Characterising group-level brain connectivity: A framework using Bayesian exponential random graph models.

The brain can be modelled as a network with nodes and edges derived from a range of imaging modalities: the nodes correspond to spatially distinct regions and the edges to the interactions between them. Whole-brain connectivity studies typically seek to determine how network properties change with a given categorical phenotype such as age-group, disease condition or mental state. To do so reliably, it is necessary to determine the features of the connectivity structure that are common across a group of brain scans. Given the complex interdependencies inherent in network data, this is not a straightforward task. Some studies construct a group-representative network (GRN), ignoring individual differences, while other studies analyse networks for each individual independently, ignoring information that is shared across individuals. We propose a Bayesian framework based on exponential random graph models (ERGM) extended to multiple networks to characterise the distribution of an entire population of networks. Using resting-state fMRI data from the Cam-CAN project, a study on healthy ageing, we demonstrate how our method can be used to characterise and compare the brain's functional connectivity structure across a group of young individuals and a group of old individuals.

Assessing dynamic functional connectivity in heterogeneous samples.

Several methods have been developed to measure dynamic functional connectivity (dFC) in fMRI data. These methods are often based on a sliding-window analysis, which aims to capture how the brain's functional organization varies over the course of a scan. The aim of many studies is to compare dFC across groups, such as younger versus older people. However, spurious group differences in measured dFC may be caused by other sources of heterogeneity between people. For example, the shape of the haemodynamic response function (HRF) and levels of measurement noise have been found to vary with age. We use a generic simulation framework for fMRI data to investigate the effect of such heterogeneity on estimates of dFC. Our findings show that, despite no differences in true dFC, individual differences in measured dFC can result from other (non-dynamic) features of the data, such as differences in neural autocorrelation, HRF shape, connectivity strength and measurement noise. We also find that common dFC methods such as k-means and multilayer modularity approaches can detect spurious group differences in dynamic connectivity due to inappropriate setting of their hyperparameters. fMRI studies therefore need to consider alternative sources of heterogeneity across individuals before concluding differences in dFC.

Aetiology of adult burns treated from 2000 to 2012 in a Swiss University Hospital.

BACKGROUND: Burns in Switzerland are frequent and lead to high economic and social costs. However, little is known about the aetiology of burns suffered by patients seeking treatment in hospital emergency departments. This knowledge could be used to develop preventive measures. METHODS: This retrospective analysis included all patients (≥16 years old) with acute thermal injuries of known cause admitted to the adult emergency department in Bern University Hospital (Switzerland, not a specialised burns unit) between 2000 and 2012. Clinical and sociodemographic data were extracted from medical records, i.e. the environment in which the burn occurred, as well as details of burn severity and aetiology. RESULTS: Seven hundred and one (701) patients with a mean age of 35.0±14.5 years (56% men) were included in the analysis. The winter season and the days around Christmas, turn of the year and Swiss National Day were identified as times with high risk of burns. Household (45%) and workplace (31%) were the most common locations/settings in which the burns occurred. Approximately every second burn was caused by scald, every fourth by flame and every seventh by hot objects. The analysis identified cooking, tar and electricity in workplace accidents, barbecues and the use of gasoline as aetiological factors in burns in leisure time, together with water in domestic thermal injuries. Burns occurred predominantly on non-protected skin on the hand and arms. The most severe burns were seen in electrical and flame burns. Men suffered more severe burns than women in all settings except psychopathology. CONCLUSIONS: The data suggest that the incidence and severity of burns in Switzerland could be reduced by preventive strategies and public campaigns, including education on fire protection systems, raising awareness about the times and locations where the risks of burns are greater, further improvement in workplace safety, particularly with cooking facilities and electrical equipment, and the development of innovative safety devices (i.e. machines, protective gloves). These findings have to be interpreted carefully, as this study includes only adult patients who presented in our ED and, in most cases, the burns covered less than 20% of the body surface.

Nanoparticulate CpG immunotherapy in RAO-affected horses: phase I and IIa study.

BACKGROUND: Recurrent airway obstruction (RAO), an asthma-like disease, is 1 of the most common allergic diseases in horses in the northern hemisphere. Hypersensitivity reactions to environmental antigens cause an allergic inflammatory response in the equine airways. Cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODN) are known to direct the immune system toward a Th1-pathway, and away from the pro-allergic Th2-line (Th2/Th1-shift). Gelatin nanoparticles (GNPs) are biocompatible and biodegradable immunological inert drug delivery systems that protect CpG-ODN against nuclease degeneration. Preliminary studies on the inhalation of GNP-bound CpG-ODN in RAO-affected horses have shown promising results. OBJECTIVES: The aim of this study was to evaluate the clinical and immunological effects of GNP-bound CpG-ODN in a double-blinded, placebo-controlled, prospective, randomized clinical trial and to verify a sustained effect post-treatment. ANIMALS AND METHODS: Twenty-four RAO-affected horses received 1 inhalation every 2 days for 5 consecutive administrations. Horses were examined for clinical, endoscopic, cytological, and blood biochemical variables before the inhalation regimen (I), immediately afterwards (II), and 4 weeks post-treatment (III). RESULTS: At time points I and II, administration of treatment rather than placebo corresponded to a statistically significant decrease in respiratory effort, nasal discharge, tracheal secretion, and viscosity, AaDO2 and neutrophil percentage, and an increase in arterial oxygen pressure. CONCLUSION AND CLINICAL IMPORTANCE: Administration of a GNP-bound CpG-ODN formulation caused a potent and persistent effect on allergic and inflammatory-induced clinical variables in RAO-affected horses. This treatment, therefore, provides an innovative, promising, and well-tolerated strategy beyond conventional symptomatic long-term therapy and could serve as a model for asthma treatment in humans.

Sociocognitive predictors of the intention of healthcare workers to receive the influenza vaccine in Belgian, Dutch and German hospital settings.

BACKGROUND: Influenza vaccination of healthcare workers (HCWs) is recommended to prevent the transmission of influenza to vulnerable patients. Nevertheless, vaccination coverage rates of HCWs in European countries have been low. AIM: To investigate the relative and combined strength of sociocognitive variables, from past research, theory and a qualitative study, in explaining the motivation of HCWs to receive the influenza vaccine. METHODS: An anonymous, online questionnaire was distributed among HCWs in hospital settings in Belgium, Germany and the Netherlands between February and April 2013. FINDINGS: Attitude and past vaccination uptake explained a considerable amount of variance in the intention of HCWs to receive the influenza vaccine. Moreover, low perceived social norms, omission bias, low moral norms, being older, having no patient contact, and being Belgian or Dutch (compared with German) increased the probability of having no intention to receive the influenza vaccine compared with being undecided about vaccination. High intention to receive the influenza vaccine was shown to be more likely than being undecided about vaccination when HCWs had high perceived susceptibility of contracting influenza, low naturalistic views, and lower motivation to receive the vaccine solely for self-protection. CONCLUSION: Country-specific interventions and a focus on different sociocognitive variables depending on the intention/lack of intention of HCWs to receive the influenza vaccine may be beneficial to promote vaccination uptake.

[Serous vascularized pigment epithelial detachment in exudative AMD. Morphological typing and risk of tears in the RPE]. / Seröse vaskularisierte Pigmentepithelabhebungen bei exsudativer altersbedingter Makuladegeneration : Morphologische Typisierung und Risiko eines Einrisses im retinalen Pigmentepithel.

PURPOSE: Are there any morphological parameters in pigment epithelial detachment (PED) in eyes with age-related macular degeneration (AMD), which could identify the development of tears (RIP) in the retinal pigment epithelium (RPE) before initiation of anti-vascular endothelial growth factor (VEGF) therapy? METHODS: Retrospectively, the spectral domain optical coherence tomography (SD-OCT), FLA and near infrared (NIR) images of 98 eyes with PED in exudative AMD before treatment (ranibizumab or bevacizumab) were analyzed. Eyes in which a tear in the RPE (RIP group) could be observed during treatment were compared to eyes without the development of RIP (PED group) in the following morphological parameters of PED: height, number of peaks, presence of hyporeflective fissures at the base of the PED, structure of the RPE, presence of floating structures in the PED with maximum hyperreflectivity, amount and localization of hyperreflectivity in the PED and hyperreflectivity in the NIR images. RESULTS: In the 80 eyes of the PED group the mean PED height was 373.7± 197 µm and in the 18 eyes of the RIP group the mean PED height was higher (694.2± 284.3 µm, p < 0.0001). A difference was also seen in the number of peaks per PED (PED group 43%, RIP group 72%, p = 0.039) and in the hyperreflectivity in NIR images (PED group 68%, RIP group 94%, p = 0.033). There were no significant differences in the other morphological parameters. A classification into four types of PED was found by the parameters height and number of peaks. The PED type with a height > 350 µm and one peak (RIP 43%) developed tears more often (p = 0.001) than the PED type < 350 µm with one peak (RIP 0%, p = 0.001). A trend in the visual acuity over 156 weeks was seen: in PED types with heights > 350 µm there was a lower increase in the visual acuity than in PED types < 350 µm (rm ANOVA p = 0.18; ɛ HH = 0.88). Furthermore, in PED types > 350 µm with multiple peaks the total number of injections necessary was higher than in the other PED types (p = 0.032). CONCLUSION: Morphological parameters, such as PED height, number of peaks per PED in OCT images and hyperreflectivity in NIR images are prognostic factors for RPE tears in exudative AMD. The PED height and number of peaks per PED are useful for classification of PED in the daily routine.

[GP medication prioritisation in older patients with multiple comorbidities recently discharged from hospital: a case-based bottom-up approach]. / Hausärztliche Arzneimittelpriorisierung bei stationär entlassenen, multimorbiden, älteren Patienten--Ein Vignetten-Ansatz aus der Hausarzt-Perspektive.

INTRODUCTION: After the hospital discharge of older patients with multiple morbidities, GPs are often faced with the task of prioritising the patients' drug regimens so as to reduce the risk of overmedication. AIM: How do GPs prioritise such medications in multimorbid elderly patients at the transition between inpatient and home care? The experience by the GPs is documented in typical case vignettes. METHOD: 44 GPs in Sachsen-Anhalt were recruited--they were engaged in focus group discussions and interviewed using semi-standardised questionnaires. Typical case vignettes were developed, relevant to the everyday care that elderly patients would typically receive from their GPs with respect to their drug optimisation. RESULTS: According to the results of the focus groups, the following issues affect GPs' decisions: drug and patient safety, their own competence in the health system, patient health literacy, evidence base, communication between secondary and primary care (and their respective influences on each other). When considering individual cases, patient safety, patient wishes, and quality of life were central. This is demonstrated by the drug dispositions of one exemplary case vignette. CONCLUSIONS: GPs do prioritise drug regimens with rational criteria. Initial problem delineation, process documentation and the design of a transferable product are interlinking steps in the development of case vignettes. Care issues of drug therapy in elderly patients with multiple morbidities should be investigated further with larger representative samples in order to clarify whether the criteria used here are applied contextually or consistently. Embedding case vignettes into further education concepts is also likely to be useful.

[Mild bleeding diathesis in a 62-year-old woman with hereditary thrombocytopenia]. / Milde Blutungsneigung bei einer 62-Jährigen mit hereditärer Thrombozytopenie.

A 62-year-old woman presented with severe, isolated thrombocytopenia. Due to the positive family history and normal thrombocyte morphology ANKRD26-associated thrombocytopenia 2 (THC2) was suspected. The diagnosis was confirmed by DNA sequencing. Although this is the first case report on THC2 in Germany, we anticipate that THC2 might be a frequent cause of hereditary thrombocytopenia. A specific therapy was not necessary, but would consist of platelet supplementation.

Ageing with an intellectual disability: the impact of personal resources on well-being.

BACKGROUND: The population of ageing people with mild and moderate intellectual disabilities (ID) is growing rapidly. This study examines how personal resources (physical health, mental health and social networks) impact the well-being of ageing people with ID. METHODS: Longitudinal survey data on 667 people with a mild or moderate ID were acquired via interviews in 2006 and 2010. Indicators of personal resources (physical health, mental health and social networks) were assessed, as were indicators of well-being (satisfaction with life, happiness and loneliness). Additionally, data on background characteristics and autonomy were gathered. RESULTS: The results show that age is positively related to decreased mobility and auditory disabilities and negatively related to independent living, autonomy in how one spends one's leisure time and autonomy in decision-making. Longitudinal analyses demonstrated that, with the exception of health that deteriorated, and social satisfaction that improved, almost all variables remained stable over the 4-year period. Further, good physical health in 2006 predicted happiness in 2010. CONCLUSION: Despite the fact that age is associated with poorer physical and mental health and a smaller social network, this study showed that older people with ID have relatively high levels of well-being. Findings are discussed in the light of coping with ageing and impact of life events.

[Clinical trials in children--between the expectations of scientific requirements, the assurance of proven treatment and ethical demands]. / Klinische Prüfung an Kindern im Spannungsfeld zwischen wissenschaftlichen Anforderungen, der Sicherstellung der korrekten Behandlung und ethischen Aspekten.

Regulation (EC) No. 1901/2006 of the European Parliament and the Council dated 12 December 2008 on medicinal products for paediatric use is the result of a survey by the European Commission, concluding that children in the European Union are inadequately treated with medicinal products. The Regulation is addressed to the pharmaceutical industry with the intention to place medicinal products on the market and to the Member States to register all information on medicinal products for the treatment of children. The pharmaceutical industry will be obliged to conduct clinical trials in children for new medicinal products and medicinal products still under patent. This will be supported by incentives and rewards. As a consequence of the requirement to conduct clinical trials in children the framework and conditions have to be defined and ethical considerations have to be respected.