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GST Primary GST Primary Best Strategies for Health Care Quality Im... Best Strategies for Health Care Quality Improvement - Diabetes Quality Improvement Strategies for Antibio... Kathryn McDonald, Stanford-UCSF Evidence-b... Systematic review assessing the effect of ... Quality Improvement Strategies for Antibiotics Management Kathryn McDonald, Stanford-UCSF Evidence-based Practice Center, 117 Encina Commons, Stanford, CA 94305-6019, Kathy.mcdonald@stanford.edu Systematic review assessing the effect of quality improvement strategies on appropriate prescribing of antibiotics and appropriate choice of antibiotics. Adherence Adherence Assistive Devices Assistive Devices Childhood Burn Hanson MacMillan Childhood Burn Hanson MacMillan CLSA_9 CLSA_9 Cyberabuse Cyberabuse Cognitive Behavioural Therapy for Violent ... This review included randomized trials abo... Cognitive Behavioural Therapy for Violent Men who Batter Their Partners This review included randomized trials about the effects of cognitive behavioral therapy on domestic violence. The intervention included programs based on the Duluth Model. The violence had to be committed by a male toward his female partner. The violence also had to be physical. The primary outcomes were new arrests and convictions, and new reports of violence. CABG vs PCI CABG vs PCI Quality Improvement Strategies for Prevent... Quality Improvement Strategies for Preventing Nosocomial Infections (Created 17-Feb-06) Quality Improvement Strategies for Asthma ... Quality Improvement Strategies for Asthma Control Erectile Dysfunction (Created 30-Jan-06) Erectile Dysfunction (Created 30-Jan-06) Inequality - Smoking Cessation to Reduce S... This review was the first part of a projec... Inequality - Smoking Cessation to Reduce Socio-Economic Differences This review was the first part of a project about inequality. It included randomized trials about the effect of smoking cessation interventions on reducing socio-economic differences. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Diet and Physical Activity to Reduce Socio... This review was the second part in a proje... Diet and Physical Activity to Reduce Socio-Economic Differences This review was the second part in a project about inequality. It included randomized trials about the effect of interventions on reducing socio-economic differences in diet and physical activity. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Workfare The data in SRS are not identical to the d... Workfare The data in SRS are not identical to the data in the published report. We used SRS only for an updated search. The review included randomized trials about the effect of welfare-to-work programs. Participants were welfare recipients. There were basically two types of programs. The educational type tried to build knowledge and skills in order to help the welfare recipients acquire jobs that could support them economically. The "work first" approach was more aimed at getting the participants quickly into a job. Exercise interventions for the management ... The objective of this systematic review wa... Exercise interventions for the management of frailty The objective of this systematic review was to examine the effectiveness of current exercise interventions on the management of frailty. A comprehensive search of Medline, Embase, Psycinfo, Cinahl, Scopus, Ageline, Eric, and SportDiscus databases was conducted and produced 1808 citations. So far we have completed 2 levels of “title and abstract” screening and we ended up with 262 articles. We have just started the full text screening. Eligibility criteria included original studies whose participants were identified as frail or prefrail with specific criteria and in which structured physical activity was included as at least one component of the intervention. Create a free account, build a dictionary with saved terms to re-use later! Public Domestic Violence - Using Cognitive Behavior Therapy Smoking Cessation to Reduce Socio-Economic Differences Diet and Physical Activity to Reduce Socio-Economic Differences Workfare Exercise Interventions for the Management of Frailty Search     Simple Advanced Refine (6 coded questions)  Any of these:   Exact Phrase: All of these: None of these: Author: Periodical: Projects: No restrictions   Libraries: Public   Select SRS Projects Show Saved Terms Select Library Show articles that do not have abstracts  Humans or Animals Humans Animals Type of Article Clinical Trial Editorial Letter Meta-Analysis Practice Guideline Randomized Controlled Trial Review Addresses Bibliography Biography Case Reports Classical Article Clinical Conference Clinical Trial, Phase I Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IV Comment Comparative Study Consensus Development Conference Consensus Development Conference, NIH Controlled Clinical Trial Corrected and Republished Article Dictionary Directory Duplicate Publication English Abstract Evaluation Studies Festschrift Government Publications Guideline Historical Article Interview In Vitro Journal Article Lectures Legal Cases Legislation Multicenter Study News Newspaper Article Overall Patient Education Handout Periodical Index Published Erratum Retracted Publication Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 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Retraction of Publication Scientific Integrity Review Support of Research Technical Report Twin Study Validation Studies Not a Primary Study or Review Unknown Primary Study Case Series Case Control Cohort Study Observational Study Qualitative Research CBA or ITS Registry Double Blind Controlled before after study Quasi-randomized trial Simple before after study Cluster-RCT Non-Randomized Study Report Book Book chapter Dissertation Conference procedings Secondary Research Not RCT Ages All Infant: birth-23 months All Child: 0-18 years All Adult: 19+ years Newborn: birth-1 month Infant: 1-23 months Preschool Child: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Middle Aged + Aged: 45+ years Aged: 65+ years 80 and over: 80+ years Undetermined Language English French German Italian Japanese Russian Spanish Afrikaans Albanian Unknown Arabic Armenian Azerbaijani Bosnian Bulgarian Catalan Chinese Croatian Czech Danish Dutch Esperanto Estonian Finnish Georgian Greek, Modern Hebrew Hindi Hungarian Icelandic Indonesian Kinyarwanda Korean Latin Latvian Lithuanian Macedonian Malay Malayalam Maori Multiple Languages Norwegian Persian Polish Portuguese Pushto Romanian Sanskrit Scottish gaelic Serbian Slovak Slovenian Swedish Thai Turkish Ukrainian Vietnamese Not English Not French Patient Demograhics Welfare recipients Unknown Not on welfare Mean Age Percent high school diploma Percent GED or high school diploma Mean number of years of education Relevant Study Notes questype Results(1-25 of 17,382) Sort By: Publication Date Relevance Took: 1.081 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 696 1 2 3 4 > Last >> (17382 articles found) The serological relationship between Theileria parva (Muguga) and Theileria lawrence from Rhodesia. May 28, 1977 J A Lawrence Thirty-eight sera from cattle from a herd in Rhodesia naturally infected with Theileria lawrencei were titrated with the indirect immunofluorescent test against schizont antigens of T parva (Muguga) and T lawrencei from Rhodesia. T lawrencei was found to be indistinguishable from T parva with the t... ( view more )est. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Relationship of lead, mercury, mirex, dichlorodiphenyldichloroethylene, hexachlorobenzene, and polychlorinated biphenyls to timing of menarche among Akwesasne Mohawk girls. Feb 2005 Melinda Denham,Lawrence M Schell,Glenn Deane,Mia V Gallo,Julia Ravenscroft,Anthony P DeCaprio,Akwesasne Task Force on the Environment BACKGROUND: Children are commonly exposed at background levels to several ubiquitous environmental pollutants, such as lead and persistent organic pollutants, that have been linked to neurologic and endocrine effects. These effects have prompted concern about alterations in human reproductive devel... ( view more )opment. Few studies have examined the effects of these toxicants on human sexual maturation at levels commonly found in the general population, and none has been able to examine multiple toxicant exposures. The aim of the current investigation was to examine the relationship between attainment of menarche and levels of 6 environmental pollutants to which children are commonly exposed at low levels, ie, dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), mirex, lead, and mercury. METHODS: This study was conducted with residents of the Akwesasne Mohawk Nation, a sovereign territory that spans the St Lawrence River and the boundaries of New York State and Ontario and Quebec, Canada. Since the 1950s, the St Lawrence River has been a site of substantial industrial development, and the Nation is currently adjacent to a US National Priority Superfund site. PCB, p,p'-DDE, HCB, and mirex levels exceeding the US Food and Drug Administration recommended tolerance limits for human consumption have been found in local animal species. The present analysis included 138 Akwesasne Mohawk Nation girls 10 to 16.9 years of age. Blood samples and sociodemographic data were collected by Akwesasne community members, without prior knowledge of participants' exposure status. Attainment of menses (menarche) was assessed as present or absent at the time of the interview. Congener-specific PCB analysis was available, and all 16 PCB congeners detected in >50% of the sample were included in analyses (International Union of Pure and Applied Chemistry numbers 52, 70, 74, 84, 87, 95, 99, 101 [+90], 105, 110, 118, 138 [+163 and 164], 149 [+123], 153, 180, and 187). Probit analysis was used to determine the median age at menarche for the sample. Binary logistic regression analysis was used to determine predictors of menarcheal status. Six toxicants (p,p'-DDE, HCB, PCBs, mirex, lead, and mercury) were entered into the logistic regression model. Age, socioeconomic status (SES), and BMI were tested as potential cofounders and were included in the model at P < .05. Interactions among toxicants were also evaluated. RESULTS: Toxicant levels were measured in blood for this sample and were consistent with long-term exposure to a variety of toxicants in multiple media. Mercury levels were at or below background levels, all lead levels were well below the Centers for Disease Control and Prevention action limit of 10 microg/dL, and PCB levels were consistent with a cumulative, continuing exposure pattern. The median age at menarche for the total sample was 12.2 years. The predicted age at menarche for girls with lead levels above the median (1.2 microg/dL) was 10.5 months later than that for girls with lead levels below the median. In the logistic regression analysis, age was the strongest predictor of menarcheal status and SES was also a significant predictor but BMI was not. The logistic regression analysis that corrected for age, SES, and other pollutants (p,p'-DDE, HCB, mirex, and mercury) indicated that, at their respective geometric means, lead (geometric mean: 0.49 microg/dL) was associated with a significantly lower probability of having reached menarche (beta = -1.29) and a group of 4 potentially estrogenic PCB congeners (E-PCB) (geometric mean: 0.12 ppb; International Union of Pure and Applied Chemistry numbers 52, 70, 101 [+90], and 187) was associated with a significantly greater probability of having reached menarche (beta = 2.13). Predicted probabilities at different levels of lead and PCBs were calculated on the basis of the logistic regression model. At the respective means of all toxicants and SES, 69% of 12-year-old girls were predicted to have reached menarche. However, at the 75th percentile of lead levels, only 10% of 12-year-old Mohawk girls were predicted to have reached menarche; at the 75th percentile of E-PCB levels, 86% of 12-year-old Mohawk girls were predicted to have reached menarche. No association was observed between mirex, p,p'-DDE, or HCB and menarcheal status. Although BMI was not a significant predictor, we tested BMI in the logistic regression model; it had little effect on the relationships between menarcheal status and either lead or E-PCB. In models testing toxicant interactions, age, SES, lead levels, and PCB levels continued to be significant predictors of menarcheal status. When each toxicant was tested in a logistic regression model correcting only for age and SES, we observed little change in the effects of lead or E-PCB on menarcheal status. CONCLUSIONS: The analysis of multichemical exposure among Akwesasne Mohawk Nation adolescent girls suggests that the attainment of menarche may be sensitive to relatively low levels of lead and certain PCB congeners. This study is distinguished by the ability to test many toxicants simultaneously and thus to exclude effects from unmeasured but coexisting exposures. By testing several PCB congener groupings, we were able to determine that specifically a group of potentially estrogenic PCB congeners affected the odds of reaching menarche. The lead and PCB findings are consistent with the literature and are biologically plausible. The sample size, cross-sectional study design, and possible occurrence of confounders beyond those tested suggest that results should be interpreted cautiously. Additional investigation to determine whether such low toxicant levels may affect reproduction and disorders of the reproductive system is warranted. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Conformational changes associated with activation of bee venom phospholipase A2. Dec 1996 T Ahmed,S M Kelly,A J Lawrence,M Mezna,N C Price Bee venom PLA2 possesses a binding site for long-chain fatty acids that can be acylated by long-chain fatty acid imidazolides [Drainas, D. and Lawrence, A.J. (1978) Eur. J. Biochem. 91, 131-138]. Occupation of the site either by oleic acid or the oleoyl residue enhances the catalytic activity by 45... ( view more ).7-fold in the presence of 20% 1-propanol and occupation of the site by the oleoyl residue increases the lytic activity against rabbit erythrocytes by 60-fold. Treatment of the enzyme with oleic acid and glutaraldehyde is known to produce irreversible activation [Lawrence, A.J. and Moores, G.R. (1975) FEBS Lett. 49, 287-291]. Here we show that reduction of the glutaraldehyde-treated enzyme with borohydride stabilizes the activated state and enables the fatty acid to be removed, revealing that a large proportion of the induced activation does not require the presence of oleic acid and indicating that activation is due to a change in the conformation rather than the hydrophobicity of the protein. A kinetic study of enzyme activated by oleoyl imidazolide showed that this modification stabilizes the protein against reversible inactivation by 1-propanol. Comparison of the CD spectra of native and oleoyl imidazolide-activated enzyme shows a change in secondary structure with apparent increase in both alpha-helix and beta-sheet content. During reaction of the enzyme with oleoyl imidazolide, the protein fluorescence shows a biphasic response with an initial fall attributed to occupation of the binding site followed by a progressive decrease with a shift of the emission maximum from 341 to 348 nm. The rate of the second phase closely matched the rate of increase in catalytic activity of the enzyme. Free oleic acid caused a rapid fall in fluorescence emission without the subsequent slow change. These results support the proposal that oleic acid or the oleoyl residue occupy a very similar site on the protein and that occupation of this site increases the exposure of one or both of the Trp residues to the aqueous environment. Binding studies show that activation by oleoyl imidazolide does not increase the affinity of the enzyme for the erythrocyte membrane. It is proposed that occupation of a long-chain fatty acid binding site on the enzyme enhances catalytic activity by changing the conformation of the protein rather than acting as a hydrophobic anchor to the substrate surface. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Membrane specializations and extracellular material associated with host astrocytes in peripheral neural transplants. Mar 1987 J M Lawrence,G Raisman The work of Aguayo and colleagues [Aguayo, David and Bray (1981) J. Exp. Biol. 95, 231-240] demonstrates that grafts of peripheral neural tissue are able to induce regenerative elongation of cut axons in the adult central nervous system. Elucidation of the mechanism of this response requires an und... ( view more )erstanding of the cellular interactions induced by these types of transplant. In previous studies [Zhou, Lawrence, Morris and Raisman (1986) Neuroscience 17, 815-827; Zhou, Lindsay, Lawrence and Raisman (1986) Neuroscience 17, 803-813] we have transplanted decapsulated adult superior cervical sympathetic ganglia or nodose ganglia into either the septal nuclei or the choroid fissure of adult syngeneic rat hosts. We found that host astrocytes invade the transplants along Schwann cell fascicles and around blood vessels. This raises the questions of what form the migrating astrocytes take, what routes they follow, and what is their fate. In the present study we have taken advantage of the fact that at longer survivals astrocytes accumulate as "paravascular cuffs", and we show that they have several specialized ultrastructural features, such as plasmalemmal caveolae, desmosomes, hemidesmosomes and accumulations of extracellular material. The specific stimuli inducing (or enhancing) these astrocytic specializations and their significance in relation to the wider morphogenetic events induced by peripheral neural transplants remain to be elucidated. However, the observations are further evidence of the remarkable mobility and plasticity of central astrocytes in transplantation situations, and in particular emphasize the involvement of the cell surface and its relationship to extracellular matrix. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles David the "Bubble Boy' and the boundaries of the human. Jan 4, 1985 R J Lawrence Lawrence is troubled by the fact that there has been little public discussion of the ethical and humanitarian issues raised by the life of David, the boy with severe combined immune deficiency syndrome who lived in a sterile bubble chamber at St. Luke's Episcopal/Texas Children's Hospital until his... ( view more ) death at the age of 12. As Director of Clinical Pastoral Education at the hospital during the first four years of David's life, Lawrence had contact with the boy and with the medical team caring for him. He describes the role of the medical team in encouraging David's conception and planning his life in the bubble, and contends that the physicians and scientists who designed the project were too isolated in the technocratic milieu of current medical practice to appreciate the dehumanizing aspects of what they were doing. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Genetic analysis of gamma-ray mutagenesis in yeast. II. Allele-specific control of mutagenesis. Oct 1979 R H McKee,C W Lawrence We find that partially different sets of gene functions are required for the production of different kinds of mutations induced by 60Co gamma rays in Saccharomyces cerevisiae. This observation is very similar to others made previously with respect to UV mutagenesis (LAWRENCE and CHRISTENSEN 1978a,b... ( view more ), 1979) and confirms the conclusion that such distinctive patterns of genetic control reflect properties of the test alleles and their genetic locations, rather than the kinds of lesions required to revert them. The data also support the model of mutagenic repair outlined in the first paper of this series (McKee and LAWRENCE 1979), in which partially different sets of gene functions are required for the production of different kinds of mutations, the formation of mutations at different genetic sites and the induction of mutations by different mutagens. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Ethnic differences in dairy and related nutrient consumption among US adults and their association with obesity, central obesity, and the metabolic syndrome. Jun 2008 May A Beydoun,Tiffany L Gary,Benjamin H Caballero,Robert S Lawrence,Lawrence J Cheskin,Youfa Wang BACKGROUND: Recent studies suggest dairy consumption and associated nutrients may be protective against some of the components of the metabolic syndrome (MetS). OBJECTIVES: We examined the association between consumption of a variety of dairy products and their related nutrients with obesity, centr... ( view more )al obesity, and MetS, and attempted to explain some of the ethnic differences in metabolic outcomes through dairy consumption using national data. DESIGN: Nationally representative indicators of obesity, central obesity, and MetS among US adults were constructed from National Health and Nutrition Examination Survey 1999-2004 data, including direct anthropometric assessments, blood pressure, and laboratory tests. Sample sizes ranged from 4519 for MetS to 14 618 for obesity. Associations between diet (assessed using 24-h recalls) and metabolic and other outcomes were tested using multivariate linear and logistic models and structural equation models. RESULTS: We found a significant inverse association between intake of whole milk, yogurt, calcium, and magnesium and metabolic disorders. Odds ratios for one more daily serving of yogurt and 100 mg Mg for MetS were 0.40 (95% CI: 0.18, 0.89) and 0.83 (95% CI: 0.72, 0.96), respectively. The opposite was found for intakes of cheese, low-fat milk, and phosphorus. Using structural equation models, ethnic differences in some MetS outcomes, such as body mass index and systolic blood pressure, were partly explained by variations in dairy-related nutrients. CONCLUSIONS: Various dairy products may have differential associations with metabolic disorders, including obesity. Ethnic differences in dairy consumption may explain in part the ethnic disparities in metabolic disorders in the US population. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Metabolic syndrome, proteinuria, and the risk of progressive CKD in hypertensive African Americans. May 2008 Janice Lea,Deanna Cheek,Denise Thornley-Brown,Lawrence Appel,Lawrence Agodoa,Gabriel Contreras,Jennifer Gassman,Jim Lash,Edgar R Miller,Otelio Randall,Xuelei Wang,William McClellan,AASK Study Investigators BACKGROUND: Chronic kidney disease (CKD) is more likely to progress to kidney failure (end-stage renal disease) in African Americans, although the reasons for this are unclear. Metabolic syndrome is a risk factor for the development of diabetes and cardiovascular disease and recently was linked to ... ( view more )incident CKD. The purpose of this study is to examine whether metabolic syndrome is associated with kidney disease progression in hypertensive African Americans. DESIGN & PARTICIPANTS: The current study design is a secondary analysis of the African-American Study of Hypertension and Kidney Disease, a randomized controlled trial of blood pressure goal and agents in hypertensive African Americans with CKD. PREDICTORS: Metabolic syndrome was defined according to the modified National Cholesterol Education Program guidelines. OUTCOMES: Decrease in glomerular filtration rate of 50% or 25 mL/min/1.73 m(2), end-stage renal disease (initiation of dialysis therapy or transplantation), death, or a composite outcome of all 3. RESULTS: 842 subjects were included in this analysis, and 41.7% met criteria for metabolic syndrome. Subjects meeting criteria for metabolic syndrome had greater levels of proteinuria. Cox regression analyses adjusted for age, sex, glomerular filtration rate, and other significant covariates except for proteinuria indicated a 31% increased risk, with a 95% confidence interval of 1.03 to 1.7 (P = 0.03) for time to reach the composite outcome in those with metabolic syndrome. Adjusting for proteinuria, the effect was abated to 16% (95% confidence interval, 0.9 to 1.5), no longer remained significant (P = 0.2), and was unchanged by adjusting randomized treatment group (blood pressure goal or antihypertensive drug). LIMITATIONS: Lack of waist circumference as a better surrogate of abdominal obesity. CONCLUSIONS: In summary, metabolic syndrome is associated with proteinuria in hypertensive African Americans, but is not independently associated with CKD progression. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Long-term effects of renin-angiotensin system-blocking therapy and a low blood pressure goal on progression of hypertensive chronic kidney disease in African Americans. Apr 28, 2008 Lawrence J Appel,Jackson T Wright,Tom Greene,John W Kusek,Julia B Lewis,Xuelei Wang,Michael S Lipkowitz,Keith C Norris,George L Bakris,Mahboob Rahman,Gabriel Contreras,Stephen G Rostand,Joel D Kopple,Francis B Gabbai,Gerald I Schulman,Jennifer J Gassman,Jeanne Charleston,Lawrence Y Agodoa,African American Study of Kidney Disease and Hypertension Collaborative Research Group BACKGROUND: Antihypertensive drugs that block the renin-angiotensin system (angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers) are recommended for patients with chronic kidney disease (CKD). A low blood pressure (BP) goal (BP, <130/80 mm Hg) is also recommended. The ... ( view more )objective of this study was to determine the long-term effects of currently recommended BP therapy in 1094 African Americans with hypertensive CKD. METHODS: Multicenter cohort study following a randomized trial. Participants were 1094 African Americans with hypertensive renal disease (glomerular filtration rate, 20-65 mL/min/1.73 m2). Following a 3x2-factorial trial (1995-2001) that tested 3 drugs used as initial antihypertensive therapy (ACEIs, calcium channel blockers, and beta-blockers) and 2 levels of BP control (usual and low), we conducted a cohort study (2002-2007) in which participants were treated with ACEIs to a BP lower than 130/80 mm Hg. The outcome measures were a composite of doubling of the serum creatinine level, end-stage renal disease, or death. RESULTS: During each year of the cohort study, the annual use of an ACEI or an angiotensin receptor blocker ranged from 83.7% to 89.0% (vs 38.5% to 49.8% during the trial). The mean BP in the cohort study was 133/78 mm Hg (vs 136/82 mm Hg in the trial). Overall, 567 participants experienced the primary outcome; the 10-year cumulative incidence rate was 53.9%. Of 576 participants with at least 7 years of follow-up, 33.5% experienced a slow decline in kidney function (mean annual decline in the estimated glomerular filtration rate, <1 mL/min/1.73 m2). CONCLUSION: Despite the benefits of renin-angiotensin system-blocking therapy on CKD progression, most African Americans with hypertensive CKD who are treated with currently recommended BP therapy continue to progress during the long term. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Corpus callosum in maltreated children with posttraumatic stress disorder: a diffusion tensor imaging study. Apr 15, 2008 Andrea P Jackowski,Heather Douglas-Palumberi,Marcel Jackowski,Lawrence Win,Robert T Schultz,Lawrence W Staib,John H Krystal,Joan Kaufman Contrary to expectations derived from preclinical studies of the effects of stress, and imaging studies of adults with posttraumatic stress disorder (PTSD), there is no evidence of hippocampus atrophy in children with PTSD. Multiple pediatric studies have reported reductions in the corpus callosum-... ( view more )-the primary white matter tract in the brain. Consequently, in the present study, diffusion tensor imaging was used to assess white matter integrity in the corpus callosum in 17 maltreated children with PTSD and 15 demographically matched normal controls. Children with PTSD had reduced fractional anisotropy in the medial and posterior corpus, a region which contains interhemispheric projections from brain structures involved in circuits that mediate the processing of emotional stimuli and various memory functions--core disturbances associated with a history of trauma. Further exploration of the effects of stress on the corpus callosum and white matter development appears a promising strategy to better understand the pathophysiology of PTSD in children. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Relationship between visual span and reading performance in age-related macular degeneration. Feb 2008 Allen M Y Cheong,Gordon E Legge,Mary G Lawrence,Sing-Hang Cheung,Mary A Ruff PURPOSE: Visual-span profiles are plots of letter-recognition accuracy as a function of letter position left and right of the point of fixation. Legge, Mansfield, and Chung [Legge, G. E., Mansfield, J. S., & Chung, S. T. L. (2001). Psychophysics of reading-XX. Linking letter recognition to reading ... ( view more )speed in central and peripheral vision. Vision Research, 41(6), 725-743] proposed that reduced size of the visual span is a spatial factor limiting reading speed in patients with age-related macular degeneration (AMD). We have recently shown that a temporal property of letter recognition--the exposure time required for a high level of accuracy--is also a factor limiting reading speed in AMD [Cheong, A. M. Y., Legge, G. E., Lawrence, M. G., Cheung, S. H., & Ruff, M. (2007). Relationship between slow visual processing and reading speed in people with macular degeneration. Vision Research, 47, 2943-2965]. We measured the visual-span profiles of AMD subjects and assessed the relationship of the spatial and temporal properties of these profiles to reading speed. METHODS: Thirteen AMD subjects and 11 age-matched normals were tested. Visual-span profiles were measured by using the trigram letter-recognition method described by Legge et al. (2001). Each individual's temporal threshold for letter recognition (80% accuracy criterion) was used as the exposure time for measuring the visual-span profile. Size of the visual span was computed as the area under the profile in bits of information transmitted. The information transfer rate in bits per second was defined as the visual-span size in bits divided by the exposure time in sec. RESULTS: AMD visual-span sizes were substantially smaller (median of 23.9 bits) than normal visual-span sizes in central vision (median of 40.8 bits, p<.01). For the nine AMD subjects with eccentric fixation, the visual-span sizes (median of 20.6 bits) were also significantly smaller than visual spans of normal controls at 10 degrees below fixation in peripheral vision (median of 29.0 bits, p=.01). Information transfer rate for the AMD subjects (median of 29.5 bits/s) was significantly slower than that for the age-matched normals at both central and peripheral vision (median of 411.7 and 290.5 bits/s respectively, ps<.01). Information transfer rates were more strongly correlated with reading speed than the size of the visual span, and explained 36% of the variance in AMD reading speed. CONCLUSION: Both visual-span size and information transfer rate were significantly impaired in the AMD subjects compared with age-matched normals. Information transfer rate, representing the combined effects of a reduced visual span and slower temporal processing of letters, was a better predictor of reading speed in AMD subjects than was the size of the visual span. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Structural basis for elastolytic substrate specificity in rodent alpha-chymases. Jan 4, 2008 Jukka Kervinen,Marta Abad,Carl Crysler,Michael Kolpak,Andrew D Mahan,John A Masucci,Shariff Bayoumy,Maxwell D Cummings,Xiang Yao,Matthew Olson,Lawrence de Garavilla,Lawrence Kuo,Ingrid Deckman,John Spurlino Divergence of substrate specificity within the context of a common structural framework represents an important mechanism by which new enzyme activity naturally evolves. We present enzymological and x-ray structural data for hamster chymase-2 (HAM2) that provides a detailed explanation for the unus... ( view more )ual hydrolytic specificity of this rodent alpha-chymase. In enzymatic characterization, hamster chymase-1 (HAM1) showed typical chymase proteolytic activity. In contrast, HAM2 exhibited atypical substrate specificity, cleaving on the carboxyl side of the P1 substrate residues Ala and Val, characteristic of elastolytic rather than chymotryptic specificity. The 2.5-A resolution crystal structure of HAM2 complexed to the peptidyl inhibitor MeOSuc-Ala-Ala-Pro-Ala-chloromethylketone revealed a narrow and shallow S1 substrate binding pocket that accommodated only a small hydrophobic residue (e.g. Ala or Val). The different substrate specificities of HAM2 and HAM1 are explained by changes in four S1 substrate site residues (positions 189, 190, 216, and 226). Of these, Asn(189), Val(190), and Val(216) form an easily identifiable triplet in all known rodent alpha-chymases that can be used to predict elastolytic specificity for novel chymase-like sequences. Phylogenetic comparison defines guinea pig and rabbit chymases as the closest orthologs to rodent alpha-chymases. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles An anti-Hick's effect in monkey and human saccade reaction times. 2008 Bonnie M Lawrence,Alex St John,Richard A Abrams,Lawrence H Snyder In order to execute movements to targets in the environment, we must first select a target in which to move, generally from an array of alternatives. Hick's Law states that reaction time (RT) increases as the number of response alternatives increases. Violations of this law, however, generally in t... ( view more )he form of the absence of a relationship between response alternatives and RT have been reported in the literature. K. Kveraga, L. Boucher, and H. C. Hughes (2002), for example, found that saccades to visual targets violate Hick's Law. To examine this violation further, we measured saccade RTs in monkeys and humans and found that saccade RTs actually decreased as the number of potential target locations increased. We hypothesize that this arises because subjects must actively inhibit premature saccades, and that the required inhibition increases as the certainty of a movement to a particular location increases. With increased inhibition, saccade onset is delayed, resulting in an anti-Hick's effect. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles The impact of privacy and confidentiality laws on the conduct of clinical trials. 2008 Jane Armitage,Robert Souhami,Lawrence Friedman,Lutz Hilbrich,Jack Holland,Lawrence H Muhlbaier,Jane Shannon,Alison Van Nie Justifiable concerns about the use of personal data in many aspects of daily life have led to the recent introduction in many countries of laws intended to regulate data use. Although participation in randomized clinical trials is generally with informed consent, recruitment procedures, complete fo... ( view more )llow-up, and the efficient conduct of trials may be substantially affected by such national or local privacy legislation. The relevant laws often have exceptions that allow the use of patient information in the public interest - including the use of data collected to improve or monitor public health or as part of medical research. However, regulatory bodies often give conflicting interpretations of the law, and this affects the conduct of large-scale trials.In particular, unnecessarily restrictive interpretation of the law may be a serious impediment to identification of potential participants for a trial, access to records to confirm events, continued follow-up of patients after the trial has been concluded, and secondary use of the trial data for purposes not directly related to the original purpose of the study. These obstacles could be overcome by better informing patients of the uses of records for medical research purposes, by using informed consent procedures that explain the nature of the research and the uses of the data, and by the use of identifiers, such as social security numbers that allow central follow-up.The clinical trial research community needs to ensure that the substantial benefits of large-scale randomized trials are explained both to the public and to those responsible for introducing legislation. The negative impact of privacy legislation on the use of personal health information and on conducting large studies needs to be understood and minimized. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. Oct 20, 2007 Matthew H Kulke,Lawrence S Blaszkowsky,David P Ryan,Jeffrey W Clark,Jeffrey A Meyerhardt,Andrew X Zhu,Peter C Enzinger,Eunice L Kwak,Alona Muzikansky,Colleen Lawrence,Charles S Fuchs PURPOSE: The addition of either capecitabine or erlotinib to gemcitabine in the first-line treatment of advanced pancreatic cancer is associated with modest improvements in overall survival. We evaluated an oral regimen of capecitabine and erlotinib in patients with advanced pancreatic cancer who h... ( view more )ad experienced treatment failure with standard first-line therapy with gemcitabine. PATIENTS AND METHODS: Thirty patients with gemcitabine-refractory metastatic pancreatic cancer were treated with capecitabine, administered at a dose of 1,000 mg/m2 twice daily for 2 weeks, followed by a 1-week break. All patients also received erlotinib 150 mg daily. Patients were observed for evidence of response, toxicity, and survival. EGFR mutational status was assessed in available tumor blocks. RESULTS: Treatment with capecitabine and erlotinib in gemcitabine-refractory patients was associated with an overall objective radiologic response rate of 10% and a median survival duration of 6.5 months. In addition, 17% of the treated patients experienced decreases in tumor marker (CA 19-9) levels of more than 50% from baseline. Common toxicities included diarrhea, skin rash, fatigue, and hand-foot syndrome. EGFR mutations were detected in two of five available tumors; no association between treatment response and EGFR mutational status was evident. CONCLUSION: The combination of capecitabine and erlotinib is active in patients with gemcitabine-refractory pancreatic cancer. This regimen may represent an acceptable treatment option in patients who experience treatment failure with standard first-line therapy with gemcitabine or for whom gemcitabine may not be an appropriate first-line treatment option. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Successful management of cervical pregnancy with medical intervention only: a case report. Oct 2007 Adelina M Emmi,Lawrence D Devoe,Daksha B Chudgar,Erin Holsten,Lawrence C Layman BACKGROUND: Cervical pregnancies are a rare form of ectopic pregnancy. They frequently present with hemorrhage and require hysterectomy to control bleeding. Their incidence may be higher with in vitro fertilization than previously considered. Since future fertility is desired in these patients, con... ( view more )servative management is frequently attempted. Increased early surveillance leads to earlier diagnosis and intervention. Most case reports to date indicated treating with either medical and surgical intervention or surgical intervention. CASE: A 36-year-old woman presented with recurrent pregnancy loss and tubal disease. In vitro fertilization was recommended. Embryo transfer resulted in a cervical pregnancy. She experienced painless vaginal bleeding shortly after her positive pregnancy test. A cervical pregnancy was diagnosed by early ultrasound. The patient underwent successful medical management and complete resolution with methotrexate alone. CONCLUSION: Cervical pregnancy, when diagnosed early, can be successfully treated with medical therapy. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Long-term observation of adolescents initiating HAART therapy: three-year follow-up. Oct 2007 Patricia M Flynn,Bret J Rudy,Jane C Lindsey,Steven D Douglas,Janet Lathey,Stephen A Spector,Jaime Martinez,Margarita Silio,Marvin Belzer,Lawrence Friedman,Lawrence D'Angelo,Elizabeth Smith,Janice Hodge,Michael D Hughes,PACTG 381 Study Team The PACTG 381 cohort included 120 adolescents infected via high-risk behaviors and treated with at least two NRTIs plus either a protease inhibitor or an efavirenz-containing HAART regimen. After 24 weeks of therapy, only 69 of 118 (59%) evaluable subjects had undetectable viral loads. We now prese... ( view more )nt findings of the study after 3 years of follow-up. Virologic, immunologic, and treatment information were collected from subjects every 12 weeks beyond the first 24 weeks of therapy through 156 weeks. Of the 120 subjects starting HAART, 44 (37%) stayed on study treatment for the 3 years of observation. Twenty-nine (24%) subjects reached and maintained undetectable viral loads. Poorer adherence (p = 0.016), higher baseline viral load (p = 0.010), and CD8 naive counts (p = 0.034) predicted virologic failure. Immunologic measurements improved from entry to the end of follow-up in the subjects with undetectable viral loads. CD4 counts at the end of study were not significantly different from HIV-uninfected youth, but CD4%, CD8 counts and percent, and CD8 activation markers remained significantly different. Adolescents infected with HIV via high-risk behaviors have less than optimal responses to HAART therapy with only 24% achieving and maintaining undetectable viral loads over 3 years. Immunologic improvement was demonstrated and CD4 counts in subjects with virologic control reached levels in HIV-uninfected adolescents. Interventions, especially those focused on adherence, are necessary to improve HAART outcomes in adolescents. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Study designs for effectiveness and translation research :identifying trade-offs. Aug 2007 Shawna L Mercer,Barbara J DeVinney,Lawrence J Fine,Lawrence W Green,Denise Dougherty BACKGROUND: Practitioners and policymakers need credible evidence of effectiveness to justify allocating resources to complex, expensive health programs. Investigators, however, face challenges in designing sound effectiveness and translation research with relevance for "real-world" settings. METHO... ( view more )DS: Research experts and federal and foundation funders (n= approximately 120) prepared for and participated in a symposium, held May 4-5, 2004, to weigh the strengths, limitations, and trade-offs between alternate designs for studying the effectiveness and translation of complex, multilevel health interventions. RESULTS: Symposium attendees acknowledged that research phases (hypothesis generating, efficacy, effectiveness, translation) are iterative and cyclical, not linear, since research in advanced phases may reveal unanswered questions in earlier phases. Research questions thus always need to drive the choice of study design. When randomization and experimental control are feasible, participants noted that the randomized controlled trial with individual random assignment remains the gold standard for safeguarding internal validity. Attendees highlighted trade-offs of randomized controlled trial variants, quasi-experimental designs, and natural experiments for use when randomization or experimental control or both are impossible or inadequately address external validity. Participants discussed enhancements to all designs to increase confidence in causal inference while accommodating greater external validity. Since no single study can establish causality, participants encouraged replication of studies and triangulation using different study designs. Participants also recommended participatory research approaches for building population relevance, acceptability, and usefulness. CONCLUSIONS: Consideration of the study design choices, trade-offs, and enhancements discussed here can guide the design, funding, completion, and publication of appropriate policy- and practice-oriented effectiveness and translational research for complex, multilevel health interventions. ( view less ) View Full Abstract View Article Details   Related Articles Recombinant group B streptococcus Beta C protein and a variant with the deletion of its immunoglobulin A-binding site are protective mouse maternal vaccines and effective carriers in conjugate vaccines. Jul 2007 Hsiao-Hui Yang,Lawrence C Madoff,Hilde-Kari Guttormsen,Yong-Dong Liu,Lawrence C Paoletti Immunogenic vaccines against group B Streptococcus (GBS) have been created by coupling the GBS capsular polysaccharides (CPS) to carrier proteins. The GBS beta C protein (BCP) serves as an effective carrier while inducing protective immunity against BCP-expressing strains. BCP also binds human immu... ( view more )noglobulin A (IgA), a characteristic that may be undesirable for use in humans. Here, we examined the immunogenicity and protective efficacy of a recombinant GBS BCP (rBCP), an rBCP modified to eliminate its IgA-binding site (rBCP(DeltaIgA)), and their corresponding GBS serotype III CPS conjugates (III-rBCP and III-rBCP(DeltaIgA)). Deletion of the IgA-binding site or conjugation to CPS did not alter antigenic BCP epitopes. Recombinant proteins and conjugates elicited specific, high-titered IgG in mice. Antisera to rBCP, rBCP(DeltaIgA), III-rBCP, and III-rBCP(DeltaIgA) opsonized GBS strains A909 (Ia/BCP(+)) and H36B (Ib/BCP(+)) for killing by HL-60 cells; antiserum to III-rBCP and III-rBCP(DeltaIgA) also opsonized strain M781 (III/BCP(-)). Vaccination of female mice with either rBCP or rBCP(DeltaIgA) protected approximately 40% of their pups challenged with GBS strain A909. Pups born to III-rBCP- or III-rBCP(DeltaIgA)-vaccinated dams survived at rates of 56% and 66%, respectively. Over 90% of pups born to dams that received the type III CPS conjugates survived challenge with GBS strain M781. In summary, rBCP and rBCP(DeltaIgA) proteins and the conjugates containing them were immunogenic in mice, inducing both CPS- and protein-specific functional IgG. These results suggest that the rBCP(DeltaIgA) could be used as a carrier to augment the immunogenicity of the CPS while expanding coverage to GBS strains bearing BCP. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles An update on short-course episodic and prevention therapies for herpes genitalis. Jun 2007 Lawrence Corey,Neil Bodsworth,Adrian Mindel,Raj Patel,Timothy Schacker,Lawrence Stanberry The prevalence of herpes genitalis (genital herpes) has increased markedly over the past three decades. The most common cause is infection with the herpes simplex virus type 2 (HSV-2), but it can also occur as a result of HSV-1 infection. Herpes genitalis can cause substantial psychosexual as well ... ( view more )as physical morbidity and, in immunocompromised individuals, such as those who are HIV-positive, HSV infection can result in severe disease with progressive and extensive lesions. The natural history of herpes genitalis and the pathways of infection are now well known; however, the factors associated with reactivation have yet to be fully defined. A number of management approaches with antiviral medications are commonly used, including episodic and suppressive treatments. For episodic therapy, the duration of both lesions and symptoms, as well as the proportion of aborted episodes, are the most important measures of efficacy. For suppressive therapy, the time to first recurrence and frequency of recurrences over time are the most important clinical measures of antiviral benefit. Regarding the duration of episodic regimens, comparisons of 1-, 2- and 3-day antiviral courses with standard 5-day regimens show similar benefits on healing and relief of symptoms, with the obvious improvement in convenience, economy and compliance. In HIV-positive patients, antiherpes therapy has proved effective in speeding healing of lesions and reducing subclinical shedding, and can be used to treat genital HSV-2 infections in this group. Suppressive antiviral therapy has been shown to decrease the risk of HSV transmission in heterosexual couples. New approaches to the prevention of HSV infection, including vaccines and topical microbicides, are under investigation. ( view less ) View Full Abstract View Article Details   Related Articles An update on short-course intermittent and prevention therapies for herpes labialis. Jun 2007 Stanley Gilbert,Lawrence Corey,Anthony Cunningham,Jean-Elie Malkin,Lawrence Stanberry,Richard Whitley,Spotswood Spruance Infection with herpes simplex virus (HSV) has increased in prevalence worldwide over the past two decades, making it a major public health concern. Approximately 90% of recurrent HSV type 1 (HSV-1) infections manifest as non-genital disease, primarily as orofacial lesions known as herpes labialis. ... ( view more )Improvements in our understanding of the natural history of herpes labialis support the rationale for early treatment (during the prodrome or erythema stages) with high doses of antiviral agents in order to maximize drug benefit. When evaluating the efficacy of different antiviral and anti-inflammatory agents in clinical trials, episode duration, lesion healing time, reduction in maximum lesion size and the proportion of aborted lesions should be used as the most reliable measures of therapeutic efficacy. There has also been considerable research into the most beneficial treatment for recurrent episodes of herpes labialis in immunocompetent individuals. Data from clinical studies confirm that short-course, high-dose oral antiviral therapy should be offered to patients with recurrent herpes labialis to accelerate healing, reduce pain and most likely increase treatment adherence. Optimal benefits may be obtained when these oral antiviral agents are combined with topical corticosteroids, but more research is needed with this combination. Patients undergoing facial cosmetic procedures (i.e.facial resurfacing) are at risk of HSV reactivation, but further data are required on the actual risk according to the specific procedure. Aciclovir, valaciclovir and famciclovir all provide effective prophylaxis against HSV-1 reactivation following ablative facial resurfacing. However, no definitive recommendations can be made regarding prophylactic therapy for minimally invasive procedures at present. ( view less ) View Full Abstract View Article Details   Related Articles Electrochemical determination of sulfide at various carbon substrates: a comparative study. Jun 2007 Jimmy Lawrence,Kay L Robinson,Nathan S Lawrence The direct electrochemical oxidation of sodium sulfide has been examined at five different carbon-based electrode substrates (glassy carbon (GC), boron-doped diamond (BDD), edge-plane pyrollytic graphite (EPPG), basal-plane pyrollytic graphite (BPPG) and carbon nanotubes (CNT)). An electrocatalytic... ( view more ) response is observed at both the EPPG and CNT electrode compared to that of the other three substrates. The higher capacitative charging currents obtained at the CNT electrode hinder its detection range and, as such, the EPPG electrode has been clearly shown to be the substrate of choice for the direct electrochemical detection of sulfide. The procedure was applied to the recovery of a sulfide spike in river water, with a recovery of 104%. ( view less ) View Full Abstract View Article Details   Related Articles Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity. May 1, 2007 Khandaker Siddiquee,Shumin Zhang,Wayne C Guida,Michelle A Blaskovich,Benjamin Greedy,Harshani R Lawrence,M L Richard Yip,Richard Jove,Mark M McLaughlin,Nicholas J Lawrence,Said M Sebti,James Turkson S3I-201 (NSC 74859) is a chemical probe inhibitor of Stat3 activity, which was identified from the National Cancer Institute chemical libraries by using structure-based virtual screening with a computer model of the Stat3 SH2 domain bound to its Stat3 phosphotyrosine peptide derived from the x-ray ... ( view more )crystal structure of the Stat3beta homodimer. S3I-201 inhibits Stat3.Stat3 complex formation and Stat3 DNA-binding and transcriptional activities. Furthermore, S3I-201 inhibits growth and induces apoptosis preferentially in tumor cells that contain persistently activated Stat3. Constitutively dimerized and active Stat3C and Stat3 SH2 domain rescue tumor cells from S3I-201-induced apoptosis. Finally, S3I-201 inhibits the expression of the Stat3-regulated genes encoding cyclin D1, Bcl-xL, and survivin and inhibits the growth of human breast tumors in vivo. These findings strongly suggest that the antitumor activity of S3I-201 is mediated in part through inhibition of aberrant Stat3 activation and provide the proof-of-concept for the potential clinical use of Stat3 inhibitors such as S3I-201 in tumors harboring aberrant Stat3. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Gamma interferon suppresses erythropoiesis via interleukin-15. May 2007 Isis K Mullarky,Frank M Szaba,Lawrence W Kummer,Lindsey B Wilhelm,Michelle A Parent,Lawrence L Johnson,Stephen T Smiley Impaired erythropoiesis causes anemia during genetic disorders, chronic disease, and infection. In studies of the underlying mechanisms researchers have increasingly focused on gamma interferon (IFN-gamma). Here, we identified a previously unrecognized role for interleukin-15 (IL-15) in red blood c... ( view more )ell homeostasis and demonstrated that IFN-gamma and signal transducer and activator of transcription protein 1-dependent pathways up-regulate expression of IL-15 in vivo. These findings identified new therapeutic targets for anemia. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Validation and application of a stability-indicating HPLC method for the in vitro determination of gastric and intestinal stability of venlafaxine. Apr 11, 2007 Ebenezer B Asafu-Adjaye,Patrick J Faustino,Mobin A Tawakkul,Lawrence W Anderson,Lawrence X Yu,Hyojong Kwon,Donna A Volpe Gastrointestinal stability of venlafaxine was evaluated in vitro in simulated gastric (SGF) and intestinal (SIF) fluids using a stability indicating HPLC method. The method was validated using a 5 microm Ascentis C18 column (150 mm x 4.6 mm) and mobile phase consisting of 30% acetonitrile in 20 mM ... ( view more )potassium phosphate buffer (pH 6.5) delivered isocratically at a flow rate of 1 mL/min with UV detection at 228 nm. Venlafaxine in USP simulated gastric and intestinal fluids (0.4 mg/mL) was incubated at 37 degrees C in a shaking water bath. The gastric stability study samples were assayed at 0, 15, 30 and 60 min intervals while sampling for the intestinal stability study was at 0, 1, 2 and 3 h. System suitability determinations gave R.S.D.s of 0.68, 0.5 and 3.9% for retention factor (k'), peak area and tailing factor, respectively. The method was shown to be accurate, precise, specific, and linear over the analytical range. Intra- and inter-day precision was <5.3%. Forced degradation studies of drug substance in basic media at 70 degrees C as well as in H2O2 for 1 h and ultra-violet photostability studies at 255 and 365 nm for 24 h did not produce any detectable degradation products. Forced degradation studies of drug substance in acidic media at 70 degrees C for 1 h produced the dehydro-venlafaxine degradant. Venlafaxine was stable in SGF (pH approximately 1.2) for the 1-h incubation period and in SIF (pH 6.8) up to 3 h with <1.5% relative difference (RD) between the amount of drug added and that found for all time points. This stability experiment in simulated gastric and intestinal fluids suggests that drug loss in the gastrointestinal tract takes place by membrane permeation rather than a degradation process. 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