Development of optimised tissue-equivalent materials for proton therapy.

Objective. In proton therapy there is a need for proton optimised tissue-equivalent materials as existing phantom materials can produce large uncertainties in the determination of absorbed dose and range measurements. The aim of this work is to develop and characterise optimised tissue-equivalent materials for proton therapy.Approach. A mathematical model was developed to enable the formulation of epoxy-resin based tissue-equivalent materials that are optimised for all relevant interactions of protons with matter, as well as photon interactions, which play a role in the acquisition of CT numbers. This model developed formulations for vertebra bone- and skeletal muscle-equivalent plastic materials. The tissue equivalence of these new materials and commercial bone- and muscle-equivalent plastic materials were theoretical compared against biological tissue compositions. The new materials were manufactured and characterised by their mass density, relative stopping power (RSP) measurements, and CT scans to evaluate their tissue-equivalence.Main results. Results showed that existing tissue-equivalent materials can produce large uncertainties in proton therapy dosimetry. In particular commercial bone materials showed to have a relative difference up to 8% for range. On the contrary, the best optimised formulations were shown to mimic their target human tissues within 1%-2% for the mass density and RSP. Furthermore, their CT-predicted RSP agreed within 1%-2% of the experimental RSP, confirming their suitability as clinical phantom materials.Significance. We have developed a tool for the formulation of tissue-equivalent materials optimised for proton dosimetry. Our model has enabled the development of proton optimised tissue-equivalent materials which perform better than existing tissue-equivalent materials. These new materials will enable the advancement of clinical proton phantoms for accurate proton dosimetry.

Adapted cardiac rehabilitation for people with sub-acute, mild-to-moderate stroke: a mixed methods feasibility study.

OBJECTIVE: To determine the recruitment strategy, acceptability, adherence, outcome measures, and adverse events for a definitive study that will explore adapted cardiac rehabilitation (CR) for people post-stroke with mild-to-moderate severity stroke in the sub-acute stage of recovery. DESIGN: Mixed methods feasibility study. SETTING: Acute hospital setting, neurology outpatients and community hospitals. PARTICIPANTS: 32 participants with stroke (mean age: 64.4 years) of median National Institutes of Health Stroke Scale (NIHSS) score 2 (range: 0 to 6) within six months of stroke. INTERVENTION: All participants attended six weeks, adapted CR within one to six months after a stroke. A combined class with people post cardiac event. MAIN OUTCOME MEASURES: Incremental shuttle walk test (ISWT), blood pressure, heart rate, weight, body mass index, quality of life, fatigue, anxiety and depression, tone, falls, stroke attitude and knowledge, physical activity (accelerometry) and functional ability. QUALITATIVE: Interviews with participants, non-participants and people post-cardiac event. Focus groups with Stroke and CR teams. RESULTS: 32 participants were recruited. The programme was acceptable to people with mild stroke (NIHSS<3) and people post cardiac events; 80% of classes attended, a mean of 9.6 classes, with six drop-outs. The ISWT was an acceptable outcome measure (for NIHSS<3) and most measures showed positive changes. There was one adverse event. CONCLUSION: A definitive study to determine the effect of six weeks of adapted CR on cardiorespiratory fitness (CRf) in people who have had a mild severity stroke (NIHSS<3) in the sub-acute phase of recovery, is feasible. Teams need specialist education and support. A more specialist service may be needed for people with a stroke severity defined by NIHSS>2. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN14861846.

The effect of patient ethnicity on the accuracy of peripheral pulse oximetry in patients with COVID-19 pneumonitis: a single-centre, retrospective analysis.

Pulse oximetry is used widely to titrate oxygen therapy and for triage in patients who are critically ill. However, there are concerns regarding the accuracy of pulse oximetry in patients with COVID-19 pneumonitis and in patients who have a greater degree of skin pigmentation. We aimed to determine the impact of patient ethnicity on the accuracy of peripheral pulse oximetry in patients who were critically ill with COVID-19 pneumonitis by conducting a retrospective observational study comparing paired measurements of arterial oxygen saturation measured by co-oximetry on arterial blood gas analysis (SaO2 ) and the corresponding peripheral oxygenation saturation measured by pulse oximetry (Sp O2 ). Bias was calculated as the mean difference between SaO2 and Sp O2 measurements and limits of agreement were calculated as bias ±1.96 SD. Data from 194 patients (135 White ethnic origin, 34 Asian ethnic origin, 19 Black ethnic origin and 6 other ethnic origin) were analysed consisting of 6216 paired SaO2 and Sp O2 measurements. Bias (limits of agreement) between SaO2 and Sp O2 measurements was 0.05% (-2.21-2.30). Patient ethnicity did not alter this to a clinically significant degree: 0.28% (1.79-2.35), -0.33% (-2.47-2.35) and -0.75% (-3.47-1.97) for patients of White, Asian and Black ethnic origin, respectively. In patients with COVID-19 pneumonitis, Sp O2 measurements showed a level of agreement with SaO2 values that was in line with previous work, and this was not affected by patient ethnicity.

Association of working shifts, inside and outside of healthcare, with severe COVID-19: an observational study.

BACKGROUND: Health and key workers have elevated odds of developing severe COVID-19; it is not known, however, if this is exacerbated in those with irregular work patterns. We aimed to investigate the odds of developing severe COVID-19 in health and shift workers. METHODS: We included UK Biobank participants in employment or self-employed at baseline (2006-2010) and with linked COVID-19 data to 31st August 2020. Participants were grouped as neither a health worker nor shift worker (reference category) at baseline, health worker only, shift worker only, or both, and associations with severe COVID-19 investigated in logistic regressions. RESULTS: Of 235,685 participants (81·5% neither health nor shift worker, 1·4% health worker only, 16·9% shift worker only, and 0·3% both), there were 580 (0·25%) cases of severe COVID-19. The odds of severe COVID-19 was higher in health workers (adjusted odds ratio: 2·32 [95% CI: 1·33, 4·05]; shift workers (2·06 [1·72, 2·47]); and in health workers who worked shifts (7·56 [3·86, 14·79]). Being both a health worker and a shift worker had a possible greater impact on the odds of severe COVID-19 in South Asian and Black and African Caribbean ethnicities compared to White individuals. CONCLUSIONS: Both health and shift work (measured at baseline, 2006-2010) were independently associated with over twice the odds of severe COVID-19 in 2020; the odds were over seven times higher in health workers who work shifts. Vaccinations, therapeutic and preventative options should take into consideration not only health and key worker status but also shift worker status.

Evaluation of procalcitonin as a contribution to antimicrobial stewardship in SARS-CoV-2 infection: a retrospective cohort study.

It can be a diagnostic challenge to identify patients with coronavirus disease 2019 in whom antibiotics can be safely withheld. This study evaluated the effectiveness of a guideline implemented at Sheffield Teaching Hospitals NHS Foundation Trust that recommends withholding antibiotics in patients with low serum procalcitonin (PCT), defined as ≤0.25 ng/mL. Results showed reduced antibiotic consumption in patients with PCT ≤0.25 ng/mL with no increase in mortality, alongside a reduction in subsequent carbapenem prescriptions during admission. The results support the effectiveness of this guideline, and further research is recommended to identify the optimal cut-off value for PCT in this setting.

Pencil Beam Scanning Proton Therapy Case Selection for Paediatric Abdominal Neuroblastoma: Effects of Tumour Location and Bowel Gas.

AIMS: Pencil beam scanning (PBS) proton therapy is an increasingly used radiation modality for childhood malignancies due to its ability to minimise dose to surrounding organs. However, the dosimetry is extremely sensitive to anatomical and density changes. The aims of this study were to investigate if there is a dosimetric benefit or detriment with PBS for paediatric abdominal neuroblastoma, assess gastrointestinal air variability and its dosimetric consequences, plus identify if there are factors that could assist case selection for PBS referral. MATERIALS AND METHODS: Twenty neuroblastoma cases were double-planned with PBS and intensity-modulated arc therapy (IMAT). Cases were divided into unilateral, midline unilateral and midline bilateral locations in relation to the kidneys. Plans were recalculated after the gastrointestinal volume was simulated as air (Hounsfield Units -700) and water (Hounsfield Units 0), then compared with nominal plans (recalculated - nominal, ΔD). Forty-three weekly cone beam computed tomography scans were analysed to quantify gastrointestinal air variability during treatment. RESULTS: PBS reduced the mean dose to normal tissues at all tumour locations, particularly unilateral tumours. However, 15% had better dosimetry with IMAT, all of which were midline tumours. Increased gastrointestinal air caused significant compromises to PBS versus IMAT plans for midline tumours [median/maximum ΔD95% clinical target volume (CTV) -2.4%/-15.7% PBS versus 1.4%/0% IMAT, P = 0.003], whereas minimal impact was observed for unilateral tumours (ΔD95% CTV -0.5%/-1.9% PBS versus 0.5%/-0.5% IMAT, P = 0.008). D95% CTV was significantly decreased in PBS plans if planning target volume (PTV) ≥400 cm3 (median -4.1%, P = 0.001) or PTV extension ≥60% anterior to vertebral body (-2.1%, P = 0.002). A larger variation in gastrointestinal air was observed in patients treated under general anaesthesia (median 38.4%) versus awake (11.5%); P = 0.004. CONCLUSION: In this planning study, tumours at the unilateral location consistently showed improved dose reductions to normal tissue with minimal dose degradation from increased gastrointestinal air with PBS plans. Tumour location, PTV volume and anterior extension of PTV are useful characteristics in facilitating patient selection for PBS.

Influence of sociodemographic characteristics on the preferred format of health education delivery in individuals with type 2 diabetes mellitus and or cardiovascular disease: a questionnaire study.

AIM: To examine the influence of sociodemographic factors of interest on preference for a particular health education format among people with type 2 diabetes and/or cardiovascular disease. METHODS: A questionnaire was used to collect information on the influence of six sociodemographic factors of interest on the preference for health education formats in people with type 2 diabetes and/or cardiovascular disease. Chi-squared tests were used to examine the distribution of preferences between groups. The characteristics of the population preferring the online format were then examined in more detail using logistic regression. RESULTS: Responses were received from 1559 participants. Overall the preferred health education format was one-to-one learning from a doctor or nurse (67%). Age, gender, diagnosis and educational level all affected the preferences expressed. The characteristics showing most consistent and significant influence were age and educational level. Overall, 29% ranked the online format highly (scores 1 or 2). This group were more likely to be aged < 65 years (P < 0.001) and to have a higher level of educational attainment (upper secondary education or higher; P < 0.001). CONCLUSIONS: Significant differences between sociodemographic groups exist in preferences for health education formats among people with type 2 diabetes and/or cardiovascular disease. Preferences should be considered when designing educational interventions to ensure they are accessible to the target group and to avoid increases in health inequality.

Leisure-time physical activity and life expectancy in people with cardiometabolic multimorbidity and depression.

BACKGROUND: Whether and to what extent leisure-time physical activity at the recommended levels of 150-min moderate activity is associated with survival in people with cardiometabolic multimorbidity and depression is unknown. METHODS: UK Biobank participants were classified into groups: (i) no disease; (ii) diabetes; (iii) cardiovascular disease (CVD); (iv) depression; (v) diabetes and CVD; (vi) diabetes and depression; (vii) CVD and depression; (viii) diabetes, CVD and depression. Leisure-time physical activity was categorized as active (meeting recommendations) or inactive. Survival models were applied to estimate life expectancy. RESULTS: A total of 480 940 participants were included (median age, 58 years; 46% men; 95% white), of whom 74% with cardiometabolic multimorbidity and depression were inactive. During a mean follow-up of 7 years, 11 006 deaths occurred. At age of 45 years, being physically active was associated with 2.34 (95% confidence interval: 0.93, 3.54) additional years of life compared with being inactive in participants with diabetes; corresponding estimates were 2.28 (1.40, 3.16) for CVD; 2.15 (0.05, 4.26) for diabetes and CVD; and 1.58 (1.27, 1.89) for no disease. Participants with a combination of diabetes, CVD and depression, being active was associated with 6.81 (-1.50, 15.31) additional years compared with being inactive; corresponding estimates were 3.07 (-2.46, 8.59) for diabetes and depression; 2.34 (-1.24, 5.91) for CVD and depression; and 0.80 (-0.46, 2.05) for depression. A similar pattern was found at 65 years. CONCLUSIONS: Meeting the recommended level of physical activity was associated with a longer life expectancy in people with cardiometabolic multimorbidity but not in those with depression.

The impact of proton LET/RBE modeling and robustness analysis on base-of-skull and pediatric craniopharyngioma proton plans relative to VMAT.

Purpose: Pediatric craniopharyngioma, adult base-of-skull sarcoma and chordoma cases are all regarded as priority candidates for proton therapy. In this study, a dosimetric comparison between volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) was first performed. We then investigated the impact of physical and biological uncertainties. We assessed whether IMPT plans remained dosimetrically superior when such uncertainty estimates were considered, especially with regards to sparing organs at risk (OARs).Methodology: We studied 10 cases: four chondrosarcoma, two chordoma and four pediatric craniopharyngioma. VMAT and IMPT plans were created according to modality-specific protocols. For IMPT, we considered (i) variable RBE modeling using the McNamara model for different values of (α/ß)x, and (ii) robustness analysis with ±3 mm set-up and 3.5% range uncertainties.Results: When comparing the VMAT and IMPT plans, the dosimetric advantages of IMPT were clear: IMPT led to reduced integral dose and, typically, improved CTV coverage given our OAR constraints. When physical robustness analysis was performed for IMPT, some uncertainty scenarios worsened the CTV coverage but not usually beyond that achieved by VMAT. Certain scenarios caused OAR constraints to be exceeded, particularly for the brainstem and optical chiasm. However, variable RBE modeling predicted even more substantial hotspots, especially for low values of (α/ß)x. Variable RBE modeling often prompted dose constraints to be exceeded for critical structures.Conclusion: For base-of-skull and pediatric craniopharyngioma cases, both physical and biological robustness analyses should be considered for IMPT: these analyses can substantially affect the sparing of OARs and comparisons against VMAT. All proton RBE modeling is subject to high levels of uncertainty, but the clinical community should remain cognizant possible RBE effects. Careful clinical and imaging follow-up, plus further research on end-of-range RBE mitigation strategies such as LET optimization, should be prioritized for these cohorts of proton patients.

Comorbid depression and risk of cardiac events and cardiac mortality in people with diabetes: A systematic review and meta-analysis.

OBJECTIVE: To examine the association of comorbid occurrence of diabetes and depression with risk of cardiovascular endpoints including cardiovascular mortality, coronary heart disease and stroke. RESEARCH DESIGN AND METHODS: A systematic review and metaanalysis. We searched PUBMED/MEDLINE, Medscape, Cochrane Library, CINAHL, EMBASE and Scopus databases assessing cardiac events and mortality associated with depression in diabetes up until 1 December 2018. Pooled hazard ratios were calculated using random- effects models. RESULTS: Nine studies met the inclusion criteria. The combined pooled hazard ratios showed a significant association of cardiac events in people with depression and type 2 diabetes, compared to those with type 2 diabetes alone. For cardiovascular mortality the pooled hazard ratio was 1.48 (95% CI: 1.185, 1.845), p = 0.001, for coronary heart disease 1.37 (1.165, 1.605), p < 0.001 and for stroke 1.33 (1.291, 1.369), p < 0.001. Heterogeneity was high in the meta-analysis for stroke events (I-squared = 84.7%) but was lower for coronary heart disease and cardiovascular mortality (15% and 43.4% respectively). Meta-regression analyses showed that depression was not significantly associated with the study level covariates mean age, duration of diabetes, length of follow-up, BMI, sex and ethnicity (p < 0.05 for all models). Only three studies were found that examined the association of depression in type 1 diabetes, there was a high degree of heterogeneity and data synthesis was not conducted for these studies. CONCLUSIONS: We have demonstrated a 47.9% increase in cardiovascular mortality, 36.8% increase in coronary heart disease and 32.9% increase in stroke in people with diabetes and comorbid depression. The presence of depression in a person with diabetes should trigger the consideration of evidence-based therapies for cardiovascular disease prevention irrespective of the baseline risk of cardiovascular disease or duration of diabetes.

Assessment of response rates and yields for Two opportunistic Tools for Early detection of Non-diabetic hyperglycaemia and Diabetes (ATTEND). A randomised controlled trial and cost-effectiveness analysis.

AIMS: To assess the opportunistic use in primary care of a computer risk score versus a self-assessment risk score for undiagnosed type 2 diabetes. METHODS: We conducted a randomised controlled trial in 11 primary care practices in the UK. 577 patients aged 40-75years with no current diagnosis of type 2 diabetes were recruited to a computer based risk score (Leicester Practice Computer Risk Score (LPCRS)) or a patient self-assessment score (Leicester Self-Assessment Score (LSAS)). RESULTS: The rate of self-referral blood tests was significantly higher for the LPCRS compared to the LSAS, 118.98 (95% CI: 102.85, 137.64) per 1000 high-risk patient years of follow-up compared to 92.14 (95% CI: 78.25, 108.49), p=0.022. Combined rate of diagnosis of type 2 diabetes and those at risk of developing the disease (i.e. impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)) was similar between the two arms, 15.12 (95% CI: 9.11, 25.08) per 1000 high-risk patient years for LPCRS compared to 14.72 (95% CI: 9.59, 22.57) for the LSAS, p=0.699. For the base case scenario the cost per new case of type 2 diabetes diagnosed was lower for the LPCRS compared to the LSAS, £168 (95% Credible Interval (CrI): 76, 364), and £352 (95% CrI: 109, 1148), respectively. CONCLUSIONS: Compared to a self-assessment risk score, a computer based risk score resulted in greater attendance to an initial blood test and is potentially more cost-effective.

What do qualitative rapid assessment collections of macroinvertebrates represent? A comparison with extensive quantitative sampling.

It is a fundamental tenet of Rapid Biological Assessments (RBA) that the samples collected reflect the community from which they are drawn. As with any biological sampling, RBA collections are subject to sampling error resulting in the omission of some taxa. The aim of this study is to compare the composition of RBA samples with an estimate of community structure based on extensive quantitative sampling. We used logistic regression to explore the relationships between the frequency of a taxon being collected in an RBA sample and its biological and ecological traits, namely its abundance, distribution, body size and habit. RBA samples and quantitative estimates of community structure were made in riffles in the Kangaroo and Nepean Rivers, New South Wales, Australia. Single RBA samples may collect up to 63% of the taxa that are collected by extensive quantitative sampling at a site. The frequency of a taxon being recorded in an RBA sample was significantly and positively related to all traits tested indicating a bias in the collection methods towards large, abundant and widely distributed taxa. Accordingly, taxa missed by RBA sampling were generally small, narrowly distributed or rare. These findings enhance our understanding of what RBA samples represent, and the bias and source of errors associated with RBA sampling. This study also quantifies the utility of RBA methods for biodiversity assessment.

Effect of patient completed agenda forms and doctors' education about the agenda on the outcome of consultations: randomised controlled trial.

OBJECTIVE: To assess the effect of patient completed agenda forms for the consultation and doctors' education on identifying patients' agendas on the outcome of consultations. DESIGN: Randomised controlled trial. SETTING: General practices in Leicestershire and Nottinghamshire, United Kingdom. PARTICIPANTS: 46 general practitioners and 976 patients. INTERVENTIONS: Education for general practitioners, with an embedded clustered randomised controlled trial of a patient agenda form. MAIN OUTCOME MEASURES: Number of problems identified, time required to manage each problem, duration of consultations, number of problems raised after the doctor considered the consultation finished ("by the way" questions), and patient satisfaction. RESULTS: Data were available from 45 doctors (98%) and 857 patients (88%). The number of problems identified in each consultation increased by 0.2 (95% confidence interval 0.1 to 0.4) with the agenda form, by 0.3 (0.1 to 0.6) with education, and by 0.5 (0.3 to 0.7) with both interventions. The time required to manage each problem was not affected. The duration of consultations with the agenda form was increased by 0.9 minutes (0.3 to 1.5 minutes) and with the combined intervention by 1.9 minutes (1.0 to 2.8 minutes). Patient satisfaction with the depth of the doctor-patient relationship was increased with the agenda form. The occurrence of "by the way" presentations did not change. CONCLUSION: A patient completed agenda form before the consultation or general practitioner education about the agenda form, or both, enabled the identification of more problems in consultations even though consultations were longer.

Tailored interventions to overcome identified barriers to change: effects on professional practice and health care outcomes.

BACKGROUND: Strategies to implement change in health professional performance have variable impact. A potential explanation is that the barriers to implementation are different in different settings and at different times. Change may be more likely if the strategies were specifically chosen to address the identified barriers. OBJECTIVES: To assess the effectiveness of strategies tailored to address specific, identified barriers to change in professional performance. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group (EPOC) specialised register and pending files until end of December 2002. English language articles only were included. SELECTION CRITERIA: Randomised controlled trials (RCTs) that reported objectively measured professional practice or health care outcomes in which at least one group received an intervention designed (or tailored) to address prospectively identified barriers to change. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed quality. We also contacted study authors to obtain any missing information. Quantitative and qualitative analyses were undertaken. MAIN RESULTS: We included 15 studies. For Comparison 1 (an intervention tailored to address identified barriers to change compared to no intervention or an intervention(s) not tailored to the barriers), there was no consistency in the results and the effect sizes varied both across and within studies.A meta-regression of a subset of the included studies, using a classical approach estimated a combined OR of 2.18 (95% CI: 1.09, 4.34), p = 0.026 in favour of tailored interventions. However, when a Bayesian approach was taken, meta-regression gave a combined OR of 2.27 (95% Credible Interval: 0.92, 4.75), which was not statistically significant. AUTHORS' CONCLUSIONS: Interventions tailored to prospectively identify barriers may improve care and patient outcomes. However, from the studies included in this review, we were unable to determine whether the barriers were valid, which were the most important barriers, whether all barriers were identified and if they had been addressed by the intervention chosen. Based on the evidence presented in this review, the effectiveness of tailored interventions remains uncertain and more rigorous trials (including process evaluations) are needed. Further research needs to address explicitly the questions of identifying and addressing barriers.

Genetic and molecular markers of the Queensland fruit fly, Bactrocera tryoni.

Twenty-six microsatellite markers, along with two restriction fragment length polymorphism (RFLP) markers and three morphological markers, have been mapped to five linkage groups, corresponding to the five autosomes of the Queensland fruit fly, Bactrocera tryoni. All these molecular and genetic markers were genotyped in three-generation pedigrees. Eight molecular markers were also localized to the salivary gland polytene chromosomes by in situ hybridization. This provides a substantial starting point for an integrated genetic and physical map of B. tryoni.

Continuous cardiac baroreceptor measurement during tilt in healthy elderly subjects.

INTRODUCTION: Abnormalities of cardiac baroreceptor sensitivity (BRS) may contribute towards the high prevalence of orthostatic hypotension and falls in the elderly. Most mathematical analyses used to determine BRS in the time or frequency domains assume a stationary physiological state and cannot be performed under dynamic change and therefore are not valid during tilt. We describe a new method of estimating BRS during tilt. METHODS: Twenty-five healthy elderly volunteers with a mean age of 69 +/- 3 years underwent head-up tilt to 70 degrees, within 5 s, 3 times on 2 separate visits. Blood pressure (BP) and heart rate were recorded continuously using a Finapres beat-to-beat BP monitor and surface ECG. A continuous estimate of BRS was obtained by combining beat-to-beat linear regression with Legendre polynomial interpolation. RESULTS: The values for supine BRS prior to tilt on the two visits, calculated using the new regression method (10.4 +/- 8.2 ms/mmHg and 12.5 +/- 9.7 ms/mmHg) were similar to those using fast Fourier analysis (10.7 +/- 6.7 ms/mmHg and 12.4 +/- 7.1 ms/mmHg). A rapid fall in BP and pulse interval along with cardiac BRS values occurred with tilt within the first 20 s of onset on both visits and remained reduced up to 90 s post tilt (p < 0.01). CONCLUSIONS: The values for cardiac BRS obtained using continuous time domain analysis agree well with those calculated using spectral methods and can be used to assess the dynamic changes in BRS to rapid perturbations in BP such as that occur with tilt.

Interventions in the management of serum lipids for preventing stroke recurrence.

BACKGROUND: A close association between serum lipid levels and the incidence of coronary heart disease (CHD) has been well proven in middle aged and older persons, up to the age of 70-75 years. Individual studies have shown interventions to reduce total and low density lipoprotein (LDL) cholesterol levels, especially with 3-hydroxy-3-methylglutaryl coenzyme a (HMG-CoA) reductase inhibitors (statins), to be of benefit in reducing CHD and stroke events in those with a history of coronary heart disease. However, the relation of serum cholesterol and cholesterol sub-fractions with cerebrovascular disease is less clear. It is unclear whether lipid levels in the post-stroke period are a predictor of recurrence and whether treatment to alter levels can prevent recurrence of either stroke or cardiovascular events. OBJECTIVES: To investigate the effect of altering serum lipids in the prevention of cardiovascular disease and stroke recurrence in subjects with a history of stroke. SEARCH STRATEGY: The Cochrane Group Trials Register was searched up to 8 May 2001 along with MEDLINE (from 1966), EMBASE (from 1980) and the Cochrane Controlled Trials Register. All pharmaceutical firms known to produce a lipid lowering agent were also contacted and asked to provide information on publications or unpublished work relevant to this review. SELECTION CRITERIA: This review included unconfounded randomised trials of subjects aged 18 years and over with a history of stroke or Transient Ischaemic Attack (TIA). DATA COLLECTION AND ANALYSIS: The data were extracted independently by the three reviewers. MetaView 4.1 was used for all statistical analyses. MAIN RESULTS: Five studies involving 1700 patients were included in the review. The active intervention in two of the studies was Clofibrate, Pravastatin in another two and Conjugated Oestrogen in the fifth. Fixed effects analysis showed no evidence of a difference in stroke recurrence between the treatment and placebo groups for those with a previous history of stroke or TIA (odds ratio 0.96, 95% confidence interval 0.71 to 1.30). In addition there was also no evidence, based on two studies, that intervention reduced the odds of all cause mortality (odds ratio 0.87, 95% confidence interval 0.55 to 1.39) nor, from one study, that there was any effect on subsequent vascular events (odds ratio 1.27, 95% confidence interval 0.84 to 1.89). REVIEWER'S CONCLUSIONS: These trials do not provide evidence for a benefit, or harm, from interventions to alter serum lipid levels in patients with a history solely of cerebrovascular disease. Their use, therefore, cannot yet be recommended routinely in this patient group, but ischaemic stroke patients with a history of myocardial infarction should receive statin therapy along the lines of the previous recommendations for those patients with a history of myocardial ischaemia. There are currently three ongoing trials which will recruit approximately 30,000 patients, including those with a history of stroke, and the results of these trials may have a significant effect on these conclusions.

The Rotational Spectra, Structure, Internal Dynamics, and Electric Dipole Moment of the Argon-Ketene van der Waals Complex.

Pulsed-beam Fourier transform microwave spectroscopy was used to observe and assign the rotational spectra of the argon-ketene van der Waals complex. Tunneling of the hydrogen or deuterium atoms splits the a- and b-type rotational transitions of H(2)CCO-Ar, H(2)(13)CCO-Ar, H(2)C(13)CO-Ar, and D(2)CCO-Ar into two states. This internal motion appears to be quenched for HDCCO-Ar where only one state is observed. The spectra of all isotopomers were satisfactorily fit to a Watson asymmetric top Hamiltonian which gave A=10 447.9248(10) MHz, B=1918.0138(16) MHz, C=1606.7642(15) MHz, Delta(J)=16.0856(70) kHz, Delta(JK)=274.779(64) kHz, Delta(K)=-152.24(23) kHz, delta(J)=2.5313(18) kHz, delta(K)=209.85(82) kHz, and h(K)=1.562(64) kHz for the A(1) state of H(2)CCO-Ar. Electric dipole moment measurements determined &mgr;(a)=0.417(10)x10(-30) C m [0.125(3) D] and &mgr;(b)=4.566(7)x10(-30) C m [1.369(2) D] along the a and b principal axes of the A(1) state of the normal isotopomer. A least squares fit of principal moments of inertia, I(a) and I(c), of H(2)CCO-Ar, H(2)(13)CCO-Ar, and H(2)C(13)CO-Ar for the A(1) states give the argon-ketene center of mass separation, R(cm)=3.5868(3) Å, and the angle between the line connecting argon with the center of mass of ketene and the C=C=O axis, θ(cm)=96.4 degrees (2). The spectral data are consistent with a planar geometry with the argon atom tilted toward the carbonyl carbon of ketene by 6.4 degrees from a T-shaped configuration. Copyright 2001 Academic Press.

Transmission electron microscopy: evaluation of damage in human oviducts caused by different surgical instruments.

Different wave length lasers (CO2, Nd-YAG, KTP-532), electrocautery and radiofrequency instruments were used to assess the degree of tissue damage in human oviducts. Excision of the human fallopian tube for tuboplasty is achieved most often by electrocautery, scalpel and, more recently, the Carbon Dioxide (CO2) Laser. There is not enough evidence at the present time to scientifically justify using one particular mode of incision which would show minimal damage to surrounding healthy tissue, especially heat lateral damage. The present study compares the tissue damage produced by the microelectrocautery, the CO2, the KTP-532, the Nd-YAG lasers and the radiofrequency surgical instrument, utilizing different power densities on the fallopian tubes freshly removed at the isthmic portion, taken from healthy women ages 30-42. Transmission electron microscopy sections at the cellular level show that the electrosurgical radiofrequency surgical instrument produces the least damage to surrounding healthy tissue. The CO2 laser with intermittent superpulse mode showed the second lowest amount of damage. The most damage was observed with the Nd-YAG laser at high power densities.