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Aims: The aim of this audit was to assess and improve the completeness and accuracy of the National Joint Registry (NJR) dataset for arthroplasty of the elbow., Methods: It was performed in two phases. In Phase 1, the completeness was assessed by comparing the NJR elbow dataset with the NHS England Hospital Episode Statistics (HES) data between April 2012 and April 2020. In order to assess the accuracy of the data, the components of each arthroplasty recorded in the NJR were compared to the type of arthroplasty which was recorded. In Phase 2, a national collaborative audit was undertaken to evaluate the reasons for unmatched data, add missing arthroplasties, and evaluate the reasons for the recording of inaccurate arthroplasties and correct them., Results: Phase 1 identified 5,539 arthroplasties in HES which did not match an arthroplasty on the NJR, and 448 inaccurate arthroplasties from 254 hospitals. Most mismatched procedures (3,960 procedures; 71%) were radial head arthroplasties (RHAs). In Phase 2, 142 NHS hospitals with 3,640 (66%) mismatched and 314 (69%) inaccurate arthroplasties volunteered to assess their records. A large proportion of the unmatched data (3,000 arthroplasties; 82%) were confirmed as being missing from the NJR. The overall rate of completeness of the NJR elbow dataset improved from 63% to 83% following phase 2, and the completeness of total elbow arthroplasty data improved to 93%. Missing RHAs had the biggest impact on the overall completeness, but through the audit the number of RHAs in the NJR nearly doubled and completeness increased from 35% to 70%. The accuracy of data was 94% and improved to 98% after correcting 212 of the 448 inaccurately recorded arthroplasties., Conclusion: The rate of completeness of the NJR total elbow arthroplasty dataset is currently 93% and the accuracy is 98%. This audit identified challenges of data capture with regard to RHAs. Collaboration with a trauma and orthopaedic trainees through the British Orthopaedic Trainee Association improved the completeness and accuracy of the NJR elbow dataset, which will improve the validity of the reports and of the associated research., Competing Interests: Z. Hamoodi reports research fellowship funding from Royal College of Surgeons, National Joint Registry, and The John Charnley Trust, related to this study. A. Sayers is senior statistician on the HQIP/NJR Lot 2 contract. M. R. Whitehouse is the principal investigator for the HQIP/NJR Lot 2 contract to provide statistical support, analysis and associated services to the NJR, related to this study, and reports multiple grants or contracts from the NIHR and Ceramtec, royalties or licenses from Taylor & Frances, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Heraeus, all of which are unrelated to this study. A. C. Watts reports royalties or licenses and patents planned, issued or pendingfrom Adler, consulting fees from Medartis, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Medartis, Stryker, and Arthrex, all of which are unrelated to this study, and is also a member of the editorial boards of the National Joint Registry and The Bone & Joint Journal., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Aims: A review of the literature on elbow replacement found no consistency in the clinical outcome measures which are used to assess the effectiveness of interventions. The aim of this study was to define core outcome domains for elbow replacement., Methods: A real-time Delphi survey was conducted over four weeks using outcomes from a scoping review of 362 studies on elbow replacement published between January 1990 and February 2021. A total of 583 outcome descriptors were rationalized to 139 unique outcomes. The survey consisted of 139 outcomes divided into 18 domains. The readability and clarity of the survey was determined by an advisory group including a patient representative. Participants were able to view aggregated responses from other participants in real time and to revisit their responses as many times as they wished during the study period. Participants were able to propose additional items for inclusion. A Patient and Public Inclusion and Engagement (PPIE) panel considered the consensus findings., Results: A total of 45 respondents completed the survey. Nine core mandatory domains were identified: 'return to work or normal daily role'; delivery of care was measured in the domains 'patient satisfaction with the outcome of surgery' and 'would the patient have the same operation again'; 'pain'; 'revision'; 'elbow function'; 'independence in activities of daily living'; 'health-related quality of life'; and 'adverse events'. 'Elbow range of motion' was identified as important by consensus but was felt to be less relevant by the PPIE panel. The PPIE panel unanimously stated that pain should be used as the primary outcome domain., Conclusion: This study defined core domains for the clinical outcomes of elbow replacement obtained by consensus from patients, carers, and healthcare professionals. Pain may be used as the primary outcome in future studies, where appropriate. Further work is required to define the instruments that should be used., Competing Interests: A. C. Watts reports grants or contracts from NIHR, Zimmer Biomet, TRB Chemedica, and Stryker, royalties or licenses and patents planned, issued or pending from Adler, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Xiros, Medartis, and Arthrex, all of which are unrelated to this study. C. McDaid reports grants or contracts from NIHR HTA and i4i panels, research funding from Hull Teaching Hospitals NHS Trust, and is the co-director of NIHR RSS, all of which are unrelated to this study., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Evidence for management of shoulder periprosthetic joint infection (PJI) has traditionally originated from the hip and knee literature. The differing microbiome, anatomy and implants used in the shoulder mean this evidence is not always directly transferrable. The 2018 Philadelphia International Consensus Meeting for the first-time produced evidence-based guidelines and diagnostic criteria relating specifically to PJI of the shoulder. These guidelines and criteria recognize the pathogenicity of lower virulence organisms in the shoulder which often means clinical presentation is less obvious than other joints. The role of Cutibacterium acnes in shoulder PJI is the subject of increasing basic science and clinical research and advances in microbiological research may help to understand the pathology behind shoulder infections. There is new evidence that outcomes after revision shoulder arthroplasty are dependent on the virulence of the causative organism. An individualised approach to treatment considering host factors, organism, soft tissues and bone stock is recommended. Debate continues in the literature regarding the indications of one- or two-stage revision and the latest evidence is discussed and synthesized in this review article. We advocate careful multidisciplinary team decision making for cases of shoulder PJI and recognize a limited role for debridement and implant retention in acute shoulder PJI (<6 weeks). There appears to be a role for one-stage revision in lower risk cases with low virulence organisms but caution against its' universal adoption. In higher risk or complex cases, there remains a clear role for two-stage revision arthroplasty, and we detail the specifics of this protocol and procedure from our tertiary shoulder and elbow unit., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

A newly identified epigenetic modifier increases fetal hemoglobin in preclinical studies.

Background: Glenoid bone loss represents a challenge in shoulder arthroplasty and often precludes standard implants. The CAD-CAM total shoulder replacement (TSR) is an option in these cases. This study aimed to assess survivorship and long-term patient outcomes of the CAD-CAM TSR., Methods: Fifty-eight patients that underwent a CAD-CAM TSR by three surgeons at a single tertiary referral centre between 2009 and 2017 were reviewed. The mean follow-up was 70 months (28-130). Data was collected on survivorship, range of movement, Oxford shoulder score (OSS, 0-48), subjective shoulder value (SSV, 0-100%), pain score (0-10), and overall patient satisfaction., Results: CAD-CAM TSR was undertaken as a primary procedure in 28% ( n  = 16) for end-stage arthritis with severe glenoid bone loss, and as a revision procedure in 72% ( n  = 42). Of the total, 17% ( n  = 10) required component revision at a mean of 24 months (4x prosthesis loosening, 3x infection, 3x periprosthetic fracture). Forward elevation improved from 45° ± 27° to 59° ± 29° (P = 0.0056), abduction from 43° ± 29° to 55° ± 26° (P = 0.034) and external rotation from 8° ± 11° to 16° ± 14° (P = 0.031). OSS improved from 15 ± 8 to 29 ± 9 (P = 0.0009), SSV from 18 ± 16 to 62 ± 23 (P < 0.0001), and pain score from 8 ± 2 to 2 ± 2 (P < 0.0001). 88% of patients would undergo the procedure again., Conclusion: CAD-CAM TSR is reserved for complex cases involving severe glenoid bone loss, offering significant improvements in pain and function with overall positive patient satisfaction., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Fractures of the distal humerus are a common fragility fracture in older adults. The purpose of this study was to systematically review the literature to produce pooled estimates of the outcomes of treatment using total elbow arthroplasty (TEA), open reduction and locking plate fixation (ORIF), hemiarthroplasty or with conservative management., Methods: A systematic review of PUBMED and EMBASE databases was conducted for studies reporting outcomes of intra-articular fractures in older adults. Data extracted included patient-reported outcome measures as well as clinical outcomes including ROM, adverse events and all-cause reoperation rates., Results: Forty-eight studies met the inclusion criteria and included 1838 acute, intra-articular distal humeral fractures. There was no clinically important difference in patient-reported pain and function measured on the Mayo Elbow Performance Score (TEA = 89.3 (SD 20.0), Hemi = 88.4 (SD 10.6), internal fixation = 85.0 (SD 14.7), non-operative = 85.1 (SD 11.0))., Discussion: Each of the treatment modalities studies resulted in a reasonable level of elbow function. The included studies were largely non-comparative and at considerable risk of bias. As elbow replacement surgery becomes centralised in the UK, there is a real need for high-quality comparative research studies to inform practice., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Objectives: To determine the effect of arthroscopic capsular shift surgery on pain and functional impairment for people with atraumatic shoulder (glenohumeral) joint instability., Methods: We conducted a randomised, placebo-controlled clinical trial in a specialist secondary care facility. Patients aged 18 years and over who reported insecurity (apprehension) in their shoulder joint and had evidence of capsulolabral damage on arthroscopic examination were included. Patients were excluded if their shoulder apprehension symptoms were precipitated by a high velocity shoulder injury, they had bony or neural damage, a rotator cuff or labral tear, or previous surgery on the symptomatic shoulder. Sixty-eight participants were randomised and received diagnostic arthroscopy, followed by arthroscopic capsular shift or diagnostic arthroscopy alone. All participants received the same postoperative clinical care. The primary outcome was pain and functional impairment measured with the Western Ontario Shoulder Instability Index. The prespecified minimum clinically important effect was a reduction in pain and disability of 10.4 points., Results: Mean reductions in pain and functional impairment for both groups were similar. Compared with diagnostic arthroscopy, arthroscopic capsular shift increased pain and functional impairment by means of 5 points (95% CI -6 to 16 points) at 6 months, 1 point (95% CI -11 to 13 points) at 12 months and 2 points (95% CI -12 to 17 points) at 24 months., Conclusions: Compared with diagnostic arthroscopy alone, arthroscopic capsular shift confers, at best, only minimal clinically important benefit in the medium term., Trial Registration Number: NCT01751490., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Anthropogenic noise is globally increasing in aquatic ecosystems, and there is concern that it may have adverse consequences in many fish species, yet the effects of noise in field settings are not well understood. Concern over the applicability of laboratory-conducted bioacoustic experiments has led to a call for, and a recent increase in, field-based studies, but the results have been mixed, perhaps due to the wide variety of techniques used and species studied. Previous reviews have explored the behavioral, physiological, and/or anatomical costs of fish exposed to anthropogenic noise, but few, if any, have focused on the field techniques and sound sources themselves. This review, therefore, aims to summarize, quantify, and interpret field-based literature, highlight novel approaches, and provide recommendations for future research into the effects of noise on fish., (© 2023 Acoustical Society of America.)

Despite ever-increasing accumulation of genomic data, the fundamental question of how individual genes are switched on during development, lineage-specification and differentiation is not fully answered. It is widely accepted that this involves the interaction between at least three fundamental regulatory elements: enhancers, promoters and insulators. Enhancers contain transcription factor binding sites which are bound by transcription factors (TFs) and co-factors expressed during cell fate decisions and maintain imposed patterns of activation, at least in part, via their epigenetic modification. This information is transferred from enhancers to their cognate promoters often by coming into close physical proximity to form a 'transcriptional hub' containing a high concentration of TFs and co-factors. The mechanisms underlying these stages of transcriptional activation are not fully explained. This review focuses on how enhancers and promoters are activated during differentiation and how multiple enhancers work together to regulate gene expression. We illustrate the currently understood principles of how mammalian enhancers work and how they may be perturbed in enhanceropathies using expression of the α-globin gene cluster during erythropoiesis, as a model., (© 2023 The Authors. BioEssays published by Wiley Periodicals LLC.)

In this study, we examined the cytokine immune response against two proteins of infectious pancreatic necrosis virus (IPNV) in rainbow trout (Oncorhynchus mykiss), the virion-associated RNA polymerase VP1 and VP2-Flagellin (VP2-Flg) fusion protein. Since VP1 is not a structural protein, we hypothesize it can induce cellular immunity, an essential mechanism of the antiviral response. At the same time, the fusion construction VP2-Flg could be highly immunogenic due to the presence of the flagellin used as an adjuvant. Fish were immunized with the corresponding antigen in Montanide™, and the gene expression of a set of marker genes of Th1, Th2, and the immune regulatory response was quantified in the head kidney of immunized and control fish. Results indicate that VP1 induced upregulation of ifn-γ, il-12p40c, il-4/13a, il-4/13b2, il-10a, and tgf-β1 in immunized fish. Expression of il-2a did not change in treated fish at the times tested. The antigen-dependent response was analysed by in vitro restimulation of head kidney leukocytes. In this assay, the group of cytokines upregulated after VP1-restimulation was consistent with those upregulated in the head kidney in vivo. Interestingly, VP1 induced il-2a expression after in vitro restimulation. The analysis of sorted lymphocytes showed that the increase of cytokines occurred in CD4-1 + T cells suggesting that Th differentiation happens in response to VP1. This is also consistent with the expression of t-bet and gata3, the master regulators for Th1/Th2 differentiation in the kidneys of immunized animals. A different cytokine expression profile was found after VP2-Flg administration, i.e., upregulation occurs for ifn-γ, il-4/13a, il-10a, and tgf-β1, while down-regulation was observed in il-4/13b2 and il-2a. The cytokine response was due to flagellin; only the il-2a effect was dependent upon VP2 in the fusion protein. To the best of our knowledge this study reports for the first-time characteristics of the adaptive immune response induced in response to IPNV VP1 and the fusion protein VP2-Flg in fish. VP1 induces cytokines able to trigger the humoral and cell-mediated immune response in rainbow trout. The analysis of the fish response against VP2-Flg revealed the immunogenic properties of Aeromonas salmonicida flagellin, which can be further tested for adjuvanticity. The novel immunogenic effects of VP1 in rainbow trout open new opportunities for further IPNV vaccine development using this viral protein., (Copyright © 2022. Published by Elsevier Ltd.)

Determining the mechanisms by which genes are switched on and off during development is a key aim of current biomedical research. Gene transcription has been widely observed to occur in a discontinuous fashion, with short bursts of activity interspersed with periods of inactivity. It is currently not known if or how this dynamic behaviour changes as mammalian cells differentiate. To investigate this, using an on-microscope analysis, we monitored mouse α-globin transcription in live cells throughout erythropoiesis. We find that changes in the overall levels of α-globin transcription are most closely associated with changes in the fraction of time a gene spends in the active transcriptional state. We identify differences in the patterns of transcriptional bursting throughout differentiation, with maximal transcriptional activity occurring in the mid-phase of differentiation. Early in differentiation, we observe increased fluctuation in transcriptional activity whereas at the peak of gene expression, in early erythroblasts, transcription is relatively stable. Later during differentiation as α-globin expression declines, we again observe more variability in transcription within individual cells. We propose that the observed changes in transcriptional behaviour may reflect changes in the stability of active transcriptional compartments as gene expression is regulated during differentiation., (© 2022. The Author(s).)

Background: Clinical coders are dependent on clear data regarding diagnoses and procedures to generate an accurate representation of clinical activity and ensure appropriate remuneration is received. The accuracy of this process may potentially be improved by collaboration with the surgical team., Methods: Between November 2017 and November 2019, 19 meetings took place between the Senior Clinical Fellow of our tertiary Shoulder & Elbow Unit and the coding validation lead of our Trust. At each meeting, the Clinical Fellow assessed the operative note of cases in which uncertainty existed as to the most suitable clinical codes to apply and selected the codes which most accurately represented the operative intervention performed., Results: Over a 24-month period, clinical coding was reviewed in 153 cases (range 3-14 per meeting, mean 8). Following review, the clinical coding was amended in 102 (67%) of these cases. A total of £115,160 additional income was generated as a result of this process (range £1677-£15,796 per meeting, mean £6061). Only 6 out of 28 (21%) cases initially coded as arthroscopic sub-acromial decompressions were correctly coded as such., Discussion: Surgeon input into clinical coding greatly improves data quality and increases remuneration received for operative interventions performed., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2021 The British Elbow & Shoulder Society.)

Background: We report an outbreak of SARS coronavirus-2 (SARS-CoV-2) infection among healthcare workers (HCW) in an NHS elective healthcare facility., Methodology: A narrative chronological account of events after declaring an outbreak of SARS-CoV-2 among HCWs. As part of the investigations, HCWs were offered testing during the outbreak. These were: (1) screening by real-time reverse transcriptase polymerase chain reaction (RT- PCR) to detect a current infection; and (2) serum samples to determine seroprevalence., Results: Over 180 HCWs were tested by real-time RT-PCR for SARS-CoV-2 infection. The rate of infection was 15.2% (23.7% for clinical or directly patient-facing HCWs vs. 4.8% in non-clinical non-patient-facing HCWs). Of the infected HCWs, 57% were asymptomatic. Seroprevalence (SARS-CoV-2 IgG) among HCWs was 13%. It was challenging to establish an exact source for the outbreak. The importance of education, training, social distancing and infection prevention practices were emphasised. Additionally, avoidance of unnecessary transfer of patients and minimising cross-site working for staff and early escalation were highlighted. Establishing mass and regular screening for HCWs are also crucial to enabling the best care for patients while maintaining the wellbeing of staff., Conclusion: To our knowledge, this is the first UK outbreak report among HCWs and we hope to have highlighted some key issues and learnings that can be considered by other NHS staff and HCWs globally when dealing with such a task in future., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background: There remains no gold standard management for deep shoulder periprosthetic joint infection (PJI). This case series aims to present our experience of two-stage revision arthroplasty, including eradication of infection and reoperation rates., Methods: We retrospectively reviewed patients undergoing revision arthroplasty for shoulder PJI between 2006 and 2015. Cases were confirmed using Musculoskeletal Infection Society (MSIS) and American Academy of Orthopaedic Surgeons (AAOS) guidelines. TSA removal, debridement and irrigation preceded antibiotic-loaded cement spacer insertion and a minimum of six weeks intravenous antibiotics. Reimplantation was performed as a second stage following a negative aspirate., Results: Twenty-eight patients underwent a first stage procedure (mean age 69 years; 16 male, 12 female). Propionibacterium acnes , Methicillin-sensitive Staphylococcus aureus , Coagulase-negative Staphylococcus and Staphylococcus epidermidis were the commonest microorganisms cultured. Five cases had mixed growths and six cases provided no growth. Three patients did not proceed to a second stage. Twenty-five patients underwent reimplantation (mean interval 6.7 months), with 80% remaining infection-free (mean follow-up 38.3 months)., Discussion: Managing complex and late presentation shoulder PJI with two-stage revision is associated with high rates of infection eradication (80%). In the absence of a management consensus, our experience supports two-stage revision arthroplasty for eradicating infection in this complex patient group., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2019 The British Elbow & Shoulder Society.)

There seems to be no report in the literature on the effect of melatonin (MT) in relieving the detrimental effects of combined application of salt stress (SS) and iron deficiency (ID). Therefore, the effect of MT on the accumulation/synthesis of endogenous nitric oxide (NO) and hydrogen sulphide (H 2 S) and how far these molecules are involved in MT-improved tolerance to the combined application of ID and SS in pepper (Capsicum annuum L) were tested. Hence, two individual trials were set up. The treatments in the first experiment comprised: Control, ID (0.1 mM FeSO 4 ), SS (100 mM NaCl) and ID + SS. The detrimental effects of combined stresses were more prominent than those by either of the single stress, with respect to growth, oxidative stress and antioxidant defense attributes. Single stress or both in combination improved the endogenous H 2 S and NO, and foliar-applied MT (100 µM) led to a further increase in NO and H 2 S levels. In the second experiment, 0.1 mM scavenger of NO, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (cPTIO) and that of H 2 S, hypotuarine (HT) were applied along with MT to get further evidence whether NO and H 2 S are involved in MT-induced tolerance to ID and SS. MT combined with cPTIO and HT under a single or combined stress showed that NO effect was reversed by the NO scavenger, cPTIO, alone but the H 2 S effect was inhibited by both scavengers. These findings suggested that tolerance to ID and SS induced by MT may be involved in downstream signal crosstalk between NO and H 2 S., (© 2019 Scandinavian Plant Physiology Society.)

β-Thalassaemia is one of the most common monogenic diseases with no effective cure in the majority of patients. Unbalanced production of α-globin in the presence of defective synthesis of β-globin is the primary mechanism for anaemia in β-thalassaemia. Clinical genetic data accumulated over three decades have clearly demonstrated that direct suppression of α-globin and induction of γ-globin are effective in reducing the globin chain imbalance in erythroid cells hence improving the clinical outcome of patients with β-thalassaemia. Here, we show that the histone deacetylase inhibitor drug, vorinostat, in addition to its beneficial effects for patients with β-thalassaemia through induction of γ-globin, has the potential to simultaneously suppress α-globin. We further show that vorinostat exhibits these synergistic beneficial effects in globin gene expression at nanomolar concentrations without perturbing erythroid expansion, viability, differentiation or the transcriptome. This new evidence will be helpful for the interpretation of existing clinical trials and future clinical studies that are directed towards finding a cure for β-thalassaemia using vorinostat.

Background: The purpose of the present study was to analyze and report the clinical outcomes following revision shoulder arthroplasty for failed humeral head resurfacing hemiarthroplasty (HHRH)., Methods: All patients who underwent revision shoulder arthroplasty for failed HHRH at our institution were retrospectively reviewed. Twenty-two shoulders in 20 patients were available for analysis. Mean age at the time of HHRH was 60 years (range 42 years to 75 years). The cohort consisted of 17 females and three males., Results: The mean time from HHRH to revision was 5 years (range 1 year to 8 years). Mean age at the time of revision surgery was 62 years (range 44 years to 80 years). Patients were followed-up for a mean of 3.3 years (range 2 years to 4 years) after revision. Following revision surgery, there was an increase in forward elevation from 67° (range 0° to 130°) to 97° (range 40° to 160°) ( p  = 0.04). This was accompanied by an improvement in both the Oxford Shoulder Score and the subjective shoulder value, which increased from 13 (range 2 to 28) to 39 (range 24 to 48) ( p  = 0.000) and from 23 (range 0 to 65) to 79 (range 25 to 100) ( p  = 0.000) respectively., Conclusions: Revision shoulder arthroplasty for failed HHRH improves functional outcome.

Background: Health services in Tasmania, Victoria and now Western Australia are changing to goals-of-care (GOC) advance care planning (ACP) documentation strategies., Aim: To compare the clinical impact of two different health department-sanctioned ACP documentation strategies., Methods: A non-blinded, pre-post, controlled study over two corresponding 6-month periods in 2016 and 2017 comparing the current discretional not-for-resuscitation (NFR) with a new, inclusive GOC strategy in two medical/oncology wards at a large private hospital. Main outcomes were the uptake of ACP forms per hospitalisation and the timing between hospital admission, ACP form completion and in-patient death. Secondary outcomes included utilisation of the rapid response team (RRT), palliative and critical care services., Results: In total, 650 NFR and 653 GOC patients underwent 1885 admissions (mean Charlson Comorbidity Index = 3.7). GOC patients had a higher uptake of ACP documentation (346 vs 150 ACP forms per 1000 admissions, P < 0.0001) and a higher proportion of ACP forms completed within the first 48 h of admission (58 vs 39%, P = 0.0002) but a higher incidence of altering the initial ACP level of care (P = 0.003). All other measures, including ACP documentation within 48 h of death (P = 0.50), activation of RRT (P = 0.73) and admission to critical (P = 0.62) or palliative (P = 0.81) care services, remained similar. GOC documentation was often incomplete, with most sub-sections left blank between 74 and 87% of occasions., Conclusion: Despite an increased uptake of the GOC form, overall use remained low, written completion was poor, and most quantitative outcomes remained statistically unchanged. Further research is required before a wider GOC implementation can be supported in Australia's healthcare systems., (© 2018 Royal Australasian College of Physicians.)

Objective: To find out ways of improving fermentation quality of silage, the comparative analysis of fermentation characteristics and in vitro digestibility of tropical grasses silage applied with cellulases produced from Acremonium or Tricoderma species were studied in Thailand., Methods: Fresh and wilted Guinea grass and Napier grass silages were prepared with cellulases from Acremonium (AC) or Trichoderma (TC) at 0.0025%, 0.005%, and 0.01% on a fresh matter (FM), and their fermentation quality, chemical composition and in vitro digestibility were analyzed., Results: All silages of fresh Napier grass were good quality with lower pH, butyric acid, and ammonia nitrogen, but higher lactic acid content than wilted Napier grass and Guinea grass silage. Silages treated with AC 0.01% had the best result in terms of fermentation quality. They also had higher in vitro dry matter digestibility and in vitro organic matter digestibility at 6 and 48 h after incubation than other silages. Silages treated with lower levels at 0.005% or 0.0025% of AC and all levels of TC did not improve silage fermentation., Conclusion: The AC could improve silage fermentation and in vitro degradation of Guinea grass and Napier grass silages, and the suitable addition ration is 0.01% (73.5 U) of FM for tropical silage preparation.

Introduction: Anaemia in women during pregnancy and child bearing age is one of the most common global health problems. Reasons are numerous, but in many cases only minimal attempts are made to elucidate the underlying causes. In this study we aim to identify aetiology of anaemia in women of child bearing age and to determine the relative contributions, effects and interactions of α- and β-thalassaemia in a region of the world where thalassaemia is endemic., Methods: A cross sectional study was conducted at the Colombo North Teaching Hospital of Sri Lanka. The patient database of deliveries between January 2015 and September 2016 at University Obstetrics Unit was screened to identify women with anaemia during pregnancy and 253 anaemic females were randomly re-called for the study. Data were collected using an interviewer-administered questionnaire and haematological investigations were done to identify aetiologies., Results: Out of the 253 females who were anaemic during pregnancy and were re-called, 8 were excluded due to being currently pregnant. Of the remaining 245 females, 117(47.8%) remained anaemic and another 22(9.0%) had non-anaemic microcytosis. Of anaemic females, 28(24.8%) were iron deficient, 40(35.4%) had low-normal serum ferritin without fulfilling the criteria for iron deficiency,18(15.3%) had β-haemoglobinopathy trait and 20(17.0%) had α-thalassaemia trait. Of females who had non-anaemic microcytosis, 14(66.0%) had α-thalassaemia trait. In 4 females, both α- and β-thalassaemia trait coexist. These females had higher levels of haemoglobin (p = 0.06), MCV (p<0.05) and MCH (p<0.01) compared to individuals with only β-thalassaemia trait. A significantly higher proportion of premature births (p<0.01) and lower mean birth weights (p<0.05) were observed in patients with α-thalassaemia trait., Conclusions: Nearly one third of anaemic females in child bearing age had thalassaemia trait of which α-thalassemia contributes to a majority. Both α- and β-thalassaemia trait can co-exist and have ameliorating effects on red cell indices in heterozygous states. α-Thalassaemia trait was significantly associated with premature births and low birth weight. It is of paramount importance to investigate the causes of anaemia in women of child bearing age and during pregnancy in addition to providing universal iron supplementation., Competing Interests: The authors have declared that no competing interests exist.

Objective: To investigate knowledge, attitudes, and practices of oncologists towards physical activity (PA) in cancer survivors, and the association between oncologists' own PA behavior and PA promotion., Methods: Oncologists (n = 123) completed a survey based on the Theory of Planned Behavior (TPB). Participants reported PA promotion behavior, PA involvement, attitudes, intentions, social norm, perceived behavioral control (PBC), and confidence and knowledge of exercise prescription. Structural equation modeling (SEM) evaluated these associations., Results: Less than half of oncologists reported regularly promoting PA to patients (46%), with 20% providing written information and 23% referrals. Only 26% were physically active. TPB SEM pathways explained 54.6% of the variance in PA promotion (comparative fit index (CFI) = 0.905, standardized root mean square residual (SRMR) = 0.040). Social norm was not only the significant pathway to intention but also a significant indirect pathway to PA promotion (p = 0.007). Confidence to promote PA, PBC, and intentions were direct significant pathways to PA promotion (p < 0.05). Exploratory SEM pathways explained 19.6% of the variance of PA behavior, which in turn explained 13.1% social norm, 10.7% attitude, 10.0% confidence to recommend, and 17.8% PA promotion behavior (CFI = 0.921, SRMR = 0.076). Instrumental attitude was a direct significant pathway to PA behavior (p = 0.001). PA behavior was a direct significant pathway to social norms, attitude, confidence to recommend, and PA promotion (p < 0.05)., Conclusions: Oncologists reported a modest ability to promote PA, low PA promotion rates, and limited knowledge of exercise prescription. Patient physical activity promotion may be improved through strategies that increase oncologists' PBC, confidence, and their own personal PA participation.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America, accounting for >30,000 deaths annually. Although somatic activating mutations in KRAS appear in 97% of PDAC patients, additional factors are required to initiate PDAC. Because mutations in genes encoding chromatin remodelling proteins have been implicated in KRAS-mediated PDAC, we investigated whether loss of chromatin remodeler ɑ-thalassemia, mental-retardation, X-linked (ATRX) affects oncogenic KRAS's ability to promote PDAC. ATRX affects DNA replication, repair, and gene expression and is implicated in other cancers including glioblastomas and pancreatic neuroendocrine tumors. The hypothesis was that deletion of Atrx in pancreatic acinar cells will increase susceptibility to injury and oncogenic KRAS., Methods: Mice allowing conditional loss of Atrx within pancreatic acinar cells were examined after induction of recurrent cerulein-induced pancreatitis or oncogenic KRAS ( KRAS G12D ). Histologic, biochemical, and molecular analysis examined pancreatic pathologies up to 2 months after induction of Atrx deletion., Results: Mice lacking Atrx showed more progressive damage, inflammation, and acinar-to-duct cell metaplasia in response to injury relative to wild-type mice. In combination with KRAS G12D , Atrx -deficient acinar cells showed increased fibrosis, inflammation, progression to acinar-to-duct cell metaplasia, and pre-cancerous lesions relative to mice expressing only KRAS G12D . This sensitivity appears only in female mice, mimicking a significant prevalence of ATRX mutations in human female PDAC patients., Conclusions: Our results indicate the absence of ATRX increases sensitivity to injury and oncogenic KRAS only in female mice. This is an instance of a sex-specific mutation that enhances oncogenic KRAS's ability to promote pancreatic intraepithelial lesion formation.

Background: Deep prosthetic infection is a potentially devastating complication after total elbow arthroplasty, with an incidence of up to 12%. This study examined the demographics, microbiologic profile, and outcomes of infected total elbow arthroplasty treated with 2-stage revision in a tertiary referral unit., Methods: We identified 19 consecutive patients (mean age, 65 years) undergoing revision arthroplasty for deep prosthetic infection. All patients underwent a first-stage procedure with removal of implants, débridement, and insertion of an antibiotic-loaded cement spacer, followed by at least 6 weeks of intravenous antibiotics. Fourteen patients required a second-stage revision., Results: Five patients did not undergo a second-stage procedure because of patient choice (n = 2), medical or surgical risk factors (n = 2), and death from an unrelated cause (n = 1). Of the 19 patients undergoing a first-stage procedure, 16 (84%) remained infection free, and 11 of the 14 patients (79%) undergoing reimplantation of an elbow prosthesis remained infection free. Six patients required further surgery (3 for recurrent infection, 3 for noninfective indications). The commonest infecting organism was Staphylococcus aureus (47%). A degree of postoperative ulnar nerve dysfunction occurred in 37% of patients, but all resolved fully without further treatment., Conclusions: Management of prosthetic joint infection using 2-stage revision can result in high rates of eradication, although rates of reoperation and transient ulnar nerve dysfunction are high., (Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.)

Objective: The effects of lactic acid bacteria (LAB) and cellulase enzyme on fermentation quality, microorganism population, chemical composition and in vitro gas production of sorghum silages were studied., Methods: Commercial inoculant Lactobacillus plantarum Chikuso 1 (CH), local selected strain Lactobacillus casei (L. casei) TH 14 and Acremonium cellulase (AC) were used as additives in sorghum silage preparation., Results: Prior to ensiling Sorghum contained 104 LAB and 106 cfu/g fresh matter coliform bacteria. The chemical compositions of sorghum was 26.6% dry matter (DM), 5.2% crude protein (CP), and 69.7% DM for neutral detergent fiber. At 30 days of fermentation after ensiling, the LAB counts increased to a dominant population; the coliform bacteria and molds decreased to below detectable level. All sorghum silages were good quality with a low pH (<3.5) and high lactic acid content (>66.9 g/kg DM). When silage was inoculated with TH14, the pH value was significantly (p<0.05) lower and the CP content significantly (p<0.05) higher compared to control, CH and AC-treatments. The ratio of in vitro methane production to total gas production and DM in TH 14 and TH 14+AC treatments were significantly (p<0.05) reduced compared with other treatments while in vitro dry matter digestibility and gas production did not differ among treatments., Conclusion: The results confirmed that L. casei TH14 could improve sorghum silage fermentation, inhibit protein degradation and decrease methane production.

Background: This study reports the clinical outcome after glenohumeral arthrodesis for recurrent type II (atraumatic structural) and type III (muscle patterning nonstructural disorder) shoulder instability., Methods: A retrospective review was conducted at a single facility. Eight consecutive patients (7 women and 1 man) with recurrent shoulder instability underwent arthrodesis and were monitored for a mean of 57 months (range, 24-123 months). Mean age at the time of surgery was 47 years (range, 21-73 years)., Results: Bony union was achieved in all patients at a mean time to fusion of 3 months (range, 1-11 months). No complications, such as routine removal of the metalwork or loosening, were noted. No residual perceived glenohumeral instability was reported, and no patient developed scapulothoracic instability or painful scapular dyskinesis. The mean Oxford Shoulder Instability Score improved from 8 preoperatively (range, 0-19) to 32 postoperatively (range, 16-41; P = .001). This was accompanied by an increase in the mean subjective shoulder value, which improved from 22 (range, 0-50) preoperatively to 73 (range, 50-100) postoperatively (P = .004)., Conclusion: In our series, glenohumeral arthrodesis was associated with no complications and was able to reduce pain, eliminate instability, and improve functional outcome. It should therefore be considered in this patient population., (Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Natural lactic acid bacteria (LAB) populations in tropical grasses and their fermentation characteristics on silage prepared with cellulase enzyme and LAB inoculants were studied. A commercial inoculant Lactobacillus plantarum Chikuso 1 (CH), a local selected strain Lactobacillus casei TH14 (TH14), and 2 cellulases, Acremonium cellulase (AC) and Maicelase (MC; Meiji Seika Pharma Co. Ltd., Tokyo, Japan), were used as additives to silage preparation with fresh and wilted (6 h) Guinea grass and Napier grass. Silage was prepared using a laboratory-scale fermentation system. Treatments were CH, TH14, AC at 0.01% fresh matter, AC 0.1%, MC 0.01%, MC 0.1%, CH+AC 0.01%, CH+AC 0.1%, CH+MC 0.01%, CH+MC 0.1%, TH14+AC 0.1%, TH14+AC 0.01%, TH14+MC 0.1%, and TH14+MC 0.01%. Microorganism counts of Guinea grass and Napier grass before ensiling were 10 2 LAB and 10 6 aerobic bacteria; these increased during wilting. Based on morphological and biochemical characteristics, and 16S rRNA gene sequence analysis, natural strains from both grasses were identified as L. plantarum, L. casei, Lactobacillus acidipiscis, Leuconostoc pseudomesenteroides, Leuconostoc garlicum, Weissella confusa, and Lactococcus lactis. Lactobacillus plantarum and L. casei are the dominant species and could grow at lower pH and produce more lactic acid than the other isolates. Crude protein and neutral detergent fiber were 5.8 and 83.7% of dry matter (DM) for Guinea grass, and 7.5 and 77.1% of DM for Napier grass. Guinea grass had a low level of water-soluble carbohydrates (0.39% of DM). Guinea grass silage treated with cellulase had a lower pH and higher lactic acid content than control and LAB treatments. The 0.1% AC and MC treatments had the best result for fermentation quality. All high water-soluble carbohydrate (2.38% DM) Napier grass silages showed good fermentation quality. Compared with control and LAB-inoculated silage, the cellulase-treated silages had significantly higher crude protein content and lower neutral detergent fiber and acid detergent fiber contents. The results confirmed that cellulase could improve tropical silage quality, inhibiting protein degradation and promoting fiber degradation., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Strains TH 14, TH 21 and TH 64 were isolated from tropical silages, namely corn stover, sugar cane top and rice straw, respectively, prepared in Thailand. These strains were selected by low pH growth range and high lactic acid-producing ability, similar to some commercial inoculants. Based on the analysis of 16S ribosomal RNA gene sequence and DNA-DNA relatedness, strain TH 14 was identified as Lactobacillus casei, and strains TH 21 and TH 64 were identified as L. plantarum. Strains TH 14, TH 21, TH 64 and two commercial inoculants, CH (L. plantarum) and SN (L. rhamnosus), were used as additives to fresh and wilted purple Guinea and sorghum silages prepared using a small-scale fermentation method. The number of epiphytic lactic acid bacteria (LAB) in the forages before ensilage was relatively low but the numbers of coliform and aerobic bacteria were higher. Sorghum silages at 30 days of fermentation were all well preserved with low pH (3.56) and high lactic acid production (72.86 g/kg dry matter). Purple Guinea silage inoculated with LAB exhibited reduced count levels of aerobic and coliform bacteria, lower pH, butyric acid and ammonia nitrogen and increased lactic acid concentration, compared with the control. Strain TH 14 more effectively improved lactic acid production compared with inoculants and other strains. © 2016 Japanese Society of Animal Science., (© 2016 Japanese Society of Animal Science.)

Accurate diagnosis of rare inherited anaemias is challenging, requiring a series of complex and expensive laboratory tests. Targeted next-generation-sequencing (NGS) has been used to investigate these disorders, but the selection of genes on individual panels has been narrow and the validation strategies used have fallen short of the standards required for clinical use. Clinical-grade validation of negative results requires the test to distinguish between lack of adequate sequencing reads at the locations of known mutations and a real absence of mutations. To achieve a clinically-reliable diagnostic test and minimize false-negative results we developed an open-source tool (CoverMi) to accurately determine base-coverage and the 'discoverability' of known mutations for every sample. We validated our 33-gene panel using Sanger sequencing and microarray. Our panel demonstrated 100% specificity and 99·7% sensitivity. We then analysed 57 clinical samples: molecular diagnoses were made in 22/57 (38·6%), corresponding to 32 mutations of which 16 were new. In all cases, accurate molecular diagnosis had a positive impact on clinical management. Using a validated NGS-based platform for routine molecular diagnosis of previously undiagnosed congenital anaemias is feasible in a clinical diagnostic setting, improves precise diagnosis and enhances management and counselling of the patient and their family., (© 2016 John Wiley & Sons Ltd.)

Aim: To report the results of fixed-fulcrum fully constrained reverse shoulder arthroplasty for the treatment of recurrent shoulder instability in patients with epilepsy., Methods: A retrospective review was conducted at a single facility. Cases were identified using a computerized database and all clinic notes and operative reports were reviewed. All patients with epilepsy and recurrent shoulder instability were included for study. Between July 2003 and August 2011 five shoulders in five consecutive patients with epilepsy underwent fixed-fulcrum fully constrained reverse shoulder arthroplasty for recurrent anterior shoulder instability. The mean duration of epilepsy in the cohort was 21 years (range, 5-51) and all patients suffered from grand mal seizures., Results: Mean age at the time of surgery was 47 years (range, 32-64). The cohort consisted of four males and one female. Mean follow-up was 4.7 years (range, 4.3-5 years). There were no further episodes of instability, and no further stabilisation or revision procedures were performed. The mean Oxford shoulder instability score improved from 8 preoperatively (range, 5-15) to 30 postoperatively (range, 16-37) (P = 0.015) and the mean subjective shoulder value improved from 20 (range, 0-50) preoperatively to 60 (range, 50-70) postoperatively (P = 0.016). Mean active forward elevation improved from 71° preoperatively (range, 45°-130°) to 100° postoperatively (range, 80°-90°) and mean active external rotation improved from 15° preoperatively (range, 0°-30°) to 40° (20°-70°) postoperatively. No cases of scapular notching or loosening were noted., Conclusion: Fixed-fulcrum fully constrained reverse shoulder arthroplasty should be considered for the treatment of recurrent shoulder instability in patients with epilepsy.

Objectives: To review the history of newborn screening for sickle cell disease with especial reference to Jamaica., Methods: A summary was done of the history, the development of associated laboratory technology and the implementation of newborn screening for sickle cell disease in Jamaica., Results: Screening was initiated at Victoria Jubilee Hospital, Kingston from 1973-1981, reactivated in 1995 and extended to the University Hospital of the West Indies in 1997 and to Spanish Town Hospital in 1998. From August 2008, there was a progressive recruitment of 12 hospitals in the south and west of Jamaica which has raised the frequency of islandwide newborn coverage from 25% in 1973 to 81%. The results of this extended programme in southwest Jamaica are presented. Dried blood spots collected from the umbilical cord proved stable, cheap and efficient; mean sample collection rates were 98%, maternal contamination occurred in < 1% and caused diagnostic confusion in < 0.1%. By March 31, 2015, a total of 54 566 births have been screened, detecting 161 with homozygous sickle cell (SS) disease, 125 with sickle cell-haemoglobin C (SC) disease and 36 with sickle cell-beta thalassaemia. Of the 327 babies with clinically significant sickle cell syndromes, all except five who died within seven days of birth were confirmed by four to six weeks and recruited to local sickle cell clinics., Conclusion: Early detection of sickle cell disease and recruitment to clinics is known to reduce its morbidity and mortality. The methods currently detailed provide an effective and economic model of newborn screening which may be of value elsewhere.

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.

Background: Patients with skeletal dysplasia are prone to the development of degenerative shoulder disease requiring shoulder arthroplasty at a younger age than in the general population. To date there have been no published reports on the complexities or outcome of shoulder arthroplasty in this unique patient group., Methods: This is a review of 13 shoulder arthroplasties in 10 patients with skeletal dysplasia with mean follow-up of 7 years (2-17.6 years). There were 4 men and 6 women with a mean age of 53.1 years (23-76 years), mean height of 148 cm (122-177 cm), and mean weight of 60 kg (27-80 kg)., Results: The mean Oxford Shoulder Score increased from 13 (5-20) preoperatively to 28 (18-38) at final follow-up. Patients improved significantly in 2 of 8 Short Form 36 health-related quality of life domains: physical function (P = .04) and bodily pain (P = .04). Function was better in those who underwent nonconstrained total shoulder arthroplasty as opposed to hemiarthroplasty. Four (31%) required reoperation: 1 excision of heterotopic ossification, 1 relocation for anterior instability, and 2 revisions for periprosthetic fracture and glenoid erosion., Conclusion: Shoulder arthroplasty is effective at relieving pain, optimizing movement, and improving function for patients with skeletal dysplasia; however, compared with the general population, there is a higher complication rate and function is not as good. Furthermore, this procedure is less effective at restoring health-related quality of life than total hip arthroplasty or total shoulder arthroplasty performed for osteoarthritis in the general population. Custom implants may be required to compensate for short stature and rotator cuff and glenoid deficiency., (Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Inherent disadvantages of reverse shoulder arthroplasty designs based on the Grammont concept have raised a renewed interest in less-medialised designs and techniques. The aim of this study was to evaluate the outcome of reverse shoulder arthroplasty (RSA) with the fully-constrained, less-medialised, Bayley-Walker prosthesis performed for the treatment of rotator-cuff-deficient shoulders with glenohumeral arthritis. A total of 97 arthroplasties in 92 patients (53 women and 44 men, mean age 67 years (standard deviation (sd) 10, (49 to 85)) were retrospectively reviewed at a mean follow-up of 50 months ((sd 25) (24 to 96)). The mean Oxford shoulder score and subjective shoulder value improved from 47 (sd 9) and 24 points (sd 18) respectively before surgery to 28 (sd 11) and 61 (sd 24) points after surgery (p < 0.001). The mean pain at rest decreased from 5.3 (sd 2.8) to 1.5 (sd 2.3) (p < 0.001). The mean active forward elevation and external rotation increased from 42(°)(sd 30) and 9(°) (sd 15) respectively pre-operatively to 78(°) (sd 39) and 24(°) (sd 17) post-operatively (p < 0.001). A total of 20 patients required further surgery for complications; 13 required revision of components. No patient developed scapular notching. The Bayley-Walker prosthesis provides reliable pain relief and reasonable functional improvement for patients with symptomatic cuff-deficient shoulders. Compared with other designs of RSA, it offers a modest improvement in forward elevation, but restores external rotation to some extent and prevents scapular notching. A longer follow-up is required to assess the survival of the prosthesis and the clinical performance over time., (©2014 The British Editorial Society of Bone & Joint Surgery.)

This third year work was carried on at Khon Kaen University during the 2008-2009 to investigate dry matter yields of grass, grass plus legumes, grown on Korat soil series (Oxic Paleustults). The experiment consisted of twelve-treatment combinations of a 3x4 factorial arranged in a Randomized Complete Block Design (RCBD) with four replications. The results showed that Dry Matter Yields (DMY) of Ruzi and Guinea grass were similar with mean values of 6,585 and 6,130 kg ha(-1) whilst Napier gave the lowest (884 kg ha(-1)). With grass plus legume, grass species and production methods gave highly significant dry matter yields where Guinea and Ruzi gave dry matter yields of 7,165 and 7,181 kg ha(-1), respectively and Napier was the least (2,790 kg ha(-1)). The production methods with the use of cattle manure gave the highest DMY (grass alone) of 10,267 kg ha(-1) followed by Wynn and Verano with values of 6,064 and 3,623 kg ha(-1), respectively. Guinea plus cattle manure gave the highest DMY of 14,599 kg ha(-1) whilst Ruzi gave 12,977 kg ha(-1). Guinea plus Wynn gave DMY of 7,082 kg ha(-1). Ruzi plus Verano gave DMY of 6,501 kg ha(-1). Forage qualities of crude protein were highest with those grown with grass plus legumes. Some prospects in improving production were discussed.

Background: Nerve injury is an acknowledged complication of total shoulder arthroplasty (TSA). Although the incidence of postoperative neurological deficit has been reported to be between 1% and 16%, the true incidence of nerve damage is considered to be higher. The present study aimed to identify the rate of intraoperative nerve injury during total shoulder arthroplasty and to determine potential risk factors., Methods: A prospective study of nerve conduction in 21 patients who underwent primary or revision TSA was carried out over a 12-month period. Nerve conduction was monitored by measuring intraoperative sensory evoked potentials (SEP). A significant neurophysiological signal change was defined as either a unilateral or bilateral decrease in SEP signal of ≥50%, a latency increase of ≥10% or a change in waveform morphology, not caused by operative or anaesthetic technique., Results: Seven (33%) patients had a SEP signal change. The only significant risk factor identified for signal change was male sex (odds ratio 15.00, 95% confidence interval). The median nerve was the most affected nerve in the operated arm. All but one signal change returned to normal before completion of the operation and no patient had a persisting postoperative clinical neurological deficit., Conclusions: The incidence of intraoperative nerve damage may be more common than previously reported. However, the loss of SEP signal is reversible and does not correlate with persisting clinical neurological deficits. The median nerve appears to be most at risk. Monitoring SEPs in the operated limb during TSA may be a valuable tool during TSA.

Background: Anterior instability of the sternoclavicular joint is uncommon and usually follows a benign course, although symptomatic patients may require surgical intervention. The optimal treatment for symptomatic instability of the sternoclavicular joint remains unclear. The aim of this study was to evaluate the clinical outcome after reconstruction of the sternoclavicular joint with use of a sternocleidomastoid tendon graft to treat chronic debilitating anterior instability of the sternoclavicular joint., Methods: Thirty-two patients underwent surgical reconstruction of the sternoclavicular joint for chronic debilitating anterior instability using the tendon of the sternal head of the ipsilateral sternocleidomastoid muscle and were followed for a mean of forty-four months. The etiology of instability was posttraumatic in fourteen patients, generalized hyperlaxity in seven patients, and degenerative instability in eleven patients. Outcome measures included the Oxford instability shoulder score, subjective shoulder value, pain rating, and postoperative grading of sternoclavicular joint stability., Results: Clinical scores and pain rating were similar for the three groups before surgery and improved significantly in all of the groups to the same extent after the surgery. At the time of the latest follow-up, eleven of fourteen patients in the posttraumatic group, six of seven patients in the generalized hyperlaxity group, and eight of eleven patients in the degenerative group reported the sternoclavicular joint as stable with no functional limitation. Two patients reported that the joint remained unstable. No other complications occurred., Conclusions: Sternoclavicular joint reconstruction using a sternocleidomastoid tendon graft is safe and offers reliable pain relief and functional improvement for patients with chronic debilitating anterior instability of the sternoclavicular joint.

Background: Late complications after humeral head replacement (HHR) for comminuted proximal humeral fractures are common and may necessitate revision surgery. This study evaluated the outcome of revision surgery of failed post-traumatic HHR with a less medialized reverse shoulder prosthesis., Methods: Thirty-three patients with failed post-traumatic HHR due to rotator-cuff insufficiency and glenoid erosion, but with sufficient preservation of the glenoid bone stock to permit primary stability of an inverted glenoid implant, underwent revision using the Bayley-Walker reverse shoulder prosthesis (Stanmore Implants, Elstree, UK) and were monitored up for a mean of 31 months. Outcome measures included the Oxford Shoulder Score, subjective shoulder value, pain rating, active range of motion, and shoulder radiographs., Results: The average postrevision Oxford Shoulder Score and subjective shoulder value improved from 50 ± 6 to 29 ± 11 and from 23 ± 19 to 51 ± 23, respectively (P < .001). Pain level decreased from 6.2 ± 2.1 to 1.4 ± 2.0 (P < .001). Active forward flexion increased from 34° ± 22° to 63° ± 30° and external rotation from 11° ± 14° to 20° ± 16°(P < .01). More patients were able to use their affected arm to reach a functional triangle consisting the mouth, opposite armpit, and ipsilateral buttock after revision (24% vs 73%; P < .001). Seven patients (21%) had postrevision complications. No glenoid loosening or scapular notching occurred., Conclusion: Revision of failed post-traumatic HHR with the Bayley-Walker shoulder offers reliable pain relief and improvement in shoulder function with a complication rate similar to other reverse prostheses. Nevertheless, revision shoulder arthroplasty remains challenging with a high rate of complications., (Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Our understanding of biological processes in humans is often based on examination of analogous processes in other organisms. The nematode worm Caenorhabditis elegans has been a particularly valuable model, leading to Nobel prize winning discoveries in development and genetics. Until recently, however, the worm has not been widely used as a model to study transcription due to the lack of a comprehensive catalogue of its RNA transcripts. A recent study by Chen et al. uses next-generation sequencing to address this issue, mapping the transcription initiation sites in C. elegans and finding many unexpected similarities between the transcription of enhancers and promoters in the worm and mammalian genomes. As well as providing a valuable resource for researchers in the C. elegans community, these findings raise the possibility of using the worm as a model to investigate some key, current questions about transcriptional regulation that remain technically challenging in more complex organisms., (© 2014 WILEY Periodicals, Inc.)

Background: Revision arthroplasty for failed post-traumatic humeral head replacement associated with rotator cuff and glenoid deficiency is challenging. Current surgical solutions are fraught with complications, and no best-practice strategy has been established. We hypothesized that the computer-assisted design/computer-assisted manufacturing (CAD/CAM) shoulder (Stanmore Implants, Elstree, UK), a total shoulder design resembling a total hip prosthesis, can offer a reliable alternative in this surgically challenging subset of patients with rotator cuff deficiency and advanced glenoid bone loss., Methods: Twenty-one patients with failed post-traumatic humeral head replacement associated with rotator cuff and glenoid deficiency underwent revision with CAD/CAM shoulders between 2005 and 2010. Clinical data were collected prospectively and analyzed at a mean follow-up of 3 years., Results: After revision, the pain rating at rest (on a 0-10 numerical scale) decreased from 5.6 ± 1.3 to 1.1 ± 1.3 (P < .001) and pain during activity decreased from 7.4 ± 1.2 to 2.1 ± 1.8 (P < .001). The Oxford shoulder score improved from 47 ± 6 to 31 ± 9 (P < .001), and the subjective shoulder value (on a 0%-100% scale) improved from 22% ± 14% to 45% ± 18% (P < .001). Active shoulder range of motion was similar before and after revision. Postoperative complications occurred in 9 patients and included 1 infection, 2 periprosthetic fractures, 2 prosthetic dislocations, and 4 fixation screw fractures. No case of glenoid loosening occurred., Conclusion: The CAD/CAM shoulder offers a reliable method of securing a glenoid component in shoulders with advanced glenoid deficiency and should be considered as an alternative to other surgical methods in these challenging cases. At 3 years' follow-up, pain and clinical scores improved significantly and no case of glenoid loosening occurred., (Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Background. The challenge in managing patients undergoing renal transplantation is how to achieve optimum levels of anticoagulation to avoid both clotting and postoperative bleeding. We report a rare case of severe postoperative retroperitoneal bleeding including psoas haematomata complicating renal transplantation. Case Report. SM, a 55-year-old female, had a past history of aortic valve replacement, cerebrovascular event, and thoracic aortic aneurysm and was on long-term warfarin that was switched to enoxaparin 60 mg daily a week prior to her living donor transplantation. Postoperatively, she was started on a heparin infusion, but this was complicated by a large retroperitoneal bleed requiring surgical evacuation on the first postoperative day. Four weeks later, she developed features compatible with acute femoral neuropathy and a CT scan revealed bilateral psoas haematomata. Following conservative management, she made steady progress and was discharged home via a community hospital 94 days after transplantation. At her last visit 18 months after transplantation, she had returned to full fitness with excellent transplant function. Conclusion. Patients in established renal failure who require significant anticoagulation are at increased risk of bleeding that may involve prolonged hospitalisation and more protracted recovery and patients should be carefully counselled about this.

The electrical Ca test was used to measure H2O vapor transmission through polyethylene naphthalate (PEN) polymer with a thickness of 200 μm. On the basis of the time required for the normalized conductance of the Ca film to reach zero, the H2O vapor transmission rate was determined versus H2O flux, temperature, and saturation of the PEN polymer with H2O. The H2O vapor transmission rate was proportional to the H2O flux and only weakly dependent on temperature at constant H2O flux. The transmission coefficient, Γ, for H2O through the PEN polymer at 70 °C was Γ ∼ 3.2 × 10(-10). The corresponding water vapor transmission rate (WVTR) at 70 °C/80% RH was 0.65 g/(m(2) day). The temperature dependence of the H2O vapor transmission rate through PEN at constant H2O flux yielded an activation barrier of E = 12.4 kJ/mol. There was no observable reservoir effect for H2O in the PEN polymer. The H2O vapor transmission rates for initially dry or H2O-saturated PEN polymer substrates were nearly identical at various temperatures. Although the time required for the normalized conductance of the Ca film to reach zero was inversely proportional to the H2O flux, the Ca film conductance did not decrease linearly versus H2O exposure. The Ca film conductance changed very little during initial H2O exposure. This behavior may be caused by the nonlinear oxidation kinetics of the Ca film.

The New Zealand bigeye, Pempheris adspersa, is a nocturnal planktivore and has recently been found to be an active sound producer. The rostral end of the swim bladder lies adjacent to Baudelot's ligament which spans between the bulla and the cleithrum bone of the pectoral girdle. The aim of this study was to use the auditory evoked potential technique to physiologically test the possibility that this structure provides an enhanced sensitivity to sound pressure in the bigeye. At 100 Hz, bigeye had hearing sensitivity similar to that of goldfish (species with a mechanical connection between the swim bladder and the inner ear mediated by the Weberian ossicles) and were much more sensitive than other teleosts without ancillary hearing structures. Severing Baudelot's ligament bilaterally resulted in a marked decrease in hearing sensitivity, as did swim bladder puncture or lateral line blockage. These results show that bigeye have an enhanced sensitivity to sound pressure and provide experimental evidence that the functional basis of this sensitivity represents a novel hearing specialization in fish involving the swim bladder, Baudelot's ligament and the lateral line.

In the underwater environment, sound propagates both as a pressure wave and as particle displacement, with particle displacement dominating close to the source (the nearfield). At the receptor level, both the fish ear and the neuromast hair cells act as displacement detectors and both are potentially stimulated by the particle motion component of sound sources, especially in the nearfield. A now common way to test 'hearing' in fish involves auditory evoked potentials (AEPs), with recordings made from electrodes implanted near the auditory brainstem. These AEP recordings are typically conducted in enclosed acoustic environments with the fish well within the nearfield, especially for lower frequencies. We tested the contribution of neuromast hair cells to AEP by first testing intact goldfish (Carassius auratus), then ablating their neuromasts with streptomycin sulphate--disabling superficial and canal neuromasts--and retesting the same goldfish. We performed a similar experiment where only the superficial neuromasts were physically ablated. At 100 and 200 Hz, there was a 10-15 dB increase in threshold after streptomycin treatment but no significant difference at higher frequencies. There was no difference in threshold in control fish or in fish that only had superficial neuromasts removed, indicating that the differential responses were driven by canal neuromasts. Taken together, these results indicate that AEP results at lower frequencies should be interpreted as multimodal responses, rather than as 'hearing'. The results also suggest that in natural situations both the ear and lateral line likely play an integrative role in detecting and localising many types of 'acoustic' stimuli.

There is little information about the management of peri-prosthetic fracture of the humerus after total shoulder replacement (TSR). This is a retrospective review of 22 patients who underwent a revision of their original shoulder replacement for peri-prosthetic fracture of the humerus with bone loss and/or loose components. There were 20 women and two men with a mean age of 75 years (61 to 90) and a mean follow-up 42 months (12 to 91): 16 of these had undergone a previous revision TSR. Of the 22 patients, 12 were treated with a long-stemmed humeral component that bypassed the fracture. All their fractures united after a mean of 27 weeks (13 to 94). Eight patients underwent resection of the proximal humerus with endoprosthetic replacement to the level of the fracture. Two patients were managed with a clam-shell prosthesis that retained the original components. The mean Oxford shoulder score (OSS) of the original TSRs before peri-prosthetic fracture was 33 (14 to 48). The mean OSS after revision for fracture was 25 (9 to 31). Kaplan-Meier survival using re-intervention for any reason as the endpoint was 91% (95% confidence interval (CI) 68 to 98) and 60% (95% CI 30 to 80) at one and five years, respectively. There were two revisions for dislocation of the humeral head, one open reduction for modular humeral component dissociation, one internal fixation for nonunion, one trimming of a prominent screw and one re-cementation for aseptic loosening complicated by infection, ultimately requiring excision arthroplasty. Two patients sustained nerve palsies. Revision TSR after a peri-prosthetic humeral fracture associated with bone loss and/or loose components is a salvage procedure that can provide a stable platform for elbow and hand function. Good rates of union can be achieved using a stem that bypasses the fracture. There is a high rate of complications and function is not as good as with the original replacement.

Objective: To compare the haematological and clinical features of homozygous sickle cell (SS) disease in Bantu and Benin haplotypes in a cross-sectional study of 115 Ugandan patients attending the Sickle Cell Clinic at Mulago Hospital, Kampala, Uganda, with 311 patients in the Jamaican Cohort Study, Methods: This involved comparison of clinical features and haematology with special reference to genetic determinants of severity including fetal haemoglobin levels, beta-globin haplotype and alpha thalassaemia status., Results: The Bantu haplotype accounted for 94% of HbS chromosomes in Ugandan patients and the Benin haplotype for 76% of HbS chromosomes in Jamaica. Ugandan patients were marginally more likely to have alpha thalassaemia, had similar total haemoglobin and fetal haemoglobin levels but had higher reticulocyte counts and total bilirubin levels consistent with greater haemolysis. Ugandan patients had less leg ulceration and priapism, but the mode of clinical presentation, prevalence of dactylitis, features of bone pain and degree of delay in sexual development, assessed by menarche, were similar in the groups. In Ugandan patients, a history of anaemic episodes was common but these were poorly documented., Conclusion: The haematological and clinical features of the Bantu haplotype in Uganda were broadly similar to the Benin haplotype in Jamaica except for less leg ulceration and priapism and possibly greater haemolysis among Ugandan subjects. Anaemic episodes in Uganda were treated empirically by transfusion often without a clear diagnosis; better documentation including reticulocyte counts and observations on spleen size is necessary to evolve appropriate models of care.