Governance of Digital Game Environments and Cultural Diversity : Transdisciplinary Enquiries. Preface

Digital game environments are of increasing economic, social and cultural value. As their influence on diverse facets of life grows, states have felt compelled to intervene and secure some public interests. Yet, the contours of a comprehensive governance model are far from recognisable and governments are grappling with the complexity and fluidity of online games and virtual worlds as private spaces and as experimentation fields for creativity and innovation. This book contributes to a more comprehensive and fine-grained understanding of digital game environments, which is a precondition for addressing any of the pressing governance questions posed. Particular attention is given to the concept and policy objective of cultural diversity, which also offers a unique entry point into the discussion of the appropriate legal regulation of digital games. Governance of Digital Game Environments and Cultural Diversity will be of interest to researchers of media law, internet law and governance, cultural studies, anthropology and sociology. As the book addresses a highly topical theme, it will attract the attention of policymakers at national, regional and international levels and will also serve as a great resource tool for scholars in new media and, in particular, digital games and virtual worlds.

Reporting standards for studies of diagnostic test accuracy in dementia: The STARDdem Initiative.

OBJECTIVE To provide guidance on standards for reporting studies of diagnostic test accuracy for dementia disorders. METHODS An international consensus process on reporting standards in dementia and cognitive impairment (STARDdem) was established, focusing on studies presenting data from which sensitivity and specificity were reported or could be derived. A working group led the initiative through 4 rounds of consensus work, using a modified Delphi process and culminating in a face-to-face consensus meeting in October 2012. The aim of this process was to agree on how best to supplement the generic standards of the STARD statement to enhance their utility and encourage their use in dementia research. RESULTS More than 200 comments were received during the wider consultation rounds. The areas at most risk of inadequate reporting were identified and a set of dementia-specific recommendations to supplement the STARD guidance were developed, including better reporting of patient selection, the reference standard used, avoidance of circularity, and reporting of test-retest reliability. CONCLUSION STARDdem is an implementation of the STARD statement in which the original checklist is elaborated and supplemented with guidance pertinent to studies of cognitive disorders. Its adoption is expected to increase transparency, enable more effective evaluation of diagnostic tests in Alzheimer disease and dementia, contribute to greater adherence to methodologic standards, and advance the development of Alzheimer biomarkers.

Abatacept in the Treatment of Severe, Longstanding, and Refractory Uveitis Associated with Juvenile Idiopathic Arthritis.

OBJECTIVE Abatacept (ABA), a selective T cell costimulation modulator that binds to CD80 and CD86 on antigen-presenting cells, was investigated for its antiinflammatory effect in treating severe chronic uveitis associated with juvenile idiopathic arthritis (JIA). METHODS Our retrospective study was conducted by members of the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC). Patients with JIA who are receiving ABA treatment for active uveitis were included. In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, immunosuppressives, and at least 1 tumor necrosis factor-α inhibitor. A standardized protocol was used to document uveitis (MIWGUC) and arthritis. Baseline visit and visits at 3, 6, 9, and 12 months before and after ABA start were evaluated. Primary outcome measure was defined as achievement of uveitis inactivity; secondary outcome measures were tapering of corticosteroid and/or immunosuppressive treatment, and occurrence of complications. RESULTS In all, 21 patients (16 female) with active uveitis (n = 21) and arthritis (n = 18) were included (mean age 11.8 ± 3.6 yrs). In 7 of 18 patients with active arthritis at baseline, inactivity was achieved following ABA treatment. Uveitis inactivity was achieved in 11 patients, but recurred later in 8 of them, and remained active in another 10 cases. Systemic corticosteroids or immunosuppression were tapered in 3 patients, but uveitis recurred in all of them during further followup. Ocular complications secondary to uveitis were present in 17 patients at baseline, while 3 patients developed new ocular complications during followup. CONCLUSION A sustained response to ABA was uncommon in patients with severe and refractory uveitis.

Inter-observer agreement for diagnostic classification of esophageal motility disorders defined in high-resolution manometry

High-resolution esophageal manometry (HRM) is a recent development used in the evaluation of esophageal function. Our aim was to assess the inter-observer agreement for diagnosis of esophageal motility disorders using this technology. Practitioners registered on the HRM Working Group website were invited to review and classify (i) 147 individual water swallows and (ii) 40 diagnostic studies comprising 10 swallows using a drop-down menu that followed the Chicago Classification system. Data were presented using a standardized format with pressure contours without a summary of HRM metrics. The sequence of swallows was fixed for each user but randomized between users to avoid sequence bias. Participants were blinded to other entries. (i) Individual swallows were assessed by 18 practitioners (13 institutions). Consensus agreement (≤2/18 dissenters) was present for most cases of normal peristalsis and achalasia but not for cases of peristaltic dysmotility. (ii) Diagnostic studies were assessed by 36 practitioners (28 institutions). Overall inter-observer agreement was 'moderate' (kappa 0.51) being 'substantial' (kappa > 0.7) for achalasia type I/II and no lower than 'fair-moderate' (kappa >0.34) for any diagnosis. Overall agreement was somewhat higher among those that had performed >400 studies (n = 9; kappa 0.55) and 'substantial' among experts involved in development of the Chicago Classification system (n = 4; kappa 0.66). This prospective, randomized, and blinded study reports an acceptable level of inter-observer agreement for HRM diagnoses across the full spectrum of esophageal motility disorders for a large group of clinicians working in a range of medical institutions. Suboptimal agreement for diagnosis of peristaltic motility disorders highlights contribution of objective HRM metrics.

Sudden cardiac death in forensic medicine – Swiss recommendations for a multidisciplinary approach

Sudden cardiac death (SCD) is by definition unexpected and cardiac in nature. The investigation is almost invariably performed by a forensic pathologist. Under these circumstances the role of the forensic pathologist is twofold: (1.) to determine rapidly and efficiently the cause and manner of death and (2.) to initiate a multidisciplinary process in order to prevent further deaths in existing family members. If the death is determined to be due to "natural" causes the district attorney in charge often refuses further examinations. However, additional examinations, i.e. extensive histopathological investigations and/or molecular genetic analyses, are necessary in many cases to clarify the cause of death. The Swiss Society of Legal Medicine created a multidisciplinary working group together with clinical and molecular geneticists and cardiologists in the hope of harmonising the approach to investigate SCD. The aim of this paper is to close the gap between the Swiss recommendations for routine forensic post-mortem cardiac examination and clinical recommendations for genetic testing of inherited cardiac diseases; this is in order to optimise the diagnostic procedures and preventive measures for living family members. The key points of the recommendations are (1.) the forensic autopsy procedure for all SCD victims under 40 years of age, (2.) the collection and storage of adequate samples for genetic testing, (3.) communication with the families, and (4.) a multidisciplinary approach including cardiogenetic counselling.

Wirksamkeit kognitiver Remediationstherapie bei schizophren Erkrankten mit ausgeprägter Negativsymptomatik

Einleitung Die Behandlung von Negativsymptomen ist bei schizophren Erkrankten bis heute wenig erfolgsversprechend. Wenige Studien zeigen inkonsistente Befunde und berichten ausschliesslich über eine dimensionale Reduktion von Negativsymptomen, jedoch nicht über Remissionsraten bei ausgeprägter Negativsymptomatik. Gegenwärtig wird der mögliche Nutzen Kognitiver Remediationstherapie zur Behandlung von Negativsymptomen diskutiert. Die von unserer Arbeitsgruppe entwickelte Integrierte Neurokognitive Therapie (INT) stellt einen Kognitiven Remediationsansatz im Gruppensetting dar und vereint Interventionen zu allen kognitiven MATRICS-Dimensionen in einem einheitlichen Therapiekonzept. Methode In einer internationalen multizentrischen RCT mit 138 ambulanten schizophrenen Patienten (DSM IV-TR) wurde die INT mit einer Standardbehandlung (TAU) verglichen. In Anlehnung an die vorgeschlagenen PANSS-Kriterien der „Remission in Schizophrenia Working Group“ (RSWG) wurden aus der Stichprobe eine Gruppe mit ausgeprägten Negativsymtomen (GN) während der Baselineerhebung definiert (n=53). Als Referenz diente eine Gruppe mit persistierenden Positivsymptomen ohne Negativsymptome (GP, n=31) sowie eine remittierte Gruppe (RG, n=54) ohne Symptome. Eine Testbatterie zu kognitiven und sozialen Funktionen sowie ein PANSS-Interview wurden vor und nach der Therapiephase von 15 Wochen sowie nach einer Einjahreskatamnese erhoben, um die Wirksamkeit von INT bei Patienten mit ausgeprägter Negativsymptomatik zu quantifizieren. Ergebnisse 1) Symptomreduktion: in der Zielgruppe GN zeigten signifikant mehr INT-Patienten (55%) als TAU-Patienten (26%) während der Therapiephase eine Remission der Negativsymptomatik. Auch nach der Katamnese erzielte INT (82%) signifiaknt höhere Remissionsraten als TAU (50%). Dagegen waren in GP keine signifikanten Symptomreduktionen gegenüber TAU nachweisbar. In RG waren signifikant geringere Rückfallraten (Symptomanstieg) bei INT (13%) gegenüber TAU (50%) nach der Therapie feststellbar. 2) Kognitive Funktionen: signifiante Effekte in GN und in RG zu Gunsten von INT konnten bezüglich der Geschwindigkeit der Informationsverarbeitung und der Aufmerksamkeit gegenüber TAU nachgewiesen werden. 3) Soziale Funktionen: INT erzielte in GN und in RG eine signifikante Überlegenheit im psychsozialen Funktionsniveau (Generalisierungeffekt). Kognitive Remediationstherapie reduziert ausgeprägte Negativsymptome, unterstützt die Rückfallprophylaxe und verbessert kognitive und soziale Funktionen auch bei Patienten mit Negativsymptomen.

The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.

BACKGROUND Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. METHODS Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency. RESULTS One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still TOL. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively. CONCLUSIONS In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.

Interobserver variations of target volume delineation in multicatheter partial breast brachytherapy after open cavity surgery

PURPOSE To investigate interobserver variations of target volume delineations in accelerated partial breast irradiation with multicatheter brachytherapy (BT) and to assess the impact of guidelines on consistency of contouring. METHODS AND MATERIALS A contouring study with two phases in interstitial accelerated partial breast irradiation after open cavity surgery was conducted by the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology Breast Cancer Working Group. Contours of cavity and planning target volume (PTV) on preimplant and postimplant CT images were delineated. In Phase 1, nine radiation oncologists defined the target volumes of 5 patients, whereas in Phase 2, four observers draw the contours of 4 patients applying guidelines. In Phase 1, experience in breast BT after open cavity surgery was assessed. The delineations were compared between Phase 1 and Phase 2, the impact of guidelines was assessed, and cavity visualization score was related to consistency of delineations. RESULTS Significant interobserver variability in delineations of lumpectomy cavity and PTV was observed among the participants. Observers with BT experience after open cavity surgery outlined the cavity and PTV more consistently (conformity indexgen: 0.52 vs. 0.48 and 0.59 vs. 0.55 for preimplant and postimplant cavities). For all volumes, the mean Vmax/Vmin was 2.2 vs. 2.8. Having used guidelines all conformity indices increased significantly. For cavity, the increase was 14% and 11%, whereas for the PTV, 28% and 17% on the preimplant and postimplant CT images, respectively. A strong correlation was found between consistency of contours and cavity visualization score. CONCLUSIONS Simple guidelines on defining the lumpectomy cavity significantly increased the consistency of contouring. Reliable consistency of target volume definition can be expected only for good cavity visibility.

Primary prevention of peri-implantitis: managing peri-implant mucositis

AIMS Over the past decades, the placement of dental implants has become a routine procedure in the oral rehabilitation of fully and partially edentulous patients. However, the number of patients/implants affected by peri-implant diseases is increasing. As there are--in contrast to periodontitis--at present no established and predictable concepts for the treatment of peri-implantitis, primary prevention is of key importance. The management of peri-implant mucositis is considered as a preventive measure for the onset of peri-implantitis. Therefore, the remit of this working group was to assess the prevalence of peri-implant diseases, as well as risks for peri-implant mucositis and to evaluate measures for the management of peri-implant mucositis. METHODS Discussions were informed by four systematic reviews on the current epidemiology of peri-implant diseases, on potential risks contributing to the development of peri-implant mucositis, and on the effect of patient and of professionally administered measures to manage peri-implant mucositis. This consensus report is based on the outcomes of these systematic reviews and on the expert opinion of the participants. RESULTS Key findings included: (i) meta-analysis estimated a weighted mean prevalence for peri-implant mucositis of 43% (CI: 32-54%) and for peri-implantitis of 22% (CI: 14-30%); (ii) bleeding on probing is considered as key clinical measure to distinguish between peri-implant health and disease; (iii) lack of regular supportive therapy in patients with peri-implant mucositis was associated with increased risk for onset of peri-implantitis; (iv) whereas plaque accumulation has been established as aetiological factor, smoking was identified as modifiable patient-related and excess cement as local risk indicator for the development of peri-implant mucositis; (v) patient-administered mechanical plaque control (with manual or powered toothbrushes) has been shown to be an effective preventive measure; (vi) professional intervention comprising oral hygiene instructions and mechanical debridement revealed a reduction in clinical signs of inflammation; (vii) adjunctive measures (antiseptics, local and systemic antibiotics, air-abrasive devices) were not found to improve the efficacy of professionally administered plaque removal in reducing clinical signs of inflammation. CONCLUSIONS Consensus was reached on recommendations for patients with dental implants and oral health care professionals with regard to the efficacy of measures to manage peri-implant mucositis. It was particularly emphasized that implant placement and prosthetic reconstructions need to allow proper personal cleaning, diagnosis by probing and professional plaque removal.