Physiological comparison of conditioned and non-conditioned university horses following semester break.

Periods of limited activity during semester break may reduce performance during return to ridden work. This study evaluated fitness and muscling of horses when returning to work, following a 12-week period during which horses either continued (conditioned) or discontinued (non-conditioned) ridden work. It was hypothesized that non-conditioned horses would have a lower level of fitness, resulting in higher resting and peak heart rates and lower levels of muscling. Twelve mature, stock type horses aged 16 ± 5 years were assigned to either a conditioned group that maintained light-to-moderate riding or a non-conditioned group receiving no formal exercise. All horses had access to voluntary exercise for 12-24hr/d on grass pasture (1.5-2.5 hectares). Following the 12-week period, all horses were placed into a light-to-moderate intensity exercise program with resting heart rate, peak heart rate, body condition score, gaskin and forearm circumference, and topline muscle measurements performed on d 0, 14, and 28. Peak and resting heart rates were not different between groups (P > 0.05) but increased for both groups throughout the study (P = 0.04). Gaskin circumference of non-conditioned horses was larger (P = 0.04), although non-conditioned horses tended to be heavier (551.4 versus 491.4 ± 21.4 kg; P = 0.07). Conditioned horses had greater average topline muscling scores (P = 0.02). Horses that were conditioned over a 12-week break had greater muscling, but changes in fitness were not detected. Pasture access could contribute to maintenance of fitness during unridden periods.

Hysteresis in phase volumes, compositions and interfacial roughness in model OPV-small-molecule/polymer thin-films.

Domain morphology and composition, and the structure of interfaces between domains are key factors in the performance and stability of organic photovoltaics (OPVs) fabricated from polymer/small-molecule blends. In this study, we investigate the evolution of composition, phase-volume and interfacial roughness in model polymer/small-molecule bilayers, in response to thermal annealing. Polystyrene/fullerene mixing is studied as a function of annealing temperature, using in situ neutron reflectivity, in thin-film bilayer samples comprising pure component or mixed layers. Remarkably, we discover that thermal annealing at temperatures around or above the reported glass transition temperatures, Tg, of the components can result in extensive mass-transfer between layers, that has the superficial appearance of equilibration, but leaves the layer compositions, thicknesses, and/or the interfacial composition profile in a non-equilibrium state. This is not merely a case of slow kinetics near Tg, as subsequent heating to higher temperatures, followed by cooling, reveals pronounced hysteresis in these systems. This has important implications for the measurement of equilibrium compositions in polymer/small-molecule mixtures for OPV applications, and for device stability during operation.

Characterisation of the immune microenvironment of primary breast cancer and brain metastasis reveals depleted T-cell response associated to ARG2 expression.

BACKGROUND: Immune checkpoint inhibition is an established treatment in programmed death-ligand 1 (PD-L1)-positive metastatic triple-negative (TN) breast cancer (BC). However, the immune landscape of breast cancer brain metastasis (BCBM) remains poorly defined. MATERIALS AND METHODS: The tumour-infiltrating lymphocytes (TILs) and the messenger RNA (mRNA) levels of 770 immune-related genes (NanoString™, nCounter™ Immuno-oncology IO360) were assessed in primary BCs and BCBMs. The prognostic role of ARG2 transcripts and protein expression in primary BCs and its association with outcome was determined. RESULTS: There was a significant reduction of TILs in the BCBMs in comparison to primary BCs. 11.5% of BCs presented a high immune infiltrate (hot), 46.2% were altered (immunosuppressed/excluded) and 34.6% were cold (no/low immune infiltrate). 3.8% of BCBMs were hot, 23.1% altered and 73.1% cold. One hundred and twelve immune-related genes including PD-L1 and CTLA4 were decreased in BCBM compared to the primary BCs (false discovery rate <0.01, log2 fold-change >1.5). These genes are involved in matrix remodelling and metastasis, cytokine-chemokine signalling, lymphoid compartment, antigen presentation and immune cell adhesion and migration. Immuno-modulators such as PD-L1 (CD274), CTLA4, TIGIT and CD276 (B7H3) were decreased in BCBMs. However, PD-L1 and CTLA4 expression was significantly higher in TN BCBMs (P = 0.01), with CTLA4 expression also high in human epidermal growth factor receptor 2-positive (P < 0.01) compared to estrogen receptor-positive BCBMs. ARG2 was one of four genes up-regulated in BCBMs. High ARG2 mRNA expression in primary BCs was associated with worse distant metastasis-free survival (P = 0.038), while ARG2 protein expression was associated with worse breast-brain metastasis-free (P = 0.027) and overall survival (P = 0.019). High transcript levels of ARG2 correlated to low levels of cytotoxic and T cells in both BC and BCBM (P < 0.01). CONCLUSION: This study highlights the immunological differences between primary BCs and BCBMs and the potential importance of ARG2 expression in T-cell depletion and clinical outcome.

Comparison of dilute and nondilute osmotic equilibrium models for erythrocytes.

Successful cryopreservation requires the addition of cryoprotective agents (CPAs). The addition of permeating CPAs, such as glycerol, is associated with some risk to the cells and tissues. These risks are both related to the CPA themselves (CPA toxicity) and to the volume response of the cell (osmotic damage). To minimize the potential for damage during cryopreservation, mathematical models are often employed to understand the interactions between protocols and cell volume responses. In the literature, this volume response is usually captured using ideal and dilute approximations of chemical potential and osmolality, an approach that has been called into question for cells in high concentrations of CPAs. To address this, the relevance of non-ideal and non-dilute models has been explored in a number of cell types in the presence of permeating CPAs. However, it has not been explored in erythrocytes, which have a cytosolic hemoglobin content of more than 20% by volume and are cryopreserved in 40% glycerol. Because hemoglobin has been suggested to be a highly non-ideal solute, if the non-ideal and non-dilute transport model is relevant to any cells, it should be relevant to erythrocytes. Here we investigate the use, and accuracy, of both the dilute and non-dilute models in predicting cell volume changes during CPA equilibration in erythrocytes, and demonstrate that using published values for the non-ideal and non-dilute model, applied to erythrocytes, leads to model predictions inconsistent with experimental data, whereas dilute approximations align well with experimental data.

Predictors of death and new disability after critical illness: a multicentre prospective cohort study.

PURPOSE: This study aimed to determine the prevalence and predictors of death or new disability following critical illness. METHODS: Prospective, multicentre cohort study conducted in six metropolitan intensive care units (ICU). Participants were adults admitted to the ICU who received more than 24 h of mechanical ventilation. The primary outcome was death or new disability at 6 months, with new disability defined by a 10% increase in the WHODAS 2.0. RESULTS: Of 628 patients with the primary outcome available (median age of 62 [49-71] years, 379 [61.0%] had a medical admission and 370 (58.9%) died or developed new disability by 6 months. Independent predictors of death or new disability included age [OR 1.02 (1.01-1.03), P = 0.001], higher severity of illness (APACHE III) [OR 1.02 (1.01-1.03), P < 0.001] and admission diagnosis. Compared to patients with a surgical admission diagnosis, patients with a cardiac arrest [OR (95% CI) 4.06 (1.89-8.68), P < 0.001], sepsis [OR (95% CI) 2.43 (1.32-4.47), P = 0.004], or trauma [OR (95% CI) 6.24 (3.07-12.71), P < 0.001] diagnosis had higher odds of death or new disability, while patients with a lung transplant [OR (95% CI) 0.21 (0.07-0.58), P = 0.003] diagnosis had lower odds. A model including these three variables had good calibration (Brier score 0.20) and acceptable discriminative power with an area under the receiver operating characteristic curve of 0.76 (95% CI 0.72-0.80). CONCLUSION: Less than half of all patients mechanically ventilated for more than 24 h were alive and free of new disability at 6 months after admission to ICU. A model including age, illness severity and admission diagnosis has acceptable discriminative ability to predict death or new disability at 6 months.

Study protocol: older people in retirement villages. A survey and randomised trial of a multi-disciplinary invention designed to avoid adverse outcomes.

BACKGROUND: There is increasing interest among older people in moving into retirement villages (RVs), an attractive option for those seeking a supportive community as they age, while still maintaining independence. Currently in New Zealand there is limited knowledge of the medical, service supports, social status and needs of RV residents. The objective of this study is to explore RV facilities and services, the health and functional status of RV residents, prospectively study their healthcare trajectories and to implement a multidisciplinary team intervention to potentially decrease dependency and impact healthcare utilization. METHODS: All RVs located in two large district health boards in Auckland, New Zealand were eligible to participate. This three-year project comprised three phases: The survey phase provided a description of RVs, residents' characteristics and health and functional status. RV managers completed a survey of size, facilities and recreational and healthcare services provided in the village. Residents were surveyed to establish reasons for entry to the village and underwent a Gerontology Nurse Specialist (GNS) assessment providing details of demographics, social engagement, health and functional status. The cohort study phase examines residents' healthcare trajectories and adverse outcomes, over three years. The final phase is a randomised controlled trial of a multidisciplinary team intervention aimed to improve health outcomes for more vulnerable residents. Residents who triggered potential unmet health needs during the assessment in the survey phase were randomised to intervention or usual care groups. Multidisciplinary team meetings included the resident and support person, a geriatrician or gerontology nurse practitioner, GNS, pharmacist and General Practitioner. The primary outcome of the randomised controlled trial will be first acute hospitalization. Secondary outcomes include all acute hospitalizations, long-term care admissions, and all-cause mortality. DISCUSSION: This paper describes the study protocol of this complex study. The study aims to inform policies and practices around health care services for residents in retirement villages. The results of this trial are expected early 2020 with publication subsequently. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry: ACTRN12616000685415 . Registered 25.5.2016. Universal Trial Number (UTN): U111-1173-6083.

Liquid-liquid equilibrium in polymer-fullerene mixtures; an in situ neutron reflectivity study.

The composition profiles of a series of model polystyrene/fullerene bilayers are measured, before, during and after thermal annealing, using in situ neutron reflectometry. In combination with grazing-incidence X-ray diffraction measurements, these experiments, which quantify layer compositions as a function of molecular weight using changes in both scattering length density and layer thickness, extend and corroborate recent measurements on ex situ annealed samples and demonstrate that the composition profiles rapidly formed in these systems correspond to two co-existing liquid-liquid phases in thermodynamic equilibrium. The measurements also demonstrate a clear and systematic onset temperature for diffusion of the fullerenes into the PS layer that correlates with the known glass-transition temperatures of both the polymer (as a function of molecular weight) and the fullerene, revealing that the molecular mobility of the fullerenes in these systems is controlled by the intrinsic mobility of the fullerenes themselves and the ability of the polymer to plasticise the fullerenes at the interface. Over the temperature range investigated (up to 145 °C), measurements of equilibrated composition profiles as a function of temperature (during gradual cooling) reveal no significant changes in composition profile, other than those associated with the known thermal expansion/contraction of polystyrene thin-films.

Evaluation of a co-facilitated information and learning programme for service users: the EOLAS programme.

BACKGROUND: The co-production and co-facilitation of recovery-focused education programmes is one way in which service users may be meaningfully involved as partners. OBJECTIVES: To evaluate the impact of a clinician and peer co-facilitated information programme on service users' knowledge, confidence, recovery attitudes, advocacy and hope, and to explore their experience of the programme. METHODS: A sequential design was used involving a pre-post survey to assess changes in knowledge, confidence, advocacy, recovery attitudes and hope following programme participation. In addition, semi-structured interviews with programme participants were completed. Fifty-three participants completed both pre- and post-surveys and twelve individuals consented to interviews. RESULTS: The results demonstrated statistically significant changes in service users' knowledge about mental health issues, confidence and advocacy. These improvements were reflected in the themes which emerged from the interviews with participants (n = 12), who reported enhanced knowledge and awareness of distress and wellness, and a greater sense of hope. In addition, the peer influence helped to normalise experiences for participants, while the dual facilitation engendered equality of participation and increased the opportunity for meaningful collaboration between service users and practitioners. CONCLUSIONS: The evaluation highlights the potential strengths of a service user and clinician co-facilitated education programme that acknowledges and respects the difference between the knowledge gained through self-experience and the knowledge gained through formal learning.

A time-driven, activity-based costing methodology for determining the costs of red blood cell transfusion in patients with beta thalassaemia major.

OBJECTIVES: To describe the methodology to estimate the total cost of administration of a single unit of red blood cells (RBC) in adults with beta thalassaemia major in an Australian specialist haemoglobinopathy centre. BACKGROUND: Beta thalassaemia major is a genetic disorder of haemoglobin associated with multiple end-organ complications and typically requiring lifelong RBC transfusion therapy. New therapeutic agents are becoming available based on advances in understanding of the disorder and its consequences. Assessment of the true total cost of transfusion, incorporating both product and activity costs, is required in order to evaluate the benefits and costs of these new therapies. METHODS: We describe the bottom-up, time-driven, activity-based costing methodology used to develop process maps to provide a step-by-step outline of the entire transfusion pathway. Detailed flowcharts for each process are described. Direct observations and timing of the process maps document all activities, resources, staff, equipment and consumables in detail. The analysis will include costs associated with performing these processes, including resources and consumables. Sensitivity analyses will be performed to determine the impact of different staffing levels, timings and probabilities associated with performing different tasks. RESULTS: Thirty-one process maps have been developed, with over 600 individual activities requiring multiple timings. These will be used for future detailed cost analyses. CONCLUSIONS: Detailed process maps using bottom-up, time-driven, activity-based costing for determining the cost of RBC transfusion in thalassaemia major have been developed. These could be adapted for wider use to understand and compare the costs and complexities of transfusion in other settings.

The relationship between early pregnancy dietary intakes and subsequent birthweight and neonatal adiposity.

Background: Maternal nutrition intakes may influence neonatal birthweight and adiposity; however, inconsistencies within the literature exist. The relationships between maternal dietary intakes in early pregnancy and both birthweight and neonatal adiposity requires elucidation. This study examined the relationship between early pregnancy dietary intakes and subsequent birthweight and neonatal adiposity. Methods: Women were recruited at their convenience after sonographic confirmation of a singleton pregnancy. Women completed a Willet food frequency questionnaire evaluating habitual food and nutrient intakes at their first antenatal visit. Neonatal body composition was measured using air-displacement plethysmography. Results: Of the 385 mother-neonate dyads, mean maternal age was 30.8 ± 5.3 years, mean Body Mass Index (BMI) was 24.5 ± 4.8 kg/m2 and 41.8% (n = 161) were nulliparous. There were no relationships between maternal food intakes and birthweight (P > 0.05) (n = 385). On multivariable analysis there was a positive relationship between polyunsaturated fat and neonatal fat mass index (FMI) (beta = 0.015, 95% CI = 0.002-0.028, P = 0.04) (n = 80). Conclusion: Dietary intakes of polyunsaturated fat in early pregnancy are positively associated with neonatal FMI at birth on multivariable analysis. Further longitudinal studies need to explore this association and the long-term implications for the neonate.

Screening for asymptomatic urogenital Chlamydia trachomatis infection at a large Dublin maternity hospital: results of a pilot study.

BACKGROUND: There are currently no Irish guidelines on screening for Chlamydia trachomatis infection in pregnancy. Prevalence rates in the antenatal population are not known which has prevented the development of screening recommendations for this group. AIMS: The objective of this study was to determine the prevalence of asymptomatic urogenital C. trachomatis infection in young women attending for care at a large maternity hospital. METHODS: All patients aged 25 years and under attending the Hospital between December 2011 and December 2013 were offered screening for urogenital C. trachomatis infection. Nucleic acid amplification testing of the C. trachomatis cryptic plasmid was performed on either endocervical swabs or first void urine samples. RESULTS: There were 2687 women tested for C. trachomatis infection, 83.4 % (2241/2687) through the antenatal clinics, 7.1 % (193/2687) through the gynaecology clinic, and 9.4 % (253/2687) through the emergency department. The rate of a positive test result was 5.6 % (151/2687) overall. The rates in women ages 16-18, 19-21 and 22-25 years were 9.1 % (31/340), 6.5 % (50/774) and 4.4 % (69/1561), respectively. A positive test result was more likely in those who were unemployed (p = 0.04), those who were Irish (p = 0.03) and those who were unmarried (p < 0.01). There were no cases of neonatal C. trachomatis infection in babies born to mothers who were screened in early pregnancy. CONCLUSIONS: The prevalence rate of detected C. trachomatis infection was 5.6 % in the study population. Screening of antenatal patients may have a role in preventing vertical transmission of infection to the neonate.

Postpartum dyslipidaemia in women diagnosed with gestational diabetes mellitus.

BACKGROUND: Diabetes mellitus is a known risk factor for cardiovascular disease which should prompt screening for other cardiovascular risk factors, including dyslipidaemia. Women diagnosed with gestational diabetes mellitus (GDM) are not routinely screened for cardiovascular risk factors. AIMS: The objective of this study was to determine the prevalence of dyslipidaemia postpartum in women with GDM. METHODS: The study was performed in a large university hospital. Women with GDM had a fasting lipid profile performed 6 weeks postnatally. Clinical details were obtained from the medical records. Lipid results in our cohort were compared with healthy women of the same age. RESULTS: The overall prevalence of postpartum dyslipidaemia was 52 % (n = 51). Total cholesterol was raised in 44 % (n = 43), low-density lipoprotein was raised in 33 % (n = 32) and triglycerides were raised in 16 % (n = 16). Of the 51 women with dyslipidaemia, 73 % (n = 37) had more than one abnormality in their lipid profile. Four of the five women with an abnormal postpartum GTT had an abnormal lipid profile. Compared with healthy women of the same age, women with GDM had higher total cholesterol (p = 0.04), higher LDL (p = 0.003), higher triglycerides (p < 0.001) and lower HDL (p < 0.04). CONCLUSIONS: Women with GDM should be screened for dyslipidaemia postpartum and protective cardiovascular interventions offered where appropriate.

Impact of co-facilitated information programmes on outcomes for service users and family members: the EOLAS programmes (paper 2).

OBJECTIVE: The present study evaluated the impact on psychosocial outcome of parallel clinician and peer-led information programmes for people with a diagnosis of schizophrenia and bipolar disorder and for family members within an Irish context. METHODS: A sequential mixed method design was used. Quantitative data were collected using pre- and post-programme questionnaires followed by an integrated qualitative component involving semi-structured interviews after the programme. The questionnaires assessed knowledge, attitudes towards recovery, hope, support, advocacy and well-being. Interviews with participants, facilitators and project workers explored their experiences and views of the programme. Findings While a number of the questionnaires did not show a statistically significant change, findings from the interviews suggest that the1 programmes had a number of positive outcomes, including increases in perceived knowledge, empowerment and support. Participants in both programmes valued the opportunity to meet people in similar circumstances, share their experiences, learn from each other and provide mutual support. CONCLUSION: The EOLAS programmes offer a novel template for communication and information sharing in a way that embodies the principles of collaboration and offers users and families a meaningful opportunity to become involved in service design, delivery and evaluation.

A participatory approach to the development of a co-produced and co-delivered information programme for users of services and family members: the EOLAS programme (paper 1).

OBJECTIVE: The EOLAS programme is a peer and clinician-led mental health information programme on recovery from mental health difficulties, specifically for people with a diagnosis of schizophrenia spectrum or bipolar disorders, their family members and significant others. METHOD: This article, the first of a two part series, outlines the background to and the rationale behind the EOLAS programme, and traces the participatory process used to inform the development and implementation of the pilot phase of the project. The aims of the programme, and the overarching principles that guided its development, delivery and evaluation, including the set-up of the project steering group are outlined and discussed. Findings Two separate programmes, one for family members and one for service users were designed. In addition, participant and facilitator handbooks were developed for each programme, including a training programme for facilitators. CONCLUSION: Central to a recovery oriented service is the involvement of service users and families in the design and delivery of services. EOLAS is one potential model for achieving this aim.

Opinions of key stakeholders concerning involuntary admission of patients under the Mental Health Act 2001.

OBJECTIVES: To evaluate and compare the opinions of key stakeholders involved in the involuntary admission and treatment of patients under the Mental Health Act (MHA) 2001 regarding their views towards the operation of the legislation. METHODS: We employed a descriptive survey design. A questionnaire was distributed to stakeholders involved in the operation of the MHA 2001 (except service users, whose views were explored in a separate qualitative study) via paper or online versions evaluating their opinions regarding the operation of the MHA 2001 in relation to assessment, care, rights, transfer and information available. RESULTS: Stakeholders agreed that in their opinion that patients generally benefit from the care they receive (79%) and that the MHA 2001 ensures an independent and fair review of the person's detention (65%). However, only 23% of stakeholders were satisfied with the process of transferring patients to hospital and with the clinical assessment procedures therein (37%), with the greatest levels of dissatisfaction amongst Gardai (Police), general practitioners (GPs) and family members. CONCLUSIONS: While the introduction of the MHA 2001 has assisted delivery of care to patients with improved adherence to international human rights frameworks applicable at the time of its enactment, substantial dissatisfaction with the implementation of the MHA 2001 in practice is experienced by stakeholders particularly at the distressing phase of clinical assessment and transfer to hospital.

Service users' experiences of mental health tribunals in Ireland: a qualitative analysis.

OBJECTIVES: To explore the mental health tribunal experiences of people admitted involuntarily under the Mental Health Act 2001. METHODS: Employing a qualitative descriptive study design, data were collected from 23 service users who had experienced mental health tribunals during a recent involuntary admission. Face-to-face semi-structured interviews were conducted ~3 months post-revocation of their involuntary admission order. Data were analysed using an inductive thematic process. RESULTS: The majority of participants reported mixed experiences comprising positive and negative aspects in relation to information provision, emotional support and an inclusive atmosphere. Some participants reported receiving accessible information about the tribunal process, felt emotionally supported throughout, and encountered respectful and dignifying practices during the tribunal proceedings. However, many participants described experiencing non-inclusive practices, reported feeling ill-informed regarding the tribunal process, emotionally unsupported during and after the tribunal, and distressed by what they perceived as adversarial tribunal proceedings. CONCLUSIONS: Systemic changes could ensure that the positive experiences encountered by the minority of participants in this study are more consistently experienced. Ongoing education and training of stakeholders in the provision of inclusive tribunal practices, and the provision of accessible information and emotional support to service users through the stages of the involuntary admission process appear likely to be beneficial. Service users should automatically be offered the option of having a support person of their choosing present during tribunals.

Detecting the Hidden Properties of Immunological Data and Predicting the Mortality Risks of Infectious Syndromes.

BACKGROUND: To extract more information, the properties of infectious disease data, including hidden relationships, could be considered. Here, blood leukocyte data were explored to elucidate whether hidden information, if uncovered, could forecast mortality. METHODS: Three sets of individuals (n = 132) were investigated, from whom blood leukocyte profiles and microbial tests were conducted (i) cross-sectional analyses performed at admission (before bacteriological tests were completed) from two groups of hospital patients, randomly selected at different time periods, who met septic criteria [confirmed infection and at least three systemic inflammatory response syndrome (SIRS) criteria] but lacked chronic conditions (study I, n = 36; and study II, n = 69); (ii) a similar group, tested over 3 days (n = 7); and (iii) non-infected, SIRS-negative individuals, tested once (n = 20). The data were analyzed by (i) a method that creates complex data combinations, which, based on graphic patterns, partitions the data into subsets and (ii) an approach that does not partition the data. Admission data from SIRS+/infection+ patients were related to 30-day, in-hospital mortality. RESULTS: The non-partitioning approach was not informative: in both study I and study II, the leukocyte data intervals of non-survivors and survivors overlapped. In contrast, the combinatorial method distinguished two subsets that, later, showed twofold (or larger) differences in mortality. While the two subsets did not differ in gender, age, microbial species, or antimicrobial resistance, they revealed different immune profiles. Non-infected, SIRS-negative individuals did not express the high-mortality profile. Longitudinal data from septic patients displayed the pattern associated with the highest mortality within the first 24 h post-admission. Suggesting inflammation coexisted with immunosuppression, one high-mortality sub-subset displayed high neutrophil/lymphocyte ratio values and low lymphocyte percents. A second high-mortality subset showed monocyte-mediated deficiencies. Numerous within- and between-subset comparisons revealed statistically significantly different immune profiles. CONCLUSION: While the analysis of non-partitioned data can result in information loss, complex (combinatorial) data structures can uncover hidden patterns, which guide data partitioning into subsets that differ in mortality rates and immune profiles. Such information can facilitate diagnostics, monitoring of disease dynamics, and evaluation of subset-specific, patient-specific therapies.