Systemic infections after acute stroke

After an acute stroke, systemic infection can complicate the recovery process and lead to a worse clinical outcome, including a higher risk of mortality. Post-stroke infection (PSI) is responsible for the majority of the mortality occurring between 1 week and 1 month after stroke, peaking towards the end of the second week. The effects of PSI on longer-term outcome and other aspects of recovery, such as cognition, mood and quality of life, are largely unknown. The cerebrovascular event itself may result in a systemic immunosuppressed state, hence lowering the threshold for subsequent systemic bacterial infections. Although there have been advances in the basic understanding of the pathophysiological mechanisms of PSI, clinical studies have not provided any clear guidelines on the best methods of managing or preventing PSI. This article provides a review of the current knowledge of the phenomenon of PSI and the possible future developments in the understanding and treatment of PSI

Quantitative Susceptibility Mapping by Inversion of a Perturbation Field Model: Correlation With Brain Iron in Normal Aging

There is increasing evidence that iron deposition occurs in specific regions of the brain in normal aging and neurodegenerative disorders such as Parkinson's, Huntington's, and Alzheimer's disease. Iron deposition changes the magnetic susceptibility of tissue, which alters the MR signal phase, and allows estimation of susceptibility differences using quantitative susceptibility mapping (QSM). We present a method for quantifying susceptibility by inversion of a perturbation model, or “QSIP.” The perturbation model relates phase to susceptibility using a kernel calculated in the spatial domain, in contrast to previous Fourier-based techniques. A tissue/air susceptibility atlas is used to estimate B[subscript 0] inhomogeneity. QSIP estimates in young and elderly subjects are compared to postmortem iron estimates, maps of the Field-Dependent Relaxation Rate Increase, and the L1-QSM method. Results for both groups showed excellent agreement with published postmortem data and in vivo FDRI: statistically significant Spearman correlations ranging from Rho=0.905 to Rho=1.00 were obtained. QSIP also showed improvement over FDRI and L1-QSM: reduced variance in susceptibility estimates and statistically significant group differences were detected in striatal and brainstem nuclei, consistent with age-dependent iron accumulation in these regions.National Institutes of Health (U.S.) (Grant P41EB015902)National Institutes of Health (U.S.) (Grant P41RR013218)National Institutes of Health (U.S.) (Grant P41EB015898)National Institutes of Health (U.S.) (Grant P41RR019703)National Institutes of Health (U.S.) (Grant T32EB0011680-06)National Institutes of Health (U.S.) (Grant K05AA017168)National Institutes of Health (U.S.) (Grant R01AA012388

Getting it right: a model for compliance assessment

Compliance is important for organisations but models and tools to aid understanding of compliance behaviour is limited. This paper argues that the understanding of the interaction between subjects and objects and their intention to comply with requirements of rules and regulations may be a predictor of compliance behaviour. Thus, a Conceptual Compliance Assessment Model (CAM) is developed by extension of Technology Acceptance Model and Activity theory for assessment of compliance behaviour. Data collected and evaluated showed that the awareness and understanding of the mediational tool is critical in realizing the outcome. It also showed that other factors like the perceived usefulness, perceived ease of use, the community and the management set up also affected compliance behaviour. Essentially, the use of CAM will be useful in assessing the compliance activities of subjects which may aid in formulation of behaviour support systems to improve compliance behaviour

In vivo model for microbial invasion of tooth root dentinal tubules

ABSTRACT Objective Bacterial penetration of dentinal tubules via exposed dentine can lead to root caries and promote infections of the pulp and root canal system. The aim of this work was to develop a new experimental model for studying bacterial invasion of dentinal tubules within the human oral cavity. Material and Methods Sections of human root dentine were mounted into lower oral appliances that were worn by four human subjects for 15 d. Roots were then fixed, sectioned, stained and examined microscopically for evidence of bacterial invasion. Levels of invasion were expressed as Tubule Invasion Factor (TIF). DNA was extracted from root samples, subjected to polymerase chain reaction amplification of 16S rRNA genes, and invading bacteria were identified by comparison of sequences with GenBank database. Results All root dentine samples with patent tubules showed evidence of bacterial cell invasion (TIF value range from 5.7 to 9.0) to depths of 200 mm or more. A spectrum of Gram-positive and Gram-negative cell morphotypes were visualized, and molecular typing identified species of Granulicatella, Streptococcus, Klebsiella, Enterobacter, Acinetobacter, and Pseudomonas as dentinal tubule residents. Conclusion A novel in vivo model is described, which provides for human root dentine to be efficiently infected by oral microorganisms. A range of bacteria were able to initially invade dentinal tubules within exposed dentine. The model will be useful for testing the effectiveness of antiseptics, irrigants, and potential tubule occluding agents in preventing bacterial invasion of dentine

The development of a new measure of quality of life in the management of gastro-oesophageal reflux disease: the Reflux Questionnaire.

INTRODUCTION This paper reports on the development of a new measure of health-related quality of life for use among patients with gastro-oesophageal reflux disease (GORD), funded as part of the REFLUX trial. This is a large UK multi centre trial that aims to compare the clinical and cost effectiveness of minimal access surgery with best medical treatment for patients with GORD within the NHS. Method Potential items were identified via a series of interviews and focus groups carried out with patients who were receiving/had received medical or surgical treatment for GORD. The final measure consisted of 31 items covering 7 categories (Heartburn; Acid reflux; Wind; Eating and swallowing; Bowel movements; Sleep; Work, physical and social activities). The measure produced two outputs: a quality of life score (RQLS) and five Reflux symptom scores. Reliability (internal consistency), criterion validity with the SF-36 and, sensitivity to change in terms of relationship with reported change in prescribed medication were assessed amongst a sample of 794 patients recruited into the trial. RESULTS The measure was shown to be internally consistent, to show criterion validity with the SF-36 and sensitive to changes in patients use of prescribed medication at baseline and 3 month follow-up. DISCUSSION The Reflux questionnaire is a new self-administered questionnaire for use amongst patients with GORD. Initial findings suggest that the new measure is valid, reliable, acceptable to respondents and simple to administer in both a clinical and research context

Effect of Using the Same vs Different Order for Second Readings of Screening Mammograms on Rates of Breast Cancer Detection A Randomized Clinical Trial

Importance Interpreting screening mammograms is a difficult repetitive task that can result in missed cancers and false-positive recalls. In the United Kingdom, 2 film readers independently evaluate each mammogram to search for signs of cancer and examine digital mammograms in batches. However, a vigilance decrement (reduced detection rate with time on task) has been observed in similar settings. Objective To determine the effect of changing the order for the second film reader of batches of screening mammograms on rates of breast cancer detection. Design, Setting, and Participants A multicenter, double-blind, cluster randomized clinical trial conducted at 46 specialized breast screening centers from the National Health Service Breast Screening Program in England for 1 year (all between December 20, 2012, and November 3, 2014). Three hundred sixty readers participated (mean, 7.8 readers per center)—186 radiologists, 143 radiography advanced practitioners, and 31 breast clinicians, all fully qualified to report mammograms in the NHS breast screening program. Interventions The 2 readers examined each batch of digital mammograms in the same order in the control group and in the opposite order to one another in the intervention group. Main Outcomes and Measures The primary outcome was cancer detection rate; secondary outcomes were rates of recall and disagreements between readers. Results Among 1 194 147 women (mean age, 59.3; SD, 7.49) who had screening mammograms (596 642 in the intervention group; 597 505 in the control group), the images were interpreted in 37 688 batches (median batch size, 35; interquartile range [IQR]; 16-46), with each reader interpreting a median of 176 batches (IQR, 96-278). After completion of all subsequent diagnostic tests, a total of 10 484 cases (0.88%) of breast cancer were detected. There was no significant difference in cancer detection rate with 5272 cancers (0.88%) detected in the intervention group vs 5212 cancers (0.87%) detected in the control group (difference, 0.01% points; 95% CI, −0.02% to 0.04% points; recall rate, 24 681 [4.14%] vs 24 894 [4.17%]; difference, −0.03% points; 95% CI, −0.10% to 0.04% points; or rate of reader disagreements, 20 471 [3.43%] vs 20 793 [3.48%]; difference, −0.05% points; 95% CI, −0.11% to 0.02% points). Conclusions and Relevance Interpretation of batches of mammograms by qualified screening mammography readers using a different order vs the same order for the second reading resulted in no significant difference in rates of detection of breast cancer. Trial Registration isrctn.org Identifier: ISRCTN4660337

Design, Synthesis, and Evaluation of Tetrasubstituted Pyridines as Potent 5-HT2C Receptor Agonists.

A series of pyrido[3,4-d]azepines that are potent and selective 5-HT2C receptor agonists is disclosed. Compound 7 (PF-04781340) is identified as a suitable lead owing to good 5-HT2C potency, selectivity over 5-HT2B agonism, and in vitro ADME properties commensurate with an orally available and CNS penetrant profile. The synthesis of a novel bicyclic tetrasubstituted pyridine core template is outlined, including rationale to account for the unexpected formation of aminopyridine 13 resulting from an ammonia cascade cyclization.We would like to thank the EPSRC (SVL, grant nº EP/K0099494/1 and nº EP/K039520/1) for financial support.This is the accepted manuscript. The final version is available from ACS at http://pubs.acs.org/doi/abs/10.1021/ml500507v

Changes in temperature and precipitation extremes in the IPCC ensemble of global coupled model simulations

Temperature and precipitation extremes and their potential future changes are evaluated in an ensemble of global coupled climate models participating in the Intergovernmental Panel on Climate Change (IPCC) diagnostic exercise for the Fourth Assessment Report (AR4). Climate extremes are expressed in terms of 20-yr return values of annual extremes of near-surface temperature and 24-h precipitation amounts. The simulated changes in extremes are documented for years 2046–65 and 2081–2100 relative to 1981–2000 in experiments with the Special Report on Emissions Scenarios (SRES) B1, A1B, and A2 emission scenarios. Overall, the climate models simulate present-day warm extremes reasonably well on the global scale, as compared to estimates from reanalyses. The model discrepancies in simulating cold extremes are generally larger than those for warm extremes, especially in sea ice–covered areas. Simulated present-day precipita-tion extremes are plausible in the extratropics, but uncertainties in extreme precipitation in the Tropics are very large, both in the models and the available observationally based datasets. Changes in warm extremes generally follow changes in the mean summertime temperature. Cold ex-tremes warm faster than warm extremes by about 30%–40%, globally averaged. The excessive warming of cold extremes is generally confined to regions where snow and sea ice retreat with global warming. With th

A two-centred pragmatic randomised controlled trial of two interventions of postnatal support

Objectives: To establish whether providing additional postnatal support during the early postnatal months influences women's physical and psychological health and to identify health service benefits. Design: Pragmatic randomised controlled trial with a 2 × 2 factorial design with two interventions. Setting: Community centres, Ayrshire and Grampian, Scotland. Population: One thousand and four primiparous women, 83% completed the baseline questionnaire, 71% at six months. Methods: (1) An invitation to a local postnatal support group run weekly with a facilitator, starting two weeks postpartum. (2) A postnatal support manual, posted two weeks postpartum. Main outcome measures: Data regarding primary outcome postnatal depression (Edinburgh Postnatal Depression Scale, EPDS), secondary outcomes, general health measures (SF-36), social support (SSQ6), use of health services and women's views of interventions were collected at two weeks postpartum and at three and six months. Results: There were no significant differences in EPDS scores between the control and trial arms at three and six months, nor were there differences in the SF-36 and the SSQ6 scores. The 95% CI for the difference in EPDS effectively excluded a change in mean score of more than 10% with either intervention. There were no differences in health service attendances in primary or secondary care between the control and trial arms. Of those women who attended the groups, 40% attended six or more. Women reported favourably on the ‘pack’ with the majority reading it a few times and feeling that it was aimed at them. Conclusions: Wide-scale provision by the National Health Service of either support groups or self-help manuals is not appropriate if the aim is to improve measurable health outcomes

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma