Extended use of raltegravir in the treatment of HIV-1 infection: optimizing therapy

Raltegravir is the first licensed compound in 2007 of the new integrase inhibitor drug class. At the dose of 400 mg twice daily, raltegravir showed a potent antiviral action in antiretroviral-naïve patients when associated with tenofovir and emtricitabine. Raltegravir was also found to be highly active in antiretroviral-experienced patients with virological failure and displaying multiresistant virus, as shown with the BENCHMRK and ANRS 139 TRIO trials. Finally, the use of raltegravir was assessed in the context of a switch strategy in antiretroviral-experienced patients with virological success [human immunodeficiency virus type 1 (HIV-1) RNA below detection limit], highlighting the following mandatory criteria in this strategy: the nucleoside reverse transcriptase inhibitors associated with raltegravir have to be fully active. In the different studies, raltegravir had a favorable safety and tolerability profile. In the clinical situation a switch in virologically suppressed patients receiving a protease inhibitor, an improvement of the lipid profile was observed. Overall, when analyzing the Phase II and III trials together, only a few patients on raltegravir discontinued for adverse events. The development of resistance to raltegravir mainly involved three resistance mutations in integrase gene: Q148H/K/R, N155H, and Y143C/H/R. In conclusion, raltegravir improved the clinical management of HIV-1 infection both in antiretroviral-naïve and in antiretroviral-experienced patients

New silicion nanocrystal materials for photovoltaic applications

This Ph.D. thesis addresses the deposition, characterization and improvement of Si nanocrystal layers embedded in a SiC matrix (Si NC/SiC) as future absorber material for top cells of an all-Si tandem solar cell. The required enlargement of the Si NC bandgap is aimed to achieve with the help of quantum confinement (QC). No unambiguous evidence of QC in Si NC/SiC samples were presented in the literature up to now. Even though this also was not possible during this Ph.D. thesis, some necessary preconditions for QC were successfully complied, which are a better understanding and control of the crystallization mechanism, size control of the Si NC and defect passivation. The deposition of amorphous SixC1-x:H layers was conducted by plasma-enhanced chemical vapor deposition. During the annealing step subsequent to layer deposition, H effusion, formation of Si NC, and crystallization of the SiC matrix occurs. All Si NC/SiC samples were subjected to a comprehensive structural and optical characterization. The application of grazing incidence X-ray diffraction, Fourier transform infrared and Raman measurements to Si NC/SiC thin films were significantly improved during this work. The Si NC size control is an indispensable precondition for quantum confinement. For this purpose, two routes were proposed in this work. The Si NC size is shown to increase with increasing Si content of the SixC1-x:H layers. Thus, the Si NC size can be adjusted by adjusting the Si content. The advantage of this method is the fact that singlelayers can be deposited instead of multilayers (ML). The disadvantage is the uncontrollability of the Si NC spacing and the wide size distribution. The second route is with the help of a ML structure. Usually, Si NC/SiC ML structures show strong intermixing during the annealing step and are therefore not suitable for Si NC size control. In this work it is shown that the ML structure can be hindered from intermixing by oxygen incorporation during deposition

Detection of delirium by family members in the intensive care unit: Translation, Cross-Cultural adaptation and validation of the Family Confusion Assessment Method for the German-Speaking area

Aim: The aim of this study was the translation, cross-cultural adaptation and validation of the Family Confusion Assessment Method in critically ill patients. Background: Delirium is a frequently unrecognized disorder in critically ill patients. Visiting family members might be the first to notice subtle changes in a patient's cognition and behaviour. The Family Confusion Assessment Method was developed to detect delirium by family members, but has not been available for the German-speaking area yet. Design: A prospective validation study was conducted between January 2020 and October 2020. Methods: The Family Confusion Assessment Method was translated into German according to the Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes. Subsequently, we compared the Family Confusion Assessment Method with the Confusion Assessment Method for the Intensive Care Unit in critically ill patients and their family members in a medical intensive care unit in Germany. Results: We included 50 dyads of critically ill patients and their family members. The prevalence of delirium measured by Confusion Assessment Method for the Intensive Care Unit was 44%. Cohen's kappa coefficient was 0.84. The German Family Confusion Assessment Method had a high sensitivity of 95.5% and specificity of 89.3%. The positive predictive value and negative predictive value were 87.5% and 96.2% respectively. Conclusions: These findings suggest that the German Family Confusion Assessment Method is an accurate assessment tool for delirium detection in the intensive care unit by family members. Furthermore, the results indicate that family members may identify delirium by the Family Confusion Assessment Method without prior training. Impact: Collaborating medical staff with patients' family members to detect delirium in the intensive care unit may lead to early recognition of delirium. Keywords: Family Confusion Assessment Method; delirium; family members; intensive care unit; nurses; validation study

Sensing and avoiding sick conspecifics requires Gαi2+ vomeronasal neurons

Rodents utilize chemical cues to recognize and avoid other conspecifics infected with pathogens. Infection with pathogens and acute inflammation alter the repertoire and signature of olfactory stimuli emitted by a sick individual. These cues are recognized by healthy conspecifics via the vomeronasal or accessory olfactory system, triggering an innate form of avoidance behavior. However, the molecular identity of the sensory neurons and the higher neural circuits involved in the detection of sick conspecifics remain poorly understood

Molecular characterization of the feline T-cell receptor γ alternate reading frame protein (TARP) ortholog

T-cell receptor γ alternate reading frame protein (TARP) is expressed by human prostate epithelial, prostate cancer, and mammary cancer cells, but is not found in normal mammary tissue. To date, this protein has only been described in humans. Additionally, no animal model has been established to investigate the potential merits of TARP as tumor marker or a target for adoptive tumor immunotherapy. In this study conducted to characterize feline T-cell receptor γ sequences, constructs very similar to human TARP transcripts were obtained by RACE from the spleen and prostate gland of cats. Transcription of TARP in normal, hyperplastic, and neoplastic feline mammary tissues was evaluated by conventional RT-PCR. In felines similarly to the situation reported in humans, a C-region encoding two open reading frames is spliced to a J-region gene. In contrast to humans, the feline J-region gene was found to be a pseudogene containing a deletion within its recombination signal sequence. Our findings demonstrated that the feline TARP ortholog is transcribed in the prostate gland and mammary tumors but not normal mammary tissues as is the case with human TARP

The European Added Value of EU Spending: Can the EU Help its Member States to Save Money? Exploratory Study

Critical public debt levels have forced EU member states to pursue fiscal consolidation. Yet, there is a flip side to the austerity policies being administered to overcome the sovereign debt crisis. Cut backs in social transfers and public service delivery erode the social welfare architecture of the European economic model. Growing social insecurity, in turn, challenges European integration. Ever declining popular approval rates for the EU speak for themselves. In addition, the scaling back of public investments seems not to be an option either. This only further strangles what is left as potential for growth

Community-based rehabilitation intervention for people with schizophrenia in Ethiopia (RISE): a 12 month mixed methods pilot study.

BACKGROUND: Community-based rehabilitation (CBR), or community-based inclusive development, is an approach to address the complex health, social and economic needs of people with schizophrenia in low and middle-income countries. Formative work was undertaken previously to design a culturally appropriate CBR intervention for people with schizophrenia in Ethiopia. The current study explored the acceptability and feasibility of CBR in practice, as well as how CBR may improve functioning among people with schizophrenia. METHODS: This mixed methods pilot study took place in rural Ethiopia between December 2014 and December 2015. Ten people with schizophrenia who were unresponsive to treatment with medication alone, and their caregivers, participated in CBR. CBR was led by lay workers with five weeks training and involved home visits (education, family intervention and support returning to work) and community mobilisation. Theory of change was used to guide the pilot evaluation. Qualitative and quantitative data were collected at baseline, six months and 12 months. Forty in-depth interviews and two focus group discussions were conducted with 31 individuals comprising people with schizophrenia, caregivers, CBR workers, supervisors, health officers and community members. RESULTS: The RISE CBR intervention may have a positive impact on functioning through the pathways of enhanced family support, improved access to health care, increased income and improved self-esteem. CBR was acceptable to CBR workers, community leaders and health officers. Some CBR workers found it challenging to accept the choices of people with schizophrenia. These concerns were felt to be resolvable with supplementary training for CBR workers. The intervention was feasible but further evaluation is needed on a larger scale. CONCLUSION: In low and middle-income countries, CBR may be an acceptable and feasible adjuvant approach to facility-based care for people with schizophrenia. However, contextual factors, including poverty and inaccessible anti-psychotic medication, remain substantial challenges. There were indications that CBR can impact on functioning but the RISE trial will determine effectiveness

Community-based Rehabilitation Intervention for people with Schizophrenia in Ethiopia (RISE): study protocol for a cluster randomised controlled trial.

BACKGROUND: Care for most people with schizophrenia is best delivered in the community and evidence-based guidelines recommend combining both medication and a psychosocial intervention, such as community-based rehabilitation. There is emerging evidence that community-based rehabilitation for schizophrenia is effective at reducing disability in middle-income country settings, yet there is no published evidence on the effectiveness in settings with fewer mental health resources. This paper describes the protocol of a study that aims to evaluate the effectiveness of community-based rehabilitation as an adjunct to health facility-based care in rural Ethiopia. METHODS: This is a cluster randomised trial set in a rural district in Ethiopia, with sub-district as the unit of randomisation. Participants will be recruited from an existing cohort of people with schizophrenia receiving treatment in primary care. Fifty-four sub-districts will be randomly allocated in a 1:1 ratio to facility-based care plus community-based rehabilitation (intervention arm) or facility-based care alone (control arm). Facility-based care consists of treatment by a nurse or health officer in primary care (antipsychotic medication, basic psychoeducation and follow-up) with referral to a psychiatric nurse-led outpatient clinic or psychiatric hospital when required. Trained community-based rehabilitation workers will deliver a manualised community-based rehabilitation intervention, with regular individual and group supervision. We aim to recruit 182 people with schizophrenia and their caregivers. Potential participants will be screened for eligibility, including enduring or disabling illness. Participants will be recruited after providing informed consent or, for participants without decision-making capacity, after the primary caregiver gives permission on behalf of the participant. The primary outcome is disability measured with the 36-item WHO Disability Assessment Schedule (WHODAS) version 2.0 at 12 months. The sample size will allow us to detect a 20 % difference in WHODAS 2.0 scores between treatment arms with 85 % power. Secondary outcomes include change in symptom severity, economic activity, physical restraint, discrimination and caregiver burden. DISCUSSION: This is the first trial of community-based rehabilitation for schizophrenia and will determine, as a proof of concept, the added value of community-based rehabilitation compared to facility-based care alone in a low-income country with scarce mental health resources. TRIAL REGISTRATION: Clinical Trials.gov Identifier NCT02160249 . Registered on 3 June 2014