Merkmal der Gegenwärtigkeit im Notwehrrecht bei neuen Konfliktmustern aus rechtsvergleichender Sicht

This research relates to the comparative study of the requirement of actuality in self-defense, which has been debated intensely since several decades in various legal systems. At the center of the debate arises the moment at which the right of self-defense can be appealed to. Another linked problem is the so-called "preventive defense" and the legal treatment of those situations where despite the absence of an aggression, you need to act immediately to neutralize the danger effectively. A good example is represented here by the hypothesis of a woman, usually battered by the "tyrant of the house", which, taking advantage of a moment of harmlessness of the partner, prevents further abuses by killing him while he sleeps

Do prior intra-articular injections impact on the risk of periprosthetic joint infection in patients undergoing total hip arthroplasty? A meta-analysis of the current evidences with a focus on the timing of injection before surgery

Purpose: Intra-articular injection is a well-established and increasingly used treatment for the patient with mild-to-moderate hip osteoarthritis. The objectives of this literature review and meta-analysis are to evaluate the effect of prior intra-articular injections on the risk of periprosthetic joint infection (PJI) in patients undergoing total hip arthroplasty (THA) and to try to identify which is the minimum waiting time between hip injection and replacement in order to reduce the risk of infection. Methods: The database of PubMed, Embase, Google Scholar and Cochrane Library was systematically and independently searched, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. To assess the potential risk of bias and the applicability of the evidence found in the primary studies to the review, the Newcastle-Ottawa scale (NOS) was used. The statistical analysis was performed by using the software 'R' version 4.2.2. Results: The pooling of data revealed an increased risk of PJI in the injection group that was statistically significative (P = 0.0427). In the attempt to identify a 'safe time interval' between the injection and the elective surgery, we conducted a further subgroup analysis: in the subgroup 0-3 months, we noted an increased risk of PJI after injection. Conclusions: Intra-articular injection is a procedure that may increase the risk of developing periprosthetic infection. This risk is higher if the injection is performed less than 3 months before hip replacement

PABS: An online platform to assist BAC-by-BAC sequencing projects

Genome sequencing projects are either based on whole genome shotgun (WGS) or on a BAC-by-BAC strategy. Although WGS is in most cases the preferred choice, sometimes the BAC-by-BAC approach may be better because it requires a much simpler assembly process. Furthermore, when the study is limited to specific regions of the genome, the WGS would require an unjustified effort, making the BAC-by-BAC the only feasible strategy. In this paper we describe an informatics pipeline called PABS (Platform Assisted BAC-by-BAC Sequencing) that we developed to provide a tool to optimize the BAC-by-BAC sequencing strategy. PABS has two main functions: (i) PABS-Select, to choose suitable overlapping clones; and (ii) PABS-Validate, to verify whether a BAC under analysis is actually overlapping the neighboring BAC

R&D experiences on FPGAs and astronomical applications at IASF Milano

The paper describes R&D activities that were or are currently developed at the INAF - IASF Milano and that involve the usage of FPGAs for astrophysical applications. They span from the emulation of radiation induced faults in SRAM-based FPGAs to the development of a backend unit for the SKA low frequency antennas and astronomical detectors

Discontinuously supervised aerobic training vs. physical activity promotion in the self-management of type 2 diabetes in older Italian patients: design and methods of the 'TRIPL-A' randomized controlled trial

Physical activity (PA) has health benefits for people with type 2 diabetes (T2D). Indeed, regular PA is considered an important part of any T2D management plan, yet most patients adopt a sedentary lifestyle. Exercise referral schemes (ERS) have the potential to effectively promote physical activity among T2D patients, and their effectiveness may be enhanced when they are supported by computer-based technologies. The 'TRIPL-A' study (i.e., a TRIal to promote PhysicaL Activity among patients in the young-old age affected by T2D) aims to assess if realizing an innovative ERS, based on a strong partnership among general practitioners, specialist physicians, exercise specialists, and patients, and supported by a web-based application (WBA), can effectively lead sedentary older T2D patients to adopt an active lifestyle

A new risk stratification score for the management of ultrasound‐detected B3 breast lesions

To develop a predictive scoring system for ultrasound-detected B3 lesions at ultrasound-guided core needle biopsy (US-CNB). A total of 2724 consecutive US-CNBs performed in our Institution (January 2011 to December 2014) were retrospectively reviewed. Inclusion criteria were as follows: (a) histopathological examination of the entire lesion or (b) availability of radiologic follow-up (FUP) ≥24 months. Patient- and lesion-related variables-patients' age, lesion consistency, lesion size, vascularization, BI-RADS category, and US-CNB result-were analyzed. Positive predictive values (PPVs) for malignancy were calculated correlating US-CNB results with excision histology or FUP. A scoring system for underlying malignancy was developed using risk factors weighting. A total of 102 B3 lesions were included: 27 atypical ductal hyperplasia (26.5%), 5 lobular intraepithelial neoplasia (4.9%), 32 radial scar (31.4%), 37 papillary lesions (36.3%), and 1 fibroepithelial lesion (0.9%). Surgery was performed on 71/102 (69.6%) lesions, and 22/71 were malignant; the remaining 31/102 lesions (30.4%) were unchanged at FUP. The overall PPV for malignancy was 21.6%. Patients' age (odds ratio [OR] = 3.63, P = 0.008), lesion consistency (OR = 5.96, P = 0.001), BI-RADS category (OR = 17.52, P < 0.001), and CNB result (OR = 3.6, P = 0.008) were associated with a higher risk of malignancy underestimation and selected as risk factors in the score definition. Two risk groups were identified: low (0-2 points) and high risk (3-5 points), with significantly different risk of malignancy underestimation (8.0% vs 59.3%, P < 0.001). The proposed score helps to predict the risk of malignancy underestimation and choose the management of B3 lesions at US-CNB

756 stable amelioration of hemophilia b in dogs by intravenous administration of lentiviral vectors expressing hyper functional factor ix

Lentiviral vectors (LVs) are attractive vehicles for liver-directed gene therapy by virtue of their ability to stably integrate in the genome of target cells and the low prevalence of pre-existing immunity against HIV in humans. Over the past years, we have developed a LV platform that can achieve stable transgene expression in the liver, induce transgene-specific immune tolerance and establish correction of hemophilia in mouse models upon systemic administration. This LV is designed to stringently target transgene expression to hepatocytes through transcriptional and microRNA-mediated regulation. We then investigated the efficacy and safety profile of portal vein administration of LVs expressing canine factor IX (FIX) in a canine model of hemophilia B. We produced large-scale batches of LVs qualified for in vivo administration and treated adult hemophilia B dog by portal vein administration. We observed long-term stable reconstitution of canine FIX activity up to 1% of normal and significant amelioration of the clinical phenotype in 3 treated dogs with 6, 3.5 and 2.5 years of follow up. LV infusion was associated with transient signs of inflammatory response and mild hepatotoxicity, which could be abrogated by pretreatment with anti-inflammatory drugs. There was no detectable long-term toxicity or development of FIX inhibitors. In the perspective of clinical translation and to increase therapeutic efficacy, we next treated two 10-kg hemophilia B dogs by peripheral vein administration of LVs expressing a codon-optimized and hyperfunctional canine FIX at a 5-fold higher dose than those previously administered. Intravenous LV administration was well tolerated with mild and self-limiting elevation of aminotransferases in one dog. In the dog that reached more than 1 year of follow up FIX activity ranged between 4-8% of normal. Treatment of two more dogs at a higher dose is underway. Overall, our studies position LV-mediated liver gene therapy for further pre-clinical development and clinical translation. LVs may thus complement other available vectors to address some of the outstanding challenges posed by liver gene therapy of hemophilia and conceivably other diseases

28. Intravenous Administration of Lentiviral Vectors Expressing Hyperactive Factor IX Converts Severe Into Mild Hemophilia B in a Canine Model

Lentiviral vectors (LVs) are attractive vehicles for liver-directed gene therapy by virtue of their ability to stably integrate in the genome of target cells and the lack of pre-existing immunity against vector components in most humans. Over the past years, we have developed a LV platform that can achieve stable transgene expression in the liver, induce transgene-specific immune tolerance and establish correction of hemophilia in mouse models upon systemic administration. This LV is designed to stringently target transgene expression to hepatocytes through transcriptional and microRNA-mediated regulation. We then investigated the efficacy and safety profile of portal vein administration of LVs expressing wild-type, codon-optimized (c.o.) or c.o. and hyperactive factor IX (FIX) in a canine model of hemophilia B. We produced large-scale batches of LVs qualified for in vivo administration and treated adult hemophilia B dog by portal vein administration. We observed long-term stable reconstitution of canine FIX activity up to 1% of normal and significant amelioration of the clinical phenotype in 3 treated dogs (>9 years cumulative follow up). LV infusion was associated with transient signs of inflammation and mild hepatotoxicity, which could be abrogated by pretreatment with anti-inflammatory drugs. There was no detectable long-term toxicity or development of FIX inhibitors. In the perspective of clinical translation and to increase therapeutic efficacy, we next treated an 11-kg, hemophilia B dog by peripheral vein administration of LVs expressing the c.o. and hyperactive canine FIX at a 5-fold higher dose than those previously administered. At the current follow-up (3 months after gene therapy) FIX activity is 6-9% of normal. Intravenous LV administration, coupled with a 1-day anti-inflammatory and anti-histamine pre-treatment, induced mild and selflimiting leukopenia and elevation of aminotransferases. Treatment of more hemophilia B dogs is underway to confirm and extend these results. Overall, our studies, which suggest comparable efficacy of LV by both portal and peripheral vein administration, position LV-mediated liver gene therapy for further pre-clinical development and clinical translation. LVs may thus complement other available vectors to address some of the outstanding challenges posed by liver gene therapy of hemophilia and conceivably other diseases

Laterally transferred elements and high pressure adaptation in Photobacterium profundum strains

BACKGROUND: Oceans cover approximately 70% of the Earth's surface with an average depth of 3800 m and a pressure of 38 MPa, thus a large part of the biosphere is occupied by high pressure environments. Piezophilic (pressure-loving) organisms are adapted to deep-sea life and grow optimally at pressures higher than 0.1 MPa. To better understand high pressure adaptation from a genomic point of view three different Photobacterium profundum strains were compared. Using the sequenced piezophile P. profundum strain SS9 as a reference, microarray technology was used to identify the genomic regions missing in two other strains: a pressure adapted strain (named DSJ4) and a pressure-sensitive strain (named 3TCK). Finally, the transcriptome of SS9 grown under different pressure (28 MPa; 45 MPa) and temperature (4°C; 16°C) conditions was analyzed taking into consideration the differentially expressed genes belonging to the flexible gene pool. RESULTS: These studies indicated the presence of a large flexible gene pool in SS9 characterized by various horizontally acquired elements. This was verified by extensive analysis of GC content, codon usage and genomic signature of the SS9 genome. 171 open reading frames (ORFs) were found to be specifically absent or highly divergent in the piezosensitive strain, but present in the two piezophilic strains. Among these genes, six were found to also be up-regulated by high pressure. CONCLUSION: These data provide information on horizontal gene flow in the deep sea, provide additional details of P. profundum genome expression patterns and suggest genes which could perform critical functions for abyssal survival, including perhaps high pressure growth