The confidence and competence of primary school staff to administer an adrenaline auto-injector.

School teachers are often inadequately prepared to use an adrenaline auto-injector (AAI), resulting in potentially dangerous treatment delays. The purpose of this study was to assess the observed competence, and self-reported confidence, of primary school teachers in the Republic of Ireland (RoI) to use an AAI. An evaluation of whether there was a link between confidence and competence was also assessed. Teachers from four primary schools in the RoI completed a questionnaire to assess their prior level of experience, training, and confidence levels with AAI administration. The four steps in administrating trainer AAI to a mannequin simulator were then assessed. A total of 61 teachers participated (out of a population of 80). The mean self-reported confidence was 1.82 out of 5 (SD = 0.96). There was no significant difference in confidence between trained and untrained participants (U = 240.5, NS). Participants who had received AAI administration training performed significantly more of the steps correctly (mean = 3.85, SD = 0.95) as compared to those who had received no training (mean = 2.97, SD = 1.10; U = 180.5, p = 0.008). There was no correlation between confidence in administrating AAI and the percentage of steps in the procedure performed correctly (rho = -0.17, NS).  Conclusion: Improvements in readiness to administer AAIs can be achieved through the application of more effective approaches to teaching clinical skills, changes to school policies and practices, and consideration of the design of AAIs in order to make their operation safer and simpler. It is important that teachers have the confidence and competence to safely administer an AAI. What is Known: • Poor ability in adrenaline auto-injector use seen across population groups-healthcare professionals, patients, carers, and school staff • Training in the use of adrenaline auto-injectors has positive impact on competency What is New: • Irish school teachers show poor levels of competency in adrenaline auto-injector use • No observed correlation between reported confidence and competency.

Muscle Injury Around the Shoulder.

Acute shoulder tendon and intra-articular injuries are common and their imaging well described. However, a subset of patients present with more unusual acute shoulder muscle injury. Of these, pectoralis major muscle injuries are encountered the most often and are increasingly prevalent due to a focus on personal fitness, particularly bench-press exercises. Other muscle injuries around the shoulder are rare. This article reviews the anatomy, mechanism of injury, and the imaging findings in relation to injuries of these muscles around the shoulder. We focus on pectoralis major injury but also review proximal triceps, latissimus dorsi, teres major, and deltoid muscle injuries, providing imaging examples.

Nisin variants from Streptococcus and Staphylococcus successfully express in NZ9800.

AIMS: Increases in antimicrobial resistance have meant that the antimicrobial potential of lantibiotics is now being investigated irrespective of the nature of the producing organism. The aim of this study was to investigate whether natural nisin variants produced by non-Generally Recognized as Safe (GRAS) strains, such as nisin H, nisin J and nisin P, could be expressed in a well-characterized GRAS host. METHODS AND RESULTS: This study involved cloning the nisin A promoter and leader sequence fused to nisin H, nisin J or nisin P structural gene sequences originally produced by Streptococcus hyointestinalis DPC 6484, Staphylococcus capitis APC 2923 and Streptococcus agalactiae DPC 7040, respectively. This resulted in their expression in Lactococcus lactis NZ9800, a genetically modified strain that does not produce nisin A. CONCLUSIONS: Induction of the nisin controlled gene expression system demonstrates that these three nisin variants could be acted on by nisin A machinery provided by the host strain. SIGNIFICANCE AND IMPACT OF THE STUDY: Describes the first successful heterologous production of three natural nisin variants by a GRAS strain, and demonstrates how such systems could be harnessed not only for lantibiotic production but also in the expansion of their structural diversity and development for use as future biotherapeutics.

Quantitative MRI in myositis patients: comparison with healthy volunteers and radiological visual assessment.

AIM: To assess whether magnetic resonance imaging (MRI)-based measurements of T2, fat fraction, diffusion tensor imaging, and muscle volume can detect differences between the muscles of myositis patients and healthy controls, and to identify how they compare with semi-quantitative MRI diagnosis. MATERIALS AND METHODS: Sixteen myositis patients and 16 age- and gender-matched healthy controls underwent MRI of their thigh. Quantitative MRI measurements and radiologists' semi-quantitative scores were assessed. Strength was assessed using an isokinetic dynamometer. RESULTS: Fat fraction and T2 values were higher in myositis patients whereas muscle volume was lower compared to healthy controls. There was no difference in diffusion. Muscle strength was lower in myositis patients compared to healthy controls. In a subgroup of eight patients, scored as unaffected by radiologists, T2 values were still significantly higher in myositis patients. CONCLUSIONS: Quantitative MRI measurements can detect differences between myositis patients and healthy controls. Changes in the muscles of myositis patients, undetected by visual, semi-quantitative scoring, can be detected using quantitative T2 measurements. This suggests that MRI T2 values may be useful for the management of myositis patients.

The effect of ageing on skeletal muscle as assessed by quantitative MR imaging: an association with frailty and muscle strength.

BACKGROUND: Skeletal muscles undergo changes with ageing which can cause sarcopenia that can result in frailty. Quantitative MRI may detect the muscle-deficit component of frailty which could help improve the understanding of ageing muscles. AIMS: To investigate whether quantitative MRI measures of T2, fat fraction (FF), diffusion tensor imaging and muscle volume can detect differences within the muscles between three age groups, and to assess how these measures compare with frailty index, gait speed and muscle power. METHODS: 18 'young' (18-30 years), 18 'middle-aged' (31-68 years) and 18 'older' (> 69 years) healthy participants were recruited. Participants had an MRI of their dominant thigh. Knee extension and flexion power and handgrip strength were measured. Frailty (English Longitudinal Study of Ageing frailty index) and gait speed were measured in the older participants. RESULTS: Young participants had a lower muscle MRI T2, FF and mean diffusivity than middle-aged and older participants; middle-aged participants had lower values than older participants. Young participants had greater muscle flexion and extension power, muscle volume and stronger hand grip than middle-aged and older participants; middle-aged participants had greater values than the older participants. Quantitative MRI measurements correlated with frailty index, gait speed, grip strength and muscle power. DISCUSSION: Quantitative MRI and strength measurements can detect muscle differences due to ageing. Older participants had raised T2, FF and mean diffusivity and lower muscle volume, grip strength and muscle power. CONCLUSIONS: Quantitative MRI measurements correlate with frailty and muscle function and could be used for identifying differences across age groups within muscle.

MRI in acute muscle tears in athletes: can quantitative T2 and DTI predict return to play better than visual assessment?

OBJECTIVES: To assess the ability of quantitative T2, diffusion tensor imaging (DTI) and radiologist's scores to detect muscle changes following acute muscle tear in soccer and rugby players. To assess the ability of these parameters to predict return to play times. METHODS: In this prospective, longitudinal study, 13 male athletes (age 19 to 34 years; mean 25 years) underwent MRI within 1 week of suffering acute muscle tear. Imaging included measurements of T2 and DTI parameters. Images were also assessed using modified Peetrons and British athletics muscle injury classification (BAMIC) scores. Participants returned for a second scan within 1 week of being determined fit to return to play. MRI measurements were compared between visits. Pearson's correlation between visit 1 measurements and return to play times was assessed. RESULTS: There were significant differences between visits in BAMIC scores (Z = - 2.088; p = 0.037), modified Peetrons (Z = - 2.530; p = 0.011) and quantitative MRI measurements; T2, 13.12 ms (95% CI, 4.82 ms, 21.42 ms; p = 0.01); mean diffusivity (0.22 (0.04, 0.39); p = 0.02) and fractional anisotropy (0.07 (0.01, 0.14); p = 0.03). BAMIC scores showed a significant correlation with return to play time (Rs = 0.64; p = 0.02), but modified Peetrons scores and quantitative parameters did not. CONCLUSIONS: T2 and DTI measurements in muscle can detect changes due to healing following muscle tear. Although BAMIC scores correlated well with return to play times, in this small study, quantitative MRI values did not, suggesting that T2 and DTI measurements are inferior predictors of return to play time compared with visual scoring. KEY POINTS: • Muscle changes following acute muscle tear can be measured using T2 and diffusion measurements on MRI. • Measurements of T2 and diffusion using MRI are not as good as a radiologist's visual report at predicting return to play time after acute muscle tear.

Irish Policy-makers' Perceptions of Barriers and Facilitators to Hand Hygiene Compliance

Aim To examine the barriers to, and facilitators of, hand hygiene (HH) practices as perceived by national and hospital-level HH policy-makers in Ireland; and identify the extent to which the issues identified are addressed in national HH guidelines. Methods Semi-structured interviews were conducted with 12 national-and hospital-level Irish HH policy-makers. Four national Irish HH policy documents were reviewed. Results The policy-makers identified a range of barriers and facilitators of HH compliance. These were found to fit into six themes, with a number of suggestions for how to improve HH compliance. All of the policy documents referenced the World Health Organization's five moments, but lacked guidance on how to improve HH compliance beyond recommending audit and feedback. Conclusion Policy-makers identified potential areas for targeting in future interventions. The varied extent to which the issues identified in the interviews were addressed in the guidelines, policies, and standards suggest that revision of such documents is required.

Case-case analysis of Campylobacter and Salmonella - using surveillance data for outbreak investigations and monitoring routine risk factors.

Utilising routine surveillance data, this study presents a method for generating a baseline comparison that can be used in future foodborne outbreak investigations following a case-case methodology. Salmonella and Campylobacter cases (2012-2015) from Maricopa County, AZ were compared to determine differences in risk factors, symptoms and demographics. For foods and other risk factors, adjusted odds ratios were developed using Campylobacter as the reference. Comparisons were also made for three major Salmonella subtypes, Typhimurium, Enteritidis and Poona as compared with Campylobacter. Salmonella cases were younger, while Campylobacter cases were more Hispanic and female. Campylobacter cases reported consuming peppers, sprouts, poultry, queso fresco, eggs and raw nuts more and reported contact with animal products, birds, visiting a farm or dairy, owning a pet, a sick pet, swimming in a river, lake or pond, or handling multiple raw meats more. Salmonella cases reported visiting a petting zoo and contact with a reptile more. There were significant variations by Salmonella subtype in both foods and exposures. We recommend departments conduct this analysis to generate a baseline comparison and a running average of relevant odds ratios allowing staff to focus on trace-back of contaminated food items earlier in the outbreak investigation process.

The Experience of the Management of Eating Disorders in a Pop-up Eating Disorder Unit

Anorexia nervosa affects 0.5% of the population (90% female) with the highest mortality of any psychiatric illness, usually suicide, or cardiovascular or neurological sequelae of either malnutrition or refeeding syndrome. The latter two conditions occur in the inpatient setting, carry a high mortality and are thoroughly avoidable with careful informed clinical management. This paper provides an overview of the service and care of these patients in a general hospital setting in Ireland. In response to a number of acute presentations a cross discipline Pop-up Eating Disorder Unit (psychiatrist, physician, dietician, nurse) was established in Sligo University Hospital in 2014 and has experience of 20 people treated according to the MARSIPAN guideline (Management of Really Sick Inpatients with Anorexia Nervosa). They are nursed in a designated ward with continuous cardiac monitoring (in addition 2 required ICU admission), with one-to-one continuous supervision, complete bed rest, careful calorie titration (usually nasogastric) with twice daily phosphate, magnesium, calcium and potassium concentrations measured and replaced. Sabotaging behaviour witnessed includes micro-exercising, requests for windows to be opened (in order to shiver/micro exercise), food concealment, faecal/urinary loading on weighing days, heavy hair accessories, vigorous page turning/toothbrushing/use of computer keypads and animated conversations. A cross disciplinary coordinated approach to this cohort, who often inventive in their resistance to treatment, allows safe management in a general hospital setting.

A Multibacteriocin Cheese Starter System, Comprising Nisin and Lacticin 3147 in Lactococcus lactis, in Combination with Plantaricin from Lactobacillus plantarum.

Functional starter cultures demonstrating superior technological and food safety properties are advantageous to the food fermentation industry. We evaluated the efficacies of single- and double-bacteriocin-producing starters of Lactococcus lactis capable of producing the class I bacteriocins nisin A and/or lacticin 3147 in terms of starter performance. Single producers were generated by mobilizing the conjugative bacteriophage resistance plasmid pMRC01, carrying lacticin genetic determinants, or the conjugative transposon Tn5276, carrying nisin genetic determinants, to the commercial starter L. lactis CSK2775. The effect of bacteriocin coproduction was examined by superimposing pMRC01 into the newly constructed nisin transconjugant. Transconjugants were improved with regard to antimicrobial activity and bacteriophage insensitivity compared to the recipient strain, and the double producer was immune to both bacteriocins. Bacteriocin production in the starter was stable, although the recipient strain proved to be a more efficient acidifier than transconjugant derivatives. Overall, combinations of class I bacteriocins (the double producer or a combination of single producers) proved to be as effective as individual bacteriocins for controlling Listeria innocua growth in laboratory-scale cheeses. However, using the double producer in combination with the class II bacteriocin producer Lactobacillus plantarum or using the lacticin producer with the class II producer proved to be most effective for reducing bacterial load. As emergence of bacteriocin tolerance was reduced 10-fold in the presence of nisin and lacticin, we suggest that the double producer in conjunction with the class II producer could serve as a protective culture providing a food-grade, multihurdle approach to control pathogenic growth in a variety of industrial applications.IMPORTANCE We generated a suite of single- and double-bacteriocin-producing starter cultures capable of generating the class I bacteriocin lacticin 3147 or nisin or both bacteriocins simultaneously via conjugation. The transconjugants exhibited improved bacteriophage resistance and antimicrobial activity. The single producers proved to be as effective as the double-bacteriocin producer at reducing Listeria numbers in laboratory-scale cheese. However, combining the double producer or the lacticin-producing starter with a class II bacteriocin producer, Lactobacillus plantarum LMG P-26358, proved to be most effective at reducing Listeria numbers and was significantly better than a combination of the three bacteriocin-producing strains, as the double producer is not inhibited by either of the class I bacteriocins. Since the simultaneous use of lacticin and nisin should reduce the emergence of bacteriocin-tolerant derivatives, this study suggests that a protective starter system produced by bacteriocin stacking is a worthwhile multihurdle approach for food safety applications.

Inhibition of Listeria monocytogenes biofilms by bacteriocin-producing bacteria isolated from mushroom substrate.

AIMS: This study was designed to investigate the ability of naturally occurring bacteria isolated from mushroom substrate to prevent biofilm formation by Listeria monocytogenes or to remove existing biofilms in mushroom production facilities. METHODS AND RESULTS: It is generally recognized that L. monocytogenes forms biofilms that can facilitate its survival in food-processing environments. Eleven bacteriocin-producing isolates were identified and the bacteriocins characterized based on heat and enzyme inactivation studies. Further characterization was undertaken by MALDI-TOF mass spectrometry, PCR and sequencing. Production of nisin Z (by Lactococcus lactis isolates), subtilomycin (by Bacillus subtilis isolates) and lichenicidin (by Bacillus licheniformis and Bacillus sonorensis isolates) was detected. In co-culture with L. monocytogenes, the bacteriocin-producing strains could prevent biofilm formation and reduce pre-formed biofilms. CONCLUSIONS: Mushroom substrate can be a source of bacteriocin-producing bacteria that can antagonize L. monocytogenes. SIGNIFICANCE AND IMPACT OF THE STUDY: The results highlight the potential of bacteriocin-producing strains from mushroom substrate to reduce L. monocytogenes biofilm in food production environments, contributing to a reduction in the risk of food contamination from the environment.

Outpatient diabetes clinical decision support: current status and future directions.

Outpatient clinical decision support systems have had an inconsistent impact on key aspects of diabetes care. A principal barrier to success has been low use rates in many settings. Here, we identify key aspects of clinical decision support system design, content and implementation that are related to sustained high use rates and positive impacts on glucose, blood pressure and lipid management. Current diabetes clinical decision support systems may be improved by prioritizing care recommendations, improving communication of treatment-relevant information to patients, using such systems for care coordination and case management and integrating patient-reported information and data from remote devices into clinical decision algorithms and interfaces.

Factors associated with failure to achieve a glycated haemoglobin target of <8.0% in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

The aim of this study was to identify the clinical features of participants in the standard therapy arm of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) glycaemia trial who failed to reach the glycated haemoglobin (HbA1c) target. We analysed 4685 participants in the standard therapy arm, comparing participants who reached the HbA1c target of <8.0% with those whose HbA1c level was ≥8.0% 12 months after randomization. Baseline and 12-month clinical characteristics were compared. At 12 months after randomization, 3194 participants had HbA1c <8.0% and 1491 had HbA1c ≥8.0%. Black race [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.61-0.89; p = 0.002], severe hypoglycaemia (OR 0.57, CI 0.37-0.89; p = 0.014) and insulin use (OR 0.51, CI 0.40-0.65; p < 0.001) were associated with failure to reach HbA1c goal at 12 months in the adjusted model. Even with free medications, free visits with clinicians and aggressive titration of medications, >30% of participants in the standard arm of the ACCORD trial had an HbA1c ≥8.0% at 1 year. Participants who were black, had severe hypoglycaemia and were on insulin were more likely to have an above-target HbA1c concentration after 12 months on the standard protocol.

Uncoiling collagen: a multidimensional mass spectrometry study.

Mass spectrometry can be used to determine structural information about ions by activating precursors and analysing the resulting series of fragments. Two-dimensional Fourier transform ion cyclotron resonance mass spectrometry (2D FT-ICR MS) is a technique that correlates the mass-to-charge (m/z) ratio of fragment and precursor ions in a single spectrum. 2D FT-ICR MS records the fragmentation of all ions in a sample without the need for isolation. To analyse specific precursors, horizontal cross-sections of the spectrum (fragment ion scans) are taken, providing an alternative to conventional tandem mass spectrometry (MS/MS) experiments. In this work, 2D FT-ICR MS has been used to study the tryptic digest of type I collagen, a large protein. Fragment ion scans have been extracted from the 2D FT-ICR MS spectrum for precursor m/z ratios: 951.81, 850.41, 634.34, and 659.34, and 2D FT-ICR MS spectra are compared with a set of 1D MS/MS spectra using different fragmentation methods. The results show that two-dimensional mass spectrometry excells at MS/MS of complex mixtures, simplifying spectra by eliminating contaminant peaks, and aiding the identification of species in the sample. Currently, with desktop computers, 2D FT-ICR MS is limited by data processing power, a limitation which should be alleviated using cluster parallel computing. In order to explore 2D FT-ICR MS for collagen, with reasonable computing time, the resolution in the fragment ion dimension is limited to 256k data points (compared to 4M data points in 1D MS/MS spectra), but the vertical precursor ion dimension has 4096 lines, so the total data set is 1G data points (4 Gbytes). The fragment ion coverage obtained with a blind, unoptimized 2D FT-ICR MS experiment was lower than conventional MS/MS, but MS/MS information is obtained for all ions in the sample regardless of selection and isolation. Finally, although all 2D FT-ICR MS peak assignments were made with the aid of 1D FT-ICR MS data, these results demonstrate the promise of 2D FT-ICR MS as a technique for studying complex protein digest mixtures.

Higher rate of fat oxidation during rowing compared with cycling ergometer exercise across a range of exercise intensities.

The relative contribution of carbohydrate and fat oxidation to energy expenditure during exercise is dependent on variables including exercise intensity, mode, and recruited muscle mass. This study investigated patterns of substrate utilization during two non-weightbearing exercise modalities, namely cycling and rowing. Thirteen young, moderately trained males performed a continuous incremental (3-min stages) exercise test to exhaustion on separate occasions on an electronically braked cycle (CYC) ergometer and an air-braked rowing (ROW) ergometer, respectively. On two further occasions, participants performed a 20-min steady-state exercise bout at ∼50%VO2peak on the respective modalities. Despite similar oxygen consumption, rates of fat oxidation (FATox ) were ∼45% higher during ROW compared with CYC (P < 0.05) across a range of power output increments. The crossover point for substrate utilization occurred at a higher relative exercise intensity for ROW than CYC (57.8 ± 2.1 vs 42.1 ± 3.6%VO2peak , P < 0.05). During steady-state submaximal exercise, the higher FATox during ROW compared with CYC was maintained (P < 0.05), but absolute FATox were 42% (CYC) and 28% (ROW) lower than during incremental exercise. FATox is higher during ROW compared with CYC exercise across a range of exercise intensities matched for energy expenditure, and is likely as a consequence of larger muscle mass recruited during ROW.

A substudy evaluating treatment intensification on medication adherence among hypertensive patients receiving home blood pressure telemonitoring and pharmacist management.

WHAT IS KNOWN AND OBJECTIVE: Hypertension is a leading cause of death and major contributor to heart attacks, strokes, heart and kidney failure. Antihypertensive (HTN medication) non-adherence contributes to uncontrolled hypertension. Effective initiatives to improve uncontrolled hypertension include a team-based approach with home blood pressure (BP) monitoring. Our study objective was to evaluate whether objectively measured medication adherence was influenced by home BP telemonitoring and pharmacist management. METHODS: We analysed HTN medication adherence in 240 patients who received home BP telemonitoring and pharmacist intervention (TI). Adherence was measured based on prescription fills and the proportion of days covered (PDC). HTN medications continued pre- to post-baseline were similar for telemonitoring intervention (TI) and usual care (UC) patients (rate ratio = 1·00, P = 0·90). RESULTS AND DISCUSSION: More HTN medications were discontinued pre- to post-baseline in TI patients (rate ratio = 1·38, P = 0·04). Similarly, more HTN medications were added in TI patients (rate ratio = 2·46, P < 0·001). The proportion with a mean PDC ≥ 0·8 for HTN medications added after baseline and overall adherence did not differ between groups. WHAT IS NEW AND CONCLUSION: Medication adherence was high in both groups; however, medication adherence was not significantly altered by the intervention. There were more medication modifications and greater medication intensification among TI patients.

Prediction of individual milk proteins including free amino acids in bovine milk using mid-infrared spectroscopy and their correlations with milk processing characteristics.

The aim of this study was to evaluate the effectiveness of mid-infrared spectroscopy in predicting milk protein and free amino acid (FAA) composition in bovine milk. Milk samples were collected from 7 Irish research herds and represented cows from a range of breeds, parities, and stages of lactation. Mid-infrared spectral data in the range of 900 to 5,000 cm(-1) were available for 730 milk samples; gold standard methods were used to quantify individual protein fractions and FAA of these samples with a view to predicting these gold standard protein fractions and FAA levels with available mid-infrared spectroscopy data. Separate prediction equations were developed for each trait using partial least squares regression; accuracy of prediction was assessed using both cross validation on a calibration data set (n=400 to 591 samples) and external validation on an independent data set (n=143 to 294 samples). The accuracy of prediction in external validation was the same irrespective of whether undertaken on the entire external validation data set or just within the Holstein-Friesian breed. The strongest coefficient of correlation obtained for protein fractions in external validation was 0.74, 0.69, and 0.67 for total casein, total ß-lactoglobulin, and ß-casein, respectively. Total proteins (i.e., total casein, total whey, and total lactoglobulin) were predicted with greater accuracy then their respective component traits; prediction accuracy using the infrared spectrum was superior to prediction using just milk protein concentration. Weak to moderate prediction accuracies were observed for FAA. The greatest coefficient of correlation in both cross validation and external validation was for Gly (0.75), indicating a moderate accuracy of prediction. Overall, the FAA prediction models overpredicted the gold standard values. Near-unity correlations existed between total casein and ß-casein irrespective of whether the traits were based on the gold standard (0.92) or mid-infrared spectroscopy predictions (0.95). Weaker correlations among FAA were observed than the correlations among the protein fractions. Pearson correlations between gold standard protein fractions and the milk processing characteristics of rennet coagulation time, curd firming time, curd firmness, heat coagulating time, pH, and casein micelle size were weak to moderate and ranged from -0.48 (protein and pH) to 0.50 (total casein and a30). Pearson correlations between gold standard FAA and these milk processing characteristics were also weak to moderate and ranged from -0.60 (Val and pH) to 0.49 (Val and K20). Results from this study indicate that mid-infrared spectroscopy has the potential to predict protein fractions and some FAA in milk at a population level.

Stability of the Baseline Holder in Readout Circuits For Radiation Detectors.

Baseline holder (BLH) circuits are used widely to stabilize the analog output of application-specific integrated circuits (ASICs) for high-count-rate applications. The careful design of BLH circuits is vital to the overall stability of the analog-signal-processing chain in ASICs. Recently, we observed self-triggered fluctuations in an ASIC in which the shaping circuits have a BLH circuit in the feedback loop. In fact, further investigations showed that methods of enhancing small-signal stabilities cause an even worse situation. To resolve this problem, we used large-signal analyses to study the circuit's stability. We found that a relatively small gain for the error amplifier and a small current in the non-linear stage of the BLH are required to enhance stability in large-signal analysis, which will compromise the properties of the BLH. These findings were verified by SPICE simulations. In this paper, we present our detailed analysis of the BLH circuits, and propose an improved version of them that have only minimal self-triggered fluctuations. We summarize the design considerations both for the stability and the properties of the BLH circuits.

Ten-year follow-up of the 'minimal MRI lesion' subgroup from the original CHAMPS Multiple Sclerosis Prevention Trial.

BACKGROUND: Patients with clinically isolated syndrome (CIS) and characteristic magnetic resonance imaging (MRI) lesions are at high risk for multiple sclerosis (MS). However, patients with a minimal MRI lesion burden (a low T2-hyperintense [low T2] lesion count) may have borderline formal diagnostic criteria, presenting a clinical management challenge. OBJECTIVE: Compare the 10-year disease progression of patients with low and higher T2 lesion counts treated over most intervals. METHODS: CIS patients from the original CHAMPS MS trial were retrospectively assigned to low-T2 (first quartile; 2-8 lesions) or higher-T2 (second through fourth quartiles; ≥ 9 lesions) groups using baseline T2 lesion counts. The 5- and 10-year open-label extension of CHAMPS (CHAMPIONS) evaluated conversion to clinically definite MS (CDMS), MRI activity, relapses, and disability. RESULTS: The vast majority of patients showed new disease activity by MRI and/or clinical criteria at 10 years (low-T2 86%; higher-T2 98%). Fewer low-T2 than higher-T2 patients developed CDMS (40% vs. 63%; p = 0.013); low-T2 patients also had fewer new brain lesions, less brain volume loss, and less disability progression. CONCLUSION: CIS patients with low T2 lesion counts show continued disease activity. However, all assessments of disease progression over 10 years indicated a significantly less severe disease course for low-T2 patients.

Medical speciality choice: does personality matter?

There has been increasing interest in the personalities of doctors. This study examined whether personality differed based upon gender, level of training or medical speciality among 200 physicians and 134 medical students. Post-internship doctors scored significantly higher on conscientiousness (p = .001) than those pursuing basic medical training. Among those pursuing basic medical training, females scored significantly higher than males on agreeableness (p < .001) and conscientiousness (p = .001). Among post-internship respondents, females scored significantly higher on agreeableness (p = .004). There were no personality differences between post-internship doctors working in different specialities. However, among those pursuing basic medical training, those interested in person-focused medical specialities scored significantly higher on extraversion (p < .001), conscientiousness (p = .001), and lower on neuroticism (p = .01) than those who had no strong preference. These results suggest that there is no unique personality profile associated with medical practice, or medical speciality. Instead, it appears that medical school may shape personality.