Psychiatry NCHD referrals to the local emergency department in the context of an in-house primary care service.

OBJECTIVES: Patients with psychiatric illness are at increased risk of developing non-psychiatric medical illnesses. There have been positive reports regarding the integration of primary care services into mental health facilities. Here, we evaluate the appropriateness of psychiatry non-consultant hospital doctors (NCHD) transfers to the local emergency department (ED) in the context of an in-house primary care service. METHODS: We reviewed the inpatient transfers from St Patrick's University Hospital (SPUH) to the local ED at St James' Hospital (SJH) from 1 January 2016 to 31 December 2017. We used inpatient admission to SJH as our primary marker of an appropriate transfer. RESULTS: 246 inpatients were transferred from SPUH to the SJH ED for medical review in the years 2016 and 2017. 27 (11%) of these were referred to the ED by the primary care service. 51% of those referred were admitted with similar rates of admission for both general practitioner (n = 27, 54% admitted) and NCHD initiated referrals (n = 219, 51% admitted). Acute neurological illness, concern regarding a cardiac illness, and deliberate self-harm were the most common reasons for referral. CONCLUSION: Our primary finding is that, of those transferred to ED by either primary care or a psychiatry NCHD, a similar proportion was judged to be in need of inpatient admission. This indicates that as a group, psychiatry NCHD assessment of acuity and need for transfer was similar to that of their colleagues in primary care.

CNS Hypomyelination Disrupts Axonal Conduction and Behavior in Larval Zebrafish.

Myelination is essential for central nervous system (CNS) formation, health and function. As a model organism, larval zebrafish have been extensively employed to investigate the molecular and cellular basis of CNS myelination, because of their genetic tractability and suitability for non-invasive live cell imaging. However, it has not been assessed to what extent CNS myelination affects neural circuit function in zebrafish larvae, prohibiting the integration of molecular and cellular analyses of myelination with concomitant network maturation. To test whether larval zebrafish might serve as a suitable platform with which to study the effects of CNS myelination and its dysregulation on circuit function, we generated zebrafish myelin regulatory factor (myrf) mutants with CNS-specific hypomyelination and investigated how this affected their axonal conduction properties and behavior. We found that myrf mutant larvae exhibited increased latency to perform startle responses following defined acoustic stimuli. Furthermore, we found that hypomyelinated animals often selected an impaired response to acoustic stimuli, exhibiting a bias toward reorientation behavior instead of the stimulus-appropriate startle response. To begin to study how myelination affected the underlying circuitry, we established electrophysiological protocols to assess various conduction properties along single axons. We found that the hypomyelinated myrf mutants exhibited reduced action potential conduction velocity and an impaired ability to sustain high-frequency action potential firing. This study indicates that larval zebrafish can be used to bridge molecular and cellular investigation of CNS myelination with multiscale assessment of neural circuit function.SIGNIFICANCE STATEMENT Myelination of CNS axons is essential for their health and function, and it is now clear that myelination is a dynamic life-long process subject to modulation by neuronal activity. However, it remains unclear precisely how changes to myelination affects animal behavior and underlying action potential conduction along axons in intact neural circuits. In recent years, zebrafish have been employed to study cellular and molecular mechanisms of myelination, because of their relatively simple, optically transparent, experimentally tractable vertebrate nervous system. Here we find that changes to myelination alter the behavior of young zebrafish and action potential conduction along individual axons, providing a platform to integrate molecular, cellular, and circuit level analyses of myelination using this model.

A systematic review of cardiovascular responses associated with ambient black carbon and fine particulate matter.

BACKGROUND: Exposure to fine particulate matter (PM2.5), an ambient air pollutant with mass-based standards promulgated under the Clean Air Act, and black carbon (BC), a common component of PM2.5, are both associated with cardiovascular health effects. OBJECTIVES: To elucidate whether BC is associated with distinct, or stronger, cardiovascular responses compared to PM2.5, we conducted a systematic review. We evaluated the associations of short- and long-term BC, or the related component elemental carbon (EC), with cardiovascular endpoints including heart rate variability, heart rhythm, blood pressure and vascular function, ST segment depression, repolarization abnormalities, atherosclerosis and heart function, in the context of what is already known about PM2.5. DATA SOURCES: We conducted a stepwise systematic literature search of the PubMed, Web of Science and TOXLINE databases and applied Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines for reporting our results. STUDY ELIGIBILITY CRITERIA: Studies reporting effect estimates for the association of quantitative measurements of ambient BC (or EC) and PM2.5, with relevant cardiovascular endpoints (i.e. meeting inclusion criteria) were included in the review. Included studies were evaluated for risk of bias in study design and results. STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias evaluations assessed aspects of internal validity of study findings based on study design, conduct, and reporting to identify potential issues related to confounding or other biases. Study results are presented to facilitate comparison of the consistency of associations with PM2.5 and BC within and across studies. RESULTS: Our results demonstrate similar associations for BC (or EC) and PM2.5 with the cardiovascular endpoints examined. Across studies, associations for BC and PM2.5 varied in their magnitude and precision, and confidence intervals were generally overlapping within studies. Where differences in the magnitude of the association between BC or EC and PM2.5 within a study could be discerned, no consistent pattern across the studies examined was apparent. LIMITATIONS: We were unable to assess the independence of the effect of BC, relative the effect of PM2.5, on the cardiovascular system, nor was information available to understand the impact of differential exposure misclassification. CONCLUSIONS: Overall, the evidence indicates that both BC (or EC) and PM2.5 are associated with cardiovascular effects but the available evidence is not sufficient to distinguish the effect of BC (or EC) from that of PM2.5 mass.

Intersection as key locations for bearded capuchin monkeys (Sapajus libidinosus) traveling within a route network.

There is evidence that wild animals are able to recall key locations and associate them with navigational routes. Studies in primate navigation suggest most species navigate through the route network system, using intersections among routes as locations of decision-making. Recent approaches presume that points of directional change may be key locations where animals decide where to go next. Over four consecutive years, we observed how a wild group of bearded capuchin monkeys used a route network system and Change Point locations (CPs) in the Brazilian ecotone of Cerrado-Caatinga. We built 200 daily routes of one wild bearded capuchin group. We used ArcGIS, the Change Point Test, Spatial Analysis in Macroecology (SAM), and statistical models to test the hypothesis that wild bearded capuchins use CPs located along routes in a different fashion than they use the CPs located at intersections of routes. A logistic regression model was used to determine the landscape variables affecting capuchins' directional changes at intersections or along routes. CPs at intersections were important points of travel path changes, whereas CPs along routes represented a zig-zag movement along the routes following the landscape features. CPs at intersections were associated with steeper terrains and shorter distances from important resources, along with better visibility of the home range. Our results support the hypothesis that intersections among routes in the route network system are located at points where monkeys have the best visibility available to make decisions on where to visit next.

The use and success of cold coagulation for the treatment of high grade squamous cervical intra-epithelial neoplasia: a retrospective review.

OBJECTIVE: Cold coagulation is recognised as a viable, cost-effective and successful treatment for cervical intraepithelial neoplasia (CIN), being used less frequently than excisional treatments for high grade lesions. We set out to demonstrate successful long term follow-up of patient with high grade CIN treated with cold coagulation. STUDY DESIGN: We conducted a retrospective review over a one-year period of women with biopsy-proven CIN 2 and 3 who were treated with cold coagulation to the cervix, attending the colposcopy service of a large tertiary referral hospital. We examined follow-up cervical smear data for three years post treatment of low and high grade CIN, evaluated the success of treatment and re-treatment rates. RESULTS: 93 patients were included in our study, with 39 (41.9%) having CIN 1 and 54 (58.1%) diagnosed with CIN 2 or 3. Follow-up smears revealed low levels of recurrent high grade changes in both groups, with 31 (79.5%) of our CIN 1 group having a negative smear one year following treatment with cold coagulation, compared to 44 (81.1%) of patients with CIN 2 and 3. Successful primary treatment (i.e. no requirement for further treatment after 3 year follow-up) occurred in 33 (84.6%) of the CIN 1 group, and 42 (77.7%) of the CIN 2/3 group, demonstrating no statistical significance between re-treatment rates between both groups. CONCLUSIONS: This study demonstrates the effectiveness of cold coagulation for the treatment of high grade cervical intraepithelial neoplasia. High success rates, and low re-treatment rates confirm that this is an acceptable primary treatment for CIN 2 and 3.

Patellar ligament rupture in the dog: repair methods and patient outcomes in 43 cases.

The medical records of dogs receiving surgery for unilateral patellar ligament rupture between 1999 and 2012 at 12 multidisciplinary referral centres were reviewed. Forty-three cases were identified; 26 were traumatic in origin; almost one-third were iatrogenic, of which over three-quarters occurred as a complication following surgical stabilisation of patellar luxation. Treatment involved primary reapposition of the ligament (36 cases). The repair was protected by circumpatellar and/or transpatellar loop(s) of orthopaedic wire, nylon, polypropylene or polydioxanone suture (34 cases). Wire loops were more likely to require surgical removal compared with loops of other materials (P=0.0014). The stifle joint was immobilised postoperatively by the applications of a transarticular external skeletal fixator (taESF) in 17 cases and by external coaptation (EC) in 8 cases; in 18 cases, no postoperative joint immobilisation was provided. Complications specific to the method of immobilisation occurred in seven of the cases with taESF and six of the cases with EC. Revision surgery to address failure of repair was required in five cases. Outcome was classified as acceptable or good in over three-quarters of the cases (31/40) and poor in less than a quarter (9/40). These data highlight patellar ligament rupture as a complication of surgical stabilisation of patellar luxation.

Spatial-temporal model of haemorrhagic disease in white-tailed deer in south-east USA, 1983 to 2000.

The present study constructed a spatial-temporal statistical model to identify the risk and protective factors for haemorrhagic disease (HD) in white-tailed deer in the five states of Alabama, Georgia, South Carolina, North Carolina and Tennessee. The response variable was binary, indicating the presence or absence of HD in an individual county, measured annually from 1983 to 2000. Predictor variables included climatic factors of temperature, rainfall, wind speed and dew point, remotely sensed data of normalised difference vegetation index (NDVI) and land surface temperature derived from archived remotely sensed advanced very-high-resolution radiometer (AVHRR) satellite data, elevation, a spatial autocorrelation (SA) term and a temporal autocorrelation term. This study first applied principal component factor analysis to reduce the volume of climatic data and remotely sensed data. Then, a generalised linear mixed model framework (GLMM) was used to develop a spatial-temporal statistical model. The results showed that the area under receiver operating characteristic curve (ROC) was 0.728, indicating a good overall fit of the model. The total prediction accuracy over the 18 year period with optimal cut-off probability was 67 per cent. The prediction accuracy for individual years ranged from 48 to 75 per cent.

Warfarin anticoagulation: a survey of patients' knowledge of their treatment.

INTRODUCTION: Warfarin is used for the treatment of thromboembolic disease. It requires careful and sustained monitoring due to its narrow therapeutic index and potentially life-threatening complications. Patient education and knowledge is, therefore, vital. AIMS: To assess, in a specialised anticoagulation clinic, the extent of patients' knowledge of their warfarin treatment. METHODS: Ethical approval was obtained. All patients, aged over 18 years, attending our anticoagulation clinic during our study period were asked to participate. RESULTS: We enrolled 181 patients, 47.9% of respondents were unaware of any potential drug interactions, 57.7% of patients were unaware of any potential side effects, 20% of patients had experienced side effects, 10.9% of patients had been hospitalised due to side effects, 58% of which were due to Haemorrhage and 79% of patients kept a personal record of their INR. CONCLUSIONS: Patients' understanding of warfarin treatment was poor, despite their high level of compliance.

The decision-making processes of pharmacists in inland Australia--a pilot study.

INTRODUCTION: Little research has been conducted analysing the organisational risks that compound and trigger dispensing and medication errors. This pilot study appraises the attitudes to and behaviours related to the dispensing errors of pharmacists practising in diverse venues and roles in inland Australia. METHODS: Twelve pharmacists working in the Riverina (Wiradjuri country) participated in a structured interview consisting of a brief survey and open-ended questions. The interviews were audio-recorded for transcription, then analysed by the interviewer for emerging themes. In this pilot study, the attitudes and actions of pharmacists in response to dispensing errors were explored to determine the nature of organisational strategies implemented to detect and recover 'slips, lapses and mistakes'. The rationale behind investigating attitudes and actions stems from the theory of planned behaviour. RESULTS: While many common themes emerged, the attitudes of each pharmacist were unique. The strategies implemented to prevent errors were venue-specific and purpose-designed to the training level of the staff and physical environment. A diverse mix of attitudes was represented by the sample, with no correlation between worksite, sex, age or role identified. Trends may emerge because, in regard to dispensing errors, subjective norms and perceived behavioural control play a greater role in forming the intention to act, rather than personal attitudes. The majority of examples given by participants was discussion of recorded errors and near misses, which included changes to procedures implemented to prevent the same error occurring. This culture of continuous quality improvement was the overarching common theme. Other common themes were the role of technology in the supply of medicines, privacy implications when drawing staff from a rural or regional centre, workload concerns with regard to management responsibility and the impact of the way error management was demonstrated during the formative early years of practice. Distraction from dispensing, through management roles in pharmacies with moderate prescription volumes, was a common contributor to errors. CONCLUSION: A culture of continuous quality improvement exists amongst pharmacists in Inland Australia, which would benefit from improved dialogue about the impact of organisational risks on the rate of dispensing errors. The safety culture, and behaviour modelling experienced during the internship program has a profound impact on the perceived behavioural control of young pharmacists. This year instils mores, which may be the result of independent survival in remote and regional settings, rather than compliance with professional practice standards. While many of the pressures and demands of minimising errors are common across the profession; unique, venue specific strategies are commonly implemented in the cycle of continuous quality improvement in regional and remote settings.

Fiber optic sensing technology for detecting gas hydrate formation and decomposition.

A fiber optic-based distributed sensing system (DSS) has been integrated with a large volume (72 l) pressure vessel providing high spatial resolution, time-resolved, 3D measurement of hybrid temperature-strain (TS) values within experimental sediment-gas hydrate systems. Areas of gas hydrate formation (exothermic) and decomposition (endothermic) can be characterized through this proxy by time series analysis of discrete data points collected along the length of optical fibers placed within a sediment system. Data are visualized as an animation of TS values along the length of each fiber over time. Experiments conducted in the Seafloor Process Simulator at Oak Ridge National Laboratory clearly indicate hydrate formation and dissociation events at expected pressure-temperature conditions given the thermodynamics of the CH(4)-H(2)O system. The high spatial resolution achieved with fiber optic technology makes the DSS a useful tool for visualizing time-resolved formation and dissociation of gas hydrates in large-scale sediment experiments.

Cumulative exposure assessment for trace-level polycyclic aromatic hydrocarbons (PAHs) using human blood and plasma analysis.

Humans experience chronic cumulative trace-level exposure to mixtures of volatile, semi-volatile, and non-volatile polycyclic aromatic hydrocarbons (PAHs) present in the environment as by-products of combustion processes. Certain PAHs are known or suspected human carcinogens and so we have developed methodology for measuring their circulating (blood borne) concentrations as a tool to assess internal dose and health risk. We use liquid/liquid extraction and gas chromatography-mass spectrometry and present analytical parameters including dynamic range (0-250 ng/ml), linearity (>0.99 for all compounds), and instrument sensitivity (range 2-22 pg/ml) for a series of 22 PAHs representing 2-6-rings. The method is shown to be sufficiently sensitive for estimating PAHs baseline levels (typical median range from 1 to 1000 pg/ml) in groups of normal control subjects using 1-ml aliquots of human plasma but we note that some individuals have very low background concentrations for 5- and 6-ring compounds that fall below robust quantitation levels.

The effects of ambient particulate matter on human alveolar macrophage oxidative and inflammatory responses.

Epidemiologic and occupational studies demonstrated that ambient particulate matter (PM) and diesel exhaust particles (DEP) exert deleterious effects on human cardiopulmonary health, including exacerbation of pre-existing lung disease and development of respiratory infections. The effects of ambient PM on lung cell responsiveness are poorly defined. Human alveolar macrophages (AM) were exposed to SRM 1649 (Washington, DC, urban dust; UD), SRM 2975 (forklift diesel exhaust particles; DEP), and fine or coarse ambient PM collected in Chapel Hill, NC, during the late fall (November) and early summer (June) of 2001-2002. AM were subsequently incubated with lipopolysaccharide (LPS), phorbol myristate acetate (PMA), or calcium ionophore A23817 for 6 or 24 h after PM exposure. UD and DEP markedly suppressed O2- release 24 h post-PM exposure. UD exposure significantly inhibited tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 release after exposure to 10 nanog/ml LPS. DEP significantly suppressed only TNF-alpha and IL-6 release. Suppressed cytokine release may also be produced by reduced cellular cytokine production. Data suggested that decreased cytokine release is not produced by the presence of benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon. Comparison of TNF-alpha release after LPS, PMA, or A23817 revealed that suppressive effects of UD are LPS dependent, whereas inhibitory effects of DEP may work across multiple mechanistic pathways. November and June Chapel Hill PM exposure stimulated TNF-alpha and IL-8 release before LPS exposure. Fine and coarse November PM exposure markedly suppressed TNF-alpha release 6 h after LPS stimulation, but appeared to exert a stimulatory effect on IL-8 release 24 h after LPS exposure. June fine and coarse PM suppressed IL-8 release after LPS exposure. Data suggest that seasonal influences on PM composition affect AM inflammatory response before and after bacterial exposure. Overall, delayed or inhibited AM immune responses to LPS after PM exposure suggest human exposure to ambient PM may enhance pulmonary susceptibility to respiratory infections.

Strengthening of a model composite restoration using shape optimization: a numerical and experimental study.

OBJECTIVE: This study aims to validate a cavity shape optimization approach for improving the debonding resistance of dental restorations by carrying out fracture tests on restored model teeth with standard and optimized cavity designs. METHOD: The bio-mimetic stress-induced material transformation (SMT) optimization method was incorporated into the finite element (FE) program ABAQUS as a user material (UMAT) subroutine. The method uses stress minimization to optimize the cavity shape of a MOD restoration in an artificial premolar with special reference to the tooth-restoration interface under occlusal loads. The mechanical performance of the optimized design was first verified through FE analysis and then compared with that of the conventional design using fracture tests on model teeth. RESULTS: The SMT optimization process indicated a T-shape cavity as a more favorable design for the MOD restoration in the artificial premolar. Compared with the conventional parallel wall, or undercut design, the T-shape cavity was shown numerically to reduce the interfacial stresses by up to 69%, and experimentally to increase the mean debonding resistance of the model teeth by 23% (p<0.05). SIGNIFICANCE: Cavity shape optimization can help increase the debonding resistance of restored teeth by reducing the interfacial stresses between tooth and restoration under occlusal loads.

Application of novel method to measure endogenous VOCs in exhaled breath condensate before and after exposure to diesel exhaust.

Polar volatile organic compounds (PVOCs) such as aldehydes and alcohols are byproducts of normal human metabolism and thus are found in blood and exhaled breath. Perturbation of the normal patterns of such metabolites may reflect exposures to environmental stressors, disease state, and human activity. Presented herein is a specific methodology for assaying PVOC biomarkers in exhaled breath condensate (EBC) samples with application to a series of samples from a controlled chamber exposure to dilute diesel exhaust (DE) or to purified air. The collection/analysis method is based on condensation of normal (at rest) exhaled breaths for 10 min (resulting in 1-2 ml of liquid) with subsequent analyte adsorption onto Tenax cartridges followed by thermal desorption and analysis by gas chromatography/mass spectrometry (GC/MS). Analytical data have linearity of response (R(2)>0.98) across a range of 0-160 ng/ml with a detection limit ranging from 0.2 to 7 ng/ml depending on the compound. Statistical analyses of the results of the controlled exposure study indicate that metabolism, as reflected in simple breath-borne oxygenated species, is not affected by exposure to ambient airborne levels of DE. Linear mixed-effects models showed that PVOC biomarker levels are affected by gender and vary significantly among nominally healthy subjects. Differences among PVOCs analyzed in clinic air, purified chamber air, and chamber air containing dilute DE confirm that most of the compounds are likely of endogenous origin as the exogenous exposure levels did not perturb the EBC measurements.

Responses measured in the exhaled breath of human volunteers acutely exposed to ozone and diesel exhaust.

Exhaled breath collection is used to identify and monitor inflammatory or oxidative components in breath. Exhaled breath sample collection is noninvasive and would greatly benefit human pollutant exposure research. We demonstrate the efficacy of exhaled breath collection and analysis in two human exposure studies to ozone (O(3)) and diesel exhaust, respectively. O(3) study: we collected exhaled breath (gas phase) from healthy human volunteers (age 18-35 years, 12 subjects) immediately before and after exposure to filtered air or 0.4 ppm O(3) for 2 h with and without intermittent exercise. Six subjects received antioxidant supplementation for 2 weeks before their O(3) exposure, while the remaining six subjects received placebo treatments. We demonstrate increased amounts of non-polar carbonyls exhaled immediately post O(3) exposure. The O(3)-induced increase in exhaled carbonyl concentrations was attenuated in the group receiving antioxidants. Our data demonstrate that exhaled exposure biomarkers can be measured in the breath gas phase in humans exposed to O(3). Diesel study: we collected exhaled breath condensate (EBC; liquid phase) from healthy human volunteers (age 18-40 years; 10 subjects) immediately before, immediately after and 20 h post filtered air or diesel exhaust (106 ± 9 µg m(-3)) exposure. Clean air and diesel exposures were separated by 3 weeks to 6 months. We obtained reproducible intra-subject EBC volumes and total protein concentrations across our six collection time points. Diesel exposure did not affect either EBC volume or total protein concentrations. Our data demonstrated EBC volume and total protein reproducibility over several months. Volume and total protein concentration may serve as normalizing factors for other EBC constituents.

Metabolic capacity regulates iron homeostasis in endothelial cells.

The sensitivity of endothelial cells to oxidative stress and the high concentrations of iron in mitochondria led us to test the hypotheses that (1) changes in respiratory capacity alter iron homeostasis, and (2) lack of aerobic metabolism decreases labile iron stores and attenuates oxidative stress. Two respiration-deficient (rho(o)) endothelial cell lines with selective deletion of mitochondrial DNA (mtDNA) were created by exposing a parent endothelial cell line (EA) to ethidium bromide. Surviving cells were cloned and mtDNA-deficient cell lines were demonstrated to have diminished oxygen consumption. Total cellular and mitochondrial iron levels were measured, and iron uptake and compartmentalization were measured by inductively coupled plasma atomic emission spectroscopy. Iron transport and storage protein expression were analyzed by real-time polymerase chain reaction and Western blot or ELISA, and total and mitochondrial reactive oxygen species (ROS) generation was measured. Mitochondrial iron content was the same in all three cell lines, but both rho(o) lines had lower iron uptake and total cellular iron. Protein and mRNA expressions of major cytosolic iron transport constituents were down-regulated in rho(o) cells, including transferrin receptor, divalent metal transporter-1 (-IRE isoform), and ferritin. The mitochondrial iron-handling protein, frataxin, was also decreased in respiration-deficient cells. The rho(o) cell lines generated less mitochondrial ROS but released more extracellular H(2)O(2), and demonstrated significantly lower levels of lipid aldehyde formation than control cells. In summary, rho(o) cells with a minimal aerobic capacity had decreased iron uptake and storage. This work demonstrates that mitochondria regulate iron homeostasis in endothelial cells.