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Pedigree-based assignment tests for reversing coyote (Canis latrans) introgression into the wild red wolf (Canis rufus) population.

The principal threat to the persistence of the endangered red wolf (Canis rufus) in the wild is hybridization with the coyote (Canis latrans). To facilitate idengification and removal of hybrids, assignment tests are developed which use genotype data to estimate identity as coyote, 1/4, 1/2, 3/4 or full red wolf. The tests use genotypes from the red wolves that founded the surviving population and the resulting pedigree, rather than a contemporary red wolf sample. The tests are evaluated by analysing both captive red wolves at 18 microsatellite loci, and data simulated under a highly parameterized, biologically reasonable model. The accuracy of assignment rates are generally high, with over 95% of known red wolves idengified correctly. There are, however, tradeoffs between ambiguous assignments and misassignments, and between misidengifying red wolves as hybrids and hybrids as red wolves. These result in a compromise between limiting introgression and avoiding demographic losses. The management priorities and level of introgression determine the combination of test and removal strategy that best balances these tradeoffs. Ultimately, we conclude that the use of the assignment tests has the capacity to arrest and reverse introgression. To our knowledge, the presented approach is novel in that it accounts for genetic drift when the genotypes under analysis are temporally separated from the reference populations to which they are being assigned. These methods may be valuable in cases where reference databases for small populations have aged substantially, pedigree information is available or data are generated from historical samples.

Animals↗

Is DSM widely accepted by Japanese clinicians?

The Diagnostic and Statistical Manual of Mental Disorders, 3rd edition (DSM-III), a new standardized diagnostic system with multiaxial diagnosis, operational criteria and renewed definitions of mental disorders, was introduced in 1980 and prompted movements to reform conventions in Japanese psychiatry. This review overviews the initial response of Japanese clinicians to accept DSM-III, and its effects on the development of systematic research of psychiatric diagnosis. These new research activities include those on reliability of psychiatric diagnosis, application of various evaluation tools, discussion on the concept of mental disorders, relation of personality disorders with depressive disorders, and Taijin-kyofusho, or culturally distinctive phobia in Japan. A reference database search to survey the latest trend on psychiatric research indicated that the number of papers published by Japanese workers increased sharply after 1987, and DSM apparently greatly influenced their internationalization. Twenty years after the publication of DSM-III, a questionnaire on the use of DSM-IV was set out in 2000 to survey how widely DSM is utilized in clinical practice in Japan. Two hundred and twelve psychiatrists answered the questionnaire, and the results show that DSM has been accepted positively by the younger generation, while the older generation (over 40s) has still less interest in DSM, and DSM is used mainly for research purposes rather than in daily practice.

Adult↗

Comparison of statistical parametric mapping and SPECT difference imaging in patients with temporal lobe epilepsy.

PURPOSE: Statistical parametric mapping (SPM) is an image-analysis tool that assesses the statistical significance of cerebral blood flow (CBF) changes on a voxel-by-voxel basis, thereby removing the subjectivity inherent in conventional region-of-interest (ROI) analysis. Our platform of single-photon emission computed tomography (SPECT) ictal-interictal difference imaging in clinical epilepsy has been validated for localizing seizure onset. We extend the tools of SPM by further applying statistical measures for the significance of perfusion changes in individual patients to localize epileptogenic foci in patients with defined temporal lobe epilepsy by using paired scans in this preliminary study. METHODS: Twelve patients with pairs of periictal and interictal SPECT scans were analyzed in this comparison study between SPECT difference imaging and SPM difference analysis by using a reference database of paired normal healthy images. These 12 patients possessed seizure foci localized to the mesial temporal lobe as confirmed by surgical outcome and by hippocampal sclerosis on pathology. SPM was used to identify clusters of increased or decreased CBF in each patient in contrast to our control group. RESULTS: The regions having the most significant increased or decreased CBF by SPM analysis were in agreement with regions identified by conventional difference imaging and visual analysis by viewers blinded to the results of the SPM analysis. Differentiated further by time of radiopharmaceutical injection, six of seven patients injected within 100 s of seizure onset displayed hyperperfusion changes localized to the corresponding epileptogenic temporal lobe by both techniques. Among patients receiving injections after 100 s, both techniques showed primarily regions of hypoperfusion, which again were similar between these two methods. CONCLUSIONS: The results provide strong evidence supporting SPM difference analysis in assessing regions of significant CBF change from baseline in concordance with our current clinically used technique of SPECT ictal--interictal difference imaging in epilepsy patients. Difference analysis using SPM could serve as a useful diagnostic tool in the evaluation of seizure focus in temporal lobe epilepsy.

Adolescent↗

Effects of vitamin D supplementation on strength, physical performance, and falls in older persons: a systematic review.

OBJECTIVES: identify, appraise, and synthesize data from randomized, controlled trials of vitamin D supplementation in older people. DESIGN: A systematic review of trials identified from searches of databases, reference lists, review articles, and recent conference proceedings. SETTING: Most studies performed in ambulatory setting. PARTICIPANTS: Older people (mean age=60). INTERVENTIONS: Vitamin D or vitamin D metabolites. MEASUREMENTS: Strength, physical performance, or falls. RESULTS: Thirteen trials involving 2,496 patients met this study's inclusion criteria. Most of the trials were small and had methodological problems. In 10 trials, there was no evidence that vitamin D or vitamin D metabolites had an effect on falls or physical function, but three trials showed a positive effect of vitamin D in combination with calcium. When available data from the four highest quality trials were pooled (n=1,317), there continued to be no evidence that vitamin D reduced the risk of falling (relative risk= 0.99, 95% confidence interval=0.89-1.11), although a single trial of vitamin D and calcium showed a positive effect. CONCLUSION: Although there is insufficient evidence that vitamin D supplementation alone improves physical performance in older people, some data suggest a benefit from vitamin D combined with calcium supplementation, but this requires confirmation in large, well-designed trials.

Accidental Falls↗

Timing of cholecystectomy for acute calculous cholecystitis: a meta-analysis.

OBJECTIVES: To compare early with delayed cholecystectomy for the treatment of acute lithiasic cholecystitis: a meta-analysis of prospective randomized trials. METHODS: Pertinent studies were selected from the Medline, Embase, Cancerlit, HealthSTAR and Cochrane Library Databases, references from published articles, and reviews. Twelve prospective randomized trials (9 addressing open cholecystectomy and 3 laparoscopic cholecystectomy) were selected. Conventional meta-analysis according to the DerSimonian and Laird method was used for the pooling of the results. The rate difference (RD) (95% CI) and the number needed to treat (NNT) were used as a measure of the therapeutic effect. RESULTS: Cumulative operative and perioperative mortality and morbidity were 0.9% and 17.8%, respectively, for open cholecystectomy and 0% and 13.1%, respectively, for laparoscopic cholecystectomy. The pooled RD for operative complications in early surgery was 1.37% (95% CI =-3.78% to 6.53%; p= 0.2) for open cholecystectomy and 3.11% (95% CI =-15.10% to 8.87%; p= 0.6) for laparoscopic cholecystectomy. In laparoscopic cholecystectomy the cumulative conversion rate to open cholecystectomy was 21.5%. The pooled RD for conversion rate in early laparoscopic cholecystectomy was -7.99% (95% CI =-18.46% to 2.47%; p= 0.1; NNT = 13). Total hospital stay (mean +/- SD) was significantly shorter in the early surgery group (9.6 +/- 2.5 days vs 17.8 +/- 5.8 days; p < 0.0001). More than 20% of patients referred to delayed surgery fail to respond to conservative management or suffer recurrent cholecystitis in the interval period. CONCLUSIONS: Early operation (open or laparoscopic) does not carry a higher risk of mortality and morbidity compared to delayed operation and should be the preferred surgical approach for patients with acute lithiasic cholecystitis.

Acute Disease↗

Systematic review of the management of atrial fibrillation in patients with heart failure.

AIMS: To systematically review the management of atrial fibrillation (AF) in patients with heart failure. METHODS: Studies investigating the management of AF in patients with heart failure published between 1967 to 1998 were identified using MEDLINE, the Cochrane register and Embase databases. Reference lists from relevant papers and reviews were hand searched for further papers. RESULTS: Eight studies pertaining to acute and twenty-four pertaining to chronic AF were identified. For patients with acute AF ventricular rate control, anticoagulation and treatment of heart failure should be pursued simultaneously before cardioversion is attempted. Digoxin is relatively ineffective at controlling ventricular response and for cardioversion. Intravenous diltiazem is rapidly effective in controlling ventricular rate and limited evidence suggests it is safe. Amiodarone controls ventricular rate rapidly and increases the rate of cardioversion. There are insufficient data to conclude that immediate anti-coagulation, trans-oesophageal echocardiography to exclude atrial thrombi followed by immediate cardioversion is an appropriate strategy. Patients with chronic AF should be anti-coagulated unless contra-indications exist. It is not clear whether the preferred strategy should be cardioversion and maintenance of sinus rhythm with amiodarone or ventricular rate control of AF combined with anticoagulation to improve outcome including symptoms, morbidity and survival. Electrical cardioversion has a high initial success rate but there is also a high risk of early relapse. Amiodarone currently appears the most effective and safest therapy for maintaining sinus rhythm post-cardioversion. Digoxin is fairly ineffective at controlling ventricular rate during exercise. Addition of a beta-blocker reduces ventricular rate and improves symptoms. Whether digoxin is required in addition to beta-blockade for the control of AF in this setting is currently under investigation. If pharmacological therapy is ineffective or not tolerated then atrio-ventricular node ablation and permanent pacemaker implantation should be considered. CONCLUSION: There is a paucity of controlled clinical trial data for the management of AF among patients with heart failure. The interaction between AF and heart failure means that neither can be treated optimally without treating both. Presently treatment should be on a case by case basis.

Acute Disease↗

Mesalamine in the maintenance treatment of Crohn's disease: a meta-analysis adjusted for confounding variables.

BACKGROUND & AIMS: The benefit of mesalamine for maintenance of remission in Crohn's disease is controversial. The aim of this study was to assess the effectiveness of mesalamine in maintaining remission of quiescent Crohn's disease. METHODS: Pertinent randomized clinical trials were selected using MEDLINE (1986-1997) database, reference lists from published articles or reviews. Fifteen randomized, controlled trials of mesalamine maintenance therapy involving a total of 2097 patients were selected. The crude rates of patients with symptomatic relapse in treated and control groups were extracted according to the intention-to-treat method. RESULTS: Therapy with mesalamine significantly reduced the risk of symptomatic relapse (pooled risk difference, -6.3%; 95% confidence interval, -10.4% to -2.1%). The pooled risk difference was significant in the postsurgical setting (-13.1%; 95% confidence interval, -21.8% to -4.5%) but not in the medical setting (-4.7%; 95% confidence interval, -9.6% to 2.8%). Multivariate model predicts that the probability of symptomatic relapse significantly decreases with mesalamine treatment, by increasing proportion of patients with ileal disease, with prolonged disease duration, and with surgically induced remission. CONCLUSIONS: Mesalamine may be recommended for maintaining remission of quiescent Crohn's disease. The benefit is mainly observed in the postsurgical setting, in patients with ileitis and with prolonged disease duration.

Anti-Inflammatory Agents, Non-Steroidal↗

Five years working with the German nosocomial infection surveillance system (Krankenhaus Infektions Surveillance System).

A national surveillance system for nosocomial infections, Krankenhaus Infektions Surveillance System (KISS), was established in Germany as a joint effort by the National Reference Center for Hospital Epidemiology (currently called the National Reference Center for the Surveillance of Nosocomial Infections) and the Robert Koch Institute. To begin with a well-accepted and proven method, surveillance protocols were developed on the basis of the National Nosocomial Infections Surveillance system. Hospitals from all parts of Germany took part voluntarily. There were 4 surveillance components: intensive care departments (227), patients undergoing operation (231 departments), neonatal intensive care departments (23 hospitals), and patients undergoing bone marrow and peripheral blood stem cell transplants (10 hospitals). Five years after the introduction of KISS many hospitals have introduced continuous surveillance activities whereby the various definitions and methods have attained wide acceptance. This has lead to much better understanding and cooperation between clinicians and infection control personnel in preventing nosocomial infections. KISS is considered the national reference database, but continuous evaluation and development of KISS are necessary to react adequately.

Cross Infection↗

Liquid-based cervical cytologic smear study and conventional Papanicolaou smears: a metaanalysis of prospective studies comparing cytologic diagnosis and sample adequacy.

OBJECTIVE: We sought to evaluate the cytologic diagnosis and sample adequacy of the liquid-based cervical cytologic smear (ThinPrep) compared with that of the conventional Papanicolaou smear. STUDY DESIGN: Prospective studies of ThinPrep and conventional Papanicolaou smears were analyzed for cytologic diagnosis and sample adequacy. Computerized databases, references in published studies, and index reviews published in English were used to identify direct-to-vial and split-sample clinical trials of cervical smears performed by conventional and liquid-based techniques. Only published studies that used the Bethesda system nomenclature with clearly documented outcome data were included. Each trial was assessed for the quality of its method, inclusion and exclusion criteria, adequacy of randomization, sampling protocols, definition of outcome, and statistical analyses. RESULTS: Twenty-five studies met inclusion criteria for this review. Odds ratios with 95% confidence intervals were calculated for each outcome. Estimates of odds ratios and risk differences for dichotomous outcomes were calculated by use of random and fixed-effects models. Homogeneity was tested across the studies. Results indicate that the ThinPrep test is as good as or superior to the conventional Papanicolaou smear in diagnosing uterine cervical premalignant abnormalities. Also the ThinPrep test provides improved sample adequacy when compared with the conventional Papanicolaou test. CONCLUSION: The ThinPrep test improved sample adequacy and led to improved diagnosis of low-grade and high-grade squamous intraepithelial lesions. However, there is no difference in the rate of atypical cells of undetermined significance diagnosis between ThinPrep and conventional smear groups. The added cost of ThinPrep cytologic screening and, hence, its cost-effectiveness are not evaluated in this study.

Cytodiagnosis↗

The prevalence of genital Chlamydia trachomatis in Australia 1997-2004: a systematic review.

OBJECTIVES: To determine by systematic review the prevalence of genital chlamydial infection in Australia between 1997 and 2004. METHODS: Electronic literature databases, reference lists, and conference proceedings were searched and health agencies and jurisdictions were contacted for published and unpublished reports. Studies were eligible if they offered a diagnostic nucleic acid amplification test to consecutive individuals presenting during the study period. As a summary measure of the available data, mean prevalence rates, weighted by sample size and irrespective of participant age, were calculated for the population sub-groups. RESULTS: 40 studies of 50 populations and 40,587 individuals met the inclusion criteria, but only one of these was population-based. The use of non-systematic methodologies prevented an assessment of time trends and a statistical comparison of population sub-groups. The mean overall prevalence of genital chlamydial infection was 4.6% (95% CI 4.4-4.8%), reflecting over-sampling of high-risk groups. The mean community-based rates were 7.5% (95% CI 6.4-8.6%) and 8.7% (95% CI 7.9-9.7%) for Indigenous men and women, and 1.5% (95% CI 1.1-1.9%) and 1.4% (95% CI 0.9-2.0%) for non-Indigenous men and women. The overall mean estimates for other groups were 3.3% (95% CI 3.0-3.7%) for female attendees of sexual health and related clinics, 5.6% (95% CI 4.9-6.4%) for adolescents and young adults, 3.3% (95% CI 2.8-3.9%) for sex workers, and 1.6% (95% CI 1.2-2.0%) for urethral infection in men who have sex with men. Clinic-based estimates were generally, although not consistently, higher than community-based estimates. There is no serial population-based data for sexually active young men and women, but the available age-specific rates suggest under-ascertainment by the routine surveillance systems. CONCLUSIONS: The prevalence of genital chlamydial infection in Indigenous Australians and young adults is unacceptably high and quality epidemiological studies are urgently required to supplement the routinely collected national notification data.

Adolescent↗

Sequence of a 189-kb segment of the chromosome of Rhodobacter capsulatus SB1003.

Cosmids from the 1A3-1A10 region of the complete miniset were individually subcloned by using the vector M13 mp18. Sequences of each cosmid were assembled from about 400 DNA fragments generated from the ends of these phage subclones and merged into one 189-kb contig. About 160 ORFs identified by the CodonUse program were subjected to similarity searches. The biological functions of 80 ORFs could be assigned reliably by using the WIT and Magpie genome investigation tools. Eighty percent of these recognizable ORFs were organized in functional clusters, which simplified assignment decisions and increased the strength of the predictions. A set of 26 genes for cobalamin biosynthesis, genes for polyhydroxyalkanoic acid metabolism, DNA replication and recombination, and DNA gyrase were among those identified. Most of the ORFs lacking significant similarity with reference databases also were grouped. There are two large clusters of these ORFs, one located between 45 and 67 kb of the map, and the other between 150 and 183 kb. Nine of the loosely identified ORFs (of 15) of the first of these clusters match ORFs from phages or transposons. The other cluster also has four ORFs of possible phage origin.

Chromosomes, Bacterial↗

Proteomics analysis of the interactome of N-myc downstream regulated gene 1 and its interactions with the androgen response program in prostate cancer cells.

NDRG1 is known to play important roles in both androgen-induced cell differentiation and inhibition of prostate cancer metastasis. However, the proteins associated with NDRG1 function are not fully enumerated. Using coimmunoprecipitation and mass spectrometry analysis, we identified 58 proteins that interact with NDRG1 in prostate cancer cells. These proteins include nuclear proteins, adhesion molecules, endoplasmic reticulum (ER) chaperons, proteasome subunits, and signaling proteins. Integration of our data with protein-protein interaction data from the Human Proteome Reference Database allowed us to build a comprehensive interactome map of NDRG1. This interactome map consists of several modules such as a nuclear module and a cell membrane module; these modules explain the reported versatile functions of NDRG1. We also determined that serine 330 and threonine 366 of NDRG1 were phosphorylated and demonstrated that the phosphorylation of NDRG1 was prominently mediated by protein kinase A (PKA). Further, we showed that NDRG1 directly binds to beta-catenin and E-cadherin. However, the phosphorylation of NDRG1 did not interrupt the binding of NDRG1 to E-cadherin and beta-catenin. Finally, we showed that the inhibition of NDRG1 expression by RNA interference decreased the ER inducible chaperon GRP94 expression, directly proving that NDRG1 is involved in the ER stress response. Intriguingly, we observed that many members of the NDRG1 interactome are androgen-regulated and that the NDRG1 interactome links to the androgen response network through common interactions with beta-catenin and heat shock protein 90. Therefore we overlaid the transcriptomic expression changes in the NDRG1 interactome in response to androgen treatment and built a dual dynamic picture of the NDRG1 interactome in response to androgen. This interactome map provides the first road map for understanding the functions of NDRG1 in cells and its roles in human diseases, such as prostate cancer, which can progress from androgen-dependent curable stages to androgen-independent incurable stages.

Androgens↗

Caries-preventive effect of fissure sealants: a systematic review.

The objectives of this study were to evaluate systematically the evidence of the caries-preventive effect of fissure sealing of occlusal tooth surfaces and to examine factors potentially modifying the effect. The search strategies included electronic databases, reference lists of articles, and selected textbooks. Inclusion criteria were randomized or quasi-randomized clinical trials or controlled clinical trials comparing fissure sealing with no treatment or another preventive treatment in children up to 14 years of age at the start; the outcome measure was caries increment; the diagnostic criteria had been described; and the follow-up time was at least 2 years. Inclusion decisions were taken and grading of the studies was done independently by two of the authors. The main measure of effect was relative risk reduction. Thirteen studies using resin-based or glass ionomer sealant materials were included in the final analysis. The results showed that most studies were performed during the 1970s and a single application had been utilized. The relative caries risk reduction pooled estimate of resin-based sealants on permanent 1st molars was 33% (relative risk = 0.67; CI = 0.55-0.83). The effect depended on retention of the sealant. In conclusion, the review suggests limited evidence that fissure sealing of 1st permanent molars with resin-based materials has a caries-preventive effect. The evidence is incomplete for permanent 2nd molars, premolars and primary molars and for glass ionomer cements. Overall, there remains a need for further trials of high quality, particularly in child populations with a low and a high caries risk, respectively.

Adolescent↗

Professional fluoride varnish treatment for caries control: a systematic review of clinical trials.

The aim of this paper was systematically to evaluate the caries-preventive effect of professional fluoride varnish treatments. A search of the literature for articles published between 1966 and August 2003 was carried out in electronic databases, reference lists of articles, and selected textbooks in accordance with the strategy of the Swedish Council on Technology Assessment in Health Care. Out of 302 identified papers, 24 randomized and controlled clinical trials comparing fluoride varnish with placebo, no active treatment or other fluoride preventive regimens of at least 2 years' study duration were included. The trials that met the inclusion criteria were assessed independently and systematically by at least two reviewers and scored from A to C according to predetermined criteria for methodology and performance. The main outcome measure was the preventive fraction expressed as a percentage. The results displayed limited evidence (evidence level 3) for the caries preventive effect of topical applications of fluoride varnishes in permanent teeth. The average prevented fraction was 30% (0-69%) when compared with untreated controls. Inconclusive evidence (evidence level 4) was found for fluoride varnish treatment in the primary dentition and in adults. This systematic review reinforces the need for future dinical research of high quality, incorporating modern concepts of dinical performance and evaluation to assess dental caries control using professional fluoride varnish.

Adolescent↗

Pooled analysis on the efficacy of the second-line treatment regimens for Helicobacter pylori infection.

BACKGROUND: Although many of the currently available Helicobacter pylori eradication regimens fail to cure 5%-12% of patients, an optimal re-treatment therapy for eradication-failure patients has still not been established. The aim of this study was to examine all reports concerning the efficacy of re-eradication regimens for H. pylori infection, and to establish optimal re-eradication regimens. METHODS: Studies concerning re-eradication regimens were retrieved from the MEDLINE database, reference lists and major congress abstract lists up through December 1999. Data from all selected reports were pooled into several groups depending on second-line or initial therapies. Pooled eradication rates of re-treatment regimens were compared using Fisher's exact test (P < 0.05). RESULTS: Sixteen articles and 24 abstracts with 75 total treatment arms were included in this study. Pooled re-eradication rates by proton-pump inhibitor (PPI)-based dual therapy, PPI-based triple therapy, ranitidine bismuth-based triple therapy and quadruple therapy were 45.8%, 69.8%, 80.2% and 75.8%, respectively. Eradication rates from studies with two new antimicobials added were higher than rates from studies with only one new antimicrobial added (P = 0.0064). CONCLUSION: Ranitidine bismuth-based triple therapies, as well as quadruple therapies, seem to be the most effective re-treatment therapies in all currently undertaken therapies. The strategy of adding two new antimicrobials to previous regimens was also effective in re-eradication therapy.

Abietanes↗

Review of epidemiologic studies of alcohol and prostate cancer: 1971-1996.

Prostate cancer is the most common cancer among American men, with few established risk factors. The association between prostate cancer and alcohol, a potentially modifiable risk factor, has been examined in numerous studies. We systematically reviewed the literature on alcohol and the incidence of prostate cancer by searching for published cohort and case-control studies using computerized databases, references, and experts, by evaluating studies for validity, and by summarizing the results and providing research recommendations. We found compelling evidence for no association between low-to-moderate alcohol consumption and prostate cancer. Most studies, however, did not assess the risk of heavy drinking, where there has been some suggestion of increased risk, or of lifetime patterns of drinking. None of the studies have used genetic markers, nor have they been conducted in populations with known familial risk. Further studies in some populations may be warranted.

Adult↗

NSAID-induced acute phase response is due to increased intestinal permeability and characterized by early and consistent alterations in hepatic gene expression.

Toxicogenomics using a reference database can provide a better understanding and prediction of toxicity, largely by creating biomarkers that tie gene expression to actual pathology events. During the course of building a toxicogenomic database, an observation was made that a number of non-steroidal anti-inflammatory compounds (NSAIDs) at supra-pharmacologic doses induced an acute phase response (APR) and displayed hepatic gene expression patterns similar to that of intravenous lipopolysaccharide (LPS). Since NSAIDs are known to cause injury along the gastrointestinal tract, it has been suggested that NSAIDs increase intestinal permeability, allowing LPS and/or bacteria into the systemic circulation and stimulating an APR detectable in the liver. A short term study was subsequently conducted examining the effects of aspirin, indomethacin, ibuprofen, and rofecoxib to rats and a variety of endpoints were examined that included serum levels of inflammatory cytokines, histologic evaluation, and hepatic gene expression. Both indomethacin and ibuprofen injured the gastrointestinal tract, induced an APR, and increased serum levels of LPS, while rofecoxib and aspirin did not affect the GI tract or induce an APR. In treatments that eventually showed a systemic inflammatory response, hepatic expression of many inflammatory genes was noted as early as 6 hours after treatment well before alterations in traditional clinical pathology markers were detected. This finding led to the creation of a hepatic gene expression biomarker of APR that was effectively shown to be an early identifier of imminent inflammatory injury. In terms of the relative gastrointestinal safety and the NSAIDs studied, an important safety distinction can be made between the presumptive efficacious dose and the APR-inducing dose for indomethacin (1-2-fold), ibuprofen (5-fold), and rofecoxib (approximately 250-fold). Our data support the notion that NSAID-induced intestinal injury results in leakage of commensural bacteria and/or LPS into the circulation, provoking a systemic inflammatory response and that hepatic gene expression-based biomarkers can be used as early and sensitive biomarkers of APR onset.

Acute-Phase Reaction↗

Transitioning from analog to digital audio recording in childhood speech sound disorders.

Few empirical findings or technical guidelines are available on the current transition from analog to digital audio recording in childhood speech sound disorders. Of particular concern in the present context was whether a transition from analog- to digital-based transcription and coding of prosody and voice features might require re-standardizing a reference database for research in childhood speech sound disorders. Two research transcribers with different levels of experience glossed, transcribed, and prosody-voice coded conversational speech samples from eight children with mild to severe speech disorders of unknown origin. The samples were recorded, stored, and played back using representative analog and digital audio systems. Effect sizes calculated for an array of analog versus digital comparisons ranged from negligible to medium, with a trend for participants' speech competency scores to be slightly lower for samples obtained and transcribed using the digital system. We discuss the implications of these and other findings for research and clinical practise.

Analog-Digital Conversion↗