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This article focuses on a study that determines that folic acid improves endothelial function in coronary artery disease (CAD) by a mechanism independent of homocysteine lowering. Previous studies have demonstrated that high dose folk acid can improve endothelial function in CAD. However, the most efficacious dose of folic acid and the significance of homocysteine lowering remain unclear. Data demonstrate that high but not low dose folic acid improves endothelial function in CAD despite a significant reduction in homocysteine in both treatment groups suggesting a mechanism independent of homocysteine lowering.

Objective: To compare survival and adverse outcome of patients with non-valvar atrial fibrillation (NVAF) treated with or without warfarin. Design: Record linkage method to identify patients with a previous hospital diagnosis of atrial fibrillation and to link these patients to international normalised ratio (INR) test results and mortality data. Setting: Cardiff and the Vale of Glamorgan, Wales. Main outcome measures: Mortality, specifically from ischaemic and thromboembolic events. Results: 6108 patients were identified with NVAF, of whom 36.4% received warfarin. Mean survival in the warfarin and non-warfarin groups was 52.0 months and 38.2 months, respectively (p < 0.001), and 14.4 months (p < 0.001) after adjustment for confounding factors. Warfarin treated patients in the upper quartile of INR control had significantly longer survival (57.5 months) than did those in the lowest quartile of control (38.1 months, p < 0.001). The risk of stroke in the warfarin group when treated was lower than that in the non-warfarin group (relative rate (RR) 0.74, p < 0.001). The risk of death from ischaemic stroke was lower in the warfarin group (RR 0.43, p < 0.001). The risk of all ischaemic and embolic events in the warfarin group was lower when they were taking warfarin (RR 0.74, p < 0.001). The risk of bleeding in the warfarin group when treated was greater (RR 1.78, p = 0.001). Conclusions: Patients with NVAF within the recommended target INR range of 2.0–3.0 survive longer and have reduced morbidity. Probably too few people are anticoagulated with warfarin in NVAF. [ABSTRACT FROM AUTHOR]

Particle mixing caused by grate movement in a packed bed of solids is an important process for biomass combustion and waste incineration. In this paper, a diffusion model for particle mixing in a burning bed is proposed and the related diffusion coefficient is measured. The diffusion model was incorporated into a combustion model for waste incineration in an actual full-scale bed and numerical calculations were carried to assess the effect of different mixing levels on the burning characteristics of the furnace. In-bed measurement of temperature, oxygen concentration and particle movement was also made using a special electronic device. It is found that the modelled flame front reaches the bed bottom at an earlier stage for a higher level of particle mixing; the average burning rate ranges from 0.05 to 0.13kg/m2s and the mass loss rate for a higher mixing level can be twice of that for a lower mixing level. However, excessive mixing can cause significant delay in ignition or even extinction of the bed combustion; the obtained local air to fuel stoichiometric ratio covers a range from sub-stoichiometric (0.6 for the highest mixing level) to super-stoichiometric (1.6 for the lowest mixing level); the carbon in ash ranges from 3.5 to 10.5%; the most reasonable range of the particle-mixing (diffusion) coefficient is from 1.8 to 6.0cm2/min for a full-scale bed, according to the calculation. [Copyright &y& Elsevier]

The regulatory environment in which long daycare centres are required to operate plays a key role in determining what early childhood professionals do and how they go about doing it. This paper reports findings from a state‐wide survey undertaken in New South Wales, Australia, which shows how early childhood professionals position themselves on four key aspects of the regulatory environment: the premises underlying regulatory requirements; its perceived support of them as professionals to provide quality care; how state regulations and the national accreditation system impact upon their daily practice; and the way these audit systems affect their professional esteem. Implications for job satisfaction are discussed. The paper concludes by asserting that regulatory requirements need to be evaluated in terms of their contribution to structural, process, contextual and work environment dimensions of quality. [ABSTRACT FROM AUTHOR]

Background While folic acid (FA) reduces plasma homocysteine (Hcy), whether the simultaneous improvement in endothelial function is dependent on Hcy lowering per se is questionable. In the present study the relationship between FA dose, Hcy lowering and endothelial function in patients with coronary artery disease (CAD) was investigated. Materials and methods Eighty-four patients with CAD received either 400 µg FA or 5 mg placebo daily for a 6-week treatment period. A further 44 patients with CAD received either 100 mg kg−1 day−1 of betaine or placebo for a 6-week treatment period. Flow-mediated dilatation (FMD), a measure of endothelial function, was assessed before and after the 6-week periods. Isometric tension and Western blotting were used to investigate the effect of FA on endothelial function and endothelial nitric oxide synthase (eNOS) dimerization in isolated rabbit aortic rings and cultured porcine aortic endothelial cells (PAEC), respectively. Results Both 400 µg day−1 and 5 mg day−1 FA significantly increased plasma folate and decreased plasma Hcy. The FMD improved significantly after 6 weeks’ treatment of 5 mg day−1 FA but did not correlate with the reduction in Hcy. There was no change in FMD in either the 400 µg FA or placebo group. In a subgroup analysis of 11 patients in the betaine group, despite a reduced Hcy, a significant impairment in FMD was observed. In the in vitro studies FA, but not betaine, reversed methionine-induced endothelial dysfunction. Moreover, the FA promoted eNOS dimerization in cultured PAEC. Conclusions These data suggest that FA dose-dependently improves endothelial function in CAD via a mechanism independently of Hcy lowering. It may involve promotion of eNOS dimerization. [ABSTRACT FROM AUTHOR]

Objective: To evaluate how well patients with non-valvar atrial fibrillation (NIVAF) were maintained within the recommended international normalised ratio (1NR) target of 2.0-3.0 and to explore the relation between achieved INR control and clinical outcomes. Design: Record linkage study of routine activity records and INR measurements. Setting: Cardiff and the Vale of Glamorgan, South Wales, UK. Participants: 2223 patients with NVAF, no history of heart valve replacement, and with at least five INIR measurements. Main outcome measures: Mortality, ischaemic stroke, all thromboembolic events, bleeding events, hospitalisation, and patterns of INR monitoring. Results: Patients treated with warfarin were outside the INR target range 32.1 % of the time, with 15.4% INR values > 3.0 and 16.7% INR values < 2.0. However, the quartile with worst control spent 71.6% of their time out of target range compared with only 16.3% out of range in the best controlled quartile. The median period between INR tests was 16 days. Time spent outside the target range decreased as the duration of INR monitoring increased, from 52% in the first three months of monitoring to 30% after two years. A multivariate logistic regression model showed that a 10% increase in time out of range was associated with an increased risk of mortality (odds ratio (OR) 1.29, p < 0.001) and of an ischaemic stroke (OR 1.10, p = 0.006) and other thromboembolic events (OR 1.12, p < 0.001). The rate of hospitalisation was higher when INR was outside the target range. Conclusions: Suboptimal anticoagulation was associated with poor clinical outcomes, even in a well controlled population. However, good control was difficult to achieve and maintain. New measures are needed to improve maintenance anticoagulation in patients with NVAF. [ABSTRACT FROM AUTHOR]

Summary objectives Hypopituitary adults with growth hormone deficiency (GHD) have an increased cardiovascular mortality, although the mechanisms remain unclear. Endothelial dysfunction, characterized by reduced nitric oxide (NO) bioavailability, is a key early event in atherogenesis and is associated with increased vascular smooth muscle tone and arterial stiffening. design and patients In a randomized, double-blind, placebo-controlled study, we investigated the effects of GH replacement on endothelial function and large-artery stiffness in 32 GHD adults (19 males, 13 females) (age range 19–64 years) over a 6-month period. Thirty-two age- and sex-matched healthy controls were also studied. measurements Endothelial function was assessed using ultrasonic wall tracking to measure flow-mediated dilatation (FMD) of the brachial artery. Large artery stiffness was assessed by pulse wave analysis of the radial artery pressure waveform, allowing determination of the corresponding central arterial pressure waveform and derivation of the augmentation index. Fasting lipid profiles, glucose and insulin were also measured. results At baseline, FMD (mean ± SD) was impaired in GH-deficient subjects vs. controls (3·4 ± 2·3 vs. 5·7 ± 2·0%, P < 0·0001), although endothelium-independent dilatation was similar. The augmentation index was higher in GH-deficient subjects vs. controls (23 ± 12 vs. 14 ± 14%, P < 0·01). GH-deficient subjects had higher LDL cholesterol (4·1 ± 0·8 vs. 3·5 ± 0·8 mmol/l, P < 0·01) and lower HDL cholesterol (1·1 ± 0·3 vs. 1·4 ± 0·4 mmol/l, P < 0·01). In GH-deficient subjects, there were inverse correlations between LDL cholesterol and FMD (r = –0·40, P < 0·05) and between FMD and the augmentation index (r = – 0·58, P < 0·01). Regression analysis identified FMD as an independent predictor of the... [ABSTRACT FROM AUTHOR]

Background: The National Institute for Health and Care Excellence (NICE) guideline quality standard for non-ST-segment elevation acute coronary syndrome (NSTEACS) pathway states that adults who have an intermediate or higher risk of future adverse cardiovascular events should undergo coronary angiography within 72 hours of first admission to hospital.The aim was to improve compliance with the 72-hour NICE quality standard for the acute coronary syndrome pathway between one district general hospital (DGH) and its cardiac tertiary centre by reducing the time from admission to angiography by 50%.Participants were front-line staff in the DGH and staff in the cardiac catheter laboratory in the tertiary centre., Methods: Continuous data were collected prospectively on all patients entering the NSTEACS pathway with time of arrival to hospital; referral to angiography; and start of angiogram to measure the NSTEACS pathway duration against the NICE quality standard. We used process mapping, ease-benefit matrix, Pareto analyses and the Institute for Healthcare Improvement (IHI) Plan-Do-Study-Act (PDSA) method of quality improvement., Intervention: Staff in both hospitals performed process mapping of their respective parts of the NSTEACS pathway. Their data informed decisions on process changes using the ease-benefit matrix. PDSA cycles were commenced, and changes were assessed using continuous measurement of pathway duration. In the tertiary centre, Pareto analysis was performed to help identify the major service constraints., Results: Between January 2021 and March 2023, there were four separate PDSA cycles, two each in the DGH and tertiary centre. Across the four PDSA cycles, the time to complete the pathway reduced from an average of 172 to 94.72 hours, an improvement of 45%, along with an overall reduction in variability of data. In the DGH, the process changes were sustained, but in the tertiary centre they were not, as PDSA 4 required staff recruitment to enable a 6-day rather than a 5-day service per week., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The study aimed to assess if specialised healthcare service interventions in Wales benefit the population equitably in work commissioned by the Welsh Health Specialised Services Committee (WHSSC)., Approach: The study utilised anonymised individual-level, population-scale, routinely collected electronic health record (EHR) data held in the Secure Anonymised Information Linkage (SAIL) Databank to identify patients resident in Wales receiving specialist cardiac interventions. Measurement was undertaken of associated patient outcomes 2-years before and after the intervention (minus a 6-month clearance period on either side) by measuring events in primary care, hospital attendance, outpatient and emergency department. The analysis controlled for comorbidity (Charlson) and deprivation (Welsh Index of Multiple Deprivation), stratified by admission type (elective or emergency) and membership of top 5% post-intervention costs. Costs were estimated by multiplying events by mean person cost estimates., Results: We identified 5,999 percutaneous coronary interventions (PCI) and 1,640 coronary artery bypass graft (CABG) between 2014-06-01 to 2020-02-29. The ratio of emergency to elective interventions was 2.85 for PCI and 1.04 for CABG. In multivariate analysis significant associations were identified for comorbidity (OR = 1.52, CI = (1.01-2.27)), deprivation (OR = 1.34, CI = (1.03-1.76)) and rurality (OR = 0.81, CI = (0.70-0.95)) for PCI interventions, and comorbidity (OR = 1.47, CI = (1.10-1.98)) for CABG. Higher costs post-intervention were associated with increased comorbidity for PCI and CABG in the top 5% cost groups, but for PCI this was not seen outside the top 5%. For PCI, moderate cost increase was associated with increased deprivation, but the picture was more mixed following CABG interventions. For both interventions, lower costs post intervention were seen in rural locations., Conclusion: We identified and compared health outcomes for selected specialist cardiac interventions amongst patients resident in Wales, with these methods and analyses, providing a template for comparing other cardiac interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Davies et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis predominantly presents with psychiatric symptoms. Psychiatrists need to be alert to this diagnostic possibility, especially in female adolescents and young adults, as exemplified by the real (de-identified) case outlined below. Earlier diagnosis and immunotherapy improves long-term outcomes. Collaboration with neurology colleagues is essential for optimal care. 'Red flags' for autoimmune encephalitis and 'diagnostic clues' act as helpful aide memoires for this uncommon condition. The gold standard for testing is the detection of NMDAR antibodies in cerebrospinal fluid, but serum can be tested as a more accessible (but less reliable) preliminary step. The results of routine blood tests, magnetic resonance imaging of the head and electroencephalograms can be normal or show non-specific changes. Diagnostic criteria exist to define probable and definite cases. Immunotherapy for anti-NMDAR encephalitis is effective for many patients, but recovery is prolonged and relapses can occur.

Introduction: Motor neuron disease (MND) can occur in patients with cancer, but there is minimal evidence that this is more than by chance. We contrast two cases of motor neuronopathies occurring in the context of systemic malignancy and argue that in one case the cause was most likely paraneoplastic, while in the other it was not. CASE 1: A 61-year-old woman developed progressive walking difficulties over 9 months with weakness and stiffness in her legs. EMG showed fibrillations and positive sharp waves in multiple lower limb muscles bilaterally, with neurogenic units and a reduced recruitment pattern. An invasive ductal carcinoma of the breast was identified and she continued to deteriorate neurologically with worsening mobility, upper limb spasticity and fasciculations. She died approximately 26 months after symptom onset. CASE 2: A 57-year-old woman developed weight loss and weakness of her right arm without any sensory symptoms. At presentation, she had wasting and fasciculations in her right upper limb muscles, with normal reflexes, normal left upper limb and lower limb examination. Over the following week, she developed left upper limb weakness and fasciculations, brisk knee reflexes, and flexor plantar responses. Her EMG showed upper and lower limb denervation. She was found to have anti-Hu and anti-CV2 antibodies present in serum. A PET-CT showed active uptake in lymph nodes in the right hilum. Biopsy confirmed a small cell lung cancer. She had chemoradiation therapy and the tumour went into remission. She has remained well on follow-up 24 months later, regaining weight and strength after her chemotherapy. She continues to be monitored for cancer recurrence, but thus far appears to be in remission., Conclusion: In cases with rapidly progressive MND, particularly of upper limb onset, consideration should be given to testing anti-neuronal antibodies and searching for an occult tumour.

Background: There is a paucity of literature when it comes to identifying predictors of in-state retention of graduate medical education (GME) graduates, such as the demographic and educational characteristics of these physicians., Objective: The purpose was to use demographic and educational predictors to identify graduates from a single Michigan GME sponsoring institution, who are also likely to practice medicine in Michigan post-GME training., Methods: We included all residents and fellows who graduated between 2000 and 2014 from 1 of 18 GME programs at a Michigan-based sponsoring institution. Predictor variables identified by logistic regression with cross-validation were used to create a scoring tool to determine the likelihood of a GME graduate to practice medicine in the same state post-GME training., Results: A 6-variable model, which included 714 observations, was identified. The predictor variables were birth state, program type (primary care versus non-primary care), undergraduate degree location, medical school location, state in which GME training was completed, and marital status. The positive likelihood ratio (+LR) for the scoring tool was 5.31, while the negative likelihood ratio (-LR) was 0.46, with an accuracy of 74%., Conclusions: The +LR indicates that the scoring tool was useful in predicting whether graduates who trained in a Michigan-based GME sponsoring institution were likely to practice medicine in Michigan following training. Other institutions could use these techniques to identify key information that could help pinpoint matriculating residents/fellows likely to practice medicine within the state in which they completed their training., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Background: In a time of threats to the funding for graduate medical education (GME) and projected physician shortages, drawing attention to the value of physician training programs may be useful. One approach is to study the number and percentage of physicians who enter practice in the state in which they trained., Objective: We sought to examine the percentage of graduates from a single Michigan-based GME institution over a 15-year period, who practiced medicine in Michigan during their career., Methods: We performed a retrospective review of historical data for all graduates currently in practice, derived from 18 GME training programs from 2000 through 2014. Practice location data were collected and confirmed using multiple sources for accuracy., Results: Data were available for 1168 graduates. The average age at the time of graduation was 32.6 ± 4.4 years (mean and standard deviation [SD]), and 60.2% were men (703 of 1168). There were 546 graduates (46.7%) who practiced in Michigan after graduation. Almost 80% of the graduates (279 of 358) who completed medical school and GME in Michigan also practiced in Michigan. Of those, 87.8% (245 of 279) also completed a bachelor's degree in Michigan., Conclusions: The findings show that graduates from our GME programs were highly likely to practice in Michigan if they completed their pre-GME education in Michigan., Competing Interests: The authors declare they have no competing interests.

Background: Tailoring is a frequent component of approaches for implementing clinical practice guidelines, although evidence on how to maximise the effectiveness of tailoring is limited. In England, overweight and obesity are common, and national guidelines have been produced by the National Institute for Health and Care Excellence. However, the guidelines are not routinely followed in primary care., Methods: A tailored implementation intervention was developed following an analysis of the determinants of practice influencing the implementation of the guidelines on obesity and the selection of strategies to address the determinants. General practices in the East Midlands of England were invited to take part in a cluster randomised controlled trial of the intervention. The primary outcome measure was the proportion of overweight or obese patients offered a weight loss intervention. Secondary outcomes were the proportions of patients with (1) a BMI or waist circumference recorded, (2) record of lifestyle assessment, (3) referred to weight loss services, and (4) any change in weight during the study period. We also assessed the mean weight change over the study period. Follow-up was for 9 months after the intervention. A process evaluation was undertaken, involving interviews of samples of participating health professionals., Results: There were 16 general practices in the control group, and 12 in the intervention group. At follow-up, 15.08 % in the control group and 13.19 % in the intervention group had been offered a weight loss intervention, odds ratio (OR) 1.16, 95 % confidence interval (CI) (0.72, 1.89). BMI/waist circumference measurement 42.71 % control, 39.56 % intervention, OR 1.15 (CI 0.89, 1.48), referral to weight loss services 5.10 % control, 3.67 % intervention, OR 1.45 (CI 0.81, 2.63), weight management in the practice 9.59 % control, 8.73 % intervention, OR 1.09 (CI 0.55, 2.15), lifestyle assessment 23.05 % control, 23.86 % intervention, OR 0.98 (CI 0.76, 1.26), weight loss of at least 1 kg 42.22 % control, 41.65 % intervention, OR 0.98 (CI 0.87, 1.09). Health professionals reported the interventions as increasing their confidence in managing obesity and providing them with practical resources., Conclusions: The tailored intervention did not improve the implementation of the guidelines on obesity, despite systematic approaches to the identification of the determinants of practice. The methods of tailoring require further development to ensure that interventions target those determinants that most influence implementation., Trial Registration: ISRCTN07457585.

Terahertz pulses are applied as an all-optical bias to ferroelectric thin-film BiFeO3 while monitoring the time-dependent ferroelectric polarization through its nonlinear optical response. Modulations in the intensity of the second harmonic light generated by the film correspond to on-off ratios of 220× gateable on femtosecond timescales. Polarization modulations comparable to the built-in static polarization are observed., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

There is increasing controversy about the use of the whip as a performance aid in Thoroughbred horseracing and its impact on horse welfare. This paper offers a critical analysis of the British Horseracing Authority's (BHA) 2011 Report Responsible Regulation: A Review of the Use of the Whip in Horseracing. It examines the BHA's process of consultation and use of science and public opinion research through the application of current scientific literature and legal analysis. This analysis suggests that the BHA's findings on the welfare impact and justification for whip use are insufficiently defended by the report. These findings indicate that the report is an inadequate basis from which to draw any definitive conclusions on the impact of whips on racehorse welfare. Further review is needed, undertaken by an independent scientific body, to advance this debate.

We scanned 25 left knees in healthy human subjects using MRI. Multiplanar reconstruction software was used to take measurements of the inferior and posterior facets of the femoral condyles and the trochlea. A 'basic circle' can be defined which, in the sagittal plane, fits the posterior and inferior facets of the lateral condyle, the posterior facet of the medial condyle and the floor of the groove of the trochlea. It also approximately fits both condyles in the coronal plane (inferior facets) and the axial plane (posterior facets). The circle fitting the inferior facet of the medial condyle in the sagittal plane was consistently 35% larger than the other circles and was termed the 'medial inferior circle'. There were strong correlations between the radii of the circles, the relative positions of the centres of the condyles, the width of the condyles, the total knee width and skeletal measurements including height. There was poor correlation between the radii of the circles and the position of the trochlea relative to the condyles. In summary, the condyles are approximately spherical except for the inferior facet medially, which has a larger radius in the sagittal plane. The size and position of the condyles are consistent and change with the size of the person. However, the position of the trochlea is variable even though its radius is similar to that of the condyles. This information has implications for understanding anterior knee pain and for the design of knee replacements., (©2014 The British Editorial Society of Bone & Joint Surgery.)

Single-cycle terahertz fields generated by coherent transition radiation from a relativistic electron beam are used to study the high field optical response of single crystal GaAs. Large amplitude changes in the sub-band-gap optical absorption are induced and probed dynamically by measuring the absorption of a broad-band optical beam generated by transition radiation from the same electron bunch, providing an absolutely synchronized pump and probe geometry. This modification of the optical properties is consistent with strong-field-induced electroabsorption. These processes are pertinent to a wide range of nonlinear terahertz-driven light-matter interactions anticipated at accelerator-based sources.

Background: Eye disease and visual impairment are common in the elderly and are associated with social and functional decline, the need to access community support services, depression, falls, nursing home placement and increased mortality., Objective: To provide guidance for general practitioners in the detection and recommended management of the most important eye conditions in the elderly in Australia: refractive error, cataract, diabetic retinopathy, age-related macular degeneration and glaucoma., Discussion: Timely detection and treatment of eye disease can greatly reduce its morbidity. Elderly patients should be encouraged to undergo eye testing every 2 years. Health professionals, including general practitioners, optometrists and ophthalmologists should work collaboratively to ensure patients have access to appropriate disease detection and treatment.

SLAC has two electron accelerators, the Linac Coherent Light Source (LCLS) and the Facility for Advanced Accelerator Experimental Tests (FACET), providing high-charge, high-peak-current, femtosecond electron bunches. These characteristics are ideal for generating intense broadband terahertz (THz) pulses via coherent transition radiation. For LCLS and FACET respectively, the THz pulse duration is typically 20 and 80 fs RMS and can be tuned via the electron bunch duration; emission spectra span 3-30 THz and 0.5 THz-5 THz; and the energy in a quasi-half-cycle THz pulse is 0.2 and 0.6 mJ. The peak electric field at a THz focus has reached 4.4 GV/m (0.44 V/Å) at LCLS. This paper presents measurements of the terahertz pulses and preliminary observations of nonlinear materials response.