Microvesicle Shedding and Lysosomal Repair Fulfill Divergent Cellular Needs during the Repair of Streptolysin O-Induced Plasmalemmal Damage

Pathogenic bacteria secrete pore-forming toxins that permeabilize the plasma membrane of host cells. Nucleated cells possess protective mechanisms that repair toxin-damaged plasmalemma. Currently two putative repair scenarios are debated: either the isolation of the damaged membrane regions and their subsequent expulsion as microvesicles (shedding) or lysosome-dependent repair might allow the cell to rid itself of its toxic cargo and prevent lysis. Here we provide evidence that both mechanisms operate in tandem but fulfill diverse cellular needs. The prevalence of the repair strategy varies between cell types and is guided by the severity and the localization of the initial toxin-induced damage, by the morphology of a cell and, most important, by the incidence of the secondary mechanical damage. The surgically precise action of microvesicle shedding is best suited for the instant elimination of individual toxin pores, whereas lysosomal repair is indispensable for mending of self-inflicted mechanical injuries following initial plasmalemmal permeabilization by bacterial toxins. Our study provides new insights into the functioning of non-immune cellular defenses against bacterial pathogens.

Cognitive Interventions with Children with Special Needs - Transfer effects and multidisciplinary perspectives

Our last study with regularly developed children demonstrated a positive effect of working memory training on cognitive abilities. Building upon these findings, the aim of this multidisciplinary study is to investigate the effects of training of core functions with children who are suffering from different learning disabilities, like AD/HD, developmental dyslexia or specific language impairment. In addition to working memory training (BrainTwister), we apply a perceptual training, which concentrates on auditory-visual matching (Audilex), as well as an implicit concept learning task. We expect differential improvements of mental capacities, specifically of executive functions (working memory, attention, auditory and visual processing), scholastic abilities (language and mathematical skills), as well as of problem solving. With that, we hope to find further directions regarding helpful and individually adapted interventions in educational settings. Interested parties are invited to discuss and comment the design, the research question, and the possibilities in recruiting the subjects.

The mini-clinical evaluation exercise during medical clerkships: are learning needs and learning goals aligned?

OBJECTIVES The generation of learning goals (LGs) that are aligned with learning needs (LNs) is one of the main purposes of formative workplace-based assessment. In this study, we aimed to analyse how often trainer–student pairs identified corresponding LNs in mini-clinical evaluation exercise (mini-CEX) encounters and to what degree these LNs aligned with recorded LGs, taking into account the social environment (e.g. clinic size) in which the mini-CEX was conducted. METHODS Retrospective analyses of adapted mini-CEX forms (trainers’ and students’ assessments) completed by all Year 4 medical students during clerkships were performed. Learning needs were defined by the lowest score(s) assigned to one or more of the mini-CEX domains. Learning goals were categorised qualitatively according to their correspondence with the six mini-CEX domains (e.g. history taking, professionalism). Following descriptive analyses of LNs and LGs, multi-level logistic regression models were used to predict LGs by identified LNs and social context variables. RESULTS A total of 512 trainers and 165 students conducted 1783 mini-CEXs (98% completion rate). Concordantly, trainer–student pairs most often identified LNs in the domains of ‘clinical reasoning’ (23% of 1167 complete forms), ‘organisation/efficiency’ (20%) and ‘physical examination’ (20%). At least one ‘defined’ LG was noted on 313 student forms (18% of 1710). Of the 446 LGs noted in total, the most frequently noted were ‘physical examination’ (49%) and ‘history taking’ (21%). Corresponding LNs as well as social context factors (e.g. clinic size) were found to be predictors of these LGs. CONCLUSIONS Although trainer–student pairs often agreed in the LNs they identified, many assessments did not result in aligned LGs. The sparseness of LGs, their dependency on social context and their partial non-alignment with students’ LNs raise questions about how the full potential of the mini-CEX as not only a ‘diagnostic’ but also an ‘educational’ tool can be exploited.

History of offending behavior in first episode psychosis patients: A marker of specific clinical needs and a call for early detection strategies among young offenders

OBJECTIVES Previous literature suggests that early psychosis (EP) patients with a history of offending behavior (HOB) have specific clinical needs. The aims of this study were to assess: (1) the prevalence of HOB in a representative sample of EP; (2) the premorbid and baseline characteristics of patients with HOB, and (3) the potential differences in short-term outcome of such patients when compared to patients without HOB. METHODS The Early Psychosis Prevention and Intervention Centre (EPPIC) admitted 786 EP patients between 1998 and 2000. Data were collected from patients' files using a standardized questionnaire. Data of 647 patients could be analyzed. RESULTS HOB patients (29% of the sample) were more likely to be male with lower level of premorbid functioning and education, have used illicit substances and have attempted suicide. They presented with a more complex clinical picture and had poorer 18-month outcome. Most importantly, they had a significantly longer duration of untreated psychosis. CONCLUSIONS On the basis of the high prevalence and specific features of EP patients with HOB, our study confirms a need for additional research in this domain and for the development of specific treatment strategies. Most importantly, it suggests a need for the promotion of early detection strategies among the populations of young offenders, considering that some of them may be going through the early phases of a psychotic disorder and that reduction of treatment delay and provision of well adapted interventions may have a significant impact at numerous levels in such patients

Unmet needs of young interventional cardiologists: proceedings from the 2nd summit of the European association of percutaneous cardiovascular interventions

Every year, the EAPCI Board invites presidents and representatives of the interventional working groups affiliated to EAPCI to discuss issues and strategies surrounding the goals of education and advanced healthcare practices in interventional cardiology. In 2013, the 2nd EAPCI Summit, organised by the EAPCI Board in collaboration with the NIFYI committee, was entirely dedicated to discussing the unmet needs of the young generation of interventional cardiologists. In this article, we highlight a selection of the key points and proposed actions highlighted during the summit.

Alignment between learning needs and learning goals of Mini-CEX in clerkships

Background: Defining learning goals (LG) in alignment with learning needs (LN) is one of the key purposes of formative workplace-based assessment, but studies about this topic are scarce. Summary of Work: We analysed quantitatively and qualitatively how often trainer-student pairs identified the same LN during Mini Clinical Evaluation Exercises (Mini-CEX) in clerkships and to what degree those LNs were in line with the recorded LGs. Multilevel logistic regression models were used to predict LGs by identified LNs, controlling for context variables. Summary of Results: 512 trainers and 165 students conducted 1783 Mini-CEX (98% completion rate). Concordantly, trainer-student pairs most often identified LNs in the domains ‘clinical reasoning’ (23% of 1167 complete forms), ‘organisation / efficiency’ (20%) and ‘physical examination’ (20%). At least one ‘defined’ LG was noted on 313 student forms (18% of 1710), with a total of 446 LGs. Of these, the most frequent LGs were ‘physical examination’ (49% of 446 LGs) and ‘history taking’ (21%); corresponding LNs as well as context variables (e.g. clinic size) were found to be predictors of these LGs. Discussion and Conclusions: Although trainer-student pairs often agreed in their identified LNs, many assessments did not result in an aligned LG or a LG at all. Interventions are needed to enhance the proportion of (aligned) LGs in Mini-CEX in order to tap into its full potential not only as a ‘diagnostic’ but also as an ‘educational tool’. Take-home messages: The sparseness of LGs, their dependency on context variables and their partial non-alignment with students’ LNs raise the question of how the effectiveness of Mini-CEX can be further enhanced.

A Quantitative Analysis of Developer Information Needs in Software Ecosystems

We present the results of an investigation into the nature of information needs of software developers who work in projects that are part of larger ecosystems. This work is based on a quantitative survey of 75 professional software developers. We corroborate the results identified in the sur- vey with needs and motivations proposed in a previous sur- vey and discover that tool support for developers working in an ecosystem context is even more meager than we thought: mailing lists and internet search are the most popular tools developers use to satisfy their ecosystem-related information needs.

Adaptable Visualisation Based On User Needs

Software developers often ask questions about software systems and software ecosystems that entail exploration and navigation, such as who uses this component?, and where is this feature implemented?. Software visualisation can be a great aid to understanding and exploring the answers to such questions, but visualisations require expertise to implement effectively, and they do not always scale well to large systems. We propose to automatically generate software visualisations based on software models derived from open source software corpora and from an analysis of the properties of typical developers queries and commonly used visualisations. The key challenges we see are (1) understanding how to match queries to suitable visualisations, and (2) scaling visualisations effectively to very large software systems and corpora. In the paper we motivate the idea of automatic software visualisation, we enumerate the challenges and our proposals to address them, and we describe some very initial results in our attempts to develop scalable visualisations of open source software corpora.

Information needs in parents of long-term childhood cancer survivors.

BACKGROUND Parents' knowledge about cancer, treatment, potential late effects and necessary follow-up is important to reassure themselves and motivate their child to participate in regular follow-up. We aimed to describe (i) parents' perception of information received during and after treatment; (ii) parents' current needs for information today, and to investigate; and (iii) associations between information needs and socio-demographic and clinical characteristics. METHODS As part of the Swiss Childhood Cancer Survivor Study, a follow-up questionnaire was sent to parents of survivors, diagnosed < 16 years and after 1990, and aged 11-17 years at study. We assessed parents' perception of information received and information needs, concerns about consequences of the cancer and socio-demographic information. Information on clinical data was available from the Swiss Childhood Cancer Registry. RESULTS Of 309 eligible parents, 189 responded (67%; mean time since diagnosis: 11.3 years, SD = 2.5). Parents perceived to have received verbal information (on illness: verbal 91%, written 40%; treatment: verbal 88%, written 46%; follow-up: verbal 85% written 27%; late effects: verbal 75%, written 19%). Many parents reported current information needs, especially on late effects (71%). The preferred source was written general (28%) or verbal information (25%), less favored was online information (12%). Information needs were associated with migration background (P = 0.039), greater concerns about consequences of cancer (P = 0.024) and no information received (P = 0.035). CONCLUSION Parents reported that they received mainly verbal information. However, they still needed further information especially about possible late effects. Individual long-term follow-up plans, including a treatment summary, should be provided to each survivor, preferably in written format.

Colonization with resistant microorganisms in patients transferred from abroad: who needs to be screened?

BACKGROUND While multi-drug resistant organisms (MDRO) are a global phenomenon, there are significant regional differences in terms of prevalence. Traveling to countries with a high MDRO prevalence increases the risk of acquiring such an organism. In this study we determined risk factors for MDRO colonization among patients who returned from a healthcare system in a high-prevalence area (so-called transfer patients). Factors predicting colonization could serve as screening criteria to better target those at highest risk. METHODS This screening study included adult patients who had been exposed to a healthcare system abroad or in a high-prevalence region in Switzerland over the past six months and presented to our 950-bed tertiary care hospital between January 1, 2012 and December 31, 2013, a 24-month period. Laboratory screening tests focused on Gram-negative MDROs and methicillin-resistant Staphylococcus aureus (MRSA). RESULTS A total of 235 transfer patients were screened and analyzed, of which 43 (18 %) were positive for an MDRO. Most of them yielded Gram-negative bacteria (42; 98 %), with only a single screening revealing MRSA (2 %); three screenings showed a combination of Gram-negative bacteria and MRSA. For the risk factor analysis we focused on the 42 Gram-negative MDROs. Most of them were ESBL-producing Escherichia coli and Klebsiella pneumoniae while only two were carbapenemase producers. In univariate analysis, factors associated with screening positivity were hospitalization outside of Europe (p < 0.001), surgical procedure in a hospital abroad (p = 0.007), and - on admission to our hospital - active infection (p = 0.002), antibiotic treatment (p = 0.014) and presence of skin lesions (p = 0.001). Only hospitalization outside of Europe (Odds Ratio, OR 3.2 (95 % CI 1.5- 6.8)) and active infection on admission (OR 2.7 (95 % CI 1.07- 6.6)) remained as independent predictors of Gram-negative MDRO colonization. CONCLUSION Our data suggest that a large proportion of patients (i.e., 82 %) transferred to Switzerland from hospitals in high MDRO prevalence areas are unnecessarily screened for MDRO colonization. Basing our screening strategy on certain criteria (such as presence of skin lesions, active infection, antibiotic treatment, history of a surgical procedure abroad and hospitalization outside of Europe) promises to be a better targeted and more cost-effective strategy.