Validation and performance comparison of two carbon isotope ratio methods to control the misuse of androgens in humans.

Carbon isotope ratio of androgens in urine specimens is routinely determined to exclude an abuse of testosterone or testosterone prohormones by athletes. Increasing application of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) in the last years for target and systematic investigations on samples has resulted in the demand for rapid sample throughput as well as high selectivity in the extraction process particularly in the case of conspicuous samples. For that purpose, we present herein the complimentary use of an SPE-based assay and an HPLC fractionation method as a two-stage strategy for the isolation of testosterone metabolites and endogenous reference compounds prior to GC/C/IRMS analyses. Assays validation demonstrated acceptable performance in terms of intermediate precision (range: 0.1-0.4 per thousand) and Bland-Altman analyses revealed no significant bias (0.2 per thousand). For further validation of this two-stage analyses strategy, all the specimens (n=124) collected during a major sport event were processed.

Commentary. The ontogeny of human memory : where are we going ?

In their review, Jabe`s and Nelson provide an update of Nelson's 1995 cognitive neuroscience model of human memory development. Here, we highlight the major changes in perspective after 20 years of advances in our understanding of the neural basis of memory, and advocate the need for more systematic investigations of memory processes across the lifespan, which combine different models and levels of analysis: from genes, to brain to behavior.

Blood, urine and vitreous isopropyl alcohol as biochemical markers in forensic investigations.

Isopropyl alcohol (IPA) is widely used as an industrial solvent and cleaning fluid. After ingestion or absorption, IPA is converted into acetone by alcohol dehydrogenase. However, in ketosis, acetone can be reduced to IPA. The aim of this study was to investigate blood IPA and acetone concentrations in a series of 400 medico-legal autopsies, including cases of diabetic ketoacidosis, hypothermia and alcohol misuse-related deaths, to illustrate the extent of ketosis at the time of death. Vitreous glucose, blood 3-β-hydroxybutyrate (3HB) and acetoacetate (AcAc) concentrations were also determined systematically. Additionally, vitreous and urine IPA, acetone, 3HB and AcAc concentrations as well as other biochemical markers, including glycated hemoglobin and carbohydrate-deficient transferrin (CDT) were also determined in selected cases. The results of this study indicate that ketosis is characterized by the presence of IPA resulting from the acetone metabolism and that IPA can be detected in several substrates. These findings confirm the importance of the systematic determination of IPA and acetone levels that is used to quantify biochemical disturbances and the importance of ketosis at the time of death.

The systematic profiling of false identity documents: method validation and performance evaluation using seizures known to originate from common and different sources

False identity documents constitute a potential powerful source of forensic intelligence because they are essential elements of transnational crime and provide cover for organized crime. In previous work, a systematic profiling method using false documents' visual features has been built within a forensic intelligence model. In the current study, the comparison process and metrics lying at the heart of this profiling method are described and evaluated. This evaluation takes advantage of 347 false identity documents of four different types seized in two countries whose sources were known to be common or different (following police investigations and dismantling of counterfeit factories). Intra-source and inter-sources variations were evaluated through the computation of more than 7500 similarity scores. The profiling method could thus be validated and its performance assessed using two complementary approaches to measuring type I and type II error rates: a binary classification and the computation of likelihood ratios. Very low error rates were measured across the four document types, demonstrating the validity and robustness of the method to link documents to a common source or to differentiate them. These results pave the way for an operational implementation of a systematic profiling process integrated in a developed forensic intelligence model.

Death caused by cardioinhibitory reflex cardiac arrest--a systematic review of cases.

Forensic pathologists often refer to the cardioinhibitory reflex cardiac arrest (CiRCA) following short neck trauma as a mechanism of death. We sought via a systematic review of the literature to identify circumstances under which carotid bifurcation stimulation could lead to death. Two independent reviewers selected case studies or reports from Medline, ISI Web of Knowledge, and Embase. Circumstances and contributory factors were extracted for each case. From the available data, authors independently assessed whether CiRCA was highly probable (no alternative explanation possible), probable (alternative explanation possible), or unlikely (alternative explanation highly probable). A narrative approach was used to define circumstances in which CiRCA remained possible. From the 48 published cases evoking CiRCA as a possible cause of death between 1881 and 2009, 28 were most likely to result of other mechanism of death (i.e., cerebral hypoxia due to carotid compression, mechanical asphyxia, myocardial infarction). CiRCA remained possible for 20 cases (including five based on anecdotal evidence only) with only one case with no alternative explanation other than CiRCA. Our findings support the presumption that reflex cardiac arrhythmia due to carotid bifurcation stimulation cannot provoke death alone. Actual state of knowledge suggests CiRCA might be contributory to death in the presence of drug abuse and/or cardiac pathology, often associated with physical and/or mental excitation.

Use of LIDAR in landslide investigations: A review

This paper presents a short history of the appraisal of laser scanner technologies in geosciences used for imaging relief by high-resolution digital elevation models (HRDEMs) or 3D models. A general overview of light detection and ranging (LIDAR) techniques applied to landslides is given, followed by a review of different applications of LIDAR for landslide, rockfall and debris-flow. These applications are classified as: (1) Detection and characterization of mass movements; (2) Hazard assessment and susceptibility mapping; (3) Modelling; (4) Monitoring. This review emphasizes how LIDARderived HRDEMs can be used to investigate any type of landslides. It is clear that such HRDEMs are not yet a common tool for landslides investigations, but this technique has opened new domains of applications that still have to be developed.

Safety and occlusion rates of surgical treatment of unruptured intracranial aneurysms: a systematic review and meta-analysis of the literature from 1990 to 2011.

BACKGROUND AND PURPOSE: Surgical clipping of unruptured intracranial aneurysms (UIAs) has recently been challenged by the emergence of endovascular treatment. We performed an updated systematic review and meta-analysis on the surgical treatment of UIAs, in an attempt to determine the aneurysm occlusion rates and safety of surgery in the modern era. METHODS: A detailed protocol was developed prior to conducting the review according to the Cochrane Collaboration guidelines. Electronic databases spanning January 1990-April 2011 were searched, complemented by hand searching. Heterogeneity was assessed using I(2), and publication bias with funnel plots. Surgical mortality and morbidity were analysed with weighted random effect models. RESULTS: 60 studies with 9845 patients harbouring 10 845 aneurysms were included. Mortality occurred in 157 patients (1.7%; 99% CI 0.9% to 3.0%; I(2)=82%). Unfavourable outcomes, including death, occurred in 692 patients (6.7%; 99% CI 4.9% to 9.0%; I(2)=85%). Morbidity rates were significantly greater in higher quality studies, and with large or posterior circulation aneurysms. Reported morbidity rates decreased over time. Studies were generally of poor quality; funnel plots showed heterogeneous results and publication bias, and data on aneurysm occlusion rates were scant. CONCLUSIONS: In studies published between 1990 and 2011, clipping of UIAs was associated with 1.7% mortality and 6.7% overall morbidity. The reputed durability of clipping has not been rigorously documented. Due to the quality of the included studies, the available literature cannot properly guide clinical decisions.

PFO closure vs. medical therapy in cryptogenic stroke or transient ischemic attack: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: This study aims to assess whether patent foramen ovale (PFO) closure is superior to medical therapy in preventing recurrence of cryptogenic ischemic stroke or transient ischemic attack (TIA). METHODS: We searched PubMed for randomized trials which compared PFO closure with medical therapy in cryptogenic stroke/TIA using the items: "stroke or cerebrovascular accident or TIA" and "patent foramen ovale or paradoxical embolism" and "trial or study". RESULTS: Among 650 potentially eligible articles, 3 were included including 2303 patients. There was no statistically significant difference between PFO-closure and medical therapy in ischemic stroke recurrence (1.91% vs. 2.94% respectively, OR: 0.64, 95%CI: 0.37-1.10), TIA (2.08% vs. 2.42% respectively, OR: 0.87, 95%CI: 0.50-1.51) and death (0.60% vs. 0.86% respectively, OR: 0.71, 95%CI: 0.28-1.82). In subgroup analysis, there was significant reduction of ischemic strokes in the AMPLATZER PFO Occluder arm vs. medical therapy (1.4% vs. 3.04% respectively, OR: 0.46, 95%CI: 0.21-0.98, relative-risk-reduction: 53.2%, absolute-risk-reduction: 1.6%, number-needed-to-treat: 61.8) but not in the STARFlex device (2.7% vs. 2.8% with medical therapy, OR: 0.93, 95%CI: 0.45-2.11). Compared to medical therapy, the number of patients with new-onset atrial fibrillation (AF) was similar in the AMPLATZER PFO Occluder arm (0.72% vs. 1.28% respectively, OR: 1.81, 95%CI: 0.60-5.42) but higher in the STARFlex device (0.64% vs. 5.14% respectively, OR: 8.30, 95%CI: 2.47-27.84). CONCLUSIONS: This meta-analysis does not support PFO closure for secondary prevention with unselected devices in cryptogenic stroke/TIA. In subgroup analysis, selected closure devices may be superior to medical therapy without increasing the risk of new-onset AF, however. This observation should be confirmed in further trials using inclusion criteria for patients with high likelihood of PFO-related stroke recurrence.

Systematic identification of genomic markers of drug sensitivity in cancer cells.

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Alcohol Brief Intervention in Primary Care: A Systematic Review

BACKGROUND: The purpose of the present review was to evaluate the evidence of the effectiveness of brief interventions aimed at reducing chronic alcohol use and harm related to alcohol consumption, conducted among individuals actively attending primary care but who were not seeking help for alcohol problems. METHODS: Randomised trials reporting at-least one outcome related to alcohol consumption and conducted in outpatients who were actively attending primary care centre or provider were selected using Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, ISI Web of Science, ETOH database, and bibliographies of the retrieved references and previous reviews. Selection and data abstraction were performed independently and in duplicate. We assessed validity of the studies and performed a meta-analysis for studies reporting alcohol consumption at 6 or 12 months follow up. RESULTS: We included 24 reports, reporting results of 19 trials and including 5,639 individuals. Seventeen trials reported a measure of alcohol consumption, eight reporting a significant effect of intervention. The meta-analysis showed a mean pooled difference of -41 (95% CI: −54; −28) g of pure ethanol per week in favour of brief intervention group. Evidences for other outcomes (laboratory values, health related quality of life, morbidity and mortality, health care utilisation) were inconclusive. CONCLUSION: Our systematic review indicated that brief intervention might be effective for both men and women in reducing alcohol consumption compared to a controlled intervention, in a primary health care population. The meta-analysis confirmed the reduction in alcohol consumption at 6 and 12 month. Further research should precise the components of effectiveness of brief intervention and the evidence of effects on morbidity, mortality, and quality of life related outcomes.

Transcriptional response to cardiac injury in the zebrafish: systematic identification of genes with highly concordant activity across in vivo models.

BACKGROUND: Zebrafish is a clinically-relevant model of heart regeneration. Unlike mammals, it has a remarkable heart repair capacity after injury, and promises novel translational applications. Amputation and cryoinjury models are key research tools for understanding injury response and regeneration in vivo. An understanding of the transcriptional responses following injury is needed to identify key players of heart tissue repair, as well as potential targets for boosting this property in humans. RESULTS: We investigated amputation and cryoinjury in vivo models of heart damage in the zebrafish through unbiased, integrative analyses of independent molecular datasets. To detect genes with potential biological roles, we derived computational prediction models with microarray data from heart amputation experiments. We focused on a top-ranked set of genes highly activated in the early post-injury stage, whose activity was further verified in independent microarray datasets. Next, we performed independent validations of expression responses with qPCR in a cryoinjury model. Across in vivo models, the top candidates showed highly concordant responses at 1 and 3 days post-injury, which highlights the predictive power of our analysis strategies and the possible biological relevance of these genes. Top candidates are significantly involved in cell fate specification and differentiation, and include heart failure markers such as periostin, as well as potential new targets for heart regeneration. For example, ptgis and ca2 were overexpressed, while usp2a, a regulator of the p53 pathway, was down-regulated in our in vivo models. Interestingly, a high activity of ptgis and ca2 has been previously observed in failing hearts from rats and humans. CONCLUSIONS: We identified genes with potential critical roles in the response to cardiac damage in the zebrafish. Their transcriptional activities are reproducible in different in vivo models of cardiac injury.

β-Glucan antigenemia assay for the diagnosis of invasive fungal infections in patients with hematological malignancies: a systematic review and meta-analysis of cohort studies from the Third European Conference on Infections in Leukemia (ECIL-3).

BACKGROUND: Invasive fungal infections (IFIs) are life-threatening complications in patients with hemato-oncological malignancies, and early diagnosis is crucial for outcome. The compound 1,3-β-D-glucan (BG), a cell wall component of most fungal species, can be detected in blood during IFI. Four commercial BG antigenemia assays are available (Fungitell, Fungitec-G, Wako, and Maruha). This meta-analysis from the Third European Conference on Infections in Leukemia (ECIL-3) assessed the performance of BG assays for the diagnosis of IFI in hemato-oncological patients. METHODS: Studies reporting the performance of BG antigenemia assays for the diagnosis of IFI (European Organization for Research and Treatment of Cancer and Mycoses Study Group criteria) in hemato-oncological patients were identified. The analysis was focused on high-quality cohort studies with exclusion of case-control studies. Meta-analysis was performed by conventional meta-analytical pooling and bivariate analysis. RESULTS: Six cohort studies were included (1771 adult patients with 414 IFIs of which 215 were proven or probable). Similar performance was observed among the different BG assays. For the cutoff recommended by the manufacturer, the diagnostic performance of the BG assay in proven or probable IFI was better with 2 consecutive positive test results (diagnostic odds ratio for 2 consecutive vs one single positive results, 111.8 [95% confidence interval {CI}, 38.6-324.1] vs 16.3 [95% CI, 6.5-40.8], respectively; heterogeneity index for 2 consecutive vs one single positive results, 0% vs 72.6%, respectively). For 2 consecutive tests, sensitivity and specificity were 49.6% (95% CI, 34.0%-65.3%) and 98.9% (95% CI, 97.4%-99.5%), respectively. Estimated positive and negative predictive values for an IFI prevalence of 10% were 83.5% and 94.6%, respectively. CONCLUSIONS: Different BG assays have similar accuracy for the diagnosis of IFI in hemato-oncological patients. Two consecutive positive antigenemia assays have very high specificity, positive predictive value, and negative predictive value. Because sensitivity is low, the test needs to be combined with clinical, radiological, and microbiological findings.

Clinician characteristics, communication, and patient outcome in oncology: a systematic review.

OBJECTIVE: The aim of this study was to review the literature on clinician characteristics influencing patient-clinician communication or patient outcome in oncology. METHODS: Studies investigating the association of clinician characteristics with quality of communication and with outcome for adult cancer patients were systematically searched in MEDLINE, PSYINFO, PUBMED, EMBASE, CINHAL, Web of Science and The Cochrane Library up to November 2012. We used the preferred reporting items for systematic reviews and meta-analyses statement to guide our review. Articles were extracted independently by two of the authors using predefined criteria. RESULTS: Twenty seven articles met the inclusion criteria. Clinician characteristics included a variety of sociodemographic, relational, and personal characteristics. A positive impact on quality of communication and/or patient outcome was reported for communication skills training, an external locus of control, empathy, a socioemotional approach, shared decision-making style, higher anxiety, and defensiveness. A negative impact was reported for increased level of fatigue and burnout and expression of worry. Professional experience of clinicians was not related to communication and/or to patient outcome, and divergent results were reported for clinician gender, age, stress, posture, and confidence or self-efficacy. CONCLUSIONS: Various clinician characteristics have different effects on quality of communication and/or patient outcome. Research is needed to investigate the pathways leading to effective communication between clinicians and patients. Copyright © 2013 John Wiley & Sons, Ltd.