LEARN 2 MOVE 2-3: a randomized controlled trial on the efficacy of child-focused intervention and context-focused intervention in preschool children with cerebral palsy

<p>Abstract</p> <p>Background</p> <p>Little is known about the efficacy and the working mechanisms of physical and occupational therapy interventions for children with cerebral palsy (CP). In recent years a shift from a child-focused intervention approach to a more context-focused intervention approach can be recognized. Until now the evidence on the efficacy and the working mechanisms of these interventions for children with CP is inconclusive. This study aims to evaluate the efficacy and working mechanisms of two intervention approaches compared to regular care intervention in improving mobility and self-care skills of children (2-3 years) with CP and their families: a child-focused intervention approach and a context-focused intervention approach.</p> <p>Methods/Design</p> <p>A multi-centre, randomized controlled trial research design will be used. Ninety-four children with CP (Gross Motor Function Classification System (GMFCS) level I-IV; age 2 to 3 years), their parents, and service providers (physical and occupational therapists) will be included. During a period of six months children will receive child-focused, context-focused or regular care intervention. Therapists will be randomly assigned to deliver either a child-focused intervention approach, a context-focused intervention approach or regular care intervention. Children follow their therapist into the allocated intervention arm. After the six months study-intervention period, all participants return to regular care intervention. Outcomes will be evaluated at baseline, after six months and at a three months follow-up period. Primary outcome is the capability of functional skills in self-care and mobility, using the Functional Skills Scale of the Pediatric Evaluation of Disability Inventory (PEDI). Other outcomes will be quality of life and the domains of the International Classification of Functioning, Disability and Health - for Children and Youth (ICF-CY), including body function and structure, activities (gross motor capacity and performance of daily activities), social participation, environmental variables (family functioning, parental empowerment).</p> <p>Discussion</p> <p>This paper presents the background information, design, description of interventions and protocol for this study on the efficacy and working mechanisms of child-focused intervention approach and context-focused intervention approach compared to regular care intervention in mobility and self-care skills of children (2-3 years) with CP.</p> <p>Trial registration</p> <p>This study is registered in the Dutch Trial Register as NTR1900</p

Immunoprotectivity of HLA-A2 CTL Peptides Derived from Respiratory Syncytial Virus Fusion Protein in HLA-A2 Transgenic Mouse

Identification of HLA-restricted CD8+ T cell epitopes is important to study RSV-induced immunity and illness. We algorithmically analyzed the sequence of the fusion protein (F) of respiratory syncytial virus (RSV) and generated synthetic peptides that can potentially bind to HLA-A*0201. Four out of the twenty-five 9-mer peptides tested: peptides 3 (F33–41), 13 (F214–222), 14 (F273–281), and 23 (F559–567), were found to bind to HLA-A*0201 with moderate to high affinity and were capable of inducing IFN-γ and IL-2 secretion in lymphocytes from HLA-A*0201 transgenic (HLA-Tg) mice pre-immunized with RSV or recombinant adenovirus expressing RSV F. HLA-Tg mice were immunized with these four peptides and were found to induce both Th1 and CD8+ T cell responses in in vitro secondary recall. Effector responses induced by these peptides were observed to confer differential protection against live RSV challenge. These peptides also caused better recovery of body weight loss induced by RSV. A significant reduction of lung viral load was observed in mice immunized with peptide 23, which appeared to enhance the levels of inflammatory chemokines (CCL17, CCL22, and IL-18) but did not increase eosinophil infiltration in the lungs. Whereas, significant reduction of infiltrated eosinophils induced by RSV infection was found in mice pre-immunized with peptide 13. Our results suggest that HLA-A2-restricted epitopes of RSV F protein could be useful for the development of epitope-based RSV vaccine

Ertüchtigung der Flachschleifmaschine ELB SF 30

Aufbauend auf dem Praktikumsbericht wird in der vorliegenden Bachelorarbeit, das Thema „Ertüchtigung der Flachschleifmaschine ELB“ weiter behandelt. Es wird dabei speziell die Einführung eines neuen Bedienpanels an der Maschine konkretisiert. Zu Beginn erfolgt die Auswahl eines geeigneten Panels, welches zu der vorhandenen Steuerung kompatibel ist. Daraufhin folgt die Vorstellung der Visualisierungssoftware, sowie der Software zum Testen der projektierten Oberfläche des Bediengerätes. Im weiteren Verlauf finden sich Erläuterungen zur Programmierung des Panels, bezogen auf das ELB-Projekt wieder. Das letzte Kapitel bezieht sich auf die konkrete SPS-Lösung zwei ausgewählter Steuerungsfunktionen, zum einen die Magnetsteuerung und zum anderen die Querantriebsteuerung

Mechanisms of respiratory syncytial virus specific T cell activation

Respiratory syncytial virus (RSV) is an important cause of severe lower respiratory tract infections (LRTI) in infants, elderly people and immune compromised individuals. Moreover, RSV causes repeated symptomatic re-infections in healthy individuals, which is presumed to be due to ineffective acquired immunity. A vaccine is currently not available. Vaccine development has been set back dramatically after a disastrous vaccine trial in the 1960s with a formalin-inactivated (FI)-RSV vaccine, which caused disease enhancement upon natural infection. RSV is highly infectious and has a high attack rate very early in life. Thus vaccine development faces major difficulties: 1. intervention is necessary soon after birth, which is challenging due to immaturity of the immune system that is characterized by a Th2 bias, which appears to be unfavorable for RSV, 2. a vaccine needs to be effective in the presence of maternal antibodies, 3. inactivated or subunit vaccines tend to induce immune pathology, 4. the fact that immune protection after natural infection is incomplete. Our study focused on the mechanism of the induction of RSV-specific T cell and antibody responses. We first addressed the role of pre-existing antibodies during the priming phase of the virus specific immune response. We showed that the balance of pre-existing virus-neutralizing versus non-neutralizing antibodies affected the balance of the antiviral CD4+/CD8+ T cell response induced upon viral infection. Neutralizing antibodies decreased the induction of CD8+ T cell responses, while both neutralizing and non-neutralizing antibodies increased CD4+ T cell responses by increasing Fc-receptor mediated antigen presentation via MHC class II molecules. We hypothesize that these antibody mediated effects might be an explanation for the low virus specific CD8+/CD4+ memory T cell ratio’s in frequently re-infected adults that contrasts with a predominantly CD8+ T cell response during primary infection in infants. We also showed that virus specific antibodies can alter the repertoire of CD8+ T cells, which resulted in the mouse model in a memory response against an enhanced epitope repertoire. We further unraveled the mechanism by which the FI-RSV vaccine caused the strong allergic (Th2 biased) response during viral challenge in a mouse model. We excluded that vaccine specific components like the structural alterations caused by formalin treatment, or the alum adjuvant present in the vaccine, or the specific characteristics of viral proteins were responsible for the Th2-biased enhanced disease mechanism. Rather the major reasons for vaccine failure are the lack of induction of a virus specific CD8+ T cell response by the inactivated vaccine and an inefficient Th1 priming, combined with the fact that natural RSV infection does not induce an innate immune response that supports local Th1 maturation. Our findings suggest that future vaccines should induce high titer neutralizing antibodies to prevent virus induced cytopathogenic effects and strong inflammatory responses. Moreover, the vaccine should induce CD8+ T cell responses to prevent allergic features during natural virus exposure. These conditions might be best created by live attenuated vaccines or replication-competent gene-based vectors

Intranasal Administration of Antibody-Bound Respiratory Syncytial Virus Particles Efficiently Primes Virus-Specific Immune Responses in Mice

<p>Infants are protected from a severe respiratory syncytial virus (RSV) infection in the first months of life by maternal antibodies or by prophylactically administered neutralizing antibodies. Efforts are under way to produce RSV-specific antibodies with increased neutralizing capacity compared to the currently licensed palivizumab. While clearly beneficial during primary infections, preexisting antibodies might affect the onset of adaptive immune responses and the ability to resist subsequent RSV infections. Therefore, we addressed the question of how virus neutralizing antibodies influence the priming of subsequent adaptive immune responses. To test a possible role of the neonatal Fc receptor (FcRn) in this process, we compared the responses in C57BL/6 wild-type (WT) and FcRn(-/-) mice. We observed substantial virus-specific T-cell priming and B-cell responses in mice primed with RSV IgG immune complexes resulting in predominantly Th1-type CD4(+) T-cell and IgG2c antibody responses upon live-virus challenge. RSV-specific CD8(+) T cells were primed as well. Activation of these adaptive immune responses was independent of FcRn. Thus, neutralizing antibodies that localize to the airways and prevent infection-related routes of antigen processing can still facilitate antigen presentation of neutralized virus particles and initiate adaptive immune responses against RSV.</p>