Pre-Existing Mature Oligodendrocytes Do Not Contribute to Remyelination following Toxin-Induced Spinal Cord Demyelination.

Remyelination is the regenerative response to demyelination. Although the oligodendrocyte progenitor is established as the major source of remyelinating cells, there is no conclusive evidence on whether mature, differentiated oligodendrocytes can also contribute to remyelination. Using two different inducible myelin-CreER mouse strains in which mature oligodendrocytes were prelabeled by the expression of membrane-bound Green fluorescent protein, we found that after focal spinal cord demyelination, the surrounding surviving labeled oligodendrocytes did not proliferate but remained at a consistent density. Furthermore, existing (prelabeled) oligodendrocytes showed no evidence of incorporation or migration into the lesioned area, or of process extension from the peripheral margins into the lesion. Thus, mature oligodendrocytes do not normally contribute to remyelination and are therefore not a promising target for regenerative therapy.Supported by European Research Council grant agreement 293544 (W.D.R.), Wellcome Trust grant WT100269AIA, Medical Research Council grant G0800575, a Royal Society-USA/Canada Exchange Fellowship (I.M.), the UK Multiple Sclerosis Society, and a Wellcome Trust Integrated Veterinary Training Fellowship (A.H.C.)

ParaMED Home: A protocol for a randomised controlled trial of paramedic assessment and referral to access medical care at home

<p>Abstract</p> <p>Background</p> <p>In Australia approximately 25% of Emergency Department (ED) attendances are via ambulance. ED overcrowding in Australia, as in many countries, is common. Measures to reduce overcrowding include the provision of enhanced timely primary care in the community for appropriate low risk injury and illness. Therefore paramedic assessment and referral to a community home hospital service, in preference to transfer to ED, may confer clinical and cost benefit.</p> <p>Methods/Design</p> <p>A randomised controlled trial. Consenting adult patients that call an ambulance and are assessed by paramedics as having an eligible low risk problem will be randomised to referral to ED via ambulance transfer or referral to a rapid response service that will assess and treat the patient in their own residence. The primary outcome measure is requirement for unplanned medical attention (in or out of hospital) in the first 48 hours. Secondary outcomes will include a number of other clinical endpoints. A cost effectiveness analysis will be conducted.</p> <p>Discussion</p> <p>If this trial demonstrates clinical non-inferiority and cost savings associated with the primary assessment service, it will provide one means to safely address ED overcrowding.</p> <p>Trial Registration</p> <p>Australian and New Zealand Clinical Trials Registry Number <a href="http://www.anzctr.org.au/trial_view.aspx?ID=335818">12610001064099</a></p

Testing the Nambu-Goldstone Hypothesis for Quarks and Leptons at the LHC

The hierarchy of the Yukawa couplings is an outstanding problem of the standard model. We present a class of models in which the first and second generation fermions are SUSY partners of pseudo-Nambu-Goldstone bosons that parameterize a non-compact Kahler manifold, explaining the small values of these fermion masses relative to those of the third generation. We also provide an example of such a model. We find that various regions of the parameter space in this scenario can give the correct dark matter abundance, and that nearly all of these regions evade other phenomenological constraints. We show that for gluino mass ~700 GeV, model points from these regions can be easily distinguished from other mSUGRA points at the LHC with only 7 fb^(-1) of integrated luminosity at 14 TeV. The most striking signatures are a dearth of b- and tau-jets, a great number of multi-lepton events, and either an "inverted" slepton mass hierarchy, narrowed slepton mass hierarchy, or characteristic small-mu spectrum.Comment: Corresponds to published versio

Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists.

BackgroundAn alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries.MethodsWe evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed.ResultsRadiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms.ConclusionsGiven the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography

Consistent phenological shifts in the making of a biodiversity hotspot: the Cape flora

Background The best documented survival responses of organisms to past climate change on short (glacial-interglacial) timescales are distributional shifts. Despite ample evidence on such timescales for local adaptations of populations at specific sites, the long-term impacts of such changes on evolutionary significant units in response to past climatic change have been little documented. Here we use phylogenies to reconstruct changes in distribution and flowering ecology of the Cape flora - South Africa's biodiversity hotspot - through a period of past (Neogene and Quaternary) changes in the seasonality of rainfall over a timescale of several million years. Results Forty-three distributional and phenological shifts consistent with past climatic change occur across the flora, and a comparable number of clades underwent adaptive changes in their flowering phenology (9 clades; half of the clades investigated) as underwent distributional shifts (12 clades; two thirds of the clades investigated). Of extant Cape angiosperm species, 14-41% have been contributed by lineages that show distributional shifts consistent with past climate change, yet a similar proportion (14-55%) arose from lineages that shifted flowering phenology. Conclusions Adaptive changes in ecology at the scale we uncover in the Cape and consistent with past climatic change have not been documented for other floras. Shifts in climate tolerance appear to have been more important in this flora than is currently appreciated, and lineages that underwent such shifts went on to contribute a high proportion of the flora's extant species diversity. That shifts in phenology, on an evolutionary timescale and on such a scale, have not yet been detected for other floras is likely a result of the method used; shifts in flowering phenology cannot be detected in the fossil record

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

Water induced sediment levitation enhances downslope transport on Mars

On Mars, locally warm surface temperatures (~293 K) occur, leading to the possibility of (transient) liquid water on the surface. However, water exposed to the martian atmosphere will boil, and the sediment transport capacity of such unstable water is not well understood. Here, we present laboratory studies of a newly recognized transport mechanism: “levitation” of saturated sediment bodies on a cushion of vapor released by boiling. Sediment transport where this mechanism is active is about nine times greater than without this effect, reducing the amount of water required to transport comparable sediment volumes by nearly an order of magnitude. Our calculations show that the effect of levitation could persist up to ~48 times longer under reduced martian gravity. Sediment levitation must therefore be considered when evaluating the formation of recent and present-day martian mass wasting features, as much less water may be required to form such features than previously thought

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

Complex Calculations: How Drug Use During Pregnancy Becomes a Barrier to Prenatal Care

Pregnant women who use drugs are more likely to receive little or no prenatal care. This study sought to understand how drug use and factors associated with drug use influence women’s prenatal care use. A total of 20 semi-structured interviews and 2 focus groups were conducted with a racially/ethnically diverse sample of low-income women using alcohol and drugs in a California county. Women using drugs attend and avoid prenatal care for reasons not connected to their drug use: concern for the health of their baby, social support, and extrinsic barriers such as health insurance and transportation. Drug use itself is a barrier for a few women. In addition to drug use, women experience multiple simultaneous risk factors. Both the drug use and the multiple simultaneous risk factors make resolving extrinsic barriers more difficult. Women also fear the effects of drug use on their baby’s health and fear being reported to Child Protective Services, each of which influence women’s prenatal care use. Increasing the number of pregnant women who use drugs who receive prenatal care requires systems-level rather than only individual-level changes. These changes require a paradigm shift to viewing drug use in context of the person and society and acceptance of responsibility for unintended consequences of public health bureaucratic procedures and messages about effects of drug use during pregnancy

SARS and hospital priority setting: a qualitative case study and evaluation

BACKGROUND: Priority setting is one of the most difficult issues facing hospitals because of funding restrictions and changing patient need. A deadly communicable disease outbreak, such as the Severe Acute Respiratory Syndrome (SARS) in Toronto in 2003, amplifies the difficulties of hospital priority setting. The purpose of this study is to describe and evaluate priority setting in a hospital in response to SARS using the ethical framework 'accountability for reasonableness'. METHODS: This study was conducted at a large tertiary hospital in Toronto, Canada. There were two data sources: 1) over 200 key documents (e.g. emails, bulletins), and 2) 35 interviews with key informants. Analysis used a modified thematic technique in three phases: open coding, axial coding, and evaluation. RESULTS: Participants described the types of priority setting decisions, the decision making process and the reasoning used. Although the hospital leadership made an effort to meet the conditions of 'accountability for reasonableness', they acknowledged that the decision making was not ideal. We described good practices and opportunities for improvement. CONCLUSIONS: 'Accountability for reasonableness' is a framework that can be used to guide fair priority setting in health care organizations, such as hospitals. In the midst of a crisis such as SARS where guidance is incomplete, consequences uncertain, and information constantly changing, where hour-by-hour decisions involve life and death, fairness is more important rather than less