A global perspective of advanced practice nursing research: A review of systematic reviews.

INTRODUCTION: The World Health Organization (WHO) called for the expansion of all nursing roles, including advanced practice nurses (APNs), nurse practitioners (NPs) and clinical nurse specialists (CNSs). A clearer understanding of the impact of these roles will inform global priorities for advanced practice nursing education, research, and policy. OBJECTIVE: To identify gaps in advanced practice nursing research globally. MATERIALS AND METHODS: A review of systematic reviews was conducted. We searched CINAHL, Embase, Global Health, Healthstar, PubMed, Medline, Cochrane Library, DARE, Joanna Briggs Institute EBP, and Web of Science from January 2011 onwards, with no restrictions on jurisdiction or language. Grey literature and hand searches of reference lists were undertaken. Review quality was assessed using the Critical Appraisal Skills Program (CASP). Study selection, data extraction and CASP assessments were done independently by two reviewers. We extracted study characteristics, country and outcome data. Data were summarized using narrative synthesis. RESULTS: We screened 5840 articles and retained 117 systematic reviews, representing 38 countries. Most CASP criteria were met. However, study selection by two reviewers was done inconsistently and language and geographical restrictions were applied. We found highly consistent evidence that APN, NP and CNS care was equal or superior to the comparator (e.g., physicians) for 29 indicator categories across a wide range of clinical settings, patient populations and acuity levels. Mixed findings were noted for quality of life, consultations, costs, emergency room visits, and health care service delivery where some studies favoured the control groups. No indicator consistently favoured the control group. There is emerging research related to Artificial Intelligence (AI). CONCLUSION: There is a large body of advanced practice nursing research globally, but several WHO regions are underrepresented. Identified research gaps include AI, interprofessional team functioning, workload, and patients and families as partners in healthcare. PROSPERO REGISTRATION NUMBER: CRD42021278532.

Psychological Status as an Effect Modifier of the Association Between Allergy Symptoms and Allergy Testing.

OBJECTIVE: Patient-reported outcome measures, while valuable, may not correlate with diagnostic test results. To better understand this potential discrepancy, our objective was to determine whether psychological health is an effect modifier of the association between patient-reported allergy outcome scores and allergy test results. STUDY DESIGN: Prospective outcomes study. SETTING: Tertiary care hospital and community-based clinic. METHODS: This study included 600 patients at least 18 years of age who presented for symptoms related to allergic rhinitis and completed the related sinonasal outcome test (SNOT), which includes validated nasal, allergy, and psychological domains. Stratified analyses of odds ratios and Spearman correlation coefficients were utilized to assess for effect modification by psychological status. RESULTS: Worse patient-reported allergic rhinitis symptoms were significantly associated with positive allergy test results (odds ratio [OR] 1.69, 95% confidence interval [CI] 1.22-2.34, P = .002) in patients with better psychological health. In contrast, there was no association in patients with worse psychological health (OR 1.06, 95% CI 0.36-3.10, P = .92). These findings were corroborated by assessments of correlation: allergy domain scores were positively correlated with allergy testing scores (Spearman rho 0.18, 95% CI 0.10-0.25, P < .001) in patients with better psychological health, while there was no correlation in patients with worse psychological health (-0.02, 95% CI -0.16-0.12, P = .77). CONCLUSIONS: Psychological status was an effect modifier of the association between allergy domain and allergy testing data. When assessing the relationship between subjective measures, such as sinonasal validated instruments, and objective measures, such as allergy test results, accounting for effect modifiers such as psychological state can provide clinical and research-related insights.

The Fight Tumour Blindness Registry: Efficient capture of high-quality real-world data in uveal melanoma.

OBJECTIVE: To describe the development of a web-based data collection tool to track the management and outcomes of uveal melanoma patients. DESIGN: Description of a clinical registry. PARTICIPANTS: Patients with uveal melanoma. METHODS: A panel of expert ocular oncologists, with input from other relevant specialties and individuals with expertise in registry development, collaborated to formulate a minimum data set to be collected to track patient centred, real-world outcomes in uveal melanoma. This data set was used to create the Fight Tumour Blindness! (FTB!) registry within Save Sight Registries. RESULTS: The data set to be collected includes patient demographics and medical history, baseline visit, follow-up visit including tumour treatment, metastatic staging and surveillance, pathology, and patient-reported questionnaires. The inbuilt mechanisms to ensure efficient and complete data collection are described. CONCLUSIONS: The FTB! registry can be used to monitor outcomes for patients with uveal melanoma. It allows benchmarking of outcomes and comparisons between different clinics and countries.

Biocompatible Electronic Skins for Cardiovascular Health Monitoring.

Cardiovascular diseases represent a significant threat to the overall well-being of the global population. Continuous monitoring of vital signs related to cardiovascular health is essential for improving daily health management. Currently, there has been remarkable proliferation of technology focused on collecting data related to cardiovascular diseases through daily electronic skin monitoring. However, concerns have arisen regarding potential skin irritation and inflammation due to the necessity for prolonged wear of wearable devices. To ensure comfortable and uninterrupted cardiovascular health monitoring, the concept of biocompatible electronic skin has gained substantial attention. In this review, biocompatible electronic skins for cardiovascular health monitoring are comprehensively summarized and discussed. The recent achievements of biocompatible electronic skin in cardiovascular health monitoring are introduced. Their working principles, fabrication processes, and performances in sensing technologies, materials, and integration systems are highlighted, and comparisons are made with other electronic skins used for cardiovascular monitoring. In addition, the significance of integrating sensing systems and the updating wireless communication for the development of the smart medical field is explored. Finally, the opportunities and challenges for wearable electronic skin are also examined.

Interprofessional teams with and without nurse practitioners and the level of adherence to best practice guidelines in cardiac surgery: A retrospective study.

AIM: To examine the level of adherence to best-practice guidelines of interprofessional teams with acute care nurse practitioners (ACNPs) compared to interprofessional teams without ACNPs. DESIGN: A retrospective observational study was conducted in 2023. METHOD: A retrospective cohort was created including 280 patients who underwent a coronary artery bypass graft and/or a valve repair and hospitalised in a cardiac surgery unit of a university affiliated hospital in Québec (Canada) between 1 January 2019 to 31 January 2020. The level of adherence to best-practice guidelines was measured from a composite score in percentage. The composite score was created from a newly developed tool including 99 items across six categories (patient information, pharmacotherapy, laboratory tests, post-operative assessment, patient and interprofessional teams' characteristics). Multivariate linear and logistic regression models were computed to examine the effect of interprofessional teams with ACNPs on the level of adherence to best-practice guidelines. RESULTS: Most of the patients of the cohort were male and underwent a coronary artery bypass graft procedure. Patients under the care of interprofessional teams with ACNP were 1.72 times more likely to reach a level of adherence higher than 80% compared to interprofessional teams without ACNPs and were 2.29 times more likely to be within the highest quartile of the scores for the level of adherence to best-practice guidelines of the cohort. IMPACT: This study provides empirical data supporting the benefits of ACNP practice for patients, interprofessional teams and healthcare organisations. RELEVANCE FOR PRACTICE: Our findings identify the important contributions of interprofessional teams that include ACNPs using a validated instrument, as well as their contribution to the delivery of high quality patient care. REPORTING METHOD: This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Validation of a Novel Allergy-Specific Domain for the 22-Item Sino-Nasal Outcomes Test.

OBJECTIVES: To develop and assess the validity of a novel allergy-specific domain for the 22-item sino-nasal outcomes test (SNOT-22), to provide a new tool that efficiently quantifies the impact of allergic rhinitis (AR) concurrent with chronic rhinosinusitis. STUDY DESIGN: Prospective validation study. SETTING: Tertiary care hospital and community-based clinic. METHODS: Proposed items were developed based on clinician and patient input, and further assessed via factor analysis and for internal consistency (n = 1987). Items were then additionally assessed for convergent and discriminant validity (n = 415), applying data from concurrent completions of the Nasal Obstruction and Septoplasty Effectiveness Scale (NOSE), Mini-Rhinoconjunctivitis Quality-of-Life Questionnaire (MiniRQLQ), and validated global health assessments. Assessments of intra-rater reliability, responsiveness to change, and qualitative input were also performed. RESULTS: Factor analysis demonstrated that proposed allergy items mapped to a single domain. Items were internally consistent (Cronbach α: 0.80 within domain, 0.91 within all SNOT). In assessments of convergent validity, domain scores were associated with MiniRQLQ (Spearman's ρ: 0.46, 95% confidence interval [CI]: 0.30-0.59) and NOSE scores (0.36, 95% CI: 0.27-0.44). The novel items also discriminated among clinical states: a 1-point increase in domain score was associated with an 8.32 (95% CI: 5.43-12.75) increase in the odds of prompting a visit for allergy-related symptoms and a 1.52 (95% CI: 1.13-2.05) increase in the odds of positive allergy testing. Intra-rater reliability was substantial (Cohen's κ: 0.8, 95% CI: 0.8-0.9), and responsiveness to change was demonstrated (mean difference: -0.6, 95% CI: -0.8 to -0.4). CONCLUSIONS: This novel domain is a valid, efficient measure of AR alongside rhinosinusitis.

Does doffing the FEES Box generate a significant cloud of particles after aerosol-generating procedures? A proof-of-concept study.

PURPOSE: The spread of airborne diseases, including coronaviruses, remains a widespread public health concern. Published studies outline the use of protective barriers to limit the spread of pathogenic particles and droplets resulting from coughing, sneezing, and talking. The findings suggest a role for these barriers during aerosol-generating procedures, such as flexible endoscopic evaluation of swallowing (FEES). However, the question remains of whether doffing a protective barrier will create a concentrated cloud of particles that will increase health professionals' exposure. METHOD: We simulated four clinical scenarios of coughing and sneezing, talking, eating and drinking, and delivering supplemental oxygen to test whether doffing the FEES Box protective barrier would result in a particle cloud. RESULT: For all scenarios simulated, doffing the FEES Box did not result in a significant increase in mean particle count. Further, the manner of FEES Box removal did not significantly influence mean particle counts on a consistent basis. CONCLUSION: These results suggest that doffing the FEES Box does not increase exposure to airborne particles. Although more research is needed to confirm these findings, FEES Box usage should be considered during aerosol-generating procedures, to protect and reassure healthcare professionals who work with patients with COVID-19 or other airborne diseases.

Pediatric ocular melanoma: a collaborative multicenter study and meta-analysis.

PURPOSE: To investigate clinical manifestations and prognoses in pediatric patients (≤12 years old) with ocular melanoma. METHODS: This was a retrospective, multicenter cohort study with individual participant data (IPD) meta-analysis pooling available published cases, and unpublished cases from an international collaboration of seven ocular oncology centers. RESULTS: There were 133 eyes of 133 pediatric patients with choroidal or ciliary body (n = 66 [50%]), iris (n = 33 [25%]), conjunctival (n = 26 [19%]), and eyelid (n = 8 [6%]) melanoma. Overall, the mean patient age at presentation was 7 years (median, 8; range, 1-12 years), with 63 males (49%). The mean age by tumor site was 6.50 ± 3.90, 7.44 ± 3.57, 9.12 ± 2.61, and 5.63 ± 2.38 years, for choroid/ciliary body, iris, conjunctiva, and eyelid melanoma, respectively (P = 0.001). Association with ocular melanocytosis was seen in 15%, 11%, 4%, and 0%, respectively (P = 0.01). Frequency of ocular melanoma family history did not vary by tumor site (7%, 17%, 9% and 12%, resp. [P = 0.26]). After mean follow-up of 74, 85, 50, and 105 months (P = 0.65), metastasis was seen in 12%, 9%, 19%, and 13% of choroid/ciliary body, iris, conjunctiva, and eyelid melanoma, respectively. Death was reported in 5%, 3%, 8%, and 0%, respectively, with survival analysis indicating higher mortality in choroidal/ciliary body and conjunctival melanoma patients. CONCLUSIONS: Ocular melanoma in the pediatric population is rare, with unique clinical features and outcomes. Iris melanoma accounts for about one-third of pediatric uveal melanoma cases.

Lapatinib dysregulates HER2 signaling and impairs the viability of human uveal melanoma cells.

Uveal melanoma (UM) is the principal type of intraocular malignancy in adults. Up to 50% of UM patients develop metastatic disease with very poor survival. There are few drugs available to treat the primary or metastatic UM. This study was undertaken to evaluate the anti-cancer effect of lapatinib and corroborate the potential of HER2 inhibition in the treatment of UM. The anti-UM activity of lapatinib was assessed using cell viability, cell death and cell cycle analysis, and its anti-metastatic actions were evaluated using would healing, invasion and colony formation assays. Immunoblotting was used to substantiate the actions of lapatinib on apoptotic and HER2 signaling. The anti-UM activity of lapatinib was further evaluated in a UM xenograft mouse model. Lapatinib decreased the viability of four UM cell lines (IC50: 3.67-6.53 µM). The antiproliferative activity of lapatinib was corroborated in three primary cell lines isolated from UM patient tumors. In UM cell lines, lapatinib promoted apoptosis and cell cycle arrest, and strongly inhibited cell migration, invasion and reproductive cell growth. Lapatinib dysregulated HER2-AKT/ERK/PI3K signalling leading to the altered expression of apoptotic factors and cell cycle mediators in UM cell lines. Importantly, lapatinib suppressed tumourigenesis in mice carrying UM cell xenografts. Together the present findings are consistent with the assertion that HER2 is a viable therapeutic target in UM. Lapatinib is active in primary and metastatic UM as a clinically approved HER2 inhibitor. The activity of lapatinib in UM patients could be evaluated in future clinical trials.

Somatic symptoms in school refusal: a qualitative study among children, adolescents, and their parents during the COVID-19 pandemic.

School refusal (SR) is commonly associated with somatic symptoms that are temporally related to school attendance. Abdominal pain, headache, vomiting, and musculoskeletal pain are frequently encountered and are usually not caused by a physical disease. School refusers, parents and health care workers are often puzzled by these impairing symptoms. In this qualitative study, we assessed somatic symptoms in a population encompassing both school refusers and their parents. We aimed at better understanding experiences and strategies in the management of these debilitating symptoms, while also investigating the journey of these symptoms and their behavioral consequences on the said population. We conducted qualitative interviews both within an Integrated Youth Health Care Unit in Paris and through a French parent-led support group improving care for school refusers. We interviewed 19 young persons with SR (aged 6-21 years old) and 20 parents. Using the Grounded Theory, three themes were identified: (1) somatic symptoms' journey in four phases (emergence, coping, crisis, and disappearance in the context of school dropout); (2) their deconstruction, indicating the patients' emotional state; and (3) their management through self-care practices as well as increased emotional and body awareness. Some parents, who could portray similar symptoms at a younger age, mentioned familial pattern of heightened emotional and sensorial sensitivity as a possible cause. Findings suggested that somatic symptoms in SR offer an insight into the patients' emotional state. We recommend that psychotherapies targeting somatic symptoms could be further assessed in SR, along with educational content aimed at increasing emotional literacy in schools and health care settings.

Pembrolizumab plus lenvatinib in second-line and third-line patients with pleural mesothelioma (PEMMELA): a single-arm phase 2 study.

BACKGROUND: The combination of pembrolizumab, an anti-PD-1 antibody, and lenvatinib, an antiangiogenic multikinase inhibitor, shows synergistic activity in preclinical and clinical studies in solid tumours. We assessed the clinical activity of this combination therapy in patients with pleural mesothelioma who progressed after platinum-pemetrexed chemotherapy. METHODS: In this single-arm, single-centre, phase 2 study, done at the Netherlands Cancer Institute in Amsterdam, The Netherlands, eligible patients (aged ≥18 years) with pleural mesothelioma with an Eastern Cooperative Oncology Group performance status of 0-1, progression after chemotherapy (no previous immunotherapy), and measurable disease according to the modified Response Evaluation Criteria In Solid Tumours (mRECIST) for mesothelioma version 1.1. Patients received 200 mg intravenous pembrolizumab once every 3 weeks plus 20 mg oral lenvatinib once per day for up to 2 years or until disease progression, development of unacceptable toxicity, or withdrawal of consent. The primary endpoint was objective response rate identified by a local investigator according to mRECIST version 1.1. This trial is registered with ClinicalTrials.gov, NCT04287829, and is recruiting for the second cohort. FINDINGS: Between March 5, 2021, and Jan 31, 2022, 42 patients were screened, of whom 38 were included in the primary endpoint and safety analyses (median age 71 years [IQR 65-75], 33 [87%] male and five [13%] female) . At data cutoff (Jan 31, 2023), with a median follow-up of 17·7 months (IQR 13·8-19·4), 22 (58%; 95% CI 41-74) of 38 patients had an objective response. The independent review showed an objective response in 17 (45%; 95% CI 29-62) of 38 patients. Serious treatment-related adverse events occurred in ten (26%) patients, including one treatment-related death due to myocardial infarction. The most common treatment-related grade 3 or worse adverse events were hypertension (eight patients [21%]) and anorexia and lymphopenia (both four patients [11%]). In 29 (76%) of 38 patients, at least one dose reduction or discontinuation of lenvatinib was required. INTERPRETATION: Pembrolizumab plus lenvatinib showed promising anti-tumour activity in patients with pleural mesothelioma with considerable toxicity, similar to that in previous studies. Available evidence from the literature suggests a high starting dose of lenvatinib for optimal anti-tumour activity. This, however, demands a high standard of supportive care. The combination therapy of pembrolizumab and lenvatinib warrants further investigation in pleural mesothelioma. FUNDING: Merck Sharp & Dohme.

Acute Calcific Tendinitis of the Longus Colli Muscle Masquerading as Acute Meningitis: A Case Report and Review of the Literature.

We present a case report of a young female who presented with acute neck pain, odynophagia, and fever. These symptoms were suggestive of possible differential diagnosis including meningitis and retropharyngeal abscess. Subsequent radiological investigations led to a diagnosis of acute calcific tendonitis of the longus colli muscle. Typical clinical presentations and radiological findings of this rare condition are discussed.

The nature of expectations of bariatric surgery in patients during the pre- and post-operative period: A unicentric, qualitative study of patient perspectives.

Many patients (20%-30%) experience suboptimal weight loss (WL) after bariatric surgery (BS), and unrealistic preoperative WL expectations may be a contributing factor. This study aimed to describe the nature of patients' general expectations of BS during the pre-surgical period, and how patients determined whether their expectations and WL goals (WLGs) were realistic. The extent to which patients' expectations and WLGs were met and/or changed during the post-surgical period was also assessed. Semi-structured interviews were conducted with 15 preoperative patients recruited approximately 6-months before surgery. Focus groups were also conducted with 14 post-operative patients recruited approximately 6-months after surgery. Interviews and focus groups were audio-recorded, transcribed verbatim and analysed using qualitative content analysis. Preoperative patients reported expectations that BS would positively impact physical and psychological health, social relationships, as well as quality of care. Preoperative patients perceived that they and their health care professionals had unrealistically high expectations of WL. Post-operative patients reported being generally satisfied with the outcomes of surgery, even though many did not reach their expected WL. Finally, most post-operative patients reported changing their expectations from pre- to post-surgery. This study provides data that may help inform the development of preoperative interventions focusing on helping patients set realistic expectations for WL and related outcomes, which could better prepare patients for the challenges they will face after surgery.

The level of adherence to best-practice guidelines by interprofessional teams with and without acute care nurse practitioners in cardiac surgery: A study protocol.

BACKGROUND: Acute care nurse practitioners (ACNPs) in postoperative cardiac surgery settings provide significant benefits to patients and organizations. Recent studies have suggested that ACNPs increase the level of adherence to best-practice guidelines by interprofessional teams. It is however, unknown whether interprofessional teams with ACNP are associated with higher levels of adherence to best-practice guidelines compared to interprofessional teams without ACNPs. Furthermore, no extraction tool is available to measure the level of adherence to best-practice guidelines by interprofessional teams in postoperative cardiac surgery settings. This project aims to measure and examine the level of adherence to best-practice guidelines of interprofessional teams with and without ACNPs in a postoperative cardiac surgery setting in Québec, Canada. METHODS: A retrospective observational study will be conducted of 300 patients hospitalized between January 1, 2019 and January 31, 2020 in a postoperative cardiac surgery unit in Québec, Canada. Data will be collected from patient health records and electronic databases. An extraction tool will be developed based on systematic review of the literature, and will include best-practice guidelines and confounding variables related to patient and interprofessional teams' characteristics. Content and criterion validation, and a pilot-test will be conducted for the development of the tool. A multivariate linear regression model will be developed and adjusted for confounding variables to examine the association between interprofessional teams with and without ACNPs, and level of adherence to best-practice guidelines by those teams. DISCUSSION: This project represents the first study to measure and examine the level of adherence to best-practice guidelines by interprofessional teams with and without ACNPs in a postoperative cardiac surgery setting. The findings of this project will generate empirical data focusing on the contribution of ACNPs within interprofessional teams, and ultimately enhance the delivery of high quality and evidence-based care for patients and families.

Role of Oligodendrocyte Lineage Cells in Multiple System Atrophy.

Multiple system atrophy (MSA) is a debilitating movement disorder with unknown etiology. Patients present characteristic parkinsonism and/or cerebellar dysfunction in the clinical phase, resulting from progressive deterioration in the nigrostriatal and olivopontocerebellar regions. MSA patients have a prodromal phase subsequent to the insidious onset of neuropathology. Therefore, understanding the early pathological events is important in determining the pathogenesis, which will assist with developing disease-modifying therapy. Although the definite diagnosis of MSA relies on the positive post-mortem finding of oligodendroglial inclusions composed of α-synuclein, only recently has MSA been verified as an oligodendrogliopathy with secondary neuronal degeneration. We review up-to-date knowledge of human oligodendrocyte lineage cells and their association with α-synuclein, and discuss the postulated mechanisms of how oligodendrogliopathy develops, oligodendrocyte progenitor cells as the potential origins of the toxic seeds of α-synuclein, and the possible networks through which oligodendrogliopathy induces neuronal loss. Our insights will shed new light on the research directions for future MSA studies.

A global perspective of advanced practice nursing research: A review of systematic reviews protocol.

INTRODUCTION: In 2020, the World Health Organization called for the expansion and greater recognition of all nursing roles, including advanced practice nurses (APNs), to better meet patient care needs. As defined by the International Council of Nurses (ICN), the two most common APN roles include nurse practitioners (NPs) and clinical nurse specialists (CNSs). They help ensure care to communities as well as patients and families with acute, chronic or complex conditions. Moreover, APNs support providers to deliver high quality care and improve access to services. Currently, there is much variability in the use of advanced practice nursing roles globally. A clearer understanding of the roles that are in place across the globe, and how they are being used will support greater role harmonization, and inform global priorities for advanced practice nursing education, research, and policy reform. OBJECTIVE: To identify current gaps in advanced practice nursing research globally. MATERIALS AND METHODS: This review of systematic reviews will provide a description of the current state of the research, including gaps, on advanced practice nursing globally. We will include reviews that examine APNs, NPs or CNSs using recognized role definitions. We will search the CINAHL, EMBASE, Global Health, HealthStar, PubMed, Medline, Cochrane Library Database of Systematic Reviews and Controlled Trials Register, Database of Abstracts of Reviews of Effects, Joanna Briggs Institute, and Web of Science electronic databases for reviews published from January 2011 onwards, with no restrictions on jurisdiction or language. We will search the grey literature and hand search the reference lists of all relevant reviews to identify additional studies. We will extract country, patient, provider, health system, educational, and policy/scope of practice data. We will assess the quality of each included review using the CASP criteria, and summarize their findings. This review of systematic reviews protocol was developed following the PRISMA-P recommendations. PROSPERO REGISTRATION NUMBER: CRD42021278532.

Additive Manufacturing Benchmark 2022 Subcontinuum Mesoscale Tensile Challenge (CHAL-AMB2022-04-MeTT) and Summary of Predictions.

This additive manufacturing benchmarking challenge asked the modelling community to predict the stress-strain behavior and fracture location and pathway of an individual meso-scale (gauge dimensions of approximately 200 µm thickness, 200 µm width, 1mm length) tension specimen that was excised from a wafer of nickel allow IN625 manufactured by laser powder bed fusion (L-PBF). The data used for the challenge questions and answers are provided in a public dataset (https://data.nist.gov/od/id/mds2-2587). Testing models against the data is still possible, although a good-faith blinded prediction should be attempted before reading this article, as the results are contained herein. The uniaxial tension test was pin loaded, conducted at quasi-static strain rates under displacement control, and strain was measured via non-contact methods (digital image correlation). The predictions are challenging since the number of grains contained in the thickness of the specimen are sub-continuum. In addition, pores can be heterogeneously distributed by the L-PBF process, as opposed to intentionally seeded defects. The challenge provided information on chemical composition, grain and subgrain structure (surface-based measurements via electron backscatter diffraction and scanning electron microscopy) and pore structure (volume-based measurements via X-Ray computed tomography) along the entire gauge length for the tension specimen. During the challenge, prediction responses were collected from six different groups. Prediction accuracy compared to the measurements varied, with elastic modulus and strain at ultimate tensile strength consistently over-predicted, while most other values were a mix of over- and under-predicted. Overall, no one model performed best at all predictions. Failure-related properties proved quite challenging to predict, likely in part due to the data provided as well as the inherent difficulty in predicting fracture. Future directions and areas of improvement are discussed in the context of improving model maturity and measurement uncertainty.

Aging-suppressor Klotho: Prospects in diagnostics and therapeutics.

INTRODUCTION: The protein Klotho (KL) was first discovered in KL-deficient mice, which developed a syndrome similar to premature aging in humans. Since then, KL has been implicated in multiple molecular signaling pathways and diseases. KL has been shown to have anti-aging, healthspan and lifespan extending, cognitive enhancing, anti-oxidative, anti-inflammatory, and anti-tumor properties. KL levels decrease with age and in many diseases. Therefore, it has been of great interest to develop a KL-boosting or restoring drug, or to supplement endogenous Klotho with exogenous Klotho genetic material or recombinant Klotho protein, and to use KL levels in the body as a marker for the efficacy of such drugs and as a biomarker for the diagnosis and management of diseases. OBJECTIVE: The goal of this study was to provide a comprehensive review of KL levels across age groups in individuals who are healthy or have certain health conditions, using four sources: blood, cerebrospinal fluid, urine, and whole biopsy/necropsy tissue. By doing so, baseline KL levels can be identified across the lifespan, in the absence or presence of disease. In turn, these findings can be used to guide the development of future KL-based therapeutics and biomarkers, which will heavily rely on an individual's baseline KL range to be efficacious. METHODS: A total of 65 studies were collected primarily using the PubMed database. Research articles that were published up to April 2022 were included. Statistical analysis was conducted using RStudio. RESULTS: Mean and median blood KL levels in healthy individuals, mean blood KL levels in individuals with renal conditions, and mean blood KL levels in individuals with metabolic or endocrine conditions were shown to decrease with age. Similarly, CSF KL levels in patients with AD also declined compared with age-matched controls. CONCLUSIONS: The present study confirms the trend that KL levels in blood decrease with age in humans, among those who are healthy, and even further among those with renal and endocrine/metabolic illnesses. Further, by drawing this trend from multiple published works, we were able to provide a general idea of baseline KL ranges, specifically in blood in these populations. These data add to the current knowledge on normal KL levels in the body and how they change with time and in disease, and can potentially support efforts to create KL-based treatments and screening tools to better manage aging, renal, and metabolic/endocrine diseases.

Handling missing data through prevention strategies in self-administered questionnaires: a discussion paper.

BACKGROUND: Self-administered questionnaires are efficient and low-cost ways of collecting data with wide cohorts. Nonetheless, their use in studies can result in a high occurrence of missing data, which can affect the statistical power, representativeness and generalisability of the findings. Imputation methods have been considered efficient statistical techniques for managing missing data. However, they have also been associated with limits, such as the risk of under-estimation of the effect, lower statistical power and decrease of correlation among variables. Recent studies have highlighted the importance of using prevention strategies to avoid missing data before the data are analysed. AIM: To identify strategies for preventing the occurrence of missing data and to discuss their effects, as well as their methodological and statistical considerations. DISCUSSION: The article discusses prevention strategies related to the administration format and follow-up and reminders. Strategies such as the use of electronic tablets, email and telephone reminders are associated with lower rates of missing data in self-administered questionnaires. However, methodological and statistical limits, including the absence of a comparison group and statistical validation of the reported results, limits the capacity to establish robust consensus. CONCLUSION: Prevention strategies represent relevant and feasible avenues for handling missing data in a wide range of clinical, nursing and epidemiological research. More projects based on robust design are needed to ensure accurate and reliable data are collected from patients, families, communities and clinicians. IMPLICATIONS FOR PRACTICE: It is important for clinicians and nurses to understand the phenomenon of missing data and the strategies available to prevent missing data, to collect data representing the patients' and families' perspectives and experiences.

The application of natural compounds in uveal melanoma drug discovery.

OBJECTIVES: Uveal melanoma (UM) is the most common primary intraocular tumour in adults. UM has a poor overall prognosis and ~50% of patients progress to metastatic disease that has a median survival of 5.2 months. There are currently no proven pharmacological treatments for primary or metastatic UM. Research efforts continue to seek new agents. Many natural compounds have shown promising anti-UM activity in in-vitro and/or in-vivo studies. This review summarises the current findings for natural compounds that may be potentially useful in treating UM. KEY FINDINGS: Literature suggests that natural compounds, such as pristimerin, picropodophyllin, oridonin, zeaxanthin, withaferin and FR-900359, may be promising candidate compounds to treat UM. Most of these compounds have demonstrated satisfactory efficacy in inhibiting in-vitro UM cell growth. SUMMARY: The evidence regarding the anti-UM effects of natural compounds is mainly limited to in-vitro studies; to date, only a small number of these agents have been evaluated in vivo. The molecular mechanisms underpinning the anti-UM properties of these compounds remain largely undefined. Further studies are required to evaluate the in-vivo anticancer activity, appropriate dosage regimen and safety of natural compounds that could be developed for use in UM.