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Abstract Background Engaging users of health research, namely knowledge users, as partners in the research process may to lead to evidence that is more relevant to the users. This may optimize the uptake of evidence in healthcare practice, resulting in improved health outcomes or more efficient healthcare systems. However, barriers to involving knowledge users in the research process exist. Theories, models and frameworks may help guide the process of involving knowledge users and address barriers to engaging with knowledge users in research; however, there is little evidence identifying or describing the theories, models and frameworks of health research partnerships. Objectives Identify and describe theories, models and frameworks of health research partnerships. Report on concepts of knowledge user engagement represented in identified theories, models and frameworks. Methods We conducted a scoping review. Database (MEDLINE, Embase, CINAHL, PCORI) and ancestry and snowball searches were utilized. Included articles were written in English, published between January 2005 and June 2021, specific to health, a research partnership, and referred to a theory, model or framework. No critical appraisal was conducted. We developed a coding framework to extract details related to the publication (e.g. country, year) and theory, model or framework (e.g. intended users, theoretical underpinning, methodology, methods of development, purpose, concepts of knowledge user engagement). One reviewer conducted data extraction. Descriptive statistics and narrative synthesis were utilized to report the results. Results We identified 21 874 articles in screening. Thirty-nine models or frameworks were included in data analysis, but no theory. Two models or frameworks (5%) were underpinned by theory. Literature review was the method (n = 11, 28%) most frequently used to develop a model or framework. Guiding or managing a partnership was the most frequently reported purpose of the model/framework (n = 14, 36%). The most represented concept of knowledge user engagement was principles/values (n = 36, 92%). Conclusions The models and frameworks identified could be utilized by researchers and knowledge users to inform aspects of a health research partnership, such as guidance or implementation of a partnership. Future research evaluating the quality and applicability of the models and frameworks is necessary to help partners decide which model or framework to implement.

Summary: Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group—robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)—at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research.

In 2021 July, PKS 1510−089 exhibited a significant flux drop in the high-energy γ -ray (by a factor 10) and optical (by a factor 5) bands and remained in this low state throughout 2022. Similarly, the optical polarization in the source vanished, resulting in the optical spectrum being fully explained through the steady flux of the accretion disk and the broad-line region. Unlike the aforementioned bands, the very-high-energy γ -ray and X-ray fluxes did not exhibit a significant flux drop from year to year. This suggests that the steady-state very-high-energy γ -ray and X-ray fluxes originate from a different emission region than the vanished parts of the high-energy γ -ray and optical jet fluxes. The latter component has disappeared through either a swing of the jet away from the line of sight or a significant drop in the photon production efficiency of the jet close to the black hole. Either change could become visible in high-resolution radio images.

Violence is a major public health problem globally, with the highest rates in low- and middle-income countries (LMICs) in the Americas and southern Africa. Parenting programmes in high-income countries can diminish risk for violence, by reducing risk factors such as child aggression and harsh parenting, and increasing protective factors such as child cognitive development and school readiness. However, there is critical need to identify low-cost programmes with replicable benefits that work in real-world LMICs contexts. A three-arm, randomised, single-blind trial evaluated effects of two low-cost, group-based parenting programmes recommended for LMICs (ACT: Raising Safe Kids; DBS: dialogic book-sharing) on child aggression (primary outcome), child development, parenting, maltreatment, and stress. Participants were 369 children with medium-high levels of aggression (mean age 3.1 years at baseline) in poor households. Interventions were implemented in city health and education services in southern Brazil. Maternal reports, filmed observations, child tasks, and hair cortisol were assessed at baseline, 1-month post-intervention, and 8-month follow-up. Intention-to-treat analyses compared each of ACT and DBS with a control group. Three hundred sixty-eight (99.7%) participants completed follow-up assessments 8 months after the interventions. There was no effect of ACT (standardised mean difference, SMD 0.11, 95% CI - 0.05, 0.27) or DBS (SMD 0.05, 95% CI - 0.11, 0.21) on the primary outcome of child aggression. ACT reduced harsh parenting behaviour post-intervention (SMD - 0.23; 95% CI - 0.46, 0.01), but not at follow-up. DBS improved book-sharing practices at both time points (e.g., maternal sensitivity at follow-up SMD 0.33; 95% CI 0.08, 0.57). There were no benefits of either programme for other parenting, child development, or stress outcomes. Two parenting programmes in Brazil had small effects on parenting practices but did not reduce child aggression or several other important risk/protective factors for violence. Effective early interventions that reduce violence in real-world LMIC settings are highly desirable but may be challenging to achieve.

The core task of reading is to look at letters and identify their sounds and meaning. In English, the spelling system is "quasiregular," meaning it includes many reliable patterns (some so reliable they could be called "rules") but also many inconsistent ones (the sound of "EA" in "heat" vs. "head"). The triangle model of reading (Seidenberg & McClelland, 1989) demonstrates that novice readers gradually learn the connections between the features of words, including their letters, the ways they make sounds, and the concepts that comprise their meaning. Learners' knowledge changes gradually based on experience pronouncing printed words. Eventually, the reader will say words with variable patterns (like how to say "EA") correctly but be unable to articulate rules associated with their pronunciation--because rules are not an inherent part of the learning process. Building robust knowledge of reading words aloud sometimes happens without any help. However, novice readers will often learn more in less time if the teacher explains the structure of the language in terms of sound-spelling rules (sometimes termed "patterns" to emphasize their variability). This type of instruction, phonics, has known value in supporting reading development. However, distinguishing between the underlying learning process (which doesn't involve rules) and associated teaching practices (which often do) has implications for practitioners. Students will benefit from a balance of implicit and explicit forms of instruction, including simple strategies for reading words, teaching high-utility rules, emphasizing practice over explanation, and using letters when doing phonemic awareness activities.

The goal of this study is to clarify research needs and identify effective practices for enhancing soil health. This was done by a synopsis of soil literature that specifically tests practices designed to maintain or enhance elements of soil health. Using an expert panel of soil scientists and practitioners, we then assessed the evidence in the soil synopsis to highlight practices beneficial to soil health, practices considered detrimental, and practices that need further investigation. A partial Spearman's correlation was used to analyse the panel's responses. We found that increased certainty in scientific evidence led to practices being considered to be more effective due to them being empirically justified. This suggests that for practices to be considered effective and put into practice, a substantial body of research is needed to support the effectiveness of the practice. This is further supported by the high proportion of practices (33 %), such as changing the timing of ploughing or amending the soil with crops grown as green manures, that experts felt had unknown effectiveness, usually due to insufficiently robust evidence. Only 7 of the 27 reviewed practices were considered to be beneficial, or likely to be beneficial in enhancing soil health. These included the use of (1) integrated nutrient management (organic and inorganic amendments); (2) cover crops; (3) crop rotations; (4) intercropping between crop rows or underneath the main crop; (5) formulated chemical compounds (such as nitrification inhibitors); (6) control of traffic and traffic timing; and (7) reducing grazing intensity. Our assessment, which uses the Delphi technique, is increasingly used to improve decision-making in conservation and agricultural policy, identified practices that can be put into practice to benefit soil health. Moreover, it has enabled us to identify practices that need further research and a need for increased communication between researchers, policy-makers, and practitioners, in order to find effective means of enhancing soil health.

Abstract Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons in the central nervous system (CNS). Mutations in the metalloenzyme SOD1 are associated with inherited forms of ALS and cause a toxic gain of function thought to be mediated by dimer destabilization and misfolding. SOD1 binds two Cu and two Zn ions in its homodimeric form. We have applied native ambient mass spectrometry imaging to visualize the spatial distributions of intact metal-bound SOD1G93A complexes in SOD1G93A transgenic mouse spinal cord and brain sections and evaluated them against disease pathology. The molecular specificity of our approach reveals that metal-deficient SOD1G93A species are abundant in CNS structures correlating with ALS pathology whereas fully metalated SOD1G93A species are homogenously distributed. Monomer abundance did not correlate with pathology. We also show that the dimer-destabilizing post-translational modification, glutathionylation, has limited influence on the spatial distribution of SOD1 dimers.

Humans can be infected with anthroponotic (Ancylostoma duodenale and Necator americanus) and with zoonotic (Ancylostoma ceylanicum, A. caninum, A. braziliense, and Uncinaria stenocephala) hookworms from dogs. Anthroponotic species are usually thought not to infect dogs. We used the internal transcribed spacer–1 (ITS1) gene in a quantitative PCR to detect anthroponotic and zoonotic hookworm species in fecal samples from 54 children and 79 dogs living in an indigenous community in tropical Northwestern Ecuador. Hookworm DNA was detected in 59.3% of children and 92.4% of dogs. Among samples from children, zoonotic hookworms were detected in 24.1% (A. ceylanicum 14.8%, A. caninum 11.1%, and A. braziliense 1.9%), whilst in dog samples, anthroponotic species were detected in 19.0% (N. americanus 12.4% and A. duodenale 6.3%). Sanger sequencing was performed successfully on 60 qPCR-positive samples (16 from children and 44 from dogs), and consensus sequences were obtained with >98% homology to GenBank references for hookworm spp. Phylogenetic analysis showed a close relationship between anthroponotic and zoonotic Ancylostoma species and no heterogeneity between A. duodenale and A. caninum; in human samples, we found A. ceylanicum but not A. braziliense sequences and we were unable to identify N. americanus in the dog samples. No infections with U. stenocephala were detected. Our data provide evidence for high rates of hookworm infections in indigenous children and dogs in a marginalized rural setting in coastal Ecuador. We also found evidence for potential cross-transmission of hookworm spp. between humans and dogs that represent a potential domestic reservoir for zoonotic and anthroponotic hookworms.

A biological survey of the Prince Edward Islands took place in December 2008. The survey repeated an earlier survey of the populations of surface-nesting seabirds on both islands and of fur seals (Arctocephalus spp.) and alien plants on Prince Edward Island in December 2001. Observations on burrowing seabirds, macro-invertebrates and plant communities on Prince Edward Island and an oceanographic survey of surrounding waters were also included. The survey confirmed many of the observations made on the earlier survey and permitted an assessment of trends in the abundance and distribution of biota since 2001.

# Background Weightlifting is growing in popularity among recreational and competitive athletes. The barbell back squat (BackS) is commonly included in these training programs, while the barbell front squat (FrontS) is commonly performed as a component of other lifts such as the power clean or clean and jerk, it is less commonly practiced in isolation. # Hypothesis/Purpose The purpose of this study was to examine the effects of VPAC performance on trunk muscle and LE biomechanical responses during loaded BackS versus FrontS in healthy subjects. # Study Design Controlled Laboratory Study # Methods Healthy male subjects with the ability to perform a sub-maximal loaded barbell squat lift were recruited. Subjects completed informed consent, demographic/medical history questionnaires and an instructional video. Subjects practiced VPAC and received feedback. Surface electromyography (sEMG) electrodes and kinematic markers were applied. Muscles included were the internal oblique (IO), external oblique (EO), rectus abdominis, iliocostalis lumborum (ICL), superficial multifidi, rectus femoris, vastus lateralis, biceps femoris, and gluteus maximus. Maximal voluntary isometric contractions established reference sEMG values. A squat one-rep-max (1RM) was predicted by researchers using a three to five repetition maximum (3RM, 5RM) load protocol. Subjects performed BackS trials at 75% 1RM while FrontS trials were performed at 75% BackS weight, both with and without VPAC. Subjects performed three repetitions of each condition with feet positioned on two adjacent force plates. Significant interactions and main effects were tested using a 2(VPAC strategy) x 2(squat variation) and 2(VPAC strategy) x 2(direction) within-subject repeated measures ANOVAs. Tukey's Post-Hoc tests identified the location of significant differences. # Results Trunk muscle activity was significantly higher during FrontS versus BackS regardless of VPAC condition. (IO: p=0.018, EO: p\

Abstract Two membrane cell envelopes act as selective permeability barriers in Gram-negative bacteria, protecting cells against antibiotics and other small molecules. Significant efforts are being directed toward understanding how small molecules permeate these barriers. In this study, we developed an approach to analyze the permeation of compounds into Gram-negative bacteria and applied it to Pseudomonas aeruginosa, an important human pathogen notorious for resistance to multiple antibiotics. The approach uses mass spectrometric measurements of accumulation of a library of structurally diverse compounds in four isogenic strains of P. aeruginosa with varied permeability barriers. We further developed a machine learning algorithm that generates a deterministic classification model with minimal synonymity between the descriptors. This model predicted good permeators into P. aeruginosa with an accuracy of 89% and precision above 58%. The good permeators are broadly distributed in the property space and can be mapped to six distinct regions representing diverse chemical scaffolds. We posit that this approach can be used for more detailed mapping of the property space and for rational design of compounds with high Gram-negative permeability.

The intention of utilizing chaperones during sensitive physical exams is to show respect to the patient, while simultaneously providing protection to both the patient and the medical provider. Despite clinical practice recommendations to offer chaperones for sensitive urologic exams, there is no data regarding the consistency of chaperone utilization. Our aim was to summarize the patient and provider perspectives on the role of chaperones in urology as well as identify barriers to implement chaperone consistency. In the present investigation, we conducted a systematic review of prospective, case-control, and retrospective studies and followed the PRISMA 2020 guidelines for data reporting. Studies were identified from PubMed, MEDLINE, and PMC using the Medical Subject Headings (MeSH) terms “chaperones, patient”, “chaperones, medical”, and keywords “chaperones”, and “urology”. Studies were included if they addressed patient/provider perspectives on chaperone utilization in urology specifically and were excluded if they investigated perspectives on chaperone utilization in other specialties. Preliminary study identification yielded 702 studies, 9 of which were eligible for this review after applying the inclusion and exclusion criteria. Of these, 4 studies focused on the patient perspective and 5 focused on the provider perspective. The percentage of patients that did not have a chaperone present during their urologic exam ranged from 52.9-88.5%. A greater proportion of these patients were male. Patients (59%) prefer a family member compared to a staff member as a chaperone. Physicians (60%) prefer staff member chaperones compared to family members. One study reported that 25.6% of patients did not feel comfortable to ask for a chaperone if they were not offered one. Two studies reported the percentage of patients who believed chaperones should be offered to all urology patients, ranging from 73-88.4%. Three studies reported the use of chaperones in the clinic which ranged from 5-72.5%. Two studies reported chaperone utilization documentation, ranging between 16-21.3%. Two studies reported the likelihood of chaperone utilization depending on gender of the physician, showing that male physicians were more likely to utilize chaperones and were 3x more likely to offer chaperones to their patients compared to female physicians. Research suggests that there are differing perspectives between patients and physicians regarding the specific role and benefits chaperones offer during a sensitive urologic examination, as well as differences in preferences of who should perform the role of the chaperone. While more work needs to be done to bridge the divide between clinical practice and patient/physician preferences, the act of offering chaperones to urologic patients, regardless if they want to utilize a chaperone for their examination is respectful of patient privacy and decision making.

Sister chromatid cohesion (SCC) is an important process in chromosome segregation. ESCO2 is essential for establishment of SCC and is often deleted/altered in human cancers. We demonstrate that esco2 haploinsufficiency results in reduced SCC and accelerates the timing of tumor onset in both zebrafish and mouse p53 heterozygous null models, but not in p53 homozygous mutant or wild-type animals. These data indicate that esco2 haploinsufficiency accelerates tumor onset in a loss of heterozygosity (LOH) sensitive background. Analysis of The Cancer Genome Atlas (TCGA) confirmed ESCO2 deficient tumors have elevated number of LOH events throughout the genome. Further, we demonstrated heterozygous loss of sgo1, important in maintaining SCC, also results in reduced SCC and accelerated tumor formation in a p53 heterozygous background. Surprisingly, while we did observe elevated levels of chromosome missegregation and micronuclei formation in esco2 heterozygous mutant animals, this chromosomal instability did not contribute to the accelerated tumor onset in a p53 heterozygous background. Interestingly, SCC also plays a role in homologous recombination, and we did observe elevated levels of mitotic recombination derived p53 LOH in tumors from esco2 haploinsufficient animals; as well as elevated levels of mitotic recombination throughout the genome of human ESCO2 deficient tumors. Together these data suggest that reduced SCC contributes to accelerated tumor penetrance through elevated mitotic recombination.