The Predictive Validity of Individualised Load-Velocity Relationships for Predicting 1RM: A Systematic Review and Individual Participant Data Meta-analysis.

BACKGROUND: Load-velocity relationships are commonly used to estimate one-repetition maximums (1RMs). Proponents suggest these estimates can be obtained at high frequencies and assist with manipulating loads according to session-by-session fluctuations. Given their increasing popularity and development of associated technologies, a range of load-velocity approaches have been investigated. OBJECTIVE: This systematic review and individual participant data (IPD) meta-analysis sought to quantify the predictive validity of individualised load-velocity relationships for the purposes of 1RM prediction. METHODS: In September 2022, a search of MEDLINE, SPORTDiscus, Web of Science and Scopus was conducted for published research, with Google Scholar, CORE and British Ethos also searched for unpublished research. Studies were eligible if they were written in English, and directly compared a measured and predicted 1RM using load-velocity relationships in the squat, bench press, deadlift, clean or snatch. IPD were obtained through requests to primary authors and through digitisation of in-text plots (e.g. Bland-Altman plots). Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and the review conducted in accordance with PRISMA-IPD guidelines and an a priori protocol. Absolute and scaled standard error of the estimates (SEE/SEE%) were calculated for two-stage aggregate analyses, with bootstrapping performed for sampling variances. Estimates were pooled using three-level hierarchical models with robust 95% confidence intervals (CIs). One-stage analyses were conducted with random intercepts to account for systematic differences across studies and prediction residuals calculated in the absolute scale (kg) and as a percentage of the measured 1RM. Moderator analyses were conducted by including a priori defined categorical variables as fixed effects. RESULTS: One hundred and thirty-seven models from 26 studies were included with each identified as having low, unclear or high risk of bias. Twenty studies comprising 434 participants provided sufficient data for meta-analyses, with raw data obtained for 8 (32%) studies. Two-stage analyses identified moderate predictive validity [SEE% 9.8, 95% CI 7.4% to 12.2%, with moderator analyses demonstrating limited differences based on the number of loads (ß2Loads:>2Loads = 0.006, 95% CI - 1.6 to 1.6%) or the use of individual or group data to determine 1RM velocity thresholds (ßGroup:Individualised = - 0.4, 95% CI - 1.9 to 1.0%)]. One-stage analyses identified that predictions tended to be overestimations (4.5, 95% CI 1.5 to 7.4 kg), which expressed as a percentage of measured 1RM was equal to 3.7 (95% CI 0.5 to 6.9% 1RM). Moderator analyses were consistent with those conducted for two-stage analyses. CONCLUSIONS: Load-velocity relationships tend to overestimate 1RMs irrespective of the modelling approach selected. On the basis of the findings from this review, practitioners should incorporate direct assessment of 1RM wherever possible. However, load-velocity relationships may still prove useful for general monitoring purposes (e.g. assessing trends across a training cycle), by providing high-frequency estimates of 1RM when direct assessment may not be logistically feasible. Given limited differences in predictions across popular load-velocity approaches, it is recommended that practitioners opting to incorporate this practice select the modelling approach that best suits their practical requirements. REGISTRATION: https://osf.io/agpfm/ .

Acoustic analysis of the effect of personal protective equipment on speech understanding: lessons for clinical environments.

OBJECTIVE: The use of various types of filtering facepiece class 3 (FFP3) mask have become commonplace since the Covid-19 outbreak. These have been evaluated in terms of efficacy regarding aerosol filtration but less emphasis has been placed on the acoustic effects of such masks and their consequences for clinical communication. DESIGN: A microphone 65 cm from a sound-producing Head and Torso Simulator (wearing the masks) was used to measure attenuation via a tone sweep. Predicted impact on speech reception in noise was assessed by weighting the attenuations of cochlear excitation patterns by the frequency importance function of the Speech Intelligibility Index. STUDY SAMPLE: We evaluated acoustic attenuation properties of seven FFP3 masks and a Type IIR surgical mask (as a comparator). RESULTS: The Type IIR mask had the smallest impact on SNR (2.6 dB with visor). Most FFP3s with an addition of a visor (if not already face covering) impacted SNR by approximately 6 dB. The 3 M 6000 was significantly worse (15.8 dB). CONCLUSIONS: Mouth-and-nose covering FFP3s masks had similar effects on SNR (≈6.2 dB with visor). The Tecmen TM-H2 had several advantages over other masks evaluated. It was reusable, allowed lipreading clues and the attenuation was similar to other FFP3s.

The Effects of Sprint Interval Training on Physical Performance: A Systematic Review and Meta-Analysis.

ABSTRACT: Hall, AJ, Aspe, RR, Craig, TP, Kavaliauskas, M, Babraj, J, and Swinton, PA. The effects of sprint interval training on physical performance: a systematic review and meta-analysis. J Strength Cond Res 37(2): 457-481, 2023-The present study aimed to synthesize findings from published research and through meta-analysis quantify the effect of sprint interval training (SIT) and potential moderators on physical performance outcomes (categorized as aerobic, anaerobic, mixed aerobic-anaerobic, or muscular force) with healthy adults, in addition to assessing the methodological quality of included studies and the existence of small study effects. Fifty-five studies were included (50% moderate methodological quality, 42% low methodological quality), with 58% comprising an intervention duration of ≤4 weeks and an array of different training protocols. Bayesian's meta-analysis of standardized mean differences (SMD) identified a medium effect of improved physical performance with SIT (ES 0.5 = 0.52; 95% credible intervals [CrI]: 0.42-0.62). Moderator analyses identified overlap between outcome types with the largest effects estimated for anaerobic outcomes (ES 0.5 = 0.61; 95% CrI: 0.48-0.75). Moderator effects were identified for intervention duration, sprint length, and number of sprints performed per session, with larger effects obtained for greater values of each moderator. A substantive number of very large effect sizes (41 SMDs > 2) were identified with additional evidence of extensive small study effects. This meta-analysis demonstrates that short-term SIT interventions are effective for developing moderate improvements in physical performance outcomes. However, extensive small study effects, likely influenced by researchers analyzing many outcomes, suggest potential overestimation of reported effects. Future research should analyze fewer a priori selected outcomes and investigate models to progress SIT interventions for longer-term performance improvements.

Interpreting magnitude of change in strength and conditioning: Effect size selection, threshold values and Bayesian updating.

The magnitude of change following strength and conditioning (S&C) training can be evaluated comparing effect sizes to thresholds. This study conducted a series of meta-analyses and compiled results to identify thresholds specific to S&C, and create prior distributions for Bayesian updating. Pre- and post-training data from S&C interventions were translated into standardised mean difference (SMDpre) and percentage improvement (%Improve) effect sizes. Bayesian hierarchical meta-analysis models were conducted to compare effect sizes, develop prior distributions, and estimate 0.25-, 0.5-, and 0.75-quantiles to determine small, medium, and large thresholds, respectively. Data from 643 studies comprising 6574 effect sizes were included in the analyses. Large differences in distributions for both SMDpre and %Improve were identified across outcome domains (strength, power, jump and sprint performance), with analyses of the tails of the distributions indicating potential large overestimations of SMDpre values. Future evaluations of S&C training will be improved using Bayesian approaches featuring the information and priors developed in this study. To facilitate an uptake of Bayesian methods within S&C, an easily accessible tool employing intuitive Bayesian updating was created. It is recommended that the tool and specific thresholds be used instead of isolated effect size calculations and Cohen's generic values when evaluating S&C training.

DAP Kinase-Related Apoptosis-Inducing Protein Kinase 2 (DRAK2) Is a Key Regulator and Molecular Marker in Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western World and it is characterized by a marked degree of clinical heterogeneity. An impaired balance between pro- and anti-apoptotic stimuli determines chemorefractoriness and outcome. The low proliferation rate of CLL cells indicates that one of the primary mechanisms involved in disease development may be an apoptotic failure. Here, we study the clinical and functional significance of DRAK2, a novel stress response kinase that plays a critical role in apoptosis, T-cell biology, and B-cell activation in CLL. We have analyzed CLL patient samples and showed that low expression levels of DRAK2 were significantly associated with unfavorable outcome in our CLL cohort. DRAK2 expression levels showed a positive correlation with the expression of DAPK1, and TGFBR1. Consistent with clinical data, the downregulation of DRAK2 in MEC-1 CLL cells strongly increased cell viability and proliferation. Further, our transcriptome data from MEC-1 cells highlighted MAPK, NF-κB, and Akt and as critical signaling hubs upon DRAK2 knockdown. Taken together, our results indicate DRAK2 as a novel marker of CLL survival that plays key regulatory roles in CLL prognosis.

Pathology and regulation for research in the UK: an overview.

The input of pathologists is essential for the conduct of many forms of research, including clinical trials. As the custodians of patient samples, pathology departments have a duty to ensure compliance with the relevant regulations, standards and guidelines to ensure the ethical and effective use for their intended investigational analysis, including when patients are participating in a research study. The results of research studies have impacts beyond the research study itself as they may inform changes in policy and practice or support the licensing of medicines and devices. Compliance with regulations and standards provides public assurance that the rights, safety and wellbeing of research participants are protected, that the data have been collected and processed to ensure their integrity and that the research will achieve its purpose. The requirements of the regulatory environment should not be seen as a barrier to research and should not significantly impact on the work of the laboratory once established and integrated into practice. This paper highlights important regulations, policy, standards and available guidance documents that apply to research involving NHS pathology departments and academic laboratories that are contributing to research involving human subjects.

Otological surgery in paediatric photosensitive patients.

There are a wide range of genetic and auto-immune conditions where UV light exposure poses a threat of UV irradiation to the external auditory canal, tympanic membrane and surrounding skin. Preoperative Ultraviolet Light (UV) measurements were taken in the operating theatre with standard operating microscope and an approved UV light meter prior to surgery on a patient with xeroderma pigmentosa. UV light meter readings of UV index 75 were taken at an operating distance of 290mm. Proceeding with otological surgery with a high UV index would result in a significant UV radiation burn. Utilising a Dermagard and a specific UV filter applied to the microscope resulted in acceptable UV light readings. We highlight the potential morbidity of otological surgery in paediatric photosensitive conditions. We also recommend a management plan to avoid damage by UV radiation in photosensitive patients.

Evaluating inter-aural hearing preservation in bilateral paediatric cochlear implantation.

OBJECTIVE: To examine inter-aural hearing preservation results in children undergoing simultaneous bilateral cochlear implantation (CI). METHODS: Retrospective case review in tertiary referral centre. All children undergoing simultaneous bilateral CI between January 2013 and June 2014 (18 months). Patients eligible for inclusion in the study had pre-operative hearing thresholds of <90 dB at 250 Hz and ≥100 dB at 500 Hz. Patients with anatomical cochlear anomalies or missing data were excluded. Seven patients were included, 1 male, 6 female, mean age of 12 years 11 months at the time of surgery. All patients had simultaneous bilateral cochlear implant surgery, using the same implant and technique. All patients had pre- and post-operative unaided pure tone audiometry. Inter-aural hearing preservation results were compared in each patient. RESULTS: The achieved hearing preservation for 14 ears was complete in 5, partial in 7, and minimal in 2. Measurable hearing preservation was achieved in 86% overall. Inter-aural analysis revealed that only 2 (subjects 1 and 4) of the 7 patients had preservation results within the same preservation group (complete/partial/minimal). The mean inter-aural preservation difference was 30.7% with a range from 12.4% to 65.2%. CONCLUSIONS: Several factors and techniques have already been identified in the wider literature to explain differences in hearing preservation results in CI. However, despite controlling for known factors, we demonstrate variable inter-aural results. This suggests that there may be more factors beyond the surgeon's control influencing our ability to provide consistent results.

Towards appropriate mainstreaming of "Theory of Change" approaches into agricultural research for development: Challenges and opportunities.

Food insecurity persists in many parts of Africa and Asia, despite ongoing agricultural research for development (AR4D) interventions. This is resulting in a growing demand for alternative approaches to designing and evaluating interventions in complex systems. Theory of Change (ToC) is an approach which may be useful because it enables stakeholders to present and test their theories and assumptions about why and how impact may occur, ideally within an environment conducive to iterative reflection and learning. However, ToC is yet to be appropriately mainstreamed into development by donors, researchers and practitioners. We carried out a literature review, triangulated by interviews with 26 experts in African and Asian food security, consisting of researchers, advisors to programs, and donors. Although 17 (65%) of the experts had adopted ToC, their responses and the literature revealed four challenges to mainstreaming: (i) different interpretations of ToC; (ii) incoherence in relationships among the constituent concepts of ToC; (iii) confused relationships between ToC and project "logframes"; and (iv) limitations in necessary skills and commitment for enacting ToC. A case study of the evolution of a ToC in a West African AR4D project over 4 years which exemplified these challenges is presented. Five recommendations arise to assist the mainstreaming of ToC: (i) select a type of ToC suited to the relative complexity of the problem and focal system of interest; (ii) state a theory or hypotheses to be tested as the intervention progresses; (iii) articulate the relationship between the ToC and parallel approaches (e.g. logframe); (iv) accept that a ToC is a process, and (v) allow time and resources for implementers and researchers to develop ToC thinking within projects. Finally, we suggest that communities of practice should be established among AR4D and donor organisations to test, evaluate and improve the contribution that ToCs can make to sustainable food security and agricultural development.

Secreting Follicle-Stimulating Hormone Pituitary Carcinoma with Cervical Metastasis.

BACKGROUND: Pituitary carcinoma is defined by either metastases outside the central nervous system or noncontiguous foci within the central nervous system. This case report details the first documented case of a pathologically isolated follicle-stimulating hormone-secreting pituitary carcinoma and its presentation of metastasis. CASE DESCRIPTION: A 63-year-old man developed intrascapular pain radiating up his neck to his occiput. He had undergone a transsphenoidal hypophysectomy 2 years previously for an atypical pituitary macroadenoma. Subsequent magnetic resonance imaging identified a focal, solitary, well-circumscribed, homogeneous T2 high-signal intradural, extramedullary enhancing mass at C2-3 in a right ventral parasagittal location, extending toward the exit foramina. On surgical excision with a laminectomy, the mass demonstrated a morphologic appearance of a malignant neuroendocrine tumor with an immunoprofile similar to the original atypical pituitary adenoma. This was in keeping with metastatic disease secondary to a follicle-stimulating hormone-secreting pituitary carcinoma. CONCLUSIONS: Although rare, metastatic spread is recognized in patients with atypical pituitary adenoma. This should form the differential diagnosis for such patients presenting with symptoms that could be attributed to metastatic lesions within the neuraxis. In these patients, who undergo regular surveillance in joint neuroendocrine clinics, more urgent investigation of new spinal pain should be instigated to exclude metastatic disease.

Ebola Holding Units at government hospitals in Sierra Leone: evidence for a flexible and effective model for safe isolation, early treatment initiation, hospital safety and health system functioning.

The 2014-2015 West African outbreak of Ebola Virus Disease (EVD) claimed the lives of more than 11,000 people and infected over 27,000 across seven countries. Traditional approaches to containing EVD proved inadequate and new approaches for controlling the outbreak were required. The Ministry of Health & Sanitation and King's Sierra Leone Partnership developed a model for Ebola Holding Units (EHUs) at Government Hospitals in the capital city Freetown. The EHUs isolated screened or referred suspect patients, provided initial clinical care, undertook laboratory testing to confirm EVD status, referred onward positive cases to an Ebola Treatment Centre or negative cases to the general wards, and safely stored corpses pending collection by burial teams. Between 29th May 2014 and 19th January 2015, our five units had isolated approximately 37% (1159) of the 3097 confirmed cases within Western Urban and Rural district. Nosocomial transmission of EVD within the units appears lower than previously documented at other facilities and staff infection rates were also low. We found that EHUs are a flexible and effective model of rapid diagnosis, safe isolation and early initial treatment. We also demonstrated that it is possible for international partners and government facilities to collaborate closely during a humanitarian crisis.

VS-501: A NOVEL, NON-ABSORBED, CALCIUM- AND ALUMINUM-FREE, HIGHLY EFFECTIVE PHOSPHATE BINDER DERIVED FROM NATURAL PLANT POLYMER.

Inadequate control of serum phosphate in chronic kidney disease can lead to pathologies of clinical importance. Effectiveness of on-market phosphate binders is limited by safety concerns and low compliance due to high pill size/burden and gastrointestinal discomfort. VS-501 is a non-absorbed, calcium- and aluminum-free, chemically-modified, plant-derived polymer. In vitro studies show that VS-501 has a high density and a low swell volume when exposed to simulated gastric fluid (vs. sevelamer). When male Sprague Dawley (SD) rats on normal diet were treated with VS-501 or sevelamer, serum phosphate was not significantly altered, but urinary phosphate levels decreased by >90%. VS-501 had no effect on serum calcium (Ca) or urinary Ca, while 3% sevelamer significantly increased serum and urine Ca. In 5/6 nephrectomized (NX) uremic SD rats on high-phosphate diet, increasing dietary phosphate led to an increase in serum and urine phosphate, which was prevented in rats treated with VS-501 or sevelamer (0.2-5% in food). High phosphate diet also increased serum FGF-23 and parathyroid hormone in 5/6 NX rats, which was prevented by VS-501 or sevelamer. VS-501 or sevelamer increased fecal phosphate in a dose-dependent manner. More aortic calcification was observed in 5/6 NX rats treated with 5% sevelamer, while VS-501 and sevelamer did not show significant effects on cardiac parameters, fibrosis, intestine histology and intestinal sodium-dependent phosphate cotransporter gene expression. These results suggest that VS-501 is effective in binding phosphate with no effects on calcium homeostasis, and may have improved pill burden and gastrointestinal side effects.

Emerging communities of child-healthcare practice in the management of long-term conditions such as chronic kidney disease: qualitative study of parents' accounts.

BACKGROUND: Parents of children and young people with long-term conditions who need to deliver clinical care to their child at home with remote support from hospital-based professionals, often search the internet for care-giving information. However, there is little evidence that the information available online was developed and evaluated with parents or that it acknowledges the communities of practice that exist as parents and healthcare professionals share responsibility for condition management. METHODS: The data reported here are part of a wider study that developed and tested a condition-specific, online parent information and support application with children and young people with chronic-kidney disease, parents and professionals. Semi-structured interviews were conducted with 19 fathers and 24 mothers who had recently tested the novel application. Data were analysed using Framework Analysis and the Communities of Practice concept. RESULTS: Evolving communities of child-healthcare practice were identified comprising three components and several sub components: (1) Experiencing (parents making sense of clinical tasks) through Normalising care, Normalising illness, Acceptance & action, Gaining strength from the affected child and Building relationships to formalise a routine; (2) Doing (Parents executing tasks according to their individual skills) illustrated by Developing coping strategies, Importance of parents' efficacy of care and Fear of the child's health failing; and (3) Belonging/Becoming (Parents defining task and group members' worth and creating a personal identity within the community) consisting of Information sharing, Negotiation with health professionals and Achieving expertise in care. Parents also recalled factors affecting the development of their respective communities of healthcare practice; these included Service transition, Poor parent social life, Psycho-social affects, Family chronic illness, Difficulty in learning new procedures, Shielding and avoidance, and Language and cultural barriers. Health care professionals will benefit from using the communities of child-healthcare practice model when they support parents of children with chronic kidney disease. CONCLUSIONS: Understanding some of the factors that may influence the development of communities of child-healthcare practice will help professionals to tailor information and support for parents learning to manage their child's healthcare. Our results are potentially transferrable to professionals managing the care of children and young people with other long-term conditions.

Role of surgery in adult obstructive sleep apnoea.

A surgical approach to treatment of obstructive sleep apnoea (OSA) remains an area of intense debate, both within and without the surgical community itself. Continuous positive airway pressure (CPAP) therapy remains the gold standard for the treatment of OSA, however surgery may be indicated to facilitate CPAP and/or improve compliance in cases where CPAP is poorly tolerated. This article summarises the current range of surgical treatment options together with the evidence base for their intervention in otolaryngology, maxillofacial and bariatric surgery. The continued evolution of technology has brought new surgical techniques to the fore and it seems likely their utilisation together with a multi-level surgical approach to the airway will continue to influence forthcoming research in OSA. Patient selection and precise evaluation will remain crucial in ensuring that when surgery is indicated, the correct procedure or procedures are performed at the correct anatomical level.

Misidentification of Mycobacterium fortuitum in an immunocompetent patient presenting with a unilateral neck mass.

A 31-year-old African man with a blameless medical history presented with an enlarging neck swelling of 6 months duration. He was systemically well with normal heamatobiochemistry. MRI of the neck demonstrated abnormal signalling in the subcutaneous fat overlying the posterior spinal muscles in the midline and the left sternocleidomastoid muscle. Scanty growth of Rhodococcus equi was reported from a turbid fine needle aspirate of the neck on two separate occasions. The swelling progressed despite numerous antibiotic combinations which necessitated surgical debridement. Analysis of debrided tissue using 16S rDNA surprisingly identified Mycobacterium fortuitum, not R equi, thereby resolving our diagnostic conundrum.

Torticollis following tympanoplasty: an index case with lessons in encountering the unexpected.

The term torticollis is derived from the Latin words 'tortis' for twisted and 'collum' for neck. Typical features include sudden onset of severe unilateral pain, with restriction of movements and deviation of the neck to that side. Although torticollis is a well recognised abnormality, there is minimal literature identifying it as a sole long-standing complication in otological surgery. We present the case of a 15-year-old boy who developed permanent torticollis following a routine tympanoplasty. A CT of the neck revealed an atlantoaxial rotatory fixation with cross fusion between C1 and C2. This case highlights a rare cause of torticollis resulting from a routine otological procedure. It also differentiates between Grisel's syndrome, which is characterised by atlantoaxial subluxation as opposed to fusion. The role of the multidisciplinary team is imperative and in particular the need for urgent discussion with the neurosurgical team to ensure prompt assessment and management of the patient takes place.