applied behavioral analysis (ABA) is regarded as the gold standard treatment for autism spectrum disorder (ASD) and has the potential to improve outcomes for patients with ASD. It can be delivered at different intensities, which are classified as comprehensive or focused treatment approaches. Comprehensive ABA targets multiple developmental domains and involves 20–40 h/week of treatment. Focused ABA targets individual behaviors and typically involves 10–20 h/week of treatment. Determining the appropriate treatment intensity involves patient assessment by trained therapists, however, the final determination is highly subjective and lacks a standardized approach. In our study, we examined the ability of a machine learning (ML) prediction model to classify which treatment intensity would be most suited individually for patients with ASD who are undergoing ABA treatment. Methods Retrospective data from 359 patients diagnosed with ASD were analyzed and included in the training and testing of an ML model for predicting comprehensive or focused treatment for individuals undergoing ABA treatment. Data inputs included demographics, schooling, behavior, skills, and patient goals. A gradient-boosted tree ensemble method, XGBoost, was used to develop the prediction model, which was then compared against a standard of care comparator encompassing features specified by the Behavior Analyst Certification Board treatment guidelines. Prediction model performance was assessed via area under the receiver-operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results The prediction model achieved excellent performance for classifying patients in the comprehensive versus focused treatment groups (AUROC: 0.895; 95% CI 0.811–0.962) and outperformed the standard of care comparator (AUROC 0.767; 95% CI 0.629–0.891). The prediction model also achieved sensitivity of 0.789, specificity of 0.808, PPV of 0.6, and NPV of 0.913. Out of 71 patients whose data were employed to test the prediction model, only 14 misclassifications occurred. A majority of misclassifications (n = 10) indicated comprehensive ABA treatment for patients that had focused ABA treatment as the ground truth, therefore still providing a therapeutic benefit. The three most important features contributing to the model’s predictions were bathing ability, age, and hours per week of past ABA treatment. Conclusion This research demonstrates that the ML prediction model performs well to classify appropriate ABA treatment plan intensity using readily available patient data. This may aid with standardizing the process for determining appropriate ABA treatments, which can facilitate initiation of the most appropriate treatment intensity for patients with ASD and improve resource allocation.

Abstract Background Traction tables have long been utilized in the management of fractures by orthopaedic surgeons. The purpose of this study was to systematically review the literature to determine the complications inherent to the use of a perineal post when treating femur fractures using a traction table. Methods A systematic review was conducted using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) using PubMed, EMBASE, and Cochrane Library. The search phrase used was “fracture” AND “perineal” AND “post” AND (“femur” OR “femoral” OR “intertrochanteric” OR “subtrochanteric”). Inclusion criteria for this review were: level of evidence (LOE) of I – IV, studies reporting on patients surgically treated for femur fractures, studies reporting on patients treated on a fracture table with a perineal post, and studies that reported the presence or absence of perineal post-related complications. The rate and duration of pudendal nerve palsy were analyzed. Results Ten studies (2 prospective and 8 retrospective studies; 2 LOE III and 8 LOE IV) were included consisting of 351 patients of which 293 (83.5%) were femoral shaft fractures and 58 (16.5%) were hip fractures. Complications associated with pudendal nerve palsies were reported in 8 studies and the mean duration of symptoms ranged between 10 and 639 days. Three studies reported a total of 11 patients (3.0%) with perineal soft tissue injury including 8 patients with scrotal necrosis and 3 patients with vulvar necrosis. All patients that developed perineal skin necrosis healed through secondary intention. No permanent complications relating to pudendal neurapraxia or soft tissue injuries were reported at final follow-up timepoints. Conclusion The use of a perineal post when treating femur fractures on a fracture table poses risks for pudendal neurapraxia and perineal soft tissue injury. Post padding is mandatory and supplemental padding may also be required. Appropriate perineal skin examination prior to use is also important. Occurring at a higher rate than previously thought, appropriate post-operative examination for any genitoperineal soft tissue complications and sensory disturbances should not be ignored.

Societal demands for group housing of social farm animals such as rabbits are increasing due to animal welfare concerns. When breeding does are housed in groups, maternal protective behaviour negatively affects the reproductive performance of the does. In part-time group housing, does are housed in single-litter cages starting shortly before parturition until the first part of lactation and then group housed for the second part after their protective behaviour has diminished and the kits are more resilient. The aim of this study was to evaluate the reproductive performance of breeding does in a part-time group housing system with provision of escape enrichment and different group size (and concomitant different stocking density, as pen size remained unchanged). For each of the four consecutive reproductive cycles, 42 does with their kits switched at 22 d post-partum (pp) from single-litter to group housing for a total period of 13 d in pens of 200×102 cm by removing walls between four adjacent single-litter cages. Newly created group pens (N =12 pens per treatment) varied in group size, stocking density and enrichment: groups of either three or four does were divided over same-size pens with or without escape enrichment (2×2 factorial design). The escape enrichment was comprised of two sets of PVC pipes and two extra elevated platforms. Does were weighed and kits counted at parturition, after which kits were cross-fostered. Kits were counted and weighed again 22 and 35 d pp. Results for mean doe fertility (90.0%), number of kits (9.1 kits/litter) and kit weight (1037.3 g/kit) at weaning were comparable with professional farms using single-litter cages. No significant effects of group size and escape enrichment were found for any of the reproductive parameters. While housed in group, seven does were removed from the experiment, from which four does were severely injured. Post-grouping kit mortality was rather low (6.7%), but three kits were euthanised due to severe injuries. In conclusion, provision of escape enrichment and altered group size (and stocking density) had no profound effect on the reproductive performance of part-time group housed does.

Abstract Total body irradiation (TBI) remains an important component in many conditioning regimens before allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Because of its frequent toxicity, patient selection is crucial, making it of interest to identify factors improving engraftment. In this retrospective single center analysis, the characteristics of 48 adult such patients were studied. Mean overall survival (OS) was 22.2 months after allo‐HSCT. Interestingly, people with an interval ≥3 days between TBI completion and allo‐HSCT showed improved OS, when compared to a shorter interval (p = 0.10). Peripheral blood kinetics after successful engraftment also differed, with a longer interval resulting in a higher platelet count and lower leukocyte and neutrophil (p

Abstract Prior research has revealed a native-accent advantage, whereby nonnative-accented speech is more difficult to process than native-accented speech. Nonnative-accented speakers also experience more negative social judgments. In the current study, we asked three questions. First, does exposure to nonnative-accented speech increase speech intelligibility or decrease listening effort, thereby narrowing the native-accent advantage? Second, does lower intelligibility or higher listening effort contribute to listeners’ negative social judgments of speakers? Third and finally, does increased intelligibility or decreased listening effort with exposure to speech bring about more positive social judgments of speakers? To address these questions, normal-hearing adults listened to a block of English sentences with a native accent and a block with nonnative accent. We found that once participants were accustomed to the task, intelligibility was greater for nonnative-accented speech and increased similarly with exposure for both accents. However, listening effort decreased only for nonnative-accented speech, soon reaching the level of native-accented speech. In addition, lower intelligibility and higher listening effort was associated with lower ratings of speaker warmth, speaker competence, and willingness to interact with the speaker. Finally, competence ratings increased over time to a similar extent for both accents, with this relationship fully mediated by intelligibility and listening effort. These results offer insight into how listeners process and judge unfamiliar speakers.

Abstract Background Daily adaptive radiation therapy (ART) of patients with non-small cell lung cancer (NSCLC) lowers organs at risk exposure while maintaining the planning target volume (PTV) coverage. Thus, ART allows an isotoxic approach with increased doses to the PTV that could improve local tumor control. Herein we evaluate daily online ART strategies regarding their impact on relevant dose-volume metrics. Methods Daily cone-beam CTs (1 × n = 28, 1 × n = 29, 11 × n = 30) of 13 stage III NSCLC patients were converted into synthetic CTs (sCTs). Treatment plans (TPs) were created retrospectively on the first-fraction sCTs (sCT1) and subsequently transferred unaltered to the sCTs of the remaining fractions of each patient (sCT2−n) (IGRT scenario). Two additional TPs were generated on sCT2−n: one minimizing the lung-dose while preserving the D95%(PTV) (isoeffective scenario), the other escalating the D95%(PTV) with a constant V20Gy(lungipsilateral) (isotoxic scenario). Results Compared to the original TPs predicted dose, the median D95%(PTV) in the IGRT scenario decreased by 1.6 Gy ± 4.2 Gy while the V20Gy(lungipsilateral) increased in median by 1.1% ± 4.4%. The isoeffective scenario preserved the PTV coverage and reduced the median V20Gy(lungipsilateral) by 3.1% ± 3.6%. Furthermore, the median V5%(heart) decreased by 2.9% ± 6.4%. With an isotoxic prescription, a median dose-escalation to the gross target volume of 10.0 Gy ± 8.1 Gy without increasing the V20Gy(lungipsilateral) and V5%(heart) was feasible. Conclusions We demonstrated that even without reducing safety margins, ART can reduce lung-doses, while still reaching adequate target coverage or escalate target doses without increasing ipsilateral lung exposure. Clinical benefits by means of toxicity and local control of both strategies should be evaluated in prospective clinical trials.

Purpose: To determine the safety and outcome profile of five-fraction stereotactic radiotherapy (FSRT) for brain metastases (BM), either as a definitive or adjuvant treatment. Methods: We assessed clinical data of patients receiving five fractions of 7 Gy each (cumulative physical dose of 35 Gy) to BM or surgical cavities. The primary endpoints were toxicity and radiation necrosis (RN) rates. Secondary endpoints were 1-year cumulative local control rate (LCR) and estimated overall survival (OS). Results: A total of 36 eligible patients receiving FSRT to a total of 49 targets were identified and included. The median follow up was 9 (1.1–56.2) months. The median age was 64.5 (34–92) years, the median ECOG score was 1, and the median Diagnostic-Specific Graded Prognostic Assessment (DS-GPA) score was 2. Treatment was well tolerated and there were no grade 3 adverse events or higher. The overall RN rate was 14.3% and the median time to RN was 12.9 (1.8–23.8) months. RN occurrence was associated with immunotherapy, young age (≤45 years), and large PTV. The cumulative 1-year local control rate was 83.1% and the estimated median local progression free-survival was 18.8 months. The estimated median overall survival was 11 (1.1–56.2) months and significantly superior in those patients presenting with RN. Conclusions: FSRT with 5 × 7 Gy represents a feasible, safe, and efficient fast track approach of intensified FSRT with acceptable LC and comparable RN rates for both the adjuvant and definitive RT settings.

Abstract Purpose Helical tomotherapy (HT) is a viable method for delivering total body irradiation (TBI) when preparing patients for allogenic stem cell or bone-marrow transplantation. TBI can be planned to reduce the amount of radiation delivered to organs at risk, such as the lungs, with the aim of decreasing toxicity. However, it is important for the ribcage to receive the prescribed radiation dose in preparation for bone-marrow transplantation. In this retrospective study, we analyzed radiation dose coverage of the lungs and ribcage in patients who underwent TBI delivered by HT to achieve lung dose sparing. Methods Thirty-five patients were included in the analysis and divided into three groups based on their prescribed radiation dose (4, 8, or 12 Gy). HT was performed using a rotating gantry to reduce radiation to the lungs. Dosimetric parameters for the lungs and ribcage as well as dose-volume histograms were calculated. Results The mean lung D95 was 60.97%, 54.77%, and 37.44% of the prescribed dose for patients receiving 4 Gy, 8 Gy, and 12 Gy, respectively. Ribcage coverage was most optimal for patients receiving 4 Gy, with a D95 of 91.27% and mean homogeneity index of 1.17, whereas patients receiving 12 Gy had a mean D95 of 78.65% and homogeneity index of 1.37, which is still within the range recommended by treatment guidelines. Conclusions Using HT to achieve lung tissue sparing is a viable approach to minimizing pulmonic complications in patients undergoing TBI. As this planning adjustment does not compromise the dose and quality of coverage received by the ribcage, it is a feasible tool within conditioning regimens for allogeneic bone-marrow transplantation.

A 72-year-old man visited cardiology for exertional chest pain, lightheadedness, and fatigue. Six years prior, he was surgically treated for cutaneous malignant melanoma of the lower back. After a negative cardiac work-up, primary care diagnosed severe iron deficiency anemia. Emergent upper and lower gastrointestinal (GI) endoscopy revealed simultaneous melanoma metastases to the stomach and colon with discrete macroscopic features. Metastatic disease, including brain, lung, and bone, was discovered on imaging. Treatment included immunotherapy with nivolumab and stereotactic radiosurgery of the brain metastases, and our patient has remained in continued remission even after 2 years. Melanoma with GI tract (GIT) metastasis has a poor prognosis and rarely presents symptomatically or with synchronous gastric and colonic lesions. This case illustrates the importance of early primary care involvement to expedite work-up for multifocal GI metastases in patients with a remote melanoma history presenting with symptoms related to iron deficiency anemia (IDA).

IntroductionLong-term weakness is common in survivors of COVID-19-associated acute respiratory distress syndrome (CARDS). We longitudinally assessed the predictors of muscle weakness in patients evaluated 6 and 12 months after intensive care unit discharge with in-person visits.MethodsMuscle strength was measured by isometric maximal voluntary contraction (MVC) of the tibialis anterior muscle. Candidate predictors of muscle weakness were follow-up time, sex, age, mechanical ventilation duration, use of steroids in the intensive care unit, the compound muscle action potential of the tibialis anterior muscle (CMAP-TA-S100), a 6-min walk test, severe fatigue, depression and anxiety, post-traumatic stress disorder, cognitive assessment, and body mass index. We also compared the clinical tools currently available for the evaluation of muscle strength (handgrip strength and Medical Research Council sum score) and electrical neuromuscular function (simplified peroneal nerve test [PENT]) with more objective and robust measures of force (MVC) and electrophysiological evaluation of the neuromuscular function of the tibialis anterior muscle (CMAP-TA-S100) for their essential role in ankle control.ResultsMVC improved at 12 months compared with 6 months. CMAP-TA-S100 (P = 0.016) and the presence of severe fatigue (P = 0.036) were independent predictors of MVC. MVC was strongly associated with handgrip strength, whereas CMAP-TA-S100 was strongly associated with PENT.DiscussionElectrical neuromuscular abnormalities and severe fatigue are independently associated with reduced MVC and can be used to predict the risk of long-term muscle weakness in CARDS survivors.

Transformation of agriculture to realise sustainable site-specific management requires comprehensive scientific support based on field experiments to capture the complex agroecological process, incite new policies and integrate them into farmers’ decisions. However, current experimental approaches are limited in addressing the wide spectrum of sustainable agroecosystem and landscape characteristics and in supplying stakeholders with suitable solutions and measures. This review identifies major constraints in current field experimentation, such as a lack of consideration of multiple processes and scales and a limited ability to address interactions between them. It emphasizes the urgent need to establish a new category of landscape experimentation that empowers agricultural research on sustainable agricultural systems, aiming at elucidating interactions among various landscape structures and functions, encompassing both natural and anthropogenic features. It extensively discusses the key characteristics of landscape experiments and major opportunities to include them in the agricultural research agenda. In particular, simultaneously considering multiple factors, and thus processes at different scales and possible synergies or antagonisms among them would boost our understanding of heterogeneous agricultural landscapes. We also highlight that though various studies identified promising approaches with respect to experimental design and data analysis, further developments are still required to build a fully functional and integrated framework for landscape experimentation in agricultural settings.

Finding consensus in definitions of commonly-used terms and concepts is a key requirement to enable cooperations between interdisciplinary scientists and practitioners in inter- or transdisciplinary projects. In research on sustainable agriculture, the term ‘landscape’ is emphasised in particular, being used in studies that range from biogeochemical to socio-economic topics. However, it is normally used in a rather unspecific manner. Moreover, different disciplines assign deviating meanings to this term, which impedes interdisciplinary understanding and synthesis. To close this gap, a systematic literature review from relevant disciplines was conducted to identify a common understanding of the term “landscape”. Three general categories of landscape conceptualizations were identified. In a small subset of studies, “landscape” is defined by area size or by natural or anthropogenic borders. The majority of reviewed papers, though, define landscapes as sets of relationships between various elements. Selection of respective elements differed widely depending on research objects. Based on these findings, a new definition of landscape is proposed, which can be operationalized by interdisciplinary researchers to define a common study object and which allows for sufficient flexibility depending on specific research questions. It also avoids over-emphasis on specific spatio-temporal relations at the “landscape scale”, which may be context-dependent. Agricultural landscape research demands for study-specific definitions which should be meticulously provided in the future.

Introduction: Extracorporeal shock wave therapy is a non-invasive and effective option for treating various musculoskeletal disorders. Recent literature indicates that the parameters for extracorporeal shock wave therapy, such as the optimal intensity, treatment frequency, and localization, are yet to be determined. Studies reporting on the effects of shock wave application on primary mesenchymal stromal cells (MSCs) as well as osteoblastic cell lines in vitro are barely available and not standardized.Methods: In this study, we designed a special setup to precisely expose primary MSCs and the osteoblastic cell line MG63 to shock waves and subsequently analyzed the resulting cellular responses using standardized protocols to investigate their viability, proliferation behavior, cytokine secretion, and osteogenic differentiation potential in vitro. The shock wave transducer was coupled to a specifically designed water bath containing a 5 mL tube holder. Primary human MSCs and MG63 cells were trypsinated and centrifuged in a 5 mL tube and exposed to single and repeated shock wave application using different intensities and numbers of pulses.Results: Single treatment of MSCs using intensities 5, 10, 15, and 20 and pulse numbers 100, 250, 500, 750, and 1,000 at a constant pulse repetition frequency of 1 Hz resulted in a decreased viability and proliferation of both cell types with an increase in the intensity and number of pulses compared to controls. No significant difference in the osteogenic differentiation was observed at different time intervals in both cell types when a single shock wave application was performed. However, repeated shock wave sessions over three consecutive days of primary MSCs using low intensity levels 0.1 and 1 showed significant osteogenic differentiation 4-fold higher than that of the extracted Alizarin Red S at day 14, whereas MG63 cells showed no significant osteogenic differentiation compared to their corresponding controls. More specifically, repeated shock wave application triggered a significant downregulation of COL1A1, upregulation of RUNX2, and sustained increase of OCN in primary MSCs but not in the cell line MG63 when induced toward the osteogenic differentiation.Discussion: The effects of shock wave application on MSCs make it an effective therapy in regenerative medicine. We established a protocol to analyze a standardized shock wave application on MSCs and were able to determine conditions that enhance the osteogenic differentiation of MSCs in vitro.

Food contact materials (FCMs) and food contact articles are ubiquitous in today’s globalized food system. Chemicals migrate from FCMs into foodstuffs, so called food contact chemicals (FCCs), but current regulatory requirements do not sufficiently protect public health from hazardous FCCs because only individual substances used to make FCMs are tested and mostly only for genotoxicity while endocrine disruption and other hazard properties are disregarded. Indeed, FCMs are a known source of a wide range of hazardous chemicals, and they likely contribute to highly prevalent non-communicable diseases. FCMs can also include non-intentionally added substances (NIAS), which often are unknown and therefore not subject to risk assessment. To address these important shortcomings, we outline how the safety of FCMs may be improved by (1) testing the overall migrate, including (unknown) NIAS, of finished food contact articles, and (2) expanding toxicological testing beyond genotoxicity to multiple endpoints associated with non-communicable diseases relevant to human health. To identify mechanistic endpoints for testing, we group chronic health outcomes associated with chemical exposure into Six Clusters of Disease (SCOD) and we propose that finished food contact articles should be tested for their impacts on these SCOD. Research should focus on developing robust, relevant, and sensitive in-vitro assays based on mechanistic information linked to the SCOD, e.g., through Adverse Outcome Pathways (AOPs) or Key Characteristics of Toxicants. Implementing this vision will improve prevention of chronic diseases that are associated with hazardous chemical exposures, including from FCMs.

Background Research infrastructures are facilities or resources that have proven fundamental for supporting scientific research and innovation. However, they are also known to be very expensive in their establishment, operation and maintenance. As by far the biggest share of these costs is always borne by public funders, there is a strong interest and indeed a necessity to develop alternative business models for such infrastructures that allow them to function in a more sustainable manner that is less dependent on public financing. Methods In this article, we describe a feasibility study we have undertaken to develop a potentially sustainable business model for a vaccine research and development (R&D) infrastructure. The model we have developed integrates two different types of business models that would provide the infrastructure with two different types of revenue streams which would facilitate its establishment and would be a measure of risk reduction. For the business model we are proposing, we have undertaken an ex ante impact assessment that estimates the expected impact for a vaccine R&D infrastructure based on the proposed models along three different dimensions: health, society and economy. Results Our impact assessment demonstrates that such a vaccine R&D infrastructure could achieve a very significant socio-economic impact, and so its establishment is therefore considered worthwhile pursuing. Conclusions The business model we have developed, the impact assessment and the overall process we have followed might also be of interest to other research infrastructure initiatives in the biomedical field.