Biomedical subjects
Publications and source records attributed to M Wilcox.
Using femtosecond microscopy, we observe subpicosecond transport of thermal energy radially outward from a micrometer-sized spot of an aluminum target following P-polarized excitation at >10(18) W/cm2 with a 24 fs pulse. The rapid expansion coincides with the onset of nonlocal energy transport dominated by radiation and hot electrons.
BACKGROUND: Up to 50% of antibiotic usage in hospitals is inappropriate. In hospitals infections caused by antibiotic-resistant bacteria are associated with higher mortality, morbidity and prolonged hospital stay compared with infections caused by antibiotic-susceptible bacteria. Clostridium difficile associated diarrhoea (CDAD) is a hospital acquired infection that is caused by antibiotic prescribing. OBJECTIVES: To estimate the effectiveness of professional interventions that alone, or in combination, are effective in promoting prudent antibiotic prescribing to hospital inpatients, to evaluate the impact of these interventions on reducing the incidence of antimicrobial resistant pathogens or CDAD and their impact on clinical outcome. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care (EPOC) specialized register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE from 1980 to November 2003. Additional studies were obtained from the bibliographies of retrieved articles SELECTION CRITERIA: We included all randomised and controlled clinical trials (RCT/CCT), controlled before and after studies (CBA) and interrupted time series (ITS) studies of antibiotic prescribing to hospital inpatients. Interventions included any professional or structural interventions as defined by EPOC. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed quality. MAIN RESULTS: Sixty six studies were included and 51 (77%) showed a significant improvement in at least one outcome. Six interventions only aimed to increase treatment, 57 interventions aimed to decrease treatment and three interventions aimed to both increase and decrease treatment. The intervention target was the decision to prescribe antibiotics (one study), timing of first dose (six studies), the regimen (drug, dosing interval etc, 61 studies) or the duration of treatment (10 studies); 12 studies had more than one target. Of the six interventions that aimed to increase treatment, five reported a significant improvement in drug outcomes and one a significant improvement in clinical outcome. Of the 60 interventions that aimed to decrease treatment 47 reported drug outcomes of which 38 (81%) significantly improved, 16 reported microbiological outcomes of which 12 (75%) significantly improved and nine reported clinical outcomes of which two (22%) significantly deteriorated and 3 (33%) significantly improved. Five studies aimed to reduce CDAD. Three showed a significant reduction in CDAD. Due to differences in study design and duration of follow up it was only possible to perform meta-regression on a few studies. AUTHORS' CONCLUSIONS: The results show that interventions to improve antibiotic prescribing to hospital inpatients are successful, and can reduce antimicrobial resistance or hospital acquired infections.
BACKGROUND: Both patients and government demand proof of quality of care and value for money. Our unit ist in a large teaching hospital, performing over 6000 procedures per year. We have designed and implemented a Quality Assurance (QA) program, the basis of which we believe could be a model for endoscopy QA. METHODS: A QA team was formed and a literature search undertaken. An initial 3 month audit was then performed into indications for, and complications of, all procedures. The results of this initial audit led us to concentrate on colonoscopy and ERCP. The specific items of data collected were based on the "Core Quality Indicators" developed by the American Society for Gastrointestinal Endoscopy (ASGE). We also analysed data relating to endoscope disinfection, equipment failure and carried out a patient satisfaction survey. The data were presented at 3-monthly QA meeting, and appropriate action taken. RESULT: We performed a detailed audit of ERCP (217 procedures) and colonoscopy (904 procedures). Patients risk was stratified using the American Society of Anaesthesiology (ASA) classification. Using these data we established our technical success and complication rates for colonoscopy and ERCP. Audit of equipment revealed that on average an endoscope was away for repair 9 % of the time. Contamination of endoscopes was frequent with glutaraldehyde disinfection; the rate of contamination fell dramatically when we changed our disinfection method. CONCLUSION: A QA program can be implemented in busy endoscopy units. There are significant problems, however, in ensuring that such a program is effective: these include inadequate funding/staffing, lack of suitable information technology and lack of clear guidelines for dealing with poor performance.
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OBJECTIVE: Endometrioid endometrial carcinoma is caused by a combination of mutational events and hormonal factors. We used large-scale messenger RNA expression analysis to discover genes that distinguish neoplastic transformation and examine the patterns of tumor expression of those genes which are normally regulated during the menstrual cycle. METHODS: Expression of approximately 6000 unique genes was quantified in 4 normal (2 proliferative, 2 secretory) and 10 malignant endometria using Affymetrix Hu6800 GeneChip probe arrays. Expression differences between normal and malignant tissue groups were measured by a test of statistical significance comparing the individual t statistic for each gene to the distribution of maximum t statistics among all genes following 1001 permutations of the tissue group assignments (Permax test). Hormonally responsive genes, selected by comparison of proliferative and secretory subsets of normal endometria using a combination of filters applied to the group means and t test rankings, were then examined in the tumors. RESULTS: Fifty genes with a Permax <0.50 provided excellent discrimination between normal and malignant groups and were predominantly characterized by diminished expression levels in the cancers. We found that 100 genes which are hormonally regulated in normal tissues are expressed in a disordered and heterogeneous fashion in cancers, with tumors resembling proliferative more than secretory endometrium. CONCLUSION: Neoplastic transformation is accompanied by predominant loss of activity of many genes constitutively expressed in normal source tissues and absence of expression profiles which characterize the antitumorigenic progestin response.
In 1998, the Department of Health (England) commissioned the first phase of national evidence-based guidelines for preventing healthcare associated infections. These focused on developing a set of standard principles for preventing infections in hospitals together with guidelines for preventing hospital-acquired infections (HAI) associated with the use of short-term indwelling ureteral catheters in acute care and with central venous catheters in acute care. These guidelines are systematically developed broad statements (principles) of good practice that all practitioners can use and which can be incorporated into local protocols. A nurse-led, multi-professional team composed of infection prevention practitioners, clinical microbiologists/retrovirologist, epidemiologists, and researchers developed the guidelines. A rigorous guideline development process was used to inform the systematic reviews, the clinical and critical appraisal of relevant evidence, and linking that evidence to evolving guidelines. Both general and specialist clinical practitioners were involved in all stages of developing these guidelines, as were representatives from relevant Royal Colleges, learned societies, other professional organisations and key stakeholders. The introduction to these guidelines describes a robust and validated guideline development model that can be used by others to develop future guidelines. This model is described in more detail in the associated technical reports that can be found on the project web site http://www.epic.tvu.ac.uk. Locating and appropriately using good quality evidence to inform guideline development in this field is challenging. Evidence from rigorously conducted experimental studies was frequently limited and consequently a range of other types of evidence were systematically retrieved and carefully appraised. The concluding discussion on implementation highlights potential issues for clinical governance and areas for future research and suggests issues that need to be addressed to allow practitioners to successfully incorporate these guidelines into routine clinical practice.
We have improved on an algorithm to track a rat swimming in a Morris Water Maze. The system is automatically configured to any pool and relative suitable light conditions. It tracks the rat's position and pose 10 times per second. The output data is displayed in a bitmap and also in a text file. The system was tested with an X-Y plotter using a simulated rat swimming in the maze. Known signals were provided to the rat and compared to the position and pose information provided by tracking algorithm.
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CONTEXT: Evidence suggests that early adverse experiences play a preeminent role in development of mood and anxiety disorders and that corticotropin-releasing factor (CRF) systems may mediate this association. OBJECTIVE: To determine whether early-life stress results in a persistent sensitization of the hypothalamic-pituitary-adrenal axis to mild stress in adulthood, thereby contributing to vulnerability to psychopathological conditions. DESIGN AND SETTING: Prospective controlled study conducted from May 1997 to July 1999 at the General Clinical Research Center of Emory University Hospital, Atlanta, Ga. PARTICIPANTS: Forty-nine healthy women aged 18 to 45 years with regular menses, with no history of mania or psychosis, with no active substance abuse or eating disorder within 6 months, and who were free of hormonal and psychotropic medications were recruited into 4 study groups (n = 12 with no history of childhood abuse or psychiatric disorder [controls]; n = 13 with diagnosis of current major depression who were sexually or physically abused as children; n = 14 without current major depression who were sexually or physically abused as children; and n = 10 with diagnosis of current major depression and no history of childhood abuse). MAIN OUTCOME MEASURES: Adrenocorticotropic hormone (ACTH) and cortisol levels and heart rate responses to a standardized psychosocial laboratory stressor compared among the 4 study groups. RESULTS: Women with a history of childhood abuse exhibited increased pituitary-adrenal and autonomic responses to stress compared with controls. This effect was particularly robust in women with current symptoms of depression and anxiety. Women with a history of childhood abuse and a current major depression diagnosis exhibited a more than 6-fold greater ACTH response to stress than age-matched controls (net peak of 9.0 pmol/L [41.0 pg/mL]; 95% confidence interval [CI], 4.7-13.3 pmol/L [21.6-60. 4 pg/mL]; vs net peak of 1.4 pmol/L [6.19 pg/mL]; 95% CI, 0.2-2.5 pmol/L [1.0-11.4 pg/mL]; difference, 8.6 pmol/L [38.9 pg/mL]; 95% CI, 4.6-12.6 pmol/L [20.8-57.1 pg/mL]; P<.001). CONCLUSIONS: Our findings suggest that hypothalamic-pituitary-adrenal axis and autonomic nervous system hyperreactivity, presumably due to CRF hypersecretion, is a persistent consequence of childhood abuse that may contribute to the diathesis for adulthood psychopathological conditions. Furthermore, these results imply a role for CRF receptor antagonists in the prevention and treatment of psychopathological conditions related to early-life stress. JAMA. 2000;284:592-597
We have developed an algorithm to track a rat swimming in a Morris Water Maze. It provides an update on rodent position 15 times per second. The tracking algorithm uses a rotation insensitive tracking template coupled with a limited exhaustive search technique to maintain lock on the moving rat. At the completion of the run, the relative time the rat spent in each quadrant is reported. The tracking algorithm was successfully used to evaluate the time course of memory loss and correlate that to tissue loss in the rat cortex following blunt trauma to the sensory cortex. Results of that study are reported in another paper. Our project budget did not allow for commercially available software to perform the tracking task which typically provide position updates 10 times per second. This paper focuses on the tracking algorithm and support equipment used to measure the rats' progress in the maze.
The effect of hyperbaric oxygen (HBO) on focal brain contusion was examined for possible prevention of neural degeneration in the central nervous system following blunt trauma. All animals were tested for memory and balance/motor skills, prior to and after injury, using the Morris water maze and beam walk test. Experimental and control groups, each containing 12 juvenile male hooded Wistar rats (Rattus norviegicus), were contused using a 20 g weight dropped from 20 cm onto the dura mater over the somatosensory cortex. The experimental group underwent 45 minute HBO dives at 2.5 atmospheres absolute (ATA) four times a day for 10 days. Memory and motor skills were tested on both groups at 3, 6 and 9 days after injury. Animals were sacrificed and their brains were sectioned and analyzed histologically for neural damage. Examination of the damage to the surface of the brain showed hole sizes in the experimental group were smaller than those in the control group (p = 0.0475). Initial examination of behavioral testing showed mixed results. Beam walk scores 3 days post contusion were significantly better for experimental vs control groups (p = 0.0442) suggesting initial benefits of HBO treatment. However, preliminary analysis of cells in the CA3 region of the hippocampus showed no significant difference between pyramidal cell counts 10 days post-contusion in the ipsilateral sides of either group.
Efficient monitoring for the emergence of resistance to various antimicrobial agents has, in the face of global trends in resistance, recently assumed great importance. Many programmes have been developed to survey resistance, each varying in scope or emphasis as well as commitment to long-term monitoring. A programme that specifically addresses pathogens from populations of the most severely ill patients is the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC). This programme was started in 1997 to monitor carbapenem activity in vitro in centres using carbapenems because their prevalent strains were resistant to other beta-lactams and drug classes. Meropenem is a broad-spectrum carbapenem and differs microbiologically from imipenem by having a greater potency in vitro against many Gram-negative pathogens and a slightly lower potency against some Gram-positive pathogens. Meropenem has improved stability to renal-based enzymatic metabolism, and does not require the addition of an enzyme inhibitor such as cilastatin. Material in this publication is based on the many abstracts and oral presentations delivered at recent national and international meetings including: the International Congress of Infectious Disease in Buenos Aires, Argentina (April, 2000); the European Congress of Chemotherapy in Madrid, Spain (May, 2000); and the European Congress of Clinical Microbiology and Infectious Disease in Stockholm, Sweden (May, 2000). All of the authors are active participants in the MYSTIC programme and bring to it experience in the design of surveillance studies and the detection of resistance mechanisms. Professor Jones discusses the most useful ways of storing and presenting susceptibility data to preserve the long-term value of all results. He argues for the publication of expanded study details and the limited use of MIC(90) values or susceptibility rates. Dr Turner has coordinated the MYSTIC programme, and he summarizes here the similarities and differences in the results seen to date between the Americas, Europe and centres in Asia and the Middle East. The Americas have been one of the most recently monitored regions. Professors Pfaller and Jones give baseline data for the USA (10 sites), Mexico and Brazil. Professor Goossen's article focuses on the results of MYSTIC in the European centres. Doctor Masterton presents a comprehensive overview of various surveillance studies and assesses their value and characteristics for the continued optimal management of infected patients.
Using genome-scan data from the Collaborative Study on the Genetics of Alcoholism (COGA), we compared results of linkage analyses using a qualitative alcoholism phenotype to results of linkage analyses using event related potential (ERP) quantitative phenotypes, and compared our results to the results of Reich et al. [1998] and Begleiter et al. [1998]. We describe a general and simple strategy for identifying regions of the genome which may harbor genes involved in alcohol dependence which takes into consideration the results of both the affection status and ERP linkage analyses.
The Behavior and Symptom Identification Scale (BASIS-32) was developed to assess mental health outcomes among patients with severe illness treated on inpatient programs. However, its applicability and utility to those treated in outpatient programs has not been determined. The objective of this study was to assess reliability, validity, and sensitivity to change of the BASIS-32 among mental health consumers treated in outpatient programs. A total of 407 outpatients completed the BASIS-32 and the Short Form Health Status Profile (SF-36) at the beginning of a treatment episode and again 30 to 90 days later. Outpatients reported less difficulty at intake than did inpatients, and the BASIS-32 detected statistically significant changes 30 to 90 days after beginning outpatient treatment. Factor structure and construct validity were partially confirmed on this sample of outpatient consumers. Analyses of data from a wide range of facilities and samples would add to validation efforts and to further refinement of the BASIS-32.