Drosophila brca2 Is Required for Mitotic and Meiotic DNA Repair and Efficient Activation of the Meiotic Recombination Checkpoint

Heterozygous mutations in the tumor suppressor BRCA2 confer a high risk of breast and other cancers in humans. BRCA2 maintains genome stability in part through the regulation of Rad51-dependent homologous recombination. Much about its precise function in the DNA damage responses is, however, not yet known. We have made null mutations in the Drosophila homolog of BRCA2 and measured the levels of homologous recombination, non-homologous end-joining, and single-strand annealing in the pre-meiotic germline of Drosophila males. We show that repair by homologous recombination is dramatically decreased in Drosophila brca2 mutants. Instead, large flanking deletions are formed, and repair by the non-conservative single-strand annealing pathway predominates. We further show that during meiosis, Drosophila Brca2 has a dual role in the repair of meiotic double-stranded breaks and the efficient activation of the meiotic recombination checkpoint. The eggshell patterning defects that result from activation of the meiotic recombination checkpoint in other meiotic DNA repair mutants can be strongly suppressed by mutations in brca2. In addition, Brca2 co-immunoprecipitates with the checkpoint protein Rad9, suggesting a direct role for Brca2 in the transduction of the meiotic recombination checkpoint signal

Heat-denatured human immunodeficiency virus type 1 protein 24 antigen: prognostic value in adults with early-stage disease

CD4(+) lymphocyte count and human immunodeficiency virus (HIV) type 1 RNA level are useful for determining when to initiate antiretroviral therapy but are not used widely in developing countries due to the high cost. Heat-denatured protein 24 (p24) antigen is an inexpensive assay that predicts disease progression among persons with advanced disease but has not been assessed among persons with early-stage disease. Plasma levels of heat-denatured p24 antigen were quantified in baseline study-visit specimens obtained from injection drug users enrolled in a longitudinal cohort study of HIV-1 infection. Of the 494 study participants (median initial CD4(+) lymphocyte count, 518 lymphocytes/mm(3)), 90 (18%) progressed to acquired immunodeficiency syndrome within 5 years. p24 antigen level correlated with both CD4(+) lymphocyte count (r=-0.34; P5 pg/mL predicted disease progression, comparable with that of cutoff CD4(+) lymphocyte count 30,000 copies/mL. Heat-denatured p24 antigen level predicted subsequent clinical disease progression in early-stage HIV-1 infection and correlated with both CD4(+) lymphocyte count and HIV-1 RNA leve

Surgical Site Infections at Donor and Recipient Sites in Patients with Iliac Crest Harvesting For Autologous Bone Grafting - A Pilot Evaluation

Surgeons harvest the iliac crest for bone grafting. The epidemiology of surgical site infections (SSI) associated with this procedure at the donor, or recipient site, is unknown. We perform a retrospective pilot evaluation of adult patients undergoing first-time orthopedic surgery at the Balgrist University Hospital between 2014-2019. We excluded patients with infection at the index surgery, diabetic foot surgeries, superficial SSIs, and revision surgeries. We included 20,088 episodes of primary orthopedic surgery, of which 467 with iliac crest bone sampling (467/20,088; 2%). Only two iliac sites (2/467; 0.4%) become infected. In contrast, surgeries with iliac crest sampling yielded more SSIs at the recipient site than those without (1.9% vs. 0.8%; χ2-test; p<0.01). These patients equally revealed more co-morbidities such as a longer duration of surgery (median 127 vs. 79 minutes), when compared to the general orthopedic population. In multivariate logistic regression analysis with the outcome “ SSI at the recipient site”, the iliac harvesting was independently associated with deep SSIs requiring surgical revision (odds ratio 2.1; 95% confidence interval 1.1-4.2). In our pilot evaluation with 20,088 primary orthopedic surgeries, the SSI risk of the iliac harvest site was low. In contrast, surgeries with supplementary iliac crest harvesting revealed a higher SSI risk than the general orthopedic population, potentially due to a mix of local independent risks of grafting together with a prolonged surgery time. Keywords : Autologous bone grafting; Deep surgical site infections; Epidemiology; Iliac crest harvesting; Revision surger

Comparison of Antimicrobial Consumption Patterns in the Swiss and Danish Cattle and Swine Production (2007–2013)

Veterinary antimicrobial consumption patterns vary considerably across Europe. These differences are not only limited to the total amount consumed but are also observed with regards to the relative proportion of the various antimicrobial classes used. Currently, most of the data on veterinary antimicrobials are reported at sales level without any information on the consumption by different animal species. This hinders a proper comparison of antimicrobial consumption at the species level between countries. However, it is imperative to improve our understanding on antimicrobial usage patterns at the species level, as well as on the drivers contributing to those differences. This will allow for development of tailored interventions with the lowest possible risk for human health, while ensuring effective treatment of diseased livestock. An important step to attain such an objective is to perform detailed comparisons of the antimicrobial consumption in each species between countries. We compared antimicrobial consumption estimates for cattle and pigs in Switzerland and Denmark, in order to distinguish species-specific patterns and trends in consumption from 2007 to 2013. Swiss data were obtained from a previous study that assessed methodologies to stratify antimicrobial sales per species; Danish antimicrobial consumption estimates were assembled from Danish Integrated Antimicrobial Resistance Monitoring and Research Programme reports. A decrease in antimicrobial consumption in milligrams per kilogram of biomass was observed for both countries (4.5% in Denmark and 34.7% in Switzerland) when comparing 2013 to 2007. For pigs and cattle, the overall consumption per kilogram of biomass of most antimicrobial classes was higher in Switzerland than in Denmark. Large variations in the relative consumption of different antimicrobial classes were also evident. Sulfonamides/trimethoprim and tetracyclines were consumed in a higher proportion in Switzerland than in Denmark, whereas the relative consumption of penicillins was higher in Denmark. The differences observed in veterinary antimicrobial consumption are not solely related to animal demographic characteristics in these two countries. Other factors, such as the level of biosecurity and farming practices, veterinarians and farmers' education, or governmental/industry programs put in place might also partly explain these variations. These differences should be taken into account when aiming to implement targeted interventions to reduce antimicrobial consumption

Quantification of antimicrobial use in Swiss pigs: comparison with other Swiss livestock species and with Danish pigs

Few countries have introduced monitoring of antimicrobial usage (AMU) per animal species. Such an achievement is an objective of the ESVAC project (European Surveillance of Veterinary Antimicrobial Consumption). Implementing these monitoring systems would allow detailed AMU comparisons between countries enabling an evaluation of interventions to reduce antimicrobial consumption effectively

Millennial changes in North American wildfire and soil activity over the last glacial cycle

Climate changes in the North Atlantic region during the last glacial cycle were dominated by the slow waxing and waning of the North American ice sheet as well as by intermittent, millennial-scale Dansgaard-Oeschger climate oscillations. However, prior to the last deglaciation, the responses of North American vegetation and biomass burning to these climate variations are uncertain. Ammonium in Greenland ice cores, a product from North American soil emissions and biomass burning events, can help to fill this gap. Here we use continuous, high-resolution measurements of ammonium concentrations between 110,000 to 10,000 years ago from the Greenland NGRIP and GRIP ice cores to reconstruct North American wildfire activity and soil ammonium emissions. We find that on orbital timescales soil emissions increased under warmer climate conditions when vegetation expanded northwards into previously ice-covered areas. For millennial-scale interstadial warm periods during Marine Isotope Stage 3, the fire recurrence rate increased in parallel to the rapid warmings, whereas soil emissions rose more slowly, reflecting slow ice shrinkage and delayed ecosystem changes. We conclude that sudden warming events had little impact on soil ammonium emissions and ammonium transport to Greenland, but did result in a substantial increase in the frequency of North American wildfires

Artificial 64-Residue HIV-1 Enhancer-Binding Peptide Is a Potent Inhibitor of Viral Replication in HIV-1-Infected Cells

An artificial HIV-1 enhancer-binding peptide was extended by nine consecutive arginine residues at the C-terminus and by the nuclear localization signal of SV40 large T antigen at the N-terminus. The resulting synthetic 64-residue peptide was found to bind to the two enhancers of the HIV-1 long terminal repeat, cross the plasma membrane and the nuclear envelope of human cells, and suppress the HIV-1 enhancer-controlled expression of a green fluorescent protein reporter gene. Moreover, HIV-1 replication is inhibited by this peptide in HIV-1-infected CEM-GFP cells as revealed by HIV-1 p24 ELISA and real-time RT-PCR of HIV-1 RNA. Rapid uptake of this intracellular stable and inhibitory peptide into the cells implies that this peptide may have the potential to attenuate HIV-1 replication in vivo

A tool to improve pre-selection for deep brain stimulation in patients with Parkinson’s disease

Determining the eligibility of patients with Parkinson’s disease (PD) for deep brain stimulation (DBS) can be challenging for general (non-specialised) neurologists. We evaluated the use of an online screening tool (Stimulus) that aims to support appropriate referral to a specialised centre for the further evaluation of DBS. Implementation of the tool took place via an ongoing European multicentre educational programme, currently completed in 15 DBS centres with 208 referring neurologists. Use of the tool in daily practice was monitored via an online data capture programme. Selection decisions of patients referred with the assistance of the Stimulus tool were compared to those of patients outside the screening programme. Three years after the start of the programme, 3,128 patient profiles had been entered. The intention for referral was made for 802 patients and referral intentions were largely in accordance with the tool recommendations. Follow-up at 6 months showed that actual referral took place in only 28%, predominantly due to patients’ reluctance to undergo brain surgery. In patients screened with the tool and referred to a DBS centre, the acceptance rate was 77%, significantly higher than that of the unscreened population (48%). The tool showed a sensitivity of 99% and a specificity of 12% with a positive and negative predictive value of 79 and 75%, respectively. The Stimulus tool is useful in assisting general neurologists to identify appropriate candidates for DBS consideration. The principal reason for not referring potentially eligible patients is their reluctance to undergo brain surgery

A prospective evaluation of the feasibility and utility of additional tools to obtain information from recently diagnosed HIV infected patients

QUESTION UNDER STUDY: Can additional information be obtained from recently HIV diagnosed individuals? METHODS: A 1-year prospective Swiss study, including all newly diagnosed HIV-infected patients. Information on circumstances of HIV infection was collected through physician- and patient questionnaires and patient interviews. Information on timing of infection was linked with an HIV-antibody avidity assay. RESULTS: Of 710 newly HIV diagnosed patients, 543 (76%) physician questionnaires (PhyQ) and 145 (20%) patient questionnaires (PaQ) were returned. PhyQ required fewer reminders (57% vs 28% spontaneous return). Patients whose doctors had returned the PhyQ were comparable to total population group. In contrast, a strong bias towards well educated recently infected Swiss men having sex with men (MSM) was seen in patients returning PaQ or agreeing to an interview. 83% of patients claimed that they knew the infection source and 85% infection place. Unprotected sexual contact was the most frequently cited infection source (92%; n = 404). Men mainly claimed occasional (43%) and women steady (61%) partners as the most likely source of HIVinfection. Serum for timing of infection was available in 98% of patients. Recent infections (RI) were highest in MSM (51%) and intravenous drug users (IDU, 54%). Compared to women, heterosexual men were more than twice as likely to be diagnosed with a RI. CONCLUSION: Relevant additional information on circumstances of HIV infection in newly diagnosed patients can easily be collected from treating physicians. Collecting information from patients is not a feasible option, with the exception of qualitative interviews in a selected group of patients

The trade-off between taxi time and fuel consumption in airport ground movement

Environmental impact is a very important agenda item in many sectors nowadays, which the air transportation sector is also trying to reduce as much as possible. One area which has remained relatively unexplored in this context is the ground movement problem for aircraft on the airport’s surface. Aircraft have to be routed from a gate to a runway and vice versa and it is still unknown whether fuel burn and environmental impact reductions will best result from purely minimising the taxi times or whether it is also important to avoid multiple acceleration phases. This paper presents a newly developed multi-objective approach for analysing the trade-off between taxi time and fuel consumption during taxiing. The approach consists of a combination of a graph-based routing algorithm and a population adaptive immune algorithm to discover different speed profiles of aircraft. Analysis with data from a European hub airport has highlighted the impressive performance of the new approach. Furthermore, it is shown that the trade-off between taxi time and fuel consumption is very sensitive to the fuel-related objective function which is used