New perspectives in the use of ink evidence in forensic science : part III : operational applications and evaluation

The research reported in this series of article aimed at (1) automating the search of questioned ink specimens in ink reference collections and (2) at evaluating the strength of ink evidence in a transparent and balanced manner. These aims require that ink samples are analysed in an accurate and reproducible way and that they are compared in an objective and automated way. This latter requirement is due to the large number of comparisons that are necessary in both scenarios. A research programme was designed to (a) develop a standard methodology for analysing ink samples in a reproducible way, (b) comparing automatically and objectively ink samples and (c) evaluate the proposed methodology in forensic contexts. This report focuses on the last of the three stages of the research programme. The calibration and acquisition process and the mathematical comparison algorithms were described in previous papers [C. Neumann, P. Margot, New perspectives in the use of ink evidence in forensic science-Part I: Development of a quality assurance process for forensic ink analysis by HPTLC, Forensic Sci. Int. 185 (2009) 29-37; C. Neumann, P. Margot, New perspectives in the use of ink evidence in forensic science-Part II: Development and testing of mathematical algorithms for the automatic comparison of ink samples analysed by HPTLC, Forensic Sci. Int. 185 (2009) 38-50]. In this paper, the benefits and challenges of the proposed concepts are tested in two forensic contexts: (1) ink identification and (2) ink evidential value assessment. The results show that different algorithms are better suited for different tasks. This research shows that it is possible to build digital ink libraries using the most commonly used ink analytical technique, i.e. high-performance thin layer chromatography, despite its reputation of lacking reproducibility. More importantly, it is possible to assign evidential value to ink evidence in a transparent way using a probabilistic model. It is therefore possible to move away from the traditional subjective approach, which is entirely based on experts' opinion, and which is usually not very informative. While there is room for the improvement, this report demonstrates the significant gains obtained over the traditional subjective approach for the search of ink specimens in ink databases, and the interpretation of their evidential value.

Clinically assessed consequences of workplace physical violence

OBJECTIVES: To assess consequences of physical violence at work and identify their predictors. METHODS: Among the patients in a medicolegal consultation from 2007 to 2010, the subsample of workplace violence victims (n = 185) was identified and contacted again in average 30 months after the assault. Eighty-six victims (47 %) participated. Ordinal logistic regression analyses assessed the effect of 9 potential risk factors on physical, psychological and work consequences summarized in a severity score (0-9). RESULTS: Severity score distribution was as follows: 4+: 14 %; 1-3: 42 %; and 0: 44 %. Initial psychological distress resulting from the violence was a strong predictor (p < 0.001) of the severity score both on work and long-term psychological consequences. Gender and age did not reach significant levels in multivariable analyses even though female victims had overall more severe consequences. Unexpectedly, only among workers whose jobs implied high awareness of the risk of violence, first-time violence was associated with long-term psychological and physical consequences (p = 0.004). Among the factors assessed at follow-up, perceived lack of employers' support or absence of employer was associated with higher values on the severity score. The seven other assessed factors (initial physical injuries; previous experience of violence; preexisting health problems; working alone; internal violence; lack of support from colleagues; and lack of support from family or friends) were not significantly associated with the severity score. CONCLUSIONS: Being a victim of workplace violence can result in long-term consequences on health and employment, their severity increases with the seriousness of initial psychological distress. Support from the employer can help prevent negative outcomes.

Intrahepatic mRNA levels of SOCS1 and SOCS3 are associated with cirrhosis but do not predict virological response to therapy in chronic hepatitis C.

BACKGROUND: Antiviral treatment of chronic hepatitis C is not invariably successful, costly and associated with serious side-effects, and therefore should be indicated only when the chances of benefitting patients exceed the potential risks. The suppressor of cytokine signalling (SOCS) family members have been suggested to affect the rate of virological response to therapy, but the published evidence is conflicting. METHODS: We measured the intrahepatic SOCS1, SOCS3 and SOCS7 mRNA levels in 107 chronic hepatitis C patients and assessed their clinical and histological correlates with the virological response to therapy and with some factors known for affecting treatment outcome. RESULTS: By multivariate analysis, SOCS1, SOCS3 and SOCS7 mRNA levels were not associated with rapid or sustained virological response. Similarly, no association was found between the levels of any intrahepatic SOCS mRNA and those of the homeostasis model assessment of insulin resistance. Conversely, SOCS1 (OR 2.185, 95% CI 1.223-3.906, P=0.0083) and SOCS3 (OR 40.601, 95% CI 2.357-699.25, P=0.0108) mRNA level (but not SOCS7), together with age (OR 1.156, 95% CI 1.049-1.275, P=0.0036), were independently associated with cirrhosis. CONCLUSIONS: Intrahepatic SOCS1, SOCS3 and SOCS7 mRNA levels do not predict virological response to therapy in chronic hepatitis C. The association between SOCS1, SOCS3 and cirrhosis warrants further study.

Hyponatremia and short-term outcomes in patients with acute pulmonary embolism

BACKGROUND: Hyponatremia, a marker of neurohormonal activation, is associated with poor outcomes in acute cardiorespiratory diseases such as myocardial infarction, right and left ventricular heart failure, and pneumonia. The prognostic value of hyponatremia in patients with acute pulmonary embolism (PE) is unknown. We sought to assess whether hyponatremia at presentation was associated with mortality and hospital readmission in patients hospitalized with PE. METHODS: We studied patient discharges with a primary diagnosis of PE from 185 acute care hospitals in Pennsylvania (1/2000-11/2002). We defined hyponatremia as a serum sodium level ≤135 mmol/l, measured at the time of patient presentation. The study outcomes were 30-day all-cause mortality and hospital readmission. We used random-intercept logistic regression to examine the association between hyponatremia and mortality. We adjusted for baseline patient (race, insurance, severity of illness using the Pulmonary Embolism Severity Index) and hospital characteristics (region, hospital size and teaching status). We used the same approach to examine the association between hyponatremia and readmission among patients who were discharged alive. RESULTS: Among 13,728 patient discharges with PE, 2907 (21.1%) had hyponatremia at the time of presentation. Patients with hyponatremia were older (P<0.001) and more likely to have a history of cancer (P<0.001), heart failure (P<0.001), or chronic lung disease (P=0.002) than patients without hyponatremia. Patients with hyponatremia had a higher unadjusted cumulative 30-day mortality (15.2% vs 8.0%;P<0.001) and readmission rate (15.9% vs 11.8%; P< 0.001) than patients without hyponatremia (Figure). After adjustment for race, insurance, severity of illness, and hospital factors, hyponatremia was associated with a significantly greater odds of death (OR 1.71, 95% CI: 1.50-1.95) and hospital readmission (OR 1.29, 95% CI: 1.14-1.46). CONCLUSIONS: In this large, statewide sample of unselected patients with acute PE, hyponatremia was relatively common and was an independent predictor of short-term mortality and hospital readmission. Given that sodium is a low-cost, easily available laboratory parameter, it may be potentially useful in risk-stratifying patients with PE.

L'entrepreneur schumpétérien est-il surhumain?

Bon nombre de commentateurs admettent l'influence de nietzsche dans la conception schumpétérienne de l'entrepreneur. mais, de notre point de vue, cette influence est sou- vent traitée exclusivement dans le contexte historique et dans une version très réduc- trice de l'entrepreneur. nous avançons que ce dernier gagnerait à se lire sous un angle philosophique, en particulier à travers une interprétation nietzschéenne axée sur la volonté de puissance, même si, évidemment, schumpeter n'a pas voulu aller si loin. Abstract: Most of Schumpeter's commentators admit Nietzsche's influence on the Schumpeterian conception of the entrepreneur. Nevertheless, from our point of view, this influence is often treated in the historical context and in a very limited definition of the entrepreneur. In this article, we argue that the latter could be interpreted from a philosophical standpoint. Although Schumpeter has not aimed to go that far, we suggest an interpretation based on Nietzschean will to power.

Ablation of human colon carcinoma in nude mice by 131I-labeled monoclonal anti-carcinoembryonic antigen antibody F(ab')2 fragments.

Pooled F(ab')2 fragments of three MAbs against distinct epitopes of carcinoembryonic antigen (CEA) were used for radioimmunotherapy of nude mice bearing a subcutaneous human colon carcinoma xenograft. 9-10 d after transplantation when tumor nodules were in exponential growth, 36 mice were treated by intravenous injection of different amounts of 131I-labeled MAb F(ab')2. All 14 mice injected with a single dose of 2,200 (n = 10) or 2,800 microCi (n = 4) showed complete tumor remission. 8 of the 10 mice treated with 2,200 microCi survived in good health for 1 yr when they were killed and shown to be tumor free. Four of nine other mice treated with four fractionated doses of 400 microCi showed no tumor relapse for more than 9 mo. In contrast, all 15 mice injected with 1,600-3,000 microCi 131I-control IgG F(ab')2 showed tumor growth retardation of only 1-4 wk, and 15 of 16 mice injected with unlabeled anti-CEA MAb F(ab')2 showed unmodified tumor progression as compared with untreated mice. From tissue radioactivity distributions it was calculated that by an injection of 2,200 microCi 131I-MAb F(ab')2 a mean dose of 8,335 rad was selectively delivered to the tumor, while the tissue-absorbed radiation doses for the normal organs were: peripheral blood, 2,093; stomach, 1,668; kidney, 1,289; lung, 1,185; liver, 617; spleen, 501; small intestine, 427; large intestine, 367; bone, 337; and muscle, 198. These treatments were well tolerated since out of 19 mice with complete tumor remission only 4 required bone marrow transplantation and 17 were in good health for 6-12 mo of observation. The results demonstrate the selective destruction of established human colon carcinoma transplants by intravenous injection of either single or fractionated doses of 131I-MAb F(ab')2.

Liver, gastrointestinal and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: Results from the PRECISION V randomized trial : B-240

Purpose: To evaluate the toxicity focussing on hepatic, gastrointestinal and cardiac parameters following PRECISION TACE with DC Bead? versus conventional transarterial chemoembolization (cTACE) in the treatment of intermediate-stage hepatocellular carcinoma (HCC). Methods and Materials: This prospective, randomized, multicentre study was conducted under best practice trial management and authorized by local institutional review boards. Informed consent was obtained. 212 patients (185 men/27 women; mean: 67 years) were randomized to be treated with DC Beads? or cTACE. The majority of both groups presented in a more advanced stage. Safety was measured by rate of adverse events (South West Oncology Group criteria) and changes in laboratory parameters. Cardiotoxicity was assessed by means of left ventricular ejection fraction (LVEF) in MRI or echocardiography. The results of the two groups were compared using the chi-square test and Student`s t-test. Results: Mean maximum alanine transaminase increase in the DC Bead group was 50% in the cTACE group (p < 0.001) and 59% for aspartate transaminase (p < 0.001). For bilirubin, mean increase was 5.30±15.13 vs. 13.53±73.89 µmol/L. Concerning gastrointestinal disorders, 120 adverse events (AEs) occurred in 57/93 (61.3%) patients in the DC Bead group vs. 114 in 49/108 (45.4%) in cTACE. Concerning hepatobiliary disorders, serious AEs occurred in 8/93 (8.6%) vs. 11/108 (10.2%) patients. LVEF showed an increase in the DC Bead group by +2.7±10.1 percentage points and a small decrease by -1.5±7.6 in the cTACE group, p=0.018. Conclusion: PRECISION TACE is safe, even in more advanced HCC patients. Serious liver and cardiac toxicity were significantly lower in the DC Bead group.

'Comfort Me With Apples': Ambivalent Allusion in Paradise Lost

Paradise Lost can be read on various levels, some of which challenge or even contradict others. The main, explicit narrative from Genesis chapters 2 and 3 is shadowed by many other related stories. Some of these buried tales question or subvert the values made explicit in the dominant narrative. An attentive reader needs to be alert to the ways in which such references introduce teasing complexities. The approach of Satan to Eve in the ninth book of Paradise Lost is loaded in just that way with allusion to the literature of Greece and Rome. The poem recovers for this long and intricately constructed passage the weight of classical reference, especially in similes, that it had during the first Satanic books. Gardens, both classical and biblical, disguised or transformed serpents, and the weight of allusions that Eve is required to bear, all threaten to undermine the meanings of the overt narrative. The narrator has difficulty rescuing Eve from the allusions she attracts, or the many stories told about her.

Neurologie [Therapeutic advances in neurology].

The neurology field has been greatly improved in 2008. The therapeutic window of intravenous thrombolysis for acute ischemic stoke is extended to 4 h 30. New studies show that the clinical progression of Parkinson's disease might be slowed by some medication. Deep brain stimulation may be beneficial early in the course of the disease. Tysabri and Fingolimod in multiple sclerosis are discussed. The pharmacopoeia for epilepsy is in constant development with new products recently released in Switzerland. CGRP receptor antagonists are about to be launched as a promising acute migraine treatment. The pharmacological approach in amyotrophic lateral sclerosis patients might be improved according to research results.

Does change talk during brief motivational interventions with young men predict change in alcohol use?

Client change talk (CT) during motivational interviewing and brief motivational interventions (BMIs) have been described as predictors of behavior change, but these links have not been clearly evaluated in research on young people. Within 127 BMIs with 20-year-old men with at-risk alcohol consumption, each CT utterance was categorized and given a strength rating using the Motivational Interviewing Skill Code 2.1. Several ways of categorizing and measuring CT were tested using stepwise regression procedures. Overall CT measures were not significantly related to changes in drinking at 6-month follow-up. Regarding CT sub-dimensions, the frequency of ability/desire/need to change and of ability/desire/need not to change, as well as the average strength of ability/desire/need, predicted significant change in the expected direction. CT length was not significantly linked to outcome. The frequency and strength with which some CT sub-dimensions are expressed during BMI seemed to be important predictors of change in drinking among young men and might thus be especially important for clinicians to notice.

The Individualized Genetic Barrier Predicts Treatment Response in a Large Cohort of HIV-1 Infected Patients.

The success of combination antiretroviral therapy is limited by the evolutionary escape dynamics of HIV-1. We used Isotonic Conjunctive Bayesian Networks (I-CBNs), a class of probabilistic graphical models, to describe this process. We employed partial order constraints among viral resistance mutations, which give rise to a limited set of mutational pathways, and we modeled phenotypic drug resistance as monotonically increasing along any escape pathway. Using this model, the individualized genetic barrier (IGB) to each drug is derived as the probability of the virus not acquiring additional mutations that confer resistance. Drug-specific IGBs were combined to obtain the IGB to an entire regimen, which quantifies the virus' genetic potential for developing drug resistance under combination therapy. The IGB was tested as a predictor of therapeutic outcome using between 2,185 and 2,631 treatment change episodes of subtype B infected patients from the Swiss HIV Cohort Study Database, a large observational cohort. Using logistic regression, significant univariate predictors included most of the 18 drugs and single-drug IGBs, the IGB to the entire regimen, the expert rules-based genotypic susceptibility score (GSS), several individual mutations, and the peak viral load before treatment change. In the multivariate analysis, the only genotype-derived variables that remained significantly associated with virological success were GSS and, with 10-fold stronger association, IGB to regimen. When predicting suppression of viral load below 400 cps/ml, IGB outperformed GSS and also improved GSS-containing predictors significantly, but the difference was not significant for suppression below 50 cps/ml. Thus, the IGB to regimen is a novel data-derived predictor of treatment outcome that has potential to improve the interpretation of genotypic drug resistance tests.

Etude des modèles de Whittle markoviens probabilisés

Etude des modèles de Whittle markoviens probabilisés Résumé Le modèle de Whittle markovien probabilisé est un modèle de champ spatial autorégressif simultané d'ordre 1 qui exprime simultanément chaque variable du champ comme une moyenne pondérée aléatoire des variables adjacentes du champ, amortie d'un coefficient multiplicatif ρ, et additionnée d'un terme d'erreur (qui est une variable gaussienne homoscédastique spatialement indépendante, non mesurable directement). Dans notre cas, la moyenne pondérée est une moyenne arithmétique qui est aléatoire du fait de deux conditions : (a) deux variables sont adjacentes (au sens d'un graphe) avec une probabilité 1 − p si la distance qui les sépare est inférieure à un certain seuil, (b) il n'y a pas d'adjacence pour des distances au-dessus de ce seuil. Ces conditions déterminent un modèle d'adjacence (ou modèle de connexité) du champ spatial. Un modèle de Whittle markovien probabilisé aux conditions où p = 0 donne un modèle de Whittle classique qui est plus familier en géographie, économétrie spatiale, écologie, sociologie, etc. et dont ρ est le coefficient d'autorégression. Notre modèle est donc une forme probabilisée au niveau de la connexité du champ de la forme des modèles de Whittle classiques, amenant une description innovante de l'autocorrélation spatiale. Nous commençons par décrire notre modèle spatial en montrant les effets de la complexité introduite par le modèle de connexité sur le pattern de variances et la corrélation spatiale du champ. Nous étudions ensuite la problématique de l'estimation du coefficent d'autorégression ρ pour lequel au préalable nous effectuons une analyse approfondie de son information au sens de Fisher et de Kullback-Leibler. Nous montrons qu'un estimateur non biaisé efficace de ρ possède une efficacité qui varie en fonction du paramètre p, généralement de manière non monotone, et de la structure du réseau d'adjacences. Dans le cas où la connexité du champ est non observée, nous montrons qu'une mauvaise spécification de l'estimateur de maximum de vraisemblance de ρ peut biaiser celui-ci en fonction de p. Nous proposons dans ce contexte d'autres voies pour estimer ρ. Pour finir, nous étudions la puissance des tests de significativité de ρ pour lesquels les statistiques de test sont des variantes classiques du I de Moran (test de Cliff-Ord) et du I de Moran maximal (en s'inspirant de la méthode de Kooijman). Nous observons la variation de puissance en fonction du paramètre p et du coefficient ρ, montrant par cette voie la dualité de l'autocorrélation spatiale entre intensité et connectivité dans le contexte des modèles autorégressifs

Impact of enterococcal colonization and infection in solid organ transplantation recipients from the Swiss Transplant Cohort Study.

BACKGROUND: The burden of enterococcal infections has increased over the last decades with vancomycin-resistant enterococci (VRE) being a major health problem. Solid organ transplantation is considered as a risk factor. However, little is known about the relevance of enterococci in solid organ transplantation recipients in areas with a low VRE prevalence. METHODS: We examined the epidemiology of enterococcal events in patients followed in the Swiss Transplant Cohort Study between May 2008 and September 2011 and analyzed risk factors for infection, aminopenicillin resistance, treatment, and outcome. RESULTS: Of the 1234 patients, 255 (20.7%) suffered from 392 enterococcal events (185 [47.2%] infections, 205 [52.3%] colonizations, and 2 events with missing clinical information). Only 2 isolates were VRE. The highest infection rates were found early after liver transplantation (0.24/person-year) consisting in 58.6% of Enterococcus faecium. The highest colonization rates were documented in lung transplant recipients (0.33/person-year), with 46.5% E. faecium. Age, prophylaxis with a betalactam antibiotic, and liver transplantation were significantly associated with infection. Previous antibiotic treatment, intensive care unit stay, and lung transplantation were associated with aminopenicillin resistance. Only 4/205 (2%) colonization events led to an infection. Adequate treatment did not affect microbiological clearance rates. Overall mortality was 8%; no deaths were attributable to enterococcal events. CONCLUSIONS: Enterococcal colonizations and infections are frequent in transplant recipients. Progression from colonization to infection is rare. Therefore, antibiotic treatment should be used restrictively in colonization. No increased mortality because of enterococcal infection was noted.