Search

In their book, Transforming Sanchez School: Shared Leadership, Equity, and Evidence, Raymond R. Isola and Jim Cummins describe their experience at Sanchez Elementary School, which serves a majority...

Various studies from the past years examine the changing conditions and challenges in the veterinary sector. Secured access to public and private care services is a prerequisite for a holistically oriented health care system ("One Health"). In the present study, a multidimensional concept of accessibility to care services was used for the first time to determine and visualize the density of the animal health care system in Switzerland. Traditional indicators used to describe care structures focus either on availability or accessibility. In order to overcome the limitations of traditional indicators, the family of methods known as Floating-Catchment-Area-Methods (FCA) has been developed in care geographical research. The strength of FCA methods lies in the fact that they output accessibility independent of administrative boundaries and at the same time consider the spatial distance and available capacities. The study provides insight into the density of animal health care services using FCA methods and geographical information systems (GIS). Data on providers of veterinary services in the companion animal sector and, on the demand side, data on dogs and cats kept in Switzerland served as illustrative example. The result was interactive maps of the density of health care and the structure of spatial accessibility to veterinary providers and consumers. As expected, high spatial accessibility is found in the urban centers and the agglomerations of the Central Plateau. In contrast, spatial accessibility to medical services for dogs and cats is often lower in peripheral areas. Due to hitherto unavailable data, various analyses had to be postponed for the time being. For example, the model could of course be extended to all animal species and all types of medical services. In addition, it would also be possible to forecast the future density of health care, or to optimize the care system. Together with the relevant industry stakeholders, these gaps could be closed, and the model and the resulting findings could be further differentiated. The results should serve private actors in the concerned value chains, but also decision-makers in the public veterinary service, governmental authorities, agricultural bodies, universities, etc. as a basis for strategic decisions regarding the issue of medical supply density and care services in the animal sector.Verschiedene Arbeiten aus den vergangenen Jahren untersuchen die sich verändernden Rahmenbedingungen und Herausforderungen im tiermedizinischen Sektor. Ein gesicherter Zugang zu öffentlichen und privaten Versorgungsangeboten ist eine Voraussetzung für ein gesamtheitlich ausgerichtetes Gesundheitswesen («One Health»). In der vorliegenden Arbeit wurde erstmals versucht mittels des mehrdimensionalen Konzepts der Zugänglichkeit zu Versorgungsangeboten, die Versorgungsdichte des tiermedizinischen Versorgungssystems in der Schweiz zu erfassen und zu visualisieren. Tra­ditionelle Indikatoren zur Beschreibung von Versorgungsstrukturen fokussieren jeweils entweder auf die Verfügbarkeit oder die Erreichbarkeit. Um den Einschränkungen traditioneller Indikatoren zu begegnen, entwickelte sich in der versorgungsgeografischen Forschung die Methodenfamilie der Floating-Catch­ment-Area-Methoden (FCA). Die Stärke von FCA-Methoden liegt darin, dass sie die Zugänglichkeit unabhängig von administrativen Grenzen sowie unter gleichzeitiger Berücksichtigung der räumlichen Distanz und der verfügbaren Kapazitäten ausgeben. Die Arbeit ermöglicht einen Einblick in die tiermedizinische Versorgungsdichte mittels FCA-Methodik und unter Einbezug von Geographischen Informationssystemen (GIS). Als Anschauungsbeispiel dienten Daten zu Anbietern tiermedizinischer Leistungen im Heimtiersektor bzw. auf der Nachfrageseite Daten zu den in der Schweiz gehaltenen Hunden und Katzen. Als Ergebnis resultierten interaktive Karten zur Versorgungsdichte und zur Struktur der räumlichen Zugänglichkeit zu tiermedizinischen Anbietern und Nachfragern. Erwartungsgemäss findet sich eine hohe räumliche Zugänglichkeit in den urbanen Zentren und den Agglomerationen des Mittellandes. Hingegen ist die räumliche Zugänglichkeit zu medizinischen Leistungen für Hunde und Katzen in peripheren Gebieten oft tiefer. Aufgrund bisher nicht verfügbarer Daten musste auf verschiedene Analysen vorerst verzichtet werden. Beispielsweise liesse sich das Modell selbstverständlich auf sämtliche Tierarten und medizinischen Angebote erweitern. Zudem wären auch Prognosen zur Versorgungsdichte in der Zukunft oder zur Versorgungsoptimierung möglich. Zusammen mit den betroffenen Branchenakteuren liessen sich diese Lücken schliessen und damit das Modell und die daraus resultierenden Ergebnisse weiter ausdifferenzieren. Die Erkenntnisse sollen privaten Akteuren der betroffenen Wertschöpfungsketten, aber auch Entscheidungsträgern des öffentlichen Veterinärdienstes, Vollzugsbehörden, Organen der Landwirtschaft, Hochschulen u.a.m. als Grundlage für strategische Entscheidungen rund um die Thematik der medizinischen Versorgungsdichte im Tiersektor dienen.Ces dernières années, divers travaux ont examiné l’évolution des conditions cadres et des défis dans le secteur vétérinaire. L’assurance d’un accès aux soins publics et privés est une condition préalable à un système de santé holistique (« One Health »). Dans le travail présent, on a tenté pour la première fois d’enregistrer et de visualiser la densité d’approvisionnement du système de soins vétérinaires en Suisse en utilisant un concept multidimensionnel d’accessibilité aux offres de soins. Les indicateurs traditionnels pour décrire les structures de soins se concentrent soit sur la disponibilité soit sur l’accessibilité. Afin de contrer les limites des indicateurs traditionnels, la famille de méthodes du Floating-Catchment-Area (FCA) s’est développée dans la recherche en géographie sanitaire. La force des méthodes FCA est qu’elles fournissent un accès indépendamment des limites administratives, tout en tenant compte de la distance spatiale et de la capacité disponible. Ce travail permet d’avoir un aperçu de la densité de l’offre vétérinaire en utilisant la méthodologie FCA en tenant compte de systèmes d’information géographique (SIG). Les données sur les prestataires de services vétérinaires dans le secteur des animaux de compagnie et sur la demande concernant les chiens et les chats vivant en Suisse ont servi d’exemple. Le résultat a été des cartes interactives de la densité de l’offre et de la structure de l’accessibilité spatiale aux prestataires vétérinaires et de celle des consommateurs. Comme prévu, il existe un degré élevé d’accessibilité spatiale dans les centres urbains et les agglomérations du plateau suisse. En revanche, l’accessibilité spatiale aux services vétérinaires pour chiens et chats est souvent plus basse dans les zones périphériques. En raison de données indisponibles précédemment, diverses analyses ont dû être abandonnées dans un premier temps. Ce modèle pourrait être étendu à toutes les espèces animales et aux diverses offres vétérinaires. En outre, il serait également possible de faire des prévisions sur la future densité de l’offre ou sur son optimisation. Conjointement avec les acteurs de la branche concernés, ces lacunes pourraient être comblées avec certitude et le modèle et les résultats qui en résulteraient seraient encore plus différenciés. Les résultats sont destinés à aider les acteurs privés dans les chaînes de valeur ajoutée, mais ils pourraient aussi servir de base aux décideurs des services vétérinaires publics, aux autorités d’exécution, aux organes de l’agriculture, aux universités, etc., pour prendre des décisions stratégiques autour du thème de la densité de l’offre médicale dans le secteur animal.Diversi studi degli anni scorsi hanno esaminato le condizioni e le difficoltà in evoluzione nel settore veterinario. L’accesso garantito ai servizi di assistenza pubblica e privata è un prerequisito per un sistema di assistenza sanitaria orientato alla globalità (“One Health”). Nel presente studio è stato utilizzato per la prima volta un concetto multidimensionale di accessibilità alle offerte di cura per registrare e visualizzare la densità del sistema di assistenza veterinaria in Svizzera. Gli indicatori tradizionali utilizzati per descrivere le strutture assistenziali si concentravano principalmente sulla disponibilità o sull’accessibilità. Al fine di superare i limiti degli indicatori tradizionali, la metodologia nota come Floating-Catchment-Area-Methods (FCA) è stata sviluppata nella ricerca geografica dell’assistenza. Il punto di forza dei metodi FCA sta nel fatto che essi producono un’accessibilità indipendente dai confini amministrativi e allo stesso tempo tengono conto della distanza spaziale e delle capacità disponibili. Lo studio offre uno sguardo sulla densità delle cure veterinarie utilizzando i metodi FCA e includendo i sistemi di informazione geografica (GIS). Come esempio ci si è serviti dei dati sui fornitori di servizi veterinari nel settore degli animali da compagnia e, dal lato della domanda, i dati sui cani e i gatti che vivono in Svizzera. Il risultato ottenuto è una mappa interattiva della densità delle cure e della struttura dell’accessibilità spaziale per i fornitori e i consumatori di servizi veterinari. Come previsto, l’elevata accessibilità territoriale si trova nei centri urbani e negli agglomerati dell’Altipiano. D’altro canto, l’accessibilità spaziale ai servizi veterinari per cani e gatti nelle aree periferiche è spesso molto più bassa. A causa dei dati non disponibili per gli anni precedenti, per il momento si è dovuto rinunciare a diverse analisi. Ad esempio, il modello potrebbe essere esteso a tutte le specie animali e a tutti i servizi medici. Inoltre, sarebbe anche possibile prevedere la densità delle cure e come ottimizzarle in futuro. Insieme agli operatori dei settori interessati, queste lacune potrebbero essere colmate con certezza e quindi il modello e i risultati che ne deriverebbero potrebbero essere ulteriormente differenziati. I risultati dovrebbero servire non solo agli attori delle catene di valore aggiunto interessate private, ma anche ai responsabili del servizio veterinario pubblico, alle autorità nazionali, agli organismi agricoli, alle università, ecc. come base per valutare le decisioni strategiche sulla questione della densità dell’offerta medica nel settore veterinario.

[Image: see text] Container-based sanitation (CBS) within a comprehensive service system value chain offers a low-cost sanitation option with potential for revenue generation but may increase microbial health risks to sanitation service workers. This study assessed occupational exposure to rotavirus and Shigella spp. during CBS urine collection and subsequent struvite fertilizer production in eThekwini, South Africa. Primary data included high resolution sequences of hand-object contacts from annotated video and measurement of fecal contamination from urine and surfaces likely to be contacted. A stochastic model incorporated chronological surface contacts, pathogen concentrations in urine, and literature data on transfer efficiencies of pathogens to model pathogen concentrations on hands and risk of infection from hand-to-mouth contacts. The probability of infection was highest from exposure to rotavirus during urine collection (∼10(–1)) and struvite production (∼10(–2)), though risks from Shigella spp. during urine collection (∼10(–3)) and struvite production (∼10(–4)) were non-negligible. Notably, risk of infection was higher during urine collection than during struvite production due to contact with contaminated urine transport containers. In the scale-up of CBS, disinfection of urine transport containers is expected to reduce pathogen transmission. Exposure data from this study can be used to evaluate the effectiveness of measures to protect sanitation service workers.

In February 2021, in response to emergence of more transmissible SARS-CoV-2 virus variants, the Canton Grisons launched a unique RNA mass testing program targeting the labour force in local businesses. Employees were offered weekly tests free of charge and on a voluntary basis. If tested positive, they were required to self-isolate for ten days and their contacts were subjected to daily testing at work. Thereby, the quarantine of contact persons could be waved.Here, we evaluate the effects of the testing program on the tested cohorts. We examined 121,364 test results from 27,514 participants during February–March 2021. By distinguishing different cohorts of employees, we observe a noticeable decrease in the test positivity rate and a statistically significant reduction in the associated incidence rate over the considered period. The reduction in the latter ranges between 18 and 50%. The variability is partly explained by different exposures to exogenous infection sources (e.g., contacts with visiting tourists or cross-border commuters). Our analysis provides the first empirical evidence that applying repetitive mass testing to a real population over an extended period of time can prevent spread of COVID-19 pandemic. However, to overcome logistic, uptake, and adherence challenges it is important that the program is carefully designed and that disease incursion from the population outside of the program is considered and controlled., Scientific Reports, 12, ISSN:2045-2322

Using social media is one important strategy to communicate research and public health guidelines to the scientific community and general public. Empirical evidence about which communication strategies are effective around breastfeeding messaging is scarce. To fill this gap, we aimed to identify influencers in the largest available Twitter database using social network analysis (n = 10,694 users), inductively analyze tweets, and explore communication strategies, motivations, and challenges via semi-structured interviews. Influencers had diverse backgrounds within and beyond the scientific health community (SHC, 42.7%): 54.7% were from the general public and 3% were companies. SHC contributed to most of the tweets (n = 798 tweets), disseminating guidelines and research findings more frequently than others (p &lt, 0.001). Influencers from the general community mostly tweeted opinions regarding the current state of breastfeeding research and advocacy. Interviewees provided practical strategies (e.g., preferred visuals, tone, and writing style) to achieve personal and societal goals including career opportunities, community support, and improved breastfeeding practices. Complex challenges that need to be addressed were identified. Ideological differences regarding infant feeding may be hampering constructive communication, including differences in influencers’ interpretation of the WHO International Code of Marketing of Breast-milk Substitutes and in perspectives regarding which social media interactions encompass conflict of interest.

This paper examines the versification style of the Romansh poet Andri Peer, who can be considered as the first “modern” poet of the Romansh literature. It focuses on Andri Peer’s most frequently used verse lines in his early free forms: the heptasyllabic and hendecasyllabic verse. A rhythmical analysis of the single verse instances revealed that the internal organisation of the line is not very elaborate. In the case of the heptasyllables found in his early free forms, only four patterns make up over 80% of all heptasyllabic verses. Regarding Peer’s hendecasyllables, it is shown that his arrangement of the prominent syllables is rather regular, especially in comparison to the hendecasyllables of his precursor Peider Lansel. This trend in Peer’s versification to use fixed dispositions of syllables is interpreted as a compensation for the loss of other structural features such as the stanza or the rhyme.

Introduction: Public health emergencies and crises such as the current COVID-19 pandemic can accelerate innovation and place renewed focus on the value of health interventions Capturing important lessons learnt, both positive and negative, is vital We aimed to document the perceived positive changes (silver linings) in cancer care that emerged during the COVID-19 pandemic and identify challenges that may limit their long-term adoption Methods: This study employed a qualitative design Semi-structured interviews (n = 20) were conducted with key opinion leaders from 14 countries The participants were predominantly members of the International COVID-19 and Cancer Taskforce, who convened in March 2020 to address delivery of cancer care in the context of the pandemic The Framework Method was employed to analyse the positive changes of the pandemic with corresponding challenges to their maintenance post-pandemic Results: Ten themes of positive changes were identified which included: value in cancer care, digital communication, convenience, inclusivity and cooperation, decentralisation of cancer care, acceleration of policy change, human interactions, hygiene practices, health awareness and promotion and systems improvement Impediments to the scale-up of these positive changes included resource disparities and variation in legal frameworks across regions Barriers were largely attributed to behaviours and attitudes of stakeholders Conclusion: The COVID-19 pandemic has led to important value-based innovations and changes for better cancer care across different health systems The challenges to maintaining/implementing these changes vary by setting Efforts are needed to implement improved elements of care that evolved during the pandemic

The detection and classification of vehicles by suitable monitoring systems is an integral part of Intelligent Transportation Systems (ITS). We report results of an ongoing research project on fine-grained vehicle classification based on images acquired from roadside and overhead based video cameras. In a previous work [1] a dataset of overall 100,000 sample images from 36 fine-grained vehicle classes has already been presented. These images were acquired from roadside based cameras and results for the classification accuracy obtained with state-of-the-art CNNs (convolutional neural networks) allowed to fulfil the challenging traffic norm TLS 8+1 A1. Here, in extension to this work, cameras in overhead perspective were used to avoid the problem of occlusion (i.e., a larger vehicle completely occluding a smaller one), which currently limits the roadside perspective to two-lane roads (with one camera per lane). Therefore, the original dataset was expanded with a new set of close to 100,000 images now taken in overhead perspective and representing the same 36 fine-grained vehicle classes. While keeping all model and hyperparameters identical (size of training and test set, resolution, CNN architecture, …) in overhead perspective a considerable drop in the classification accuracy was observed with respect to the roadside perspective. Analysis of the confusion matrix reveals that important details of the vehicles, which are essential for the distinction among certain classes, are not sufficiently well represented in the CNN in overhead position. These results seem to indicate, that standard CNNs come to their limits for the present task of fine-grained vehicle classification and other, part-based approaches are required to solve this problem.

Using Twitter to implement public health awareness campaigns is on the rise, but campaign monitoring and evaluation are largely dependent on basic Twitter Analytics. To establish the potential of social network theory-based metrics in better understanding public health campaigns, we analyzed real-time user interactions on Twitter during the 2020 World Breastfeeding Week (WBW) as an exemplar case. Social network analysis (SNA), including community and influencer identification, as well as topic modeling were used to compare the activity ofn= 29,958 campaign participants andn= 10,694 reference users from the six-months pre-campaign period. Users formed more inter-connected relationships during the campaign, retweeting and mentioning each other 46,161 times compared to 10,662 times in the prior six months. Campaign participants formed identifiable communities that were not only based on their geolocation, but also based on interests and professional background. While influencers who dominated the WBW conversations were disproportionally members of the scientific community, the campaign did mobilize influencers from the general public who seemed to play a “bridging” role between the public and the scientific community. Users communicated about the campaign beyond its original themes to also discuss breastfeeding within the context of social and racial inequities. Applying SNA allowed understanding of the breastfeeding campaign’s messaging and engagement dynamics across communities and influencers. Moving forward, WBW could benefit from improving targeting to enhance geographic coverage and user interactions. As this exemplar case indicates, social network theory and analysis can be used to inform other public health campaigns with data on user interactions that go beyond traditional metrics.

Few studies have examined the brokering role that some educators play in providing access to research evidence. Our study uses social network analysis to examine the type of brokering roles that exist, as well as identify who plays these roles, and to understand how research evidence moves through formal and informal relationships. Our results show that Area Superintendents are an important source of research evidence, serving key brokering roles between disconnected actors. Individuals in these formal leadership positions bridge research evidence between actors. Findings speak to the important role that brokers play in diffusing research evidence in school systems, highlight a disconnect between formal district structures and the informal interactions between leaders, and indicate that additional attention is needed by policymakers to retain key leaders.

With an ongoing shift from managing disease toward the inclusion of maintaining health and preventing disease, the world has seen the rise of increasingly sophisticated physiological monitoring and analytics. Innovations range from wearables, smartphone-based spot monitoring to highly complex noncontact, remote monitoring, utilizing different mechanisms. These tools empower the individual to better navigate their own health. They also generate powerful insights towards the detection of subclinical symptoms or processes via existing and novel digital biomarkers. In that context, a topic that is receiving increasing interest is the modulation of human physiology around an individual "baseline" in everyday life and the impact thereof on other sensorineural body functions such as hearing. More and more fully contextualized and truly long-term physiological data are becoming available that allows deeper insights into the response of the human body to our behavior, immediate environment and the understanding of how chronic conditions are evolving. Hearing loss often goes hand in hand with chronic conditions, such as diabetes, cognitive impairment, increased risk of fall, mental health, or cardiovascular risk factors. This inspires an interest to not only look at hearing impairment itself but to take a broader view, for example, to include contextualized vital signs. Interestingly, stress and its physiological implications have also been shown to be a relevant precursor to hearing loss and other chronic conditions. This article deduces the requirements for wearables and their ecosystems to detect relevant dynamics and connects that to the need for more ecologically valid data towards an integrated and more holistic mapping of hearing characteristics.

Introduction An increasing global need for pharmacovigilance training cannot be met with classroom courses alone. Several e-learning modules have been developed by Uppsala Monitoring Centre (UMC). With distance learners and technological challenges such as poor internet bandwidth to be considered, UMC opted for the microlearning approach based on small learning units connected to specific learning objectives. The aim of this study was to evaluate how this e-learning course was received. Methods The course was evaluated through usage data and the results of two user surveys, one for modules 1–4, signal detection and causality assessment, and the other for module 5, statistical reasoning and algorithms in pharmacovigilance. The evaluation model used was based on the Unified Theory of Acceptance and Use of Technology (UTAUT). A questionnaire was developed, divided into demographic profile, performance expectancy, effort expectancy, educational compatibility and behavioural intention. The two surveys were disseminated to 2067 learners for modules 1–4 and 1685 learners for module 5. Results Learners from 137 countries participated, predominantly from industry (36.6%), national pharmacovigilance centres (22.6%) and academia (16.3%). The overall satisfaction level was very high for all modules, with over 90% of the learners rating it as either ‘excellent’ or ‘good’. The majority were satisfied with the learning platform, the course content and the lesson duration. Most learners thought they would be able to apply the knowledge in practice. Almost 100% of the learners would recommend the modules to others and would also study future modules. Suggested improvements were an interactive forum, more practical examples in the lessons and practical exercises. Conclusion This e-learning course in pharmacovigilance based on microlearning was well received with a global coverage among relevant professional disciplines. Electronic supplementary material The online version of this article (10.1007/s40264-020-00981-w) contains supplementary material, which is available to authorized users.

Background Cancer patients’ experience is dependent on the complex interaction between the patient, carer, healthcare practitioners and healthcare system. The aim of the study was to assess the experience of cancer patients in Assam in order to identify potential areas for improvement in delivering high quality cancer care. Methods A cross sectional patient experience survey was conducted in 400 patients using structured interviews and pre-tested questionnaires that collected patient-reported outcomes including access to cancer care, experience while availing cancer services across the pathway, waiting times, communication and counselling support, out-of-pocket expenditure and advice regarding available insurance schemes and financial support. Results The cancer patient’s experience of accessing healthcare in Assam is variable with principal challenges being financial constraint and geographical distance to healthcare facilities. Overall, patients’ experience during registration, first consultation, pre-treatment and during treatment was good with high satisfaction rates expressed in several of the areas assessed. Areas that were identified for improvement were better explanation of long-term side effects of treatment, enhanced guidance in choosing treatment options and greater support from healthcare professionals to help patients cope with the psychological, emotional and physical aspects of their cancer diagnosis, treatment and recovery. Conclusion Understanding cancer patient experiences across their journey is critical to delivering accessible and affordable care. Effective, adaptive and responsive communication remains the anchor of excellent patient-centred care especially in resource constraint settings. Policy statement The paper provides an insight into critical areas focusing on diagnosis, treatment, continuum of care and communication during cancer patients’ care in India. Healthcare policy needs to focus on developing a robust, holistic, healthcare system in terms of accessibility, affordability and psychosocial care, including counselling and financial support, to ensure better cancer outcomes.

Post-transplant lymphoproliferative disorder (PTLD) is a rare but potentially life-threatening complication, frequently associated with Epstein-Barr virus (EBV), which develops after solid organ or stem cell transplantation. Immunosuppression received by transplant recipients has a significant impact on the development of PTLD by suppressing the function of T cells. The preferential proliferation of NKG2A-positive natural killer (NK) cells during primary symptomatic EBV infection known as infectious mononucleosis (IM) and their reactivity toward EBV-infected B cells point to a role of NK cell in the immune control of EBV. However, NK cell-mediated immune response to EBV in immunosuppressed transplant recipients who develop PTLD remains unclear. In this study, we longitudinally analyzed the phenotype and function of different NK cell subsets in a cohort of pediatric liver transplant patients who develop PTLD and compared them to those of children with IM. We found persistently elevated plasma EBV DNA levels in the PTLD patients indicating suboptimal anti-viral immune control. PTLD patients had markedly decreased frequency of CD56dimNKG2A+Killer Immunoglobulin-like receptor (KIR)− NK cells from the time of diagnosis through remission compared to those of IM patients. Whilst the proliferation of CD56dimNKG2A+KIR− NK cells was diminished in PTLD patients, this NK cell subset maintained its ability to potently degranulate against EBV-infected B cells. Compared to cytomegalovirus (CMV)-seropositive and -negative IM patients, PTLD patients co-infected with CMV and EBV had significantly higher levels of a CMV-associated CD56dimNKG2ChiCD57+NKG2A−KIR+ NK cell subset accumulating at the expense of NKG2A+KIR− NK cells. Taken together, our data indicate that co-infection of CMV and EBV diminishes the frequency of CD56dimNKG2A+KIR− NK cells and contributes to suboptimal control of EBV in immunosuppressed children with PTLD.

Elderly patients are the main users of drugs and they differ from younger patients. They are a heterogeneous population that cannot be defined only by age but should rather be stratified based on their frailty. The elderly have distinctive pharmacokinetic and pharmacodynamic characteristics, are frequently polymorbid, and are therefore treated with multiple drugs. They may experience adverse reactions that are difficult to recognize, since some of them present non-specific symptoms easily mistaken for geriatric conditions. Paradoxically, the elderly are underrepresented in clinical trials, especially the frail individuals whose pharmacological response and expected treatment outcome can be different from those of non-frail patients. This means that the benefit–risk balance of drugs used in frail elderly patients is frequently unknown. We present some proposals to overcome the barriers preventing the enrollment of frail elderly patients in clinical trials, and strategies for monitoring their therapy to minimize the risk of adverse reactions. Automated alerts for drug and drug–disease interactions could help appropriate prescribing but should flag only clinically relevant interactions. Pharmaceutical forms should be designed to allow easy dose adjustment and, together with packaging and labeling, should account for the physical and cognitive limitations of frail elderly patients. Aggregate pharmacovigilance reports should summarize the safety profile in the elderly, but rather than presenting the results by age they should focus on patients’ frailty, perhaps using the number of comorbidities as a proxy when information on frailty is not available.

Flexible bronchoscopy (FB) is a cornerstone of modern pulmonary medicine. However, considerable heterogeneity persists with respect to education, training, and the performance of sedation during FB. Sedation administered by a non-anesthesiologist during FB has been demonstrated to be safe and effective, although comorbidities and respiratory disease severity must be taken into account regarding choice of sedation and monitoring. There is undoubtedly room for improvement concerning basic education and training in this field. In addition, current study heterogeneity complicates comparisons between various sedation regimens which in turn limit state of the art recommendations. To reach a broad acceptance of non-anesthesiologist administered sedation, future studies and guidelines must increasingly focus on education and training. Research should be performed to establish a concept of harmonized patient selection for different sedation practices.

Hintergrund Das Auftreten von Laktatazidosen unter Metformin-Therapie ist seit Medikamenteneinfuhrung bekannt, die Genese dessen jedoch stark umstritten. Die Inzidenz Metformin-assoziierter Laktatazidosen (MALA) liegt gemas aktueller Studienlage bei 3,0 – 16,7 Falle pro 100 000 Patientenjahre. In Vergangenheit wurde ein kausaler Zusammenhang zwischen Niereninsuffizienz und MALA suggeriert, was zu einem restriktiven Metformineinsatz bei niereninsuffizienten Patienten fuhrte. Neuere Studien zeigen jedoch kein gehauftes Auftreten von Laktatazidosen bei chronischer leicht bis mittelgradiger Niereninsuffizienz. Methode Fallserie. Ergebnisse Bei einer Haufung mit 4 Fallberichten manifester Laktatazidosen unter Metformin-Behandlung im Spital Limmattal im Zeitraum von 9 Monaten fiel eine beinahe identische klinische Vorgeschichte mit vorgangig Brechdurchfall bei bisher nierengesunden Patienten mit Diabetes mellitus Typ II auf. Bei allen 4 Patienten bestand zum Eintrittszeitpunkt ein akutes Nierenversagen AKIN III, wobei eine Hamofiltration notwendig wurde. Nach maximal 24h-stundiger Hamofiltration zeigten sich die Laktatazidose normalisiert und die Nierenretentionsparameter regredient. 7 Tage nach Eintritt prasentierten sich 2 Patienten mit einer normalen und 2 Patienten mit einer reduzierten Nierenfunktion (Stadium III, bzw. IV). Schlussfolgerung Bei Auftreten von Diarrho und Emesis bei mit Metformin behandelten Diabetikern ist, unabhangig von der bisherigen Nierenfunktion, die fruhzeitige aktive Suche einer moglichen Laktatazidose essenziell, da die Diagnosestellung und Therapie einer MALA eine gute Prognose ermoglicht.

Zusammenfassung. Die neusten Erkenntnisse zu der Pathogenese des Zervixkarzinoms führten zu Anpassungen in der zytologischen und histologischen Nomenklatur seiner Vorstufen. Die aktuelle, 2014 eingeführte histologische WHO-Terminologie unterscheidet, analog zum zytologischen Bethesda-System, zwischen zwei histologischen Stufen der HPV-bedingten Veränderungen: LSIL und HSIL, die mit unterschiedlichen Risiken der Progredienz zum invasiven Karzinom einhergehen und klinisch entsprechend unterschiedlich gehandhabt werden sollen. Die immunhistochemische Detektion des p16-Proteins als Surrogat der neoplastischen Transformation der HPV-infizierten Zellen hilft, die rein mikroskopische Diagnose zu objektivieren und zu sichern, und ist ein wichtiges Hilfsmittel in der Histopathologie. Die Verfügbarkeit der HPV-Impfung und die HPV-Detektion werden in den kommenden Jahren die Abläufe in der Frühentdeckung und die Epidemiologie der Zervixkarzinom-Vorstufen beeinflussen.

Background Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCT) are rare tumors of low malignancy. In the past, these tumors were mainly treated by hysterectomy. More recently, some authors have proposed conservative surgical management for women wishing to preserve fertility. This article is the first to report on organ-preserving treatment in the case of recurrence or disease persistence. Cases We report on three patients with UTROSCT, two of them young, not having completed family planning. One even gave birth to a healthy child after fertility-preserving treatment of a persistent UTROSCT. To our knowledge, this is the first pregnancy reported after surgical treatment of a persistent UTROSCT so far. Conclusion A fertility-sparing approach should always be considered in young women with UTROSCT who wish to preserve their fertility, also in cases of recurrence or disease persistence., Highlights • First report on organ-preserving treatment in case of UTROSCT recurrence • First pregnancy reported after surgical treatment of a persistent UTROSCT • Fertility-preserving approach also in cases of recurrence or disease persistence

Background Cancer patients in the North East Region (NER) of India have poorer survival rates compared with the rest of India. This is due to late stage at presentation related to poor awareness, risk factors such as use of tobacco, alcohol consumption and less physical activity, This study aims to determine the association between socio-demographic characters and use of tobacco, alcohol consumption and physical activity among people in the NER. Methods A cross-sectional study of 1400 participants was conducted across Assam, Nagaland and Meghalaya in the NER. A questionnaire was developed to study the socio-demographic profile and factors such as use of tobacco, alcohol consumption and physical activity among participants. Multivariate analysis was performed to understand tobacco and alcohol use and physical activity and a logistic regression analysis was performed to understand the association of different independent variables with lifestyle practice. Results Use of tobacco and alcohol consumption was highest amongst males, 25−44 years age range and middle income group as defined in this study. The main reasons given for quitting tobacco and alcohol were becoming aware of the harmful effects of using tobacco, pressure from family and friends, and noticing a deterioration in health. Over 90 % of tobacco users and consumers of alcohol initiated this between 10–30 years of age. In all, 62 % of participants rarely or never engaged in any physical recreational activity. Conclusion Patterns of use of tobacco and consumption of alcohol and recreational physical activity undertaken in the NER show a strong relationship with gender, age and household income. Policy implications The paper finds a close association of different pattern of modifiable habits which are the risk factors for cancer in the Northeast Region. The limited awareness about the risk factors strengthen the case of context specific prevention strategies and constant reinforcement of behavior communication strategies by using multipronged approach.

In this article, we discuss the advantages and disadvantages of the survey as a methodological tool in social studies of cancer. Drawing on our own research on the accessibility and affordability of cancer care in India, we present examples from interviews and identify some limitations inherent in survey-based research approaches. We argue that social studies of cancer require a more rigorous methodology to produce robust and reliable data.

Purpose The purpose of this study is to uncover previously unrecognised risks of medicines in paediatric pharmacovigilance reports and thereby advance a safer use of medicines in paediatrics. Methods Individual case safety reports (ICSRs) with ages less than 18 years were retrieved from VigiBase, the World Health Organization (WHO) global database of ICSRs, in September 2014. The reports were grouped according to the following age spans: 0 to 27 days; 28 days to 23 months; 2 to 11 years; and 12 to 17 years. vigiRank, a data‐driven predictive model for emerging safety signals, was used to prioritise the list of drug events by age groups. The list was manually assessed, and potential signals were identified to undergo in‐depth assessment to determine whether a signal should be communicated. Results A total of 472 drug‐event pairs by paediatric age groups were the subject of an initial manual assessment. Twenty‐seven drug events from the two older age groups were classified as potential signals. An in‐depth assessment resulted in eight signals, of which one concerned harm in connection with off‐label use of dextromethorphan and another with accidental overdose of olanzapine by young children, and the remaining signals referred to potentially new causal associations for atomoxetine (two signals), temozolamide, deferasirox, levetiracetam, and desloratadine that could be relevant also for adults. Conclusions Clinically relevant signals were uncovered in VigiBase by using vigiRank applied to paediatric age groups. Further refinement of the methodology is needed to identify signals in reports with ages under 2 years and to capture signals specific to the paediatric population as a risk group.

Even if still at an early stage of development, non-invasive continuous glucose monitoring (NI-CGM) sensors represent a promising technology for optimizing diabetes therapy. Recent studies showed that the Multisensor provides useful information about glucose dynamics with a mean absolute relative difference (MARD) of 35.4% in a fully prospective setting. Here we propose a method that, exploiting the same Multisensor measurements, but in a retrospective setting, achieves a much better accuracy. Data acquired by the Multisensor during a long-term study are retrospectively processed following a two-step procedure. First, the raw data are transformed to a blood glucose (BG) estimate by a multiple linear regression model. Then, an enhancing module is applied in cascade to the regression model to improve the accuracy of the glucose estimation by retrofitting available BG references through a time-varying linear model. MARD between the retrospectively reconstructed BG time-series and reference values is 20%. Here, 94% of values fall in zone A or B of the Clarke Error Grid. The proposed algorithm achieved a level of accuracy that could make this device a potential complementary tool for diabetes management and also for guiding prediabetic or nondiabetic users through life-style changes.

Chocron and colleagues discuss cannabinoid hyperemesis syndrome.1 We would like to emphasise the importance of cyclic vomiting syndrome (CVS) as a differential diagnosis, especially in patients presenting to emergency departments. Such patients require different pharmacological treatment from those with cannabinoid hyperemesis syndrome. Most patients with CVS present at emergency departments with episodes of vomiting, …

Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication after organ transplantation frequently associated with the Epstein-Barr virus (EBV). Immunosuppressive treatment is thought to allow the expansion of EBV-infected B cells, which often express all eight oncogenic EBV latent proteins. Here, we assessed whether HLA-A2 transgenic humanized NSG mice treated with the immunosuppressant FK506 could be used to model EBV-PTLD. We found that FK506 treatment of EBV-infected mice led to an elevated viral burden, more frequent tumor formation and diminished EBV-induced T cell responses, indicative of reduced EBV-specific immune control. EBV latency III and lymphoproliferation-associated cellular transcripts were up-regulated in B cells from immunosuppressed animals, akin to the viral and host gene expression pattern found in EBV-PTLD. Utilizing an unbiased gene expression profiling approach, we identified genes differentially expressed in B cells of EBV-infected animals with and without FK506 treatment. Upon investigating the most promising candidates, we validated sCD30 as a marker of uncontrolled EBV proliferation in both humanized mice and in pediatric patients with EBV-PTLD. High levels of sCD30 have been previously associated with EBV-PTLD in patients. As such, we believe that humanized mice can indeed model aspects of EBV-PTLD development and may prove useful for the safety assessment of immunomodulatory therapies., Author summary Transplant recipients are medicated with potent immunosuppressive drugs, like FK506, to prevent graft rejection by the host’s adaptive immune system. Such treatments can lead to the emergence of post-transplant lymphoproliferative disorders (PTLD) driven by the Epstein-Barr virus (EBV), a ubiquitous human oncovirus that is usually kept under control by T cells. Here, we aimed to establish a model of human EBV-PTLD. To this end, we investigated immunodeficient mice harboring human immune system components reconstituted from human hematopoietic progenitor cells, termed humanized mice. This model enables both the infection of human B cells with EBV and the examination of effects of immunosuppressive compounds on lymphocytes in vivo. We found that EBV-associated lymphoproliferations in humanized mice express characteristic viral and human genes observed in EBV-PTLD patients and found similarities in the profiles of serum proteins known for their association with the disease. As such, we believe that EBV-infected humanized mice treated with the immunosuppressive drug FK506 can be used to model specific aspects of EBV-PTLD. Conversely, similar models may prove useful in the preclinical risk-assessment of novel compounds in relation to EBV-associated lymphoproliferation and our study may serve as a template of how one could approach such investigations.

The mass media fascination with mass death and mass disease has a long history. But what makes a disease communicable in our culture of media? In this think piece, I argue that the mass media has found in the idea of the next pandemic an ideal opportunity to corroborate its own discursive problematic.

We investigated whether alterations of the Her2 gene could be detected in breast cancer samples following primary chemotherapy in advanced breast cancer. The prospective study involved 23 patients with stage-II, -III or -IV breast cancer. All patients were treated with two to six cycles of fluorouracil-epirubicin and/or cyclophosphamid/epi-docetaxel. The Her2 protein and gene were assessed both on core needle biopsies prior to and on surgical specimens after completing chemotherapy using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods. Estrogen and progesterone receptors (ER/PR) were also determined on both samples using IHC. Her2 status was modified in eight patients using IHC (35%) and in three patients using FISH (13%). Changes in ER/PR expression were detected in seven patients (30%). Our data suggest that alterations of the Her2 gene can occur, although not usually after primary or neoadjuvant chemotherapy. However, changes in ER/PR status seem to be a more common event; thus, both can lead to different therapeutic options. Intratumoral heterogeneity as well as sampling variations can contribute to modification of the Her2 status after primary chemotherapy.

Study objectives To assess adverse drug reaction reports of "abnormal sleep related events" associated with varenicline, a partial agonist to the α4β2 subtype of nicotinic acetylcholine receptors on neurones, indicated for smoking cessation. Design Twenty-seven reports of "abnormal sleep related events" often associated with abnormal dreams, nightmares, or somnambulism, which are known to be associated with varenicline use, were identified in the World Health Organisation (WHO) Global Individual Case Safety Reports Database. Original anonymous reports were obtained from the four national pharmacovigilance centers that submitted these reports and assessed for reaction description and causality. Measurements and results These 27 reports include 10 of aggressive activity occurring during sleep and seven of other sleep related harmful or potentially harmful activities, such as apparently deliberate self-harm, moving a child or a car, or lighting a stove or a cigarette. Assessment of these 17 reports of aggression or other actual or potential harm showed that nine patients recovered or were recovering on varenicline withdrawal and there were no consistent alternative explanations. Thirteen patients experienced single events, and two had multiple events. Frequency was not stated for the remaining two patients. Conclusions The descriptions of the reports of aggression during sleep with violent dreaming are similar to those of rapid eye movement sleep behavior disorder and also nonrapid eye movement (NREM) sleep parasomnias in some adults. Patients who experience somnambulism or dreams of a violent nature while taking varenicline should be advised to consult their health providers. Consideration should be given to clarifying the term sleep disorders in varenicline product information and including sleep related harmful and potentially harmful events.

Background: Extensive past work showed that noninvasive continuous glucose monitoring with a wearable Multisensor device worn on the upper arm provides useful information about glucose trends to improve diabetes therapy in controlled and semicontrolled conditions. Methods: To test previous findings also in uncontrolled in-clinic and outpatient conditions, a long-term study has been conducted to collect Multisensor and reference glucose data in a population of 20 type 1 diabetes subjects. A total of 1072 study days were collected and a fully on-line compatible algorithmic routine linking Multisensor data to glucose applied to estimate glucose trends noninvasively. The operation of a digital log book, daily semiautomated data transfer and at least 10 daily SMBG values were requested from the patient. Results: Results showed that the Multisensor is capable of indicating glucose trends. It can do so in 9 out of 10 cases either correctly or with one level of discrepancy. This means that in 90% of all cases the Multisensor shows the glucose dynamic to rapidly increase or at least increase. Conclusions: The Multisensor and the algorithmic routine used in controlled conditions can track glucose trends in all patients, also in uncontrolled conditions. Training of the patient proved to be essential. The workload imposed on patients was significant and should be reduced in the next step with further automation. The feature of glucose trend indication was welcomed and very much appreciated by patients; this value creation makes a strong case for the justification of wearing a wearable.

Summary Background We previously reported the 5-year results of the phase 3 IBCSG 23-01 trial comparing disease-free survival in patients with breast cancer with one or more micrometastatic (≤2 mm) sentinel nodes randomly assigned to either axillary dissection or no axillary dissection. The results showed no difference in disease-free survival between the groups and showed non-inferiority of no axillary dissection relative to axillary dissection. The current analysis presents the results of the study after a median follow-up of 9·7 years (IQR 7·8–12·7). Methods In this multicentre, randomised, controlled, open-label, non-inferiority, phase 3 trial, participants were recruited from 27 hospitals and cancer centres in nine countries. Eligible women could be of any age with clinical, mammographic, ultrasonographic, or pathological diagnosis of breast cancer with largest lesion diameter of 5 cm or smaller, and one or more metastatic sentinel nodes, all of which were 2 mm or smaller and with no extracapsular extension. Patients were randomly assigned (1:1) before surgery (mastectomy or breast-conserving surgery) to no axillary dissection or axillary dissection using permuted blocks generated by a web-based congruence algorithm, with stratification by centre and menopausal status. The protocol-specified primary endpoint was disease-free survival, analysed in the intention-to-treat population (as randomly assigned). Safety was assessed in all randomly assigned patients who received their allocated treatment (as treated). We did a one-sided test for non-inferiority of no axillary dissection by comparing the observed hazard ratios (HRs) for disease-free survival with a margin of 1·25. This 10-year follow-up analysis was not prespecified in the trial's protocol and thus was not adjusted for multiple, sequential testing. This trial is registered with ClinicalTrials.gov, number NCT00072293. Findings Between April 1, 2001, and Feb 8, 2010, 6681 patients were screened and 934 randomly assigned to no axillary dissection (n=469) or axillary dissection (n=465). Three patients were ineligible and were excluded from the trial after randomisation. Disease-free survival at 10 years was 76·8% (95% CI 72·5–81·0) in the no axillary dissection group, compared with 74·9% (70·5–79·3) in the axillary dissection group (HR 0·85, 95% CI 0·65–1·11; log-rank p=0·24; p=0·0024 for non-inferiority). Long-term surgical complications included lymphoedema of any grade in 16 (4%) of 453 patients in the no axillary dissection group and 60 (13%) of 447 in the axillary dissection group, sensory neuropathy of any grade in 57 (13%) in the no axillary dissection group versus 85 (19%) in the axillary dissection group, and motor neuropathy of any grade (14 [3%] in the no axillary dissection group vs 40 [9%] in the axillary dissection group). One serious adverse event (postoperative infection and inflamed axilla requiring hospital admission) was attributed to axillary dissection; the event resolved without sequelae. Interpretation The findings of the IBCSG 23-01 trial after a median follow-up of 9·7 years (IQR 7·8–12·7) corroborate those obtained at 5 years and are consistent with those of the 10-year follow-up analysis of the Z0011 trial. Together, these findings support the current practice of not doing an axillary dissection when the tumour burden in the sentinel nodes is minimal or moderate in patients with early breast cancer. Funding International Breast Cancer Study Group.

BACKGROUND: Complex gastrointestinal (GI) motility disorders such as chronic intestinal pseudo-obstruction (CIPO) or Hirschsprung's disease (HD) are challenging to diagnose and treat appropriately. Thorough assessment of patient history, radiographic exams, endoscopy, and motility measurements aid in diagnostic workup, yet underlying histology is the cornerstone to enable a more distinct diagnosis of neuromuscular GI disorders. Traditionally, surgical procedures have been performed to obtain specimen suitable for accurate histologic analysis. METHODS: We performed endoscopic full-thickness resection (eFTR) using a full-thickness-resection device (FTRD) under moderate propofol sedation in four patients with suspected severe neuromuscular gut disorders including CIPO. KEY RESULTS: The mean age of the four patients was 43 y (range 19-56 y). Technical and histological success providing large colonic full-thickness tissue samples of excellent quality was achieved in all four patients (success rate 100%). The mean procedure time was 12 min (range 5-20 min). The mean diameter of the resected specimen was 21 mm (range 20-22 mm). No adverse events connected to the procedure itself occurred. Histology ranged from aganglionosis such as Hirschsprung's disease (HD) to hypoganglionosis and eosinophilic leiomyositis combined with lymphocytic ganglionitis in a third patient. Histology was unspecific in one patient. CONCLUSION AND INFERENCES: EFTR allows safe and minimal invasive harvesting of ample full-thickness tissue samples for accurate histological analysis in patients with suspicion of neuromuscular gut disorders.

Ameloblastic fibro-odontoma (AFO) is a rare benign tumor which contributes to 1–3% of all odontogenic tumors. AFO is mainly localized in the posterior region of the mandible and typical patients are children who present to their dentists due to non-erupting teeth. We describe an unusual example of a large AFO located in the upper right maxilla and maxillary sinus of a 3-year-old girl. The aims of this case report are to strengthen the knowledge of and to stimulate the discussion about AFO and to point out, that a conservative surgical procedure with regular follow up is highly recommended.

This paper describes a general workflow for the registration of terrestrial radar interferometric data with 3D point clouds derived from terrestrial photogrammetry and structure from motion. After the determination of intrinsic and extrinsic orientation parameters, data obtained by terrestrial radar interferometry were projected on point clouds and then on the initial photographs. Visualisation of slope deformation measurements on photographs provides an easily understandable and distributable information product, especially of inaccessible target areas such as steep rock walls or in rockfall run-out zones. The suitability and error propagation of the referencing steps and final visualisation of four approaches are compared: (a) the classic approach using a metric camera and stereo-image photogrammetry; (b) images acquired with a metric camera, automatically processed using structure from motion; (c) images acquired with a digital compact camera, processed with structure from motion; and (d) a markerless approach, using images acquired with a digital compact camera using structure from motion without artificial ground control points. The usability of the completely markerless approach for the visualisation of high-resolution radar interferometry assists the production of visualisation products for interpretation.

Life cycle assessment (LCA) studies include a vast amount of different products. Often, extrapolations are necessary to obtain the life cycle inventory of a specific product. This article provides quantitative scaling factors with power (heat output) for product properties and life cycle impact assessment results of heat pump and biomass furnace technologies. Included in the study are 508 heat pumps and furnaces with differences in power over three orders of magnitude per product group. The key properties of the heat pump system were defined as mass, refrigerant use, and coefficient of performance. For the biomass furnaces, the key properties analyzed were mass, electrical input, and efficiency. The results indicated that both the mass and the refrigerant use increased subproportionally to power. For coefficient of performance and furnace efficiency, no scaling effect was found. Subproportional growth was found between two environmental impacts (global warming and ozone depletion) and power for the production phase. This scaling behavior was similar to conventional cost scaling. The results of our study imply that in LCA, scaling factors can be applied to estimate key properties and corresponding life cycle impact assessment results. This is particularly useful for prospective technology assessments with limited data available.

A 16-month-old boy presented with failure to thrive despite sufficient caloric intake, hypersalivation, abdominal pain, chronic diarrhea and blepharitis. An eosinophilic esophagitis (EoE) was diagnosed by esophageal biopsy. Dietary restrictions and topical steroid treatment lead to no improvement. Further diagnostic work-up revealed an intrathoracal, paraspinal ganglioneuroblastoma. After operative extirpation of the tumour, all initial symptoms resolved. An esophageal control biopsy 4 weeks after tumour resection was normal. This is the first report of eosinophilic esophagitis as part of a paraneoplastic syndrome in a patient with a malignant disease other than a carcinoma.

Aims Epithelial ovarian cancer (EOC) can be classified into four major types (serous, endometrioid, clear cell, mucinous). The prevalence of driver gene mutations in the different subtypes is controversial. High-grade serous carcinomas show frequent TP53 mutations, whereas KRAS and BRAF mutations are less common. In non-serous EOC, the relevance of these gene mutations remains to be elucidated. Methods We investigated 142 formalin-fixed, paraffin-embedded EOC, including serous (n = 63), endometrioid (n = 29), clear cell (n = 25), mucinous (n = 14), and others (n = 11) for mutations in TP53 exons 5–8, KRAS exons 2 and 3, and BRAF exon 15 by pyro-sequencing using the GS Junior 454 platform. The mutational status was correlated with clinicopathological features and patient overall survival. Results We identified mutations in the coding region of TP53 in 51.4% (73/142), and of KRAS in 9.9% (14/142) but not of BRAF . TP53 mutations occurred frequently not only in high-grade serous carcinomas (58.7%), but also in mucinous (57%) and clear cell EOC (52%). TP53 mutations were associated with high-grade carcinomas (p = 0.014), advanced FIGO stage (p = 0.001), intraoperative residual disease > 1 cm (p = 0.004), as well as poor overall survival (p = 0.002). KRAS mutations were mainly identified in mucinous EOC (57%) and were concomitantly with TP53 mutations in five mucinous carcinomas (36%). Conclusions TP53 gene driver mutations are a common feature of all advanced ovarian cancer subtypes, whereas BRAF mutations seem to be a rare event in EOC. KRAS mutations with synchronous TP53 mutations occur predominantly in low-grade mucinous carcinomas, suggesting a specific molecular background of this ovarian cancer type.

In diabetes research, non-invasive continuous glucose monitoring (NI-CGM) devices represent a new and appealing frontier. In the last years, some multi-sensor devices for NI-CGM have been proposed, which exploit several sensors measuring phenomena of different nature, not only for measuring glucose related signals, but also signals reflecting some possible perturbing processes (temperature, blood perfusion). Estimation of glucose levels is then obtained combining these signals through a mathematical model which requires an initial calibration step exploiting one reference blood glucose (RBG) sample. Even if promising results have been obtained, especially in hospitalized volunteers, at present the temporal accuracy of NI-CGM sensors may suffer because of environmental and physiological interferences. The aim of this work is to develop a general methodology, based on Monte Carlo (MC) simulation, to assess the robustness of the calibration step used by NI-CGM devices against these disturbances. The proposed methodology is illustrated considering two examples: the first concerns the possible detrimental influence of sweat events, while the second deals with calibration scheduling. For implementing both examples, 45 datasets collected by the Solianis Multisensor system are considered. In the first example, the MC methodology suggests that no further calibration adjustments are needed after the occurrence of sweat events, because the “Multisensor+model” system is able to deal with the disturbance. The second case study shows how to identify the best time interval to update the model’s calibration for improving the accuracy of the estimated glucose. The methodology proposed in this work is of general applicability and can be helpful in making those incremental steps in NI-CGM devices development needed to further improve their performance.

Enteroviruses are a leading cause of viral infections in children. While most enteroviral infections are mild and self-limiting, severe disease such as a viral sepsis syndrome, myocarditis, hepatitis and meningoencephalitis may occur. We present two cases of neonatal enteroviral myocarditis. Cardiorespiratory failure occurred in both cases, and severe shock refractory to conventional treatment required support with extracorporeal membrane oxygenation (ECMO). One child with coxsackievirus B3 myocarditis failed to recover and died after 3 weeks on ECMO, while one child could be decannulated successfully after 9 days of ECMO and recovered completely subsequently. In conclusion, neonatal myocarditis has a very high mortality, and ECMO should be considered early in neonates with rapid clinical and echocardiographic deterioration despite adequate inotropic support.

The aim of regulation in drug safety is to state as clearly as possible and to enforce the legal responsibility of the involved parties (regulators, marketing authorization holders and health care professionals where applicable), and to provide guidance on how the respective duties should be complied with. The guidelines issued have as a significant impact on the outcome as the law itself, as they determine the stakeholders’ compliance and performance.

Worldwide, various autopsy studies have shown a decrease in the diagnostic error rate over the last years. The cause of this positive development is mainly due to the improvement of modern medicine. However, intensive care unit patients are thought to have a higher risk for diagnostic errors, which is documented in several studies in the adult population. In contrast, there is only limited information about diagnostic errors in pediatrics, particularly in pediatric and neonatal intensive care units. The aims of this study were to analyze the spectrum of childhood death, determine the prevalence and distribution of autopsy-confirmed diagnostic errors, and describe patient characteristics that might have influenced the discordance between antemortem and postmortem findings. We analyzed 143 autopsy reports from 2004 to 2013 and correlated these with clinical reports. The overall autopsy rate during this interval was 20.3%. The leading causes of death were congenital malformations (28%), diseases closely associated with perinatal disorders (25%), disorders of the cardiovascular system (18%), and infections (15%). Additional findings were obtained in 23% of the autopsies. Major diagnostic errors were found in 6%, the lowest reported value in a developed country as yet. Most cases (75%) showed complete concordance between clinical diagnoses and postmortem findings, in line with improvements in diagnostic and therapeutic processes over the last decades. In conclusion, autopsy of neonates, infants, and children represents an important tool for monitoring the quality of pediatric and neonatal medical care.

167 adverse reactions of Swissmedic-authorized veterinary medicinal products were reported during the year 2011 (2010: 160). Species and drug classes remain comparable with previous years: most of the reactions occurred following the use of antiparasitic products (39 %), antiinfectives (20 %) or non-steroidal antiinflammatory drugs (11 %) in companion animals (85 dogs and 27 cats) followed by cattle/calves (37). We received 15 cases of adverse reactions following reconverted use, 8 of them in treated cats. Additionally the Swiss Toxicological Information Centre in Zurich processed 84 enquiries and transmitted them to Swissmedic. One case of a successful new therapy to treat ivermectin poisoning in a pony is presented. Finally, the vaccinovigilance program received 60 declarations following the application of various vaccines, mainly to dogs or cats.

About 15 years ago, the Swiss Society of Pathology has developed and implemented a board examination in anatomical pathology. We describe herein the contents covered by this 2-day exam (autopsy pathology, cytology, histopathology, molecular pathology, and basic knowledge about mechanisms of disease) and its exact modalities, sketch a brief history of the exam, and finish with a concise discussion about the possible objectives and putative benefits weighed against the hardship that it imposes on the candidates.

A male Caucasian patient developed nodular erythematous skin lesions, malaise, and clinical signs of progressive heart failure 4 months after renal transplantation. Bronchoscopy with bronchoalveolar lavage performed for a small infiltrate seen on a computed tomography scan revealed Trypanosoma, which had at this point not been suspected as a cause. Parasitemia was present, and reactivation rather than transmission of Chagas' disease was established by performing polymerase chain reaction and serology in the donor and recipient. Treatment with benznidazole and allopurinol successfully reduced parasitemia, but the clinical course was fatal owing to progression of severe myocarditis. The patient had never lived in an endemic area, but had an extensive travel history in South America. The last visit was more than 5 years before transplantation. In non-endemic countries (United States, Europe), reactivation after transplantation has only been very rarely reported. Given the rising numbers of transplantations in patients with a migration background and extensive travel histories, specific screening procedures have to be considered.

Wind energy is a fast-growing and promising renewable energy source. The investment costs of wind turbines have decreased over the years, making wind energy economically competitive to conventionally produced electricity. Size scaling in the form of a power law, experience curves and progress rates are used to estimate the cost development of ever-larger turbines. In life cycle assessment, scaling and progress rates are seldom applied to estimate the environmental impacts of wind energy. This study quantifies whether the trend toward larger turbines affects the environmental profile of the generated electricity. Previously published life cycle inventories were combined with an engineering-based scaling approach as well as European wind power statistics. The results showed that the larger the turbine is, the greener the electricity becomes. This effect was caused by pure size effects of the turbine (micro level) as well as learning and experience with the technology over time (macro level). The environmental progress rate was 86%, indicating that for every cumulative production doubling, the global warming potential per kWh was reduced by 14%. The parameters, hub height and rotor diameter were identified as Environmental Key Performance Indicators that can be used to estimate the environmental impacts for a generic turbine.