Influence of temperature and relative humidity on patterns formed in dried plasma and serum droplets

In the present methodological study, we investigated the influence of different evaporation conditions upon patterns formed in desiccated plasma and serum droplets; furthermore, we determined the potential of such patterns to distinguish between four donors. Our results show that the development of different pattern features strongly depended on relative humidity: lower relative humidity triggered the formation of cracks, whereas higher relative humidity favored the development of inner crystalline structures. Settings that allowed for the best donor differentiation and at the same time showed high stability of the experimental system were 24.5 ◦C /15% rH and 30.5 ◦C /45% rH for plasma and 30.5 ◦C /15% rH and 36.6 ◦C /45% rH for serum droplets. The results suggest that for the development of diagnostic tests based on pattern formation in evaporating plasma and serum droplets the choice of right evaporation conditions may influence the experimental system stability as also the test accuracy

Taxane-Induced Neuropathy and Its Ocular Effects—A Longitudinal Follow-up Study in Breast Cancer Patients

A common severe neurotoxic side effect of breast cancer (BC) therapy is chemotherapy-induced peripheral neuropathy (CIPN) and intervention is highly needed for the detection, prevention, and treatment of CIPN at an early stage. As the eye is susceptible to neurotoxic stimuli, the present study aims to determine whether CIPN signs in paclitaxel-treated BC patients correlate with ocular changes by applying advanced non-invasive biophotonic in vivo imaging. Patients (n = 14, 10 controls) underwent monitoring sessions after diagnosis, during, and after therapy (T0-T3). Monitoring sessions included general anamnesis, assessment of their quality of life, neurological scores, ophthalmological status, macular optical coherence tomography (OCT), and imaging of their subbasal nerve plexus (SNP) by large-area confocal laser-scanning microscopy (CLSM). At T0, no significant differences were detected between patients and controls. During treatment, patients’ scores significantly changed while the greatest differences were found between T0 and T3. None of the patients developed severe CIPN but retinal thickenings could be detected. CLSM revealed large SNP mosaics with identical areas while corneal nerves remained stable. The study represents the first longitudinal study combining oncological examinations with advanced biophotonic imaging techniques, demonstrating a powerful tool for the objective assessment of the severity of neurotoxic events with ocular structures acting as potential biomarkers

Comprehensive genomic profiles of small cell lung cancer

We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer

Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older. Methods Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health. Findings Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week. Interpretation Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.Peer reviewe

Monitoring quality and coverage of harm reduction services for people who use drugs: a consensus study.

BACKGROUND AND AIMS: Despite advances in our knowledge of effective services for people who use drugs over the last decades globally, coverage remains poor in most countries, while quality is often unknown. This paper aims to discuss the historical development of successful epidemiological indicators and to present a framework for extending them with additional indicators of coverage and quality of harm reduction services, for monitoring and evaluation at international, national or subnational levels. The ultimate aim is to improve these services in order to reduce health and social problems among people who use drugs, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection, crime and legal problems, overdose (death) and other morbidity and mortality. METHODS AND RESULTS: The framework was developed collaboratively using consensus methods involving nominal group meetings, review of existing quality standards, repeated email commenting rounds and qualitative analysis of opinions/experiences from a broad range of professionals/experts, including members of civil society and organisations representing people who use drugs. Twelve priority candidate indicators are proposed for opioid agonist therapy (OAT), needle and syringe programmes (NSP) and generic cross-cutting aspects of harm reduction (and potentially other drug) services. Under the specific OAT indicators, priority indicators included 'coverage', 'waiting list time', 'dosage' and 'availability in prisons'. For the specific NSP indicators, the priority indicators included 'coverage', 'number of needles/syringes distributed/collected', 'provision of other drug use paraphernalia' and 'availability in prisons'. Among the generic or cross-cutting indicators the priority indicators were 'infectious diseases counselling and care', 'take away naloxone', 'information on safe use/sex' and 'condoms'. We discuss conditions for the successful development of the suggested indicators and constraints (e.g. funding, ideology). We propose conducting a pilot study to test the feasibility and applicability of the proposed indicators before their scaling up and routine implementation, to evaluate their effectiveness in comparing service coverage and quality across countries. CONCLUSIONS: The establishment of an improved set of validated and internationally agreed upon best practice indicators for monitoring harm reduction service will provide a structural basis for public health and epidemiological studies and support evidence and human rights-based health policies, services and interventions

Evaluation und Anpassung methodologischer Instrumente für eine wirkungsvolle hochschuldidaktische Beratung

Cet article s’intéresse à l’impact des conseillers pédagogiques dans l’enseignement supérieur en se focalisant sur la méthodologie de l’évaluation de la portée de leurs actions. Dans un premier temps, des étapes, critères et indicateurs utiles lors d’une telle évaluation ont été identifiés à partir de modèles existants. Mis à l’épreuve au travers d’une démarche d’auto- et hétéro-évaluation d’actions représentatives des activités des conseillers, les résultats de cette étape ont été soumis ensuite à l’avis d’experts rassemblés à l’occasion d’une rencontre de conseillers pédagogiques. Celle-ci a servi de cadre pour l’analyse critique et l’adaptation d’outils utiles à l’évaluation de la portée de leurs actions. Cette réflexion a mis en lumière la complexité de la démarche d’évaluation de la portée de leurs missions ainsi que ses enjeux. L’article propose en résultat des outils directement utilisables. (DIPF/Orig.)Dieser Artikel befasst sich mit dem Einfluss von Lehrberatern und –beraterinnen im Universitätsbetrieb. Er richtet seinen Fokus auf die Methodologie der Beurteilung der Tragweite von deren Tätigkeit. In einem ersten Schritt wurden mit Hilfe bereits bestehender Modelle Etappen, Kriterien und nützliche Indikatoren identifiziert. Die Ergebnisse dieses Schrittes wurden einer Eigen- und Fremdüberprüfung in Bezug auf repräsentative Tätigkeiten von Lehrberatern und -beraterinnen unterzogen; anschliessend wurden sie anlässlich einer Tagung von Lehrberatern und -beraterinnen diesen Experten zur Beurteilung vorgelegt. Deren Beurteilung diente als Rahmen für die kritische Analyse und allfällige Anpassung der Werkzeuge zur Beurteilung der Tragweite der Tätigkeit von Lehrberatern und -beraterinnen, und brachte insgesamt die Komplexität dieses Beurteilungsprozesses und die daraus folgenden Herausforderungen zum Vorschein. Der Artikel schlägt als Endresultat unmittelbar verwendbare Werkzeuge und Methoden vor. (DIPF/Orig.

Évaluer la portée des actions des conseillers pédagogiques dans l’enseignement supérieur: mise à l’épreuve et adaptation d’outils méthodologiques

Cet article s’intéresse à l’impact des conseillers pédagogiques dans l’enseignement supérieur en se focalisant sur la méthodologie de l’évaluation de la portée de leurs actions. Dans un premier temps, des étapes, critères et indicateurs utiles lors d’une telle évaluation ont été identifiés à partir de modèles existants. Mis à l’épreuve au travers d’une démarche d’auto- et hétéro-évaluation d’actions représentatives des activités des conseillers, les résultats de cette étape ont été soumis ensuite à l’avis d’experts rassemblés à l’occasion d’une rencontre de conseillers pédagogiques. Celle-ci a servi de cadre pour l’analyse critique et l’adaptation d’outils utiles à l’évaluation de la portée de leurs actions. Cette réflexion a mis en lumière la complexité de la démarche d’évaluation de la portée de leurs missions ainsi que ses enjeux. L’article propose en résultat des outils directement utilisables

Taxane-Induced Neuropathy and Its Ocular Effects—A Longitudinal Follow-up Study in Breast Cancer Patients

A common severe neurotoxic side effect of breast cancer (BC) therapy is chemotherapy-induced peripheral neuropathy (CIPN) and intervention is highly needed for the detection, prevention, and treatment of CIPN at an early stage. As the eye is susceptible to neurotoxic stimuli, the present study aims to determine whether CIPN signs in paclitaxel-treated BC patients correlate with ocular changes by applying advanced non-invasive biophotonic in vivo imaging. Patients (n = 14, 10 controls) underwent monitoring sessions after diagnosis, during, and after therapy (T0-T3). Monitoring sessions included general anamnesis, assessment of their quality of life, neurological scores, ophthalmological status, macular optical coherence tomography (OCT), and imaging of their subbasal nerve plexus (SNP) by large-area confocal laser-scanning microscopy (CLSM). At T0, no significant differences were detected between patients and controls. During treatment, patients’ scores significantly changed while the greatest differences were found between T0 and T3. None of the patients developed severe CIPN but retinal thickenings could be detected. CLSM revealed large SNP mosaics with identical areas while corneal nerves remained stable. The study represents the first longitudinal study combining oncological examinations with advanced biophotonic imaging techniques, demonstrating a powerful tool for the objective assessment of the severity of neurotoxic events with ocular structures acting as potential biomarkers