A further case of chondrodysplasia with growth failure occurring after hematopoietic stem cell transplantation (HSCT).

There is an emerging body of evidence showing that young patients, post haematopoietic stem cell transplantation (HSCT), can develop skeletal changes that mimic an osteochondrodysplasia process. The key discriminator is that these children have had otherwise normal growth and skeletal development before the therapeutic intervention (HSCT), typically for a haematological malignancy. Herein we present that case of a boy who underwent HSCT for Haemophagocytic Lymphohistiocytosis (HLH) aged 2 years. Following Intervention with HSCT this boy's growth has severely decelerated (stature less than 1st centile matched for age) and he has developed a spondyloepiphyseal dysplasia.

Disordered eating is not associated with musculoskeletal injury in university athletes.

TAKE HOME MESSAGE: Musculoskeletal injuries and disordered eating are prevalent in varsity-level athletes but are not associated in our participants.

Evaluation of a national clinical programme for the management of self-harm in hospital emergency departments: impact on patient outcomes and the provision of care.

BACKGROUND: Emergency departments are important points of intervention, to reduce the risk of further self-harm and suicide. A national programme to standardise the management of people presenting to the emergency department with self-harm and suicidal ideation (NCPSHI) was introduced in Ireland in 2014. The aim of this study was to evaluate the impact of the NCPSHI on patient outcomes and provision of care. METHODS: Data on self-harm presentations were obtained from the National Self-Harm Registry Ireland from 2012 to 2017. The impacts of the NCPSHI on study outcomes (3-month self-harm repetition, biopsychosocial assessment provision, admission, post-discharge referral, and self-discharge) were examined at an individual and aggregate (hospital) level, using a before and after study design and interrupted time series analyses, respectively. The 15 hospitals that implemented the programme by January 2015 (of a total of 24 between 2015 and 2017) were included in the analyses. RESULTS: There were 31,970 self-harm presentations during the study period. In hospitals with no service for self-harm (n = 4), risk of patients not being assessed reduced from 31.8 to 24.7% following the introduction of the NCPSHI. Mental health referral in this hospital group increased from 42.2 to 59.0% and medical admission decreased from 27.5 to 24.3%. Signs of a reduction in self-harm repetition were observed for this hospital group, from 35.1 to 30.4% among individuals with a history of self-harm, but statistical evidence was weak. In hospitals with a pre-existing liaison psychiatry service (n = 7), risk of self-discharge was lower post-NCPSHI (17.8% vs. 14.8%). In hospitals with liaison nurse(s) pre-NCPSHI (n = 4), medical admission reduced (27.5% vs. 24.3%) and there was an increase in self-harm repetition (from 5.2 to 7.8%. for those without a self-harm history). CONCLUSION: The NCPSHI was associated with improvements in the provision of care across hospital groups, particularly those with no prior service for self-harm, highlighting the need to consider pre-existing context in implementation planning. Our evaluation emphasises the need for proper resourcing to support the implementation of clinical guidelines on the provision of care for people presenting to hospital with self-harm.

Spiraling Risk: Visualizing the multilevel factors that socially pattern HIV risk among gay, bisexual & other men who have sex with men using Complex Systems Theory.

PURPOSE OF REVIEW: Global disparities in HIV infection, particularly among gay, bisexual, and other men who have sex with men (GBMSM), indicate the importance of exploring the multi-level processes that shape HIV's spread. We used Complex Systems Theory and the PRISMA guidelines to conduct a systematic review of 63 global reviews to understand how HIV is socially patterned among GBMSM. The purpose was to conduct a thematic analysis of the reviews to (1) synthesize the multi-level risk factors of HIV risk, (2) categorize risk across the socioecological model, and (3) develop a conceptual model that visualizes the interrelated factors that shape GBMSMS's HIV "risk." RECENT FINDINGS: We included 49 studies of high and moderate quality studies. Results indicated that GBMSM's HIV risk stems from the individual, interpersonal, and structural levels of the socioecological model. We identified a few themes that shape GBMSM's risk of HIV infection related to biomedical prevention methods; sexual and sex-seeking behaviors; behavioral prevention methods; individual-level characteristics and syndemic infections; lived experiences and interpersonal relationships; country-level income; country-level HIV prevalence; and structural stigma. The multi-level factors, in tandem, serve to perpetuate GBMSM's risk of HIV infection globally. The amalgamation of our thematic analyses from our systematic reviews of reviews suggests that the risk of HIV infection operates in an emergent, dynamic, and complex nature across multiple levels of the socioecological model. Applying complex systems theory indicates how multilevel factors create a dynamic and reinforcing system of HIV risk among GBMSM.

Effects of a Multi-component, Resistance-Based Exercise Program Combined with Additional Lean Red Meat on Health-Related Quality of Life in Older Adults: Secondary Analysis of a 6-Month Randomized Controlled Trial.

OBJECTIVES: To assess whether consumption of lean red meat on three exercise training days per week can promote greater improvements than exercise alone in health-related quality of life (HR-QoL) in community-dwelling older adults. DESIGN: This study is a secondary analysis from a 6 month, two-arm, parallel randomized controlled trial conducted in 2014 and 2015. SETTING: Community-dwelling older adults living in metropolitan Melbourne, Australia. PARTICIPANTS: One hundred and fifty-four men and women aged ≥65 years. INTERVENTION: All participants were enrolled in a multi-component, resistance-based exercise program (3 d/week) and randomly allocated to either a group asked to consume lean red meat (2x80g cooked servings/day) on each of the three training days (Ex+Meat, n=77) or a control group asked to consume one serving of carbohydrates (1/2 cup rice/pasta or 1 medium potato; Ex+C, n=77). MEASUREMENTS: HR-QoL was assessed using the Short-Form (SF)-36 health survey. RESULTS: Overall 62% of the participants were female, the mean age was 70.7 years (range 65 to 84 years), approximately 67% of participants were classified as either overweight or obese, and the average number of chronic conditions was two. A total of 145 participants (94%) completed the study. Mean baseline HR-QoL scores were comparable to the mean for the Australian population [Global HR-QoL (mean ± SD): Ex+Meat, 49.99 ± 6.57; Ex+C, 50.49 ± 5.27]. General Linear Mixed Models examining within and between group changes over time revealed that after 6 months, there were no within-group changes in either Ex+Meat or Ex+C nor any between-group differences for any measure of HR-QoL, with the exception that the mental health subscale improved in Ex+C versus Ex+Meat [net difference for change, -2.32 (95% CI), -4.73, 0.09, P=0.048] after adjusting for relevant covariates and the physical function subscale improved in Ex+Meat relative to baseline [mean change (95% CI), 1.88 (0.37, 3.39), P=0.011]. CONCLUSION: A multi-component resistance-based training program performed with and without the provision of lean red meat in line with current Australian dietary guidelines on each of the three training days, did not improve HR-QoL in healthy community-dwelling older adults.

Designing rare disease care pathways in the Republic of Ireland: a co-operative model.

BACKGROUND: Rare diseases (RDs) are often complex, serious, chronic and multi-systemic conditions, associated with physical, sensory and intellectual disability. Patients require follow-up management from multiple medical specialists and health and social care professionals involving a high level of integrated care, service coordination and specified care pathways. METHODS AND OBJECTIVES: This pilot study aimed to explore the best approach for developing national RD care pathways in the Irish healthcare system in the context of a lack of agreed methodology. Irish clinical specialists and patient/lived experience experts were asked to map existing practice against evidence-based clinical practice guidelines (CPGs) and best practice recommendations from the European Reference Networks (ERNs) to develop optimal care pathways. The study focused on the more prevalent, multisystemic rare conditions that require multidisciplinary care, services, supports and therapeutic interventions. RESULTS: 29 rare conditions were selected across 18 ERNs, for care pathway development. Multidisciplinary input from multiple specialisms was relevant for all pathways. A high level of engagement was experienced from clinical leads and patient organisations. CPGs were identified for 26 of the conditions. Nurse specialist, Psychology, Medical Social Work and Database Manager roles were deemed essential for all care pathways. Access to the therapeutic Health Service Professionals: Physiotherapy, Occupational Therapy, and Speech and Language Therapy were seen as key requirements for holistic care. Genetic counselling was highlighted as a core discipline in 27 pathways demonstrating the importance of access to Clinical Genetics services for many people with RDs. CONCLUSIONS: This study proposes a methodology for Irish RD care pathway development, in collaboration with patient/service user advocates. Common RD patient needs and health care professional interventions across all pathways were identified. Key RD stakeholders have endorsed this national care pathway initiative. Future research focused on the implementation of such care pathways is a priority.

Omega-3 Long-Chain Polyunsaturated Fatty Acids: Are They Beneficial for Physical and Cognitive Functioning in Older Adults?

BACKGROUND: There is equivocal evidence about beneficial properties of omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA) for older adults. OBJECTIVE: This study investigated the relationship between circulating ω-3 LCPUFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels and their corresponding dietary intakes with cognition and physical function in a cohort of community-dwelling older adults at risk of dementia. METHODS: A cross-sectional analysis was conducted among 142 community-dwelling older adults (60-85 years) with subjective memory complaints. Erythrocyte fatty acids (ω-3 LCPUFA) and the omega-3 index were measured; dietary DHA and EPA were assessed with a LCPUFA specific questionnaire. Cognition was measured using the Cogstate computerised battery and Trail-making tests. Muscle strength was assessed by grip strength and physical function via the four-square step test, 30-second sit-to-stand, timed up-and-go test, and 4-m walk test. Multiple regression analysis was used to assess the relationship between erythrocyte ω-3 LCPUFA, dietary intake, cognitive and physical function. RESULTS: Higher dietary DHA and EPA were associated with better global cognitive function (DHA: ß=0.164, p=0.042; EPA: ß=0.188, p=0.020). Higher dietary EPA was associated with better attention/psychomotor composite scores (ß=0.196, p=0.024), mobility (four-square step test: ß=-0.202, p=0.015) and gait speed (4m walk test: ß=-0.200, p=0.017). No associations were found between erythrocyte ω-3 LCPUFA and cognitive or functional performance measures. CONCLUSIONS: In community-dwelling older adults with subjective memory complaints, higher dietary ω-3 LCPUFA intake was associated with better cognitive and physical function, supporting the evidence that ω-3 fatty acids play a role in optimising physical and cognitive health during ageing.

Neutrophils can promote clotting via FXI and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitro.

Neutrophils and neutrophil extracellular traps (NETs) have been shown to be involved in coagulation. However, the interactions between neutrophils or NETs and fibrin(ogen) in clots, and the mechanisms behind these interactions are not yet fully understood. In this in vitro study, the role of neutrophils or NETs on clot structure, formation and dissolution was studied with a combination of confocal microscopy, turbidity and permeation experiments. Factor (F)XII, FXI and FVII-deficient plasmas were used to investigate which factors may be involved in the procoagulant effects. We found both neutrophils and NETs promote clotting in plasma without the addition of other coagulation triggers, but not in purified fibrinogen, indicating that other factors mediate the interaction. The procoagulant effects of neutrophils and NETs were also observed in FXII- and FVII-deficient plasma. In FXI-deficient plasma, only the procoagulant effects of NETs were observed, but not of neutrophils. NETs increased the density of clots, particularly in the vicinity of the NETs, while neutrophils-induced clots were less stable and more porous. In conclusion, NETs accelerate clotting and contribute to the formation of a denser, more lysis resistant clot architecture. Neutrophils, or their released mediators, may induce clotting in a different manner to NETs, mediated by FXI.

Advances in understanding and in multi-disciplinary methodology used to assess lipid regulation of signalling cascades from the cancer cell plasma membrane.

The lipid bilayer is a functional component of cells, forming a stable platform for the initiation of key biological processes, including cell signalling. There are distinct changes in the lipid composition of cell membranes during oncogenic transformation resulting in aberrant activation and inactivation of signalling transduction pathways. Studying the role of the cell membrane in cell signalling is challenging, since techniques are often limited to by timescale, resolution, sensitivity, and averaging. To overcome these limitations, combining 'computational', 'wet-lab' and 'semi-dry' approaches offers the best opportunity to resolving complex biological processes involved in membrane organisation. In this review, we highlight analytical tools that have been applied for the study of cell signalling initiation from the cancer cell membranes through computational microscopy, biological assays, and membrane biophysics. The cancer therapeutic potential of extracellular membrane-modulating agents, such as cholesterol-reducing agents is also discussed, as is the need for future collaborative inter-disciplinary research for studying the role of the cell membrane and its components in cancer therapy.

Location-specific reflex epilepsy: a novel reflex epilepsy phenotype.

Reflex epilepsies are rare syndromes where seizures are triggered by particular stimuli or activities that may be motor, sensory or cognitive in nature. Triggers are diverse, may be extrinsic or intrinsic in nature and heterogeneous phenotypes have been described over the years. We give an account of a case of location-specific reflex epilepsy which we suggest is a novel reflex epilepsy phenotype relating to higher cortical function (HCF), and review the literature in relation to features of HCF reflex epilepsies described to date.

Author Correction: Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The impact of point-of-care testing for influenza A and B on patient flow and management in a medical assessment unit of a general hospital.

OBJECTIVES: Timely implementation of influenza infection control and treatment can significantly reduce the impact on Hospital resources and patient management when demand is at peak. Turnaround times of Laboratory based screening tests for the diagnosis of influenza may have an impact on the implementation of infection control measures and treatment. In this study the objectives included determining the correlation between the Abbott ID NOW point-of-care testing (POCT) instrument using the Influenza A&B2 test and the laboratory based GeneXpert Flu+RSV kit. In addition the impact of the POCT instrument on the prescription of antivirals and antibiotics was evaluated by comparing with practice when the instrument was not in place. RESULTS: The results of the correlation study with a cohort of 54 patients revealed the Abbott ID NOW POCT has 92% sensitivity for the detection of Influenza A, while specificity was 100% for both Influenza A and B. The impact of the POCT instrument on the frequency of prescription of antivirals and amount of antibiotics consumed (33% reduction in antibiotic consumption in a cohort of 65 (2017) and 61 (2018)) was significant. In addition the average patient length of Hospital stay was significantly reduced from 5.26 days to 3.73 days.

National Guidelines on the Provision of Outpatient Parenteral Antimicrobial Therapy (OPAT).

Aim Outpatient parenteral antimicrobial therapy (OPAT) is an option in patients who require parenteral antimicrobial administration and are clinically well enough for hospital discharge. This is an update of the Irish National OPAT guidelines which were last reviewed in 2011. Methods The guideline was devised through a collaborative process with the national OPAT Working Group and a review of the literature. It is intended for clinicians who prescribe any intravenous (IV) antimicrobials outside of the inpatient setting in the Republic of Ireland. Results Patient care while on OPAT should be provided by a designated OPAT service, with clear managerial and clinical governance lines of responsibility. It should be conducted using a team approach with a clinical lead on each site either as an infection specialist, or a general medical physician with infection specialist input and an OPAT nurse. An antimicrobial pharmacist is also desirable. Several factors must be considered when assessing patient's suitability for OPAT including exclusion criteria, infection-specific factors, and patient specific factors such as physical, social and logistic criteria. Conclusion This updated guideline advocates a more individualised OPAT approach, with the recognition that specific antimicrobials and/or specific delivery models may be more appropriate for certain patient groups. Full guidelines are available through www.opat.ie.

Development of an Insulin-Prescribing Chart for Paediatric Diabetes

Aim Our aim was to design a new insulin prescribing tool in compliance with the Irish Medicines Safety Network recommendations. Methods In 2015, we undertook a review of the existing paediatric subcutaneous insulin-prescribing sheet introduced to Cork University Hospital in 2013. This involved a retrospective analysis of 15 consecutive in-patient insulin prescribing charts and a questionnaire distributed to health professionals. Following this a new insulin prescribing chart was designed and implemented in 2016 and a re-audit was performed in 2017. Results The 2017 re-audit demonstrated that the new insulin chart was viewed as easier (95% of previous users n=18) and safer (n=16) to use. There was less confusion (2017: 28%, n=11/39 vs 2015: 50%, n=17/34 2015) and the ALERT system helped staff standardise hypo/hyperglycaemia management (71%, n=28). Conclusion The new paediatric insulin prescribing chart has improved safety and ease of prescribing insulin. The colour coded quasi graph and ALERT system has made it easier to appreciate capillary blood glucose trends and manage them safely.

Measurements of Nonsinglet Moments of the Nucleon Structure Functions and Comparison to Predictions from Lattice QCD for Q

We present extractions of the nucleon nonsinglet moments utilizing new precision data on the deuteron F_{2} structure function at large Bjorken-x determined via the Rosenbluth separation technique at Jefferson Lab Experimental Hall C. These new data are combined with a complementary set of data on the proton previously measured in Hall C at similar kinematics and world datasets on the proton and deuteron at lower x measured at SLAC and CERN. The new Jefferson Lab data provide coverage of the upper third of the x range, crucial for precision determination of the higher moments. In contrast to previous extractions, these moments have been corrected for nuclear effects in the deuteron using a new global fit to the deuteron and proton data. The obtained experimental moments represent an order of magnitude improvement in precision over previous extractions using high x data. Moreover, recent exciting developments in lattice QCD calculations provide a first ever comparison of these new experimental results with calculations of moments carried out at the physical pion mass, as well as a new approach that first calculates the quark distributions directly before determining moments.

High Rates of Diabetic Ketoacidosis in Patients with New and Known Type 1 Diabetes over a Six-Year Period

Aims To analyse all paediatric patients who presented with diabetic ketoacidosis (DKA) from 2012 to 2017. Methods A retrospective observational study was carried out analysing all cases of diabetic ketoacidosis admitted to a regional centre from 2012-2017. Results We identified 133 cases of DKA, 81 (61%) were newly diagnosed patients and 52 (39%) were patients with known T1DM. There were 215 new diagnoses of T1DM during the study period giving a DKA rate at diagnosis of 38%. Among the 52 cases with established T1DM, 13 cases (25%) presented in severe DKA and 37 cases (71%) occurred in adolescents aged over 12 years. Precipitating factors included chronic suboptimal control and psychosocial factors (28/52), acute illness (16/52), and pump technical failure (5/52). There were two cases treated for suspected cerebral oedema and one case each of subarachnoid haemorrhage and cardiac arrhythmia. Conclusion The current proportion of new T1DM presenting in DKA is higher than international data. The high frequency of DKA in known T1DM indicates a need for particular focus on adolescents.

Coincident molecular auxeticity and negative order parameter in a liquid crystal elastomer.

Auxetic materials have negative Poisson's ratios and so expand rather than contract in one or several direction(s) perpendicular to applied extensions. The auxetics community has long sought synthetic molecular auxetics - non-porous, inherently auxetic materials which are simple to fabricate and avoid porosity-related weakening. Here, we report, synthetic molecular auxeticity for a non-porous liquid crystal elastomer. For strains above ~0.8 applied perpendicular to the liquid crystal director, the liquid crystal elastomer becomes auxetic with the maximum negative Poisson's ratio measured to date being -0.74 ± 0.03 - larger than most values seen in naturally occurring molecular auxetics. The emergence of auxeticity coincides with the liquid crystal elastomer backbone adopting a negative order parameter, QB = -0.41 ± 0.01 - further implying negative liquid crystal ordering. The reported behaviours consistently agree with theoretical predictions from Warner and Terentjev liquid crystal elastomer theory. Our results open the door for the design of synthetic molecular auxetics.

A Unique Case of Concurrent Long Bone Osteomyelitis and Empyema Caused by Fusobacterium nucleatum.

We describe a patient presenting with constitutional symptoms, poor oral hygiene and leg swelling who was diagnosed with Fusobacterium nucleatum osteomyelitis of femur and empyema. Long bone osteomyelitis is rarely caused by this microorganism. This unusual case was successfully managed with drainage and antimicrobial therapy.