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IntroductionPatient and Public Involvement (PPI) can have a positive impact on research. PPI can make research more meaningful and appropriate as well as preventing research waste. For decades, patient advocates with HIV have played a key part in public health and research. This article presents the PPI activity undertaken during a doctoral study. The aim of this article is to demonstrate how PPI was embedded into a doctoral study that explored the feasibility of HIV testing in dental settings.MethodsPatients and the public were invited to be involved with the feasibility study through various organisations and charities. A comprehensive PPI activity strategy was devised, and appropriate funding was obtained. Patients and the public were predominantly consulted or collaboratively involved with several aspects of the study.FindingsPatients and the public positively contributed to the intervention development and the resources supporting its implementation. As a result, the study resources (i.e., questionnaire and information leaflets) were easier to read, and the intervention was more appropriate to the needs of patients. Furthermore, the training and focus groups conducted with dental patients and people with HIV benefitted from input of people with lived experience.ConclusionsPPI can be embedded within doctoral studies provided there is sufficient funding, flexibility, and supervisory support. However, PPI activity may be impacted by limited resource and a priori research protocol and funding agreements.

Abstract Objective Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder that predominantly affects children and young people. The pathophysiology and molecular mechanisms of CNO remain poorly understood, and diagnostic criteria and biomarkers are lacking. As a result, treatment is empiric and follows personal experience, case series and expert consensus plans. Methods A survey was designed to gain insight on clinician and patient experiences of diagnosing and treating CNO and to collate opinions on research priorities. A version containing 24 questions was circulated among international expert clinicians and clinical academics (27 contacted, 21 responses). An equivalent questionnaire containing 20 questions was shared to explore the experience and priorities of CNO patients and family members (93 responses). Results Responses were used to select topics for four moderated roundtable discussions at the “International Conference on CNO and autoinflammatory bone disease” (Liverpool, United Kingdom, May 25-26th, 2022). The group identified deciphering the pathophysiology of CNO to be the highest priority, followed by clinical trials, necessary outcome measures and classification criteria. Surprisingly, mental wellbeing scored behind these items. Conclusions Agreement exists among clinicians, academics, patients and families that deciphering the pathophysiology of CNO is of highest priority to inform clinical trials that will allow for the approval of medications for the treatment of CNO by regulatory agencies.

There is now a consensus that global temperatures are rising and that the world is in a climate emergency. Science has proven unequivocally that there is a relationship between anthropogenic carbon emissions and global warming. Reducing anthropogenic carbon emissions to net zero by 2050 is now one of the highest priorities for many governments around the world. Network Rail (NR), as the GB mainline railway infrastructure manager, have a need to align themselves with the legal requirement to meet net zero by 2050. At present the quantities of carbon in railway geotechnical assets, in particular embankments and cuttings, are not well understood or recorded as separate entities. The research described in this paper aims to fill this gap through the accurate measurement of carbon emissions associated with railway embankments and cuttings in a business as usual (BAU) scenario. This data can then be interrogated to identify potential areas of savings. Carbon sequestration measures such as afforestation and enhanced weathering may also be deployed as part of this effort to balance the carbon in a project to net zero. This paper outlines a proposed framework to measure the lifetime carbon associated with earthworks assets and identify areas of carbon intensity (‘hot spots’). It then discusses potential solutions to reduce carbon and thus assist NR in meeting its science-based targets via a move from a linear to a resource cycle analysis, taking into account circularity principles.

Abstract Background A treat-to-target (T2T) approach, where treatment is escalated until a specific target is achieved, and re-escalated if the target is lost, has been proposed as a strategy to improve Childhood Systemic Lupus Erythematosus (cSLE) outcomes. Previous studies involving children and young people (CYP) have identified that the concept of T2T can be difficult to understand by CYP and their families. We aimed to explore the views of CYP participating in existing public and patient involvement (PPI) groups in relation to a proposed animation that is being developed to explain the concept of T2T to CYP who will be eligible for a future cSLE T2T trial. Methods An illustrated animation storyboard was developed on PowerPoint, to be used alongside a contemporaneous voiceover to simulate the animation for CYP participating in three existing CYP PPI groups (GenerationR, Lupus UK, and YOUR RHEUM). Mixed methods were used to generate CYP feedback on the resource, including on-line surveys and qualitative topic-guided discussion, noting CYP suggestions for improvement. Changes were made iteratively to the resources. Pre/post workshop questionnaires to assess the impact of the resource on their understanding of T2T were completed anonymously. Results 40 CYP were consulted; 16/40 (40%) from GenerationR (median age 15-years [IQR 12–15]), 12/40 (30%) from Lupus UK (median age 27-years [IQR 22–30]), and 12/40 (30%) from YOUR RHEUM (median age 17-years [IQR 16–21]). 62% of respondents had an underlying rheumatic condition. Pre-workshop median participant understanding of T2T was 2/10 [IQR 1–4], on a 1–10 scale (1 = “no understanding at all”, 10 = “completely confident in my understanding”). After viewing the resource, participant understanding improved to a median of 9/10 [IQR 8–10], p

Background: The Rotator Cuff Quality of Life (RC-QOL) index was developed to evaluate quality of life in patients with rotator cuff disease. This study provides additional psychometric testing in accordance with the Consensus-Based Standards for the Selection of Health Measurement Instruments guidelines. Methods: This was a 2-year follow-up study on 66 patients (mean age, 59 ± 10 years) originally presenting with chronic full-thickness rotator cuff tears to a tertiary care center. The methodology involved testing internal consistency, content validity, and criterion validity. Responsiveness was evaluated using 3 strategies: 1) standardized response mean of the raw change scores; 2) Guyatt’s Responsiveness Index; and 3) Global Rating Scales of improvement correlated to a quality of life measure. Results: Content validity was confirmed with a Cronbach α of 0.92 (95% confidence interval, 0.92-0.95) and absence of floor and ceiling effects. Criterion validity was confirmed using the Western Ontario Rotator Cuff Index as a reference standard (r = 0.87, P

IntroductionSorghum is a resilient and widely cultivated grain crop used for feed and food. However, it’s grain is deficient in lysine, an essential amino acid. This is due to the primary seed storage proteins, the alpha-kafirins, lacking lysine. It has been observed that reductions in alpha-kafirin protein results in rebalancing of the seed proteome and a corresponding increase in non-kafirin proteins which leads to an increased lysine content. However, the mechanisms underlying proteome rebalancing are unclear. This study characterizes a previously developed gene edited sorghum line, with deletions at the alpha kafirin locus.MethodsA single consensus guide RNA leads to tandem deletion of multiple members of the gene family in addition to the small target site mutations in remaining genes. RNA-seq and ATAC-seq were utilized to identify changes in gene expression and chromatin accessibility in developing kernels in the absence of most alpha-kafirin expression. ResultsSeveral differentially accessible chromatin regions and differentially expressed genes were identified. Additionally, several genes upregulated in the edited sorghum line were common with their syntenic orthologues differentially expressed in maize prolamin mutants. ATAC-seq showed enrichment of the binding motif for ZmOPAQUE 11, perhaps indicating the transcription factor’s involvement in the kernel response to reduced prolamins.DiscussionOverall, this study provides a resource of genes and chromosomal regions which may be involved in sorghum’s response to reduced seed storage proteins and the process of proteome rebalancing.

Tujuan dari penelitian ini adalah untuk mengantisipasi terjadinya kebakaran yang sangat besar dengan memantau kondisi panel listrik yang ada di kapal. Penelitian ini menggunakan kontrol listrik miniatur berukuran tinggi 35,5 cm, panjang 27cm dan lebar 9. Perancangan fire detector panel listrik berbasis mikrokontroler tipe 328 digunakan untuk memonitor keberadaan benda api dan suhu yang melebihi batas maksimal dengan menggunakan sensor suhu DHT22 dan sensor nyala api yang ada pada panel listrik di kapal. Hasil pembacaan sensor akan diproses menggunakan mikrokontroler Atmega 328 yang ditampilkan dalam aplikasi IDE, dalam bentuk data deteksi kebakaran, pembacaan suhu dan kondisi pada panel. Ketika sensor mendeteksi api dan suhu melebihi batas buzzer maksimum dan LED akan menyala untuk menginformasikan alarm dan ketika sensor sensor tidak mendeteksi objek kebakaran atau suhu melebihi batas, buzzer dan LED akan mati.

The impact of asparaginases on plasma asparagine and glutamine is well established. However, the effect of asparaginases, particularly those derived from Erwinia chrysanthemi (also called crisantaspase), on circulating levels of other amino acids is unknown. We examined comprehensive plasma amino acid panel measurements in healthy immunodeficient/immunocompetent mice as well as in preclinical mouse models of acute myeloid leukemia (AML) and pancreatic ductal adenocarcinoma (PDAC) using long-acting crisantaspase, and in an AML clinical study (NCT02283190) using short-acting crisantaspase. In addition to the expected decrease of plasma glutamine and asparagine, we observed a significant increase in plasma serine and glycine post-crisantaspase. In PDAC tumors, crisantaspase treatment significantly increased expression of serine biosynthesis enzymes. We then systematically reviewed clinical studies using asparaginase products to determine the extent of plasma amino acid reporting and found that only plasma levels of glutamine/glutamate and asparagine/aspartate were reported, without measuring other amino acid changes post-asparaginase. To the best of our knowledge, we are the first to report comprehensive plasma amino acid changes in mice and humans treated with asparaginase. As dysregulated serine metabolism has been implicated in tumor development, our findings offer insights into how leukemia/cancer cells may potentially overcome glutamine/asparagine restriction, which can be used to design future synergistic therapeutic approaches.

Objective: To assess if a surgical boot camp improves laparoscopic skill among reproduction endocrinology and infertility (REI) fellows and increases fellow desire to incorporate surgical skills into practice and to examine whether fellowship in vitro fertilization (IVF) volume correlates with surgical efficiency. Design: Prospective evaluation. Setting: Simulation Center. Patient(s): Forty REI fellows. Intervention(s): Fellows were timed before and after training in laparoscopic suturing and knot tying and while using virtual simulators. Fellows were surveyed before boot camp on prior experience with IVF and reproductive surgery, and immediately and 1 month after boot camp on their desire to incorporate surgical skills into practice. Main Outcome Measure(s): Efficiency of laparoscopic suturing and knot tying before and after boot camp; likelihood and persistence of incorporating surgical skills into practice immediately and 1 month after boot camp; and correlation between fellowship IVF volume and fellow surgical efficiency. Result(s): Fellows experienced significant improvement in laparoscopic suturing (44 sec), intracorporeal knot tying (82 sec), and extracorporeal knot tying (71 sec). Fellows reported being more likely to incorporate operative hysteroscopy (89%), operative laparoscopy (87%), and laparoscopic suturing (84%) into practice immediately following boot camp with no difference 1 month later. Fifty-four percent of fellows reported being more likely to perform robotic surgery after the boot camp, increasing to 70% 1 month later. There were weak correlations between IVF case volume and efficiency in laparoscopic suturing or hysteroscopic polypectomy (Spearman correlation coefficients, -0.14 and -0.03). Conclusion(s): An intensive surgical boot camp enhances surgical skill among REI fellows.

To date, sport-related concussion diagnosis and management is primarily based on subjective clinical tests in the absence of validated biomarkers. A major obstacle to clinical validation and application is a lack of studies exploring potential biomarkers in non-injured populations. This cross-sectional study examined the associations between saliva telomere length (TL) and multiple confounding variables in a healthy university athlete population. One hundred eighty-three (108 male and 75 female) uninjured varsity athletes were recruited to the study and provided saliva samples at either pre- or mid-season, for TL analysis. Multiple linear regression was used to determine the associations between saliva TL and history of concussion, sport contact type, time in season (pre vs. mid-season collection), age, and sex. Results showed no significant associations between TL and history of concussion, age, or sport contact type. However, TL from samples collected mid-season were longer than those collected pre-season [β = 231.4, 95% CI (61.9, 401.0), p = 0.008], and males had longer TL than females [β = 284.8, 95% CI (111.5, 458.2), p = 0.001] when adjusting for all other variables in the model. These findings population suggest that multiple variables may influence TL. Future studies should consider these confounders when evaluating saliva TL as a plausible fluid biomarker for SRC.

Laboratory Animal Professionals experience many positive and rewarding interactions when caring for and working with research animals. However, these professionals also may experience conflicting feelings and exhaustion when the work is stressful due to factors such as limited resources, making end of life decisions, dealing with conflicting priorities, and negotiating animal care priorities with colleagues. These stresses may be further complicated by each individual's self-understanding and emotional investment in the human-animal bond. The term used for this type of complex emotional conflict and exhaustion is Compassion Fatigue. Compassion Fatigue in the Laboratory Animal Science setting is a combination of physical, emotional and psychological depletion associated with working with and caring for animals and their well-being in a research environment. The University of Washington has developed a Compassion in Science Program called Dare2Care which emphasizes self-care and helps Laboratory Animal Professionals identify stress factors and work toward a personal solution to relieve stress. The first step in developing a resiliency program is to assess the current culture and needs of the organization. At an institutional level we identified that we needed increased communication concerning study endpoints, as well as identified individuals with whom affected personnel can talk about personal concerns. We also implemented community events to reflect on the positive aspects of this field of work. We improved the physical work environment, and provided outlets established for personnel to express feelings via written word or artistically. Lastly, we started working with our Center for One Health to encompass a holisitic approach to the occupational health of our animal caregivers. One health is the relationship and interplay between people, animals and the environment and we needed to include emotional well-being in our assessment of the health of our personnel. A question was added to our occupational health screening form to include additional health or workplace concerns (e.g., Compassion Fatigue) not covered by the questionnaire, and we added a component of Compassion Fatigue awareness in our training program. Here we review the importance of identifying Compassion Fatigue in the animal research setting, focus on developing a compassion resiliency culture and provide tools and coping strategies to validate and strengthen the human-animal bond with research animals and to sustain the care that is necessary for both people and research animals.

Abstract Background Measuring quality in healthcare is vital in evaluating patient outcomes and system performance. The availability of reliable and valid information about the quality of care for patients presenting with rotator cuff disorders (RCD) in Alberta, Canada is scarce. The objective of this study is to measure quality of care for patients with RCD in order to identify areas of improvement. Methods This study employs descriptive survey research design. Between March 2015 and November 2016, a convenience sample of patients presenting with chronic, full-thickness rotator cuff tears to two sport medicine centres in Calgary and Edmonton, Alberta completed two questionnaires: the Healthcare Access and Patient Satisfaction Questionnaire (HAPSQ) and the Rotator Cuff Quality-of-Life Index (RC-QOL). Data collected using both questionnaires were used to make judgments about quality of care. Quality of care was evaluated using six dimensions of quality defined by the Alberta Quality Matrix for Health: accessibility, acceptability, efficiency, effectiveness, appropriateness, and safety. Data was also used to compare current patient clinical pathways to ideal clinical pathway algorithms and used to make judgments about the appropriateness and safety of healthcare practices. Results One hundred seventy-one patients participated in the study. The longest mean waiting times for medical services in Alberta were for magnetic resonance imaging (MRI) received in the public sector (103 days) and consultation by orthopaedic surgeon (172 days). Patient satisfaction with respect to quality of care was lowest for emergency room physician and highest for orthopaedic surgeon visits. Patients were treated by a mean of 2.5 physicians (SD: 0.77, range: 2–7). The total aggregate average cost per patient was $4541.19. The mean RC-QOL score for all patients was 42 (SD: 22). Only 54 patients (64%) requiring surgery were able to consult with a surgeon within benchmark timeframes. A comparison of current to ideal clinical pathway algorithms found that 38 patients (22%) experienced indirect clinical pathways, whereby care was fragmented and patients received care from multiple and often, redundant healthcare professionals. Conclusion There is a discrepancy between current and ideal clinical pathways whereby some patients are experiencing quality of care that is inefficient, disjointed, and less than ideal.

Abstract Background Inflammation is associated with the onset and progression of osteoarthritis in multiple joints. It is well known that mechanical properties differ between different joints, however, it remains unknown if the inflammatory process is similar/distinct in patients with hip vs. knee OA. Without complete understanding of the role of any specific cytokine in the inflammatory process, understanding the ‘profile’ of inflammation in a given patient population is an essential starting point. The aim of this study was to identify serum cytokine profiles in hip Osteoarthritis (OA), and investigate the association between cytokine concentrations and clinical measurements within this patient population and compare these findings to knee OA and healthy control cohorts. Methods In total, 250 serum samples (100 knee OA, 50 hip OA and 100 control) and 37 synovial fluid samples (8 knee OA, 14 hip OA and 15 control) were analyzed using a multiplex ELISA based approach. Synovial biopsies were also obtained and examined for specific cytokines. Pain, physical function and activity within the hip OA cohort were examined using the HOOS, SF-36, HHS and UCLA outcome measures. Results The three cohorts showed distinct serum cytokine profiles. EGF, FGF2, MCP3, MIP1α, and IL8 were differentially expressed between hip and knee OA cohorts; while FGF2, GRO, IL8, MCP1, and VEGF were differentially expressed between hip OA and control cohorts. Eotaxin, GRO, MCP1, MIP1β, VEGF were differentially expressed between knee OA and control cohorts. EGF, IL8, MCP1, MIP1β were differentially expressed in synovial fluid from a sub-set of patients from each cohort. Specifically within the hip OA cohort, IL-6, MDC and IP10 were associated with pain and were also found to be present in synovial fluid and synovial membrane (except IL-6) of patients with hip OA. Conclusion OA may include different inflammatory subtypes according to affected joints and distinct inflammatory processes may drive OA in these joints. IL6, MDC and IP10 are associated with hip OA pain and these proteins may be able to provide additional information regarding pain in hip OA patients.

Abstract Background Patients presenting to the healthcare system with rotator cuff pathology do not always receive high quality care. High quality care occurs when a patient receives care that is accessible, appropriate, acceptable, effective, efficient, and safe. The aim of this study was twofold: 1) to develop a clinical pathway algorithm that sets forth a stepwise process for making decisions about the diagnosis and treatment of rotator cuff pathology presenting to primary, secondary, and tertiary healthcare settings; and 2) to establish clinical practice guidelines for the diagnosis and treatment of rotator cuff pathology to inform decision-making processes within the algorithm. Methods A three-step modified Delphi method was used to establish consensus. Fourteen experts representing athletic therapy, physiotherapy, sport medicine, and orthopaedic surgery were invited to participate as the expert panel. In round 1, 123 best practice statements were distributed to the panel. Panel members were asked to mark “agree” or “disagree” beside each statement, and provide comments. The same voting method was again used for round 2. Round 3 consisted of a final face-to-face meeting. Results In round 1, statements were grouped and reduced to 44 statements that met consensus. In round 2, five statements reached consensus. In round 3, ten statements reached consensus. Consensus was reached for 59 statements representing five domains: screening, diagnosis, physical examination, investigations, and treatment. The final face-to-face meeting was also used to develop clinical pathway algorithms (i.e., clinical care pathways) for three types of rotator cuff pathology: acute, chronic, and acute-on-chronic. Conclusion This consensus guideline will help to standardize care, provide guidance on the diagnosis and treatment of rotator cuff pathology, and assist in clinical decision-making for all healthcare professionals.

This paper considers the issues and challenges associated with ageism relating to the Baby Boomer generation in Corporate America. Stereotypes about older workers are examined along with types of discrimination facing Boomers. The TEAM approach is proposed to combat ageism in the workplace. The strategy includes using intergenerational teams, education and training, awareness, accountability, and accommodation and mentoring as key components.

Summary: Maize grain is deficient in lysine. While the opaque2 mutation increases grain lysine, o2 is a transcription factor that regulates a wide network of genes beyond zeins, which leads to pleiotropic and often negative effects. Additionally, the drastic reduction in 19 kDa and 22 kDa alpha‐zeins causes a floury kernel, unsuitable for agricultural use. Quality protein maize (QPM) overcame the undesirable kernel texture through the introgression of modifying alleles. However, QPM still lacks a functional o2 transcription factor, which has a penalty on non‐lysine amino acids due to the o2 mutation. CRISPR/cas9 gives researchers the ability to directly target genes of interest. In this paper, gene editing was used to specifically target the 19 kDa alpha zein gene family. This allows for proteome rebalancing to occur without an o2 mutation and without a total alpha‐zein knockout. The results showed that editing some, but not all, of the 19 kDa zeins resulted in up to 30% more lysine. An edited line displayed an increase of 30% over the wild type. While not quite the 55% lysine increase displayed by QPM, the line had little collateral impact on other amino acid levels compared to QPM. Additionally, the edited line containing a partially reduced 19 kDa showed an advantage in kernel texture that had a complete 19 kDa knockout. These results serve as proof of concept that editing the 19 kDa alpha‐zein family alone can enhance lysine while retaining vitreous endosperm and a functional O2 transcription factor. [ABSTRACT FROM AUTHOR]