A national survey on violence and discrimination among people with disabilities

Background: The aim of the study was to quantify levels of violence and discrimination among people with disabilities and analyze the effects of gender and the type and degree of disability. Methods: The study analyzed data on self-reported violence and discrimination from a Danish national survey of 18,019 citizens, of whom 4519 reported a physical disability and 1398 reported a mental disability. Results: Individuals with disabilities reported significantly higher levels of violence than those without. Specifically, individuals reporting a mental disability reported higher levels of violence and discrimination. Significant gender differences were found with regard to type of violence: while men with disabilities were more likely to report physical violence, women with disabilities were more likely to report major sexual violence, humiliation and discrimination. Neither severity nor visibility of disability was found to be a significant factor for risk of violence. Conclusions: This large-scale study lends support to existing research showing that people with disabilities are at greater risk of violence than people without disabilities. Further, the study found that people with mental disabilities were significantly more likely to report all types of violence and discrimination than those with physical disabilities. The findings also show that gender is significant in explaining the type of violence experienced and the experience of discrimination

Differentially expressed alternatively spliced genes in Malignant Pleural Mesothelioma identified using massively parallel transcriptome sequencing

<p>Abstract</p> <p>Background</p> <p>Analyses of Expressed Sequence Tags (ESTs) databases suggest that most human genes have multiple alternative splice variants. The alternative splicing of pre-mRNA is tightly regulated during development and in different tissue types. Changes in splicing patterns have been described in disease states. Recently, we used whole-transcriptome shotgun pryrosequencing to characterize 4 malignant pleural mesothelioma (MPM) tumors, 1 lung adenocarcinoma and 1 normal lung. We hypothesized that alternative splicing profiles might be detected in the sequencing data for the expressed genes in these samples.</p> <p>Methods</p> <p>We developed a software pipeline to map the transcriptome read sequences of the 4 MPM samples and 1 normal lung sample onto known exon junction sequences in the comprehensive AceView database of expressed sequences and to count how many reads map to each junction. 13,274,187 transcriptome reads generated by the Roche/454 sequencing platform for 5 samples were compared with 151,486 exon junctions from the AceView database. The exon junction expression index (EJEI) was calculated for each exon junction in each sample to measure the differential expression of alternative splicing events. Top ten exon junctions with the largest EJEI difference between the 4 mesothelioma and the normal lung sample were then examined for differential expression using Quantitative Real Time PCR (qRT-PCR) in the 5 sequenced samples. Two of the differentially expressed exon junctions (ACTG2.aAug05 and CDK4.aAug05) were further examined with qRT-PCR in additional 18 MPM and 18 normal lung specimens.</p> <p>Results</p> <p>We found 70,953 exon junctions covered by at least one sequence read in at least one of the 5 samples. All 10 identified most differentially expressed exon junctions were validated as present by RT-PCR, and 8 were differentially expressed exactly as predicted by the sequence analysis. The differential expression of the AceView exon junctions for the ACTG2 and CDK4 genes were also observed to be statistically significant in an additional 18 MPM and 18 normal lung samples examined using qRT-PCR. The differential expression of these two junctions was shown to successfully classify these mesothelioma and normal lung specimens with high sensitivity (89% and 78%, respectively).</p> <p>Conclusion</p> <p>Whole-transcriptome shotgun sequencing, combined with a downstream bioinformatics pipeline, provides powerful tools for the identification of differentially expressed exon junctions resulting from alternative splice variants. The alternatively spliced genes discovered in the study could serve as useful diagnostic markers as well as potential therapeutic targets for MPM.</p

Factors influencing physical activity and rehabilitation in survivors of critical illness: a systematic review of quantitative and qualitative studies

PURPOSE: To identify, evaluate and synthesise studies examining the barriers and enablers for survivors of critical illness to participate in physical activity in the ICU and post-ICU settings from the perspective of patients, caregivers and healthcare providers. METHODS: Systematic review of articles using five electronic databases: MEDLINE, CINAHL, EMBASE, Cochrane Library, Scopus. Quantitative and qualitative studies that were published in English in a peer-reviewed journal and assessed barriers or enablers for survivors of critical illness to perform physical activity were included. Prospero ID: CRD42016035454. RESULTS: Eighty-nine papers were included. Five major themes and 28 sub-themes were identified, encompassing: (1) patient physical and psychological capability to perform physical activity, including delirium, sedation, illness severity, comorbidities, weakness, anxiety, confidence and motivation; (2) safety influences, including physiological stability and concern for lines, e.g. risk of dislodgement; (3) culture and team influences, including leadership, interprofessional communication, administrative buy-in, clinician expertise and knowledge; (4) motivation and beliefs regarding the benefits/risks; and (5) environmental influences, including funding, access to rehabilitation programs, staffing and equipment. CONCLUSIONS: The main barriers identified were patient physical and psychological capability to perform physical activity, safety concerns, lack of leadership and ICU culture of mobility, lack of interprofessional communication, expertise and knowledge, and lack of staffing/equipment and funding to provide rehabilitation programs. Barriers and enablers are multidimensional and span diverse factors. The majority of these barriers are modifiable and can be targeted in future clinical practice

Molecular and cellular strategies to enhance efficacy of T cell-based cancer therapy [Elektronisk resurs]

A combined approach of vaccination with β2-microglobulin (β2m)-deficient dendritic cells (DCs) and granulocyte-macrophage colony-stimulating factor (GM-CSF) as a potent adjuvant may link cellular and molecular strategies to further enhance anti-tumor T-cell responses. T lymphocytes can mediate a potent anti-tumor immune response. CD8+ T lymphocytes screen and recognize antigen in complex with a major histocompatibility complex (MHC) class I heavy chain (HQ and the β2m light chain. Metastatic cells commonly escape from "conventional" T lymphocyte-mediated recognition and elimination as a result of impaired cell surface expression of MHC class I antigen molecules. This impaired cell surface expression can be caused by loss or down-regulation of expression of different components of the MHC class I antigen processing machinery, such as MHC class I HCs, β2m, or the transporter associated with antigen processing (TAP). Such immune evasion poses a problem for autologous T cell-based cancer therapy. In the first study we demonstrated protection against growth Of β2m-deficient tumor cells in syngeneic C57Bl/6 (B6) mice, following vaccination with β2m-deficient DCs. In vitro analysis of an effector cell population from vaccinated mice pointed to that CD3+ cells had been generated with the capability to induce apoptosis in syngeneic β2m-deficient tumor and nonmalignant cells. Further investigation of target cell recognition suggested that also tumor target cells lacking expression of classical MHC class I HCs and functional TAP were recognized by CD3+ effector cells from vaccinated mice. This study points to a new possible strategy to counteract the growth of metastatic cells. The cytokine composition in the tumor microenvironment is a critical factor for an effective antitumor immune response. GM-CSF has been shown to be a very promising cytokine in anti-tumor immunomodulation. Continuously high concentrations of GM-CSF in the local tumor environment seem to be crucial to reach a therapeutic threshold. Such a favorable cytokine milieu can promote recruitment of DCs and augment DC activation with increased number of DCs expressing MHC and co-stimulatory molecules. GM-CSF can enhance tumor infiltration of T lymphocytes and their cross-priming. Furthermore, GM-CSF seems to trigger an increased and significantly more effective tumor lysis mediated by lymphocytes. GM-CSF has elicited anti-tumor immune responses in animal studies and clinical trials. However, the clinical efficacy has been limited, with local GM-CSF levels being therapeutically insufficient or systemic toxicity being a limiting factor. In the second study, we developed and characterized a novel GM-CSF expression vector, pAD-HotAmp-GM-CSF, which can provide heat-inducible high-level expression of GM-CSF. In cytokine immunotherapy of cancer it is critical to deliver sufficiently high local cytokine concentrations in order to reach the therapeutic threshold needed for clinical efficacy. The novel vector, pAD-HotAmp-GM-CSF successfully integrates inducible and amplifying elements into a one-plasmid system. Moderate hyperthermia at 42°C for 30 min induced amplification of GM-CSF expression in pAD-HotAmp-GM-CSF that was over 2,8 fold higher than levels achieved with the prototypical human cytomegalovirus (CMV) promoter. Thus, the inducible amplifier vector, pAD-HotAmp-GM-CSF, represents a novel system for regulated and enhanced GM-CSF expression, which enables both greater efficacy and safety in cytokine immunotherapy of cancer

Finding friends online: Online activities by deaf students and their well-being

Contains fulltext : 125129.pdf (publisher's version ) (Open Access)Generally, deaf and hard of hearing (D/HH) children have fewer friends than hearing peers and their friendships are of a lower quality. The research hypothesis was that using the computer to communicate with new online friends through social network sites or playing games with offline friends is associated with D/HH friendship qualities, because it removes certain communication barriers D/HH face in offline communication settings. With online questionnaires the relation between computer use and online, mixed (offline friend who you also speak in online settings), and offline friendship quality of D/HH and hearing students (18–25 years) was compared in both the Netherlands (n = 100) and the United States (n = 122). In addition, the study examined whether the different friendship qualities were related to the participants' well-being. Results showed that, in general, D/HH students' friendship qualities and levels of well-being were similar to their hearing peers. The quality of the mixed friendships was positively related to well-being. Furthermore, the frequency of pc use with both online and offline friends was positively related to friendships qualities in both hearing and D/HH students. A combination of the online and offline friendship seems to be the most important friendship type for both hearing and D/HH students and it is worthwhile to encourage this friendship type.10 p

Hörgeräte mit mehrkanaliger nicht-linearer Frequenzkompression - eine Studie bei Kindern

Einleitung: Für die Sprachproduktion und den Spracherwerb sind die Identifikation und die Verständlichkeit hochfrequenter Sprachsignale von großer Bedeutung . Hochgradig schwerhörige Kinder haben zumeist eine stark reduzierte Fähigkeit, hochfrequente Laute wie /f/, /s/, /sch/ zu erkennen. Die Firma Phonak hat einen Signalverarbeitungsalgorithmus entwickelt, der mit einer mehrkanaligen nicht-linearen Frequenzkompression arbeitet. Dieser Algorithmus komprimiert Frequenzen oberhalb eines bestimmten Frequenzbereiches und verschiebt sie zu tieferen Frequenzen, wohingegen die tiefen Frequenzen ohne Frequenzkompression verstärkt werden. Methode: Diese Signalverarbeitungsstrategie wurde bei 13 hochgradig schwerhörigen Kindern im Alter von 6-15 Jahren eingesetzt. Die Vorberechnung der "cut off frequency" und der Kompressionsrate (first fit) und die Langzeitergebnisse nach sechsmonatigem Tragen des Hörsystems (anhand von Fragebögen und Sprachverständnistests in Ruhe und im Störgeräusch: Göttinger II, Freiburger, AAST) wurden evaluiert. Ergebnisse: Zweisilber in Ruhe verstanden alle, Zweisilber im Störgeräusch verstanden 12 Patienten besser, einer zeigte keine Verbesserung. Die ABK bei 4 kHz war bei 12 Patienten besser, bei einem schlechter, subjektiv waren alle Patienten besser (Fragebogen Eltern, Lehrer, Kinder). Schlussfolgerung: Die mehrkanalige nicht-lineare Frequenzkompression scheint für eine Subgruppe der schwerhörigen Kinder eine sehr viel versprechende Option