Diagnostic Utility of Cerebral White Matter Integrity in Early Alzheimer\u27s Disease

We compared white matter integrity with brain atrophy in healthy controls and participants with very mild dementia (Clinical Dementia Rating 0 vs. 0.5) from the Brain Aging Project, a longitudinal study of aging and memory at the University of Kansas Medical Center. Structural magnetic resonance imaging and diffusion tensor imaging (DTI) including fractional anisotropy and mean diffusivity were performed on 27 patients with very mild dementia (Clinical Dementia Rating = 0.5) of the Alzheimer\u27s type (DAT), and 32 cognitively normal subjects. Patient groups were compared across 6 volumetric measures and 14 DTI regions of interest. Very mildly demented patients showed expected disease-related patterns of brain atrophy with reductions in whole-brain and hippocampal volumes most prominent. DTI indices of white matter integrity were mixed. Right parahippocampus showed significant but small disease-related reductions in fractional anisotropy. Right parahippocampus and left internal capsule showed greater mean diffusivity in early DAT compared with controls. A series of discriminant analyses demonstrated that gray matter atrophy was a significantly better predictor of dementia status than were DTI indices. Brain atrophy was most strongly related to very mild DAT. Modest disease-related white matter anomalies were present in temporal cortex, and deep white matter had limited discriminatory diagnostic power, probably because of the very mild stage of disease in these participants

Diagnostic Utility of Cerebral White Matter Integrity in Early Alzheimer's Disease

This is an Accepted Manuscript of an article published by Taylor & Francis in International Journal of Neuroscience on August 2010, available online: http://www.tandfonline.com/10.3109/00207454.2010.494788.We compared white matter integrity with brain atrophy in healthy controls and participants with very mild dementia (Clinical Dementia Rating 0 vs. 0.5) from the Brain Aging Project, a longitudinal study of aging and memory at the University of Kansas Medical Center. Structural magnetic resonance imaging and diffusion tensor imaging (DTI) including fractional anisotropy and mean diffusivity were performed on 27 patients with very mild dementia (Clinical Dementia Rating = 0.5) of the Alzheimer's type (DAT), and 32 cognitively normal subjects. Patient groups were compared across 6 volumetric measures and 14 DTI regions of interest. Very mildly demented patients showed expected disease-related patterns of brain atrophy with reductions in whole-brain and hippocampal volumes most prominent. DTI indices of white matter integrity were mixed. Right parahippocampus showed significant but small disease-related reductions in fractional anisotropy. Right parahippocampus and left internal capsule showed greater mean diffusivity in early DAT compared with controls. A series of discriminant analyses demonstrated that gray matter atrophy was a significantly better predictor of dementia status than were DTI indices. Brain atrophy was most strongly related to very mild DAT. Modest disease-related white matter anomalies were present in temporal cortex, and deep white matter had limited discriminatory diagnostic power, probably because of the very mild stage of disease in these participants

Problem based learning in mental health nursing : the students experience.

Problem based learning (PBL) is well established within the field of health-care education for professionals worldwide, although little has been done to explore the experiences of students undertaking a PBL course in mental health nursing. Without firm evidence of the benefits of PBL, educationalists in mental health might be reluctant to view it as an option in curricula design. This UK study examined the experiences of pre-registration post-graduate mental health student nurses undertaking a 2-year educational course in which all teaching and assessment followed a PBL philosophy. Focus groups were used throughout the course to elicit in-depth qualitative data that was analysed by applying a constant comparative method. The analysis of the data uncovered the following broad themes: ‘moves to autonomy, ’surviving the groups' and ‘the impact of PBL’. The findings show that participants had mainly positive experiences and gained a range of study and interpersonal skills central to mental health nursing. Participants described initial anxieties resulting from engagement in PBL. However, they increasingly gained confidence in this approach, exercising increasing control over the PBL process. Despite this increased autonomy, participants continued to value the input of skilled facilitators. A recurring issue centred on the potential for interpersonal conflict within the student group and its impact on their learning. It is suggested that more research is needed examining the use of PBL in mental health nursing

The XMM Large Scale Structure Survey: Properties and Two-Point Angular Correlations of Point-like Sources

We analyze X-ray sources detected over 4.2 pseudo-contiguous sq. deg. in the 0.5-2 keV and 2-10 keV bands down to fluxes of 2x10^{-15} and 8x10^{-15} erg/s/cm^2 respectively, as part of the XMM Large Scale Structure Survey. The logN-logS in both bands shows a steep slope at bright fluxes, but agrees well with other determinations below ~2x10^{-14} erg/s/cm^2. The detected sources resolve close to 30 per cent of the X-ray background in the 2-10 keV band. We study the two-point angular clustering of point sources using nearest neighbours and correlation function statistics and find a weak, positive signal for ~1130 sources in the 0.5-2 keV band, but no correlation for ~400 sources in the 2-10 keV band below scales of 100 arcsec. A sub-sample of ~200 faint sources with hard X-ray count ratios, that is likely to be dominated by obscured AGN, does show a positive signal with the data allowing for a large scaling of the angular correlation length, but only at the ~2 (3) sigma level, based on re-sampling (Poisson) statistics. We discuss possible implications and emphasize the importance of wider, complete surveys in order to fully understand the large scale structure of the X-ray sky.Comment: A&A in press; High resolution version at http://www-xray.ast.cam.ac.uk/~pg/publications.htm

Metabolic loss of deuterium from isotopically labeled glucose

The isotopically substituted molecule (6- 13 C, 1, 6, 6- 2 H 3 )glucose was evaluated to determine whether metabolic 2 H loss would prevent its use in quantitating pentose phosphate pathway (PPP) activity. PPP activity causes the C1 of glucose to be lost as CO 2 , while C6 can appear in lactate. 2 H NMR analysis of the lactate produced from this glucose can distinguish (3- 2 H)-lactate (from C1 of glucose) from (3- 13 C, 3, 3- 2 H Z )lactate (from C6 of glucose). 2 H NMR spectroscopic analysis of medium containing (4- 13 C, 1,6,6 −2 H 3 ) glucose after incubation with cultured rat 9L glioma cells suggested a 30.8 ± 2.1% PPP activity as compared with 6.0 ± 0.8% from separate, parallel incubations with (1- 13 C)glucose and (6- 13 C)glucose. Subsequent experiments with other isotopically labeled glucose molecules suggest that this discrepancy is due to selective loss of 2 H from the C1 position of glucose, catalyzed by phosphoman-nose isomerase. Failure to consider 2 H exchange from the C1 and C6 positions of glucose can lead to incorrect conclusions in metabolic studies utilizing this and other deuterated or tritiated glucose molecules.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38491/1/1910320317_ftp.pd

The Sparrow Question: Social and Scientific Accord in Britain, 1850-1900.

During the latter-half of the nineteenth century, the utility of the house sparrow (Passer domesticus) to humankind was a contentious topic. In Britain, numerous actors from various backgrounds including natural history, acclimatisation, agriculture and economic ornithology converged on the bird, as contemporaries sought to calculate its economic cost and benefit to growers. Periodicals and newspapers provided an accessible and anonymous means of expression, through which the debate raged for over 50 years. By the end of the century, sparrows had been cast as detrimental to agriculture. Yet consensus was not achieved through new scientific methods, instruments, or changes in practice. This study instead argues that the rise and fall of scientific disciplines and movements paved the way for consensus on "the sparrow question." The decline of natural history and acclimatisation stifled a raging debate, while the rising science of economic ornithology sought to align itself with agricultural interests: the latter overwhelmingly hostile to sparrows

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome