Recombination is a complex biological process that results from a cascade of multiple events during meiosis. Understanding the genetic determinism of recombination can help to understand if and how ...these events are interacting. To tackle this question, we studied the patterns of recombination in sheep, using multiple approaches and data sets. We constructed male recombination maps in a dairy breed from the south of France (the Lacaune breed) at a fine scale by combining meiotic recombination rates from a large pedigree genotyped with a 50K SNP array and historical recombination rates from a sample of unrelated individuals genotyped with a 600K SNP array. This analysis revealed recombination patterns in sheep similar to other mammals but also genome regions that have likely been affected by directional and diversifying selection. We estimated the average recombination rate of Lacaune sheep at 1.5 cM/Mb, identified ∼50,000 crossover hotspots on the genome, and found a high correlation between historical and meiotic recombination rate estimates. A genome-wide association study revealed two major loci affecting interindividual variation in recombination rate in Lacaune, including the
and
genes and possibly two other loci of smaller effects including the
and
genes. The comparison of these new results to those obtained previously in a distantly related population of domestic sheep (the Soay) revealed that Soay and Lacaune males have a very similar distribution of recombination along the genome. The two data sets were thus combined to create more precise male meiotic recombination maps in Sheep. However, despite their similar recombination maps, Soay and Lacaune males were found to exhibit different heritabilities and QTL effects for interindividual variation in genome-wide recombination rates. This highlights the robustness of recombination patterns to underlying variation in their genetic determinism.
Push-out tests are frequently used to evaluate the bone-implant interfacial strength of orthopedic implants, particularly dental and craniomaxillofacial applications. There currently is no standard ...method for performing push-out tests on calvarial models, leading to a variety of inconsistent approaches. In this study, fixtures and methods were developed to perform push-out tests in accordance with the following design objectives: (i) the system rigidly fixes the explanted calvarial sample, (ii) it minimizes lateral bending, (iii) it positions the defect accurately, and (iv) it permits verification of the coaxial alignment of the defect with the push-out rod. The fixture and method was first validated by completing push-out experiments on 30 explanted murine cranial caps and two explanted leporine cranial caps, all induced with bilateral sub-critical defects (5.0 mm and 8.0 mm nominal diameter for the murine and leporine models, respectively). Defects were treated with an autograft (i.e., excised tissue flap), a shape memory polymer (SMP) scaffold, or a PEEK implant. Additional validation was performed on 24 murine cranial caps induced with a single, unilateral critically-sized defect (8.0 mm nominal diameter) and treated with an autograft or a SMP scaffold.•A novel fixture was developed for performing push-out mechanical tests to characterize the strength of a bone-implant interface in calvarial defect repair.•The fixture uses a 3D printed vertical clamp with mating alignment component to fix the sample in place without inducing lateral bending and verify coaxial alignment of push-out rod with the defect.•The fixture can be scaled to different calvarial defect geometries as validated with 5.0 mm bilateral and 8.0 mm single diameter murine calvarial defect model and 8.0 mm bilateral leporine calvarial defect model.
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Summary
Background
In patients with a first eradication failure, a second (rescue) therapy still fails in > 20% of cases.
Aim
To compare rifabutin and levofloxacin rescue regimens in patients with ...two consecutive Helicobacter pylori eradication failures.
Methods
Patients, in whom first treatment with omeprazole–clarithromycin–amoxicillin and a second trial with omeprazole–bismuth–tetracycline–metronidazole (or ranitidine bismuth citrate with these antibiotics) had failed, received 10 days of treatment with either rifabutin (150 mg b.d.) or levofloxacin (500 mg b.d.), plus amoxicillin (1 g b.d.) and omeprazole (20 mg b.d.). Cure rates were evaluated by the 13C‐urea breath test.
Results
Twenty patients received rifabutin, and 20 levofloxacin. All the patients returned for follow‐up. Compliance in the rifabutin group was 100%. Four patients in the levofloxacin group did not take the medication correctly (in two cases due to adverse effects: myalgia and rash). Side effects in the rifabutin and levofloxacin groups were reported in 60% and 50% of the cases, respectively. Five patients (25%) treated with rifabutin presented with leucopenia, and six (30%) treated with levofloxacin presented with myalgias. Per‐protocol cure rates were 45% (95% confidence interval, 26–66%) in the rifabutin group, and 81% (57–93%) in the levofloxacin group (P < 0.05). Intention‐to‐treat cure rates were, 45% (26–66%) and 85% (64–95%), respectively (P < 0.01).
Conclusions
After two previous H. pylori eradication failures, a 10‐day triple levofloxacin‐based rescue regimen is more effective than the same regimen with rifabutin.
The LAgrangian Kite SimulAtor (LAKSA) is a freely available software for the dynamic analysis of tethered flying vehicles, such as kites and fixed-wing drones, applied to airborne wind energy ...generation. This software comprises four simulators. The one, two and four-line simulators, which consider flexible but inelastic tethers, are based on minimal coordinate Lagragian formulations and can be used for the analysis of fly and ground generation systems, kite-based traction systems, and kitesurfing applications, respectively. The configuration of the mechanical system in the fourth simulator can be defined by the user, who can select the number of flying vehicles and the properties of the elastic and flexible tethers linking them. In all the software tools, the kites or tethered fixed-wing drones are represented as rigid bodies and the dynamic equations of the tether-bridle-vehicle systems, together with the user-defined and time-dependent control variables, are solved self-consistently. Academic and research analysis can take advantage of the modularity of the simulators and their inputs and outputs interfaces, which follow a common and user-friendly architecture.
Background: VCN-01 is a selective oncolytic adenovirus with hyaluronid-ase activity. This study aimed to determine the safety, pharmacokinetics (PK) and anti-tumor activity of a single intravenous ...injection of VCN-01, either alone or combined with nab-paclixatel/gemcitabine (AG) and to define the recommended phase II dose (RP2D) of VCN-01 alone or in combination with AG. Material and Methods: VCN-01 was administered IV to patients with advanced solid tumors with ECOG 0-1 at doses ranging from 1E11 to 1E13 viral particles per patient (vp) as a single agent and at from 3.3E12 to 1E13 vp + AG at standard doses. Blood VCN-01 DNA was measured at different time-points after treatment. Viral shedding was assessed in sputum, urine and stool. IL-6 and IL-12 levels were also measured. Viral DNA and lymphocytic populations were analyzed in tumor biopsies. Response was assessed using RECIST v1.1 criteria. Results: Twenty three patients have been treated to date including 16 patients who received VCN-01 alone (patients with gastrointestinal solid tumors, except 1 head & neck tumor) and 7 patients who received combined treatment (all having pancreatic adenocarcinoma). Neutralizing antibodies (NAb) levels against adenovirus of < 1/320 were detected in all patients at screening. The most common related toxicities after injection of VCN-01 alone were: pyrexia (81%), arthralgia & myalgia (25%), AST elevation (18%), anorexia and vomiting (18%). One dose-limiting toxicity consisting of G4 liver toxicity that spontaneously solved was evidence at 1E13 vp. Common toxicities after combination with chemotherapy were: neutropenia, thrombocytopenia, and pyrexia (86%). One episode of DLT consisting of febrile neutropenia G4 recovered adequately after 10 days. Twelve of 23 patients showed secondary viremia peaks, all of them receiving 3.3E12 vp and 1E13 vp. Shedding of VCN-01 was observed in all tested biologic fluids mostly until day 8. Preliminary PK calculations show linearity in dose ratio. All analyzed biopsies at day 8 post-injection (4 of 4) were positive for VCN-01 presence. Increased CD8 infiltration was observed within tumor tissue. PET evaluation at 4 weeks after VCN-01 administration indicated metabolic improvement in a majority of patients (4/7) and more than 50% of patients treated with VCN-01 + AG showed PR at 16 weeks by RECIST with 2 out of 3 patients maintaining PR at 32 weeks. Conclusions: VCN-01 shows evidences of clinical activity at well-tolerated dose levels. Pharmacodynamic observations confirm viral infiltrate in tumor tissue where active replication may modulate intratumor immune response.
Al2O3-TiO2 coatings were deposited on austenitic stainless steel coupons from nanostructured powders by atmospheric plasma spraying (APS). Commercial suspensions of nanosized Al2O3 and TiO2 particles ...were used as starting materials. Mixtures of these suspensions and of more concentrated suspensions of Al2O3 and TiO2 were then agglomerated into plasma sprayable feedstock. Agglomeration was performed by spray drying, followed by consolidation thermal treatment. These powders were successfully deposited, yielding coatings that were well bonded to the substrates. The coating microstructure thus consisted of semi-molten feedstock agglomerates surrounded by fully molten particles that acted as binders. Agglomerates from suspensions with higher solids contents yielded coatings with lower porosity and fewer semi-molten areas.
This study provides a series of updated, evidence-based recommendations for the management of acute stroke. We aim to lay a foundation for the development of individual centres’ internal protocols, ...serving as a reference for nursing care.
We review the available evidence on acute stroke care. The most recent national and international guidelines were consulted. Levels of evidence and degrees of recommendation are based on the Oxford Centre for Evidence-Based Medicine classification.
The study describes prehospital acute stroke care, the operation of the code stroke protocol, care provided by the stroke team upon the patient’s arrival at hospital, reperfusion treatments and their limitations, admission to the stroke unit, nursing care in the stroke unit, and discharge from hospital.
These guidelines provide general, evidence-based recommendations to guide professionals who care for patients with acute stroke. However, limited data are available on some aspects, showing the need for continued research on acute stroke management.
Proporcionar un conjunto de recomendaciones actualizadas y basadas en la evidencia disponible para el manejo del ictus agudo. Nuestro objetivo es proporcionar una base para el desarrollo de los protocolos internos de cada centro, sirviendo de referencia para los cuidados de enfermería.
Revisión de evidencias disponibles sobre los cuidados del ictus agudo. Se han consultado las guías nacionales e internacionales más recientes. Los niveles de evidencia y grados de recomendación se han basado en la clasificación del Centro de Medicina Basada en la Evidencia de Oxford.
Se describen la atención y los cuidados del ictus agudo en la fase prehospitalaria, el funcionamiento de código ictus, la atención por el equipo de ictus a la llegada al hospital, los tratamientos de reperfusión y sus limitaciones, el ingreso en la unidad de ictus (UI), los cuidados de enfermería en la UI y el alta hospitalaria.
Estas pautas proporcionan recomendaciones generales basadas en la evidencia actualmente disponible para guiar a los profesionales que atienden a pacientes con ictus agudo. En algunos casos, sin embargo, existen datos limitados demostrando la necesidad de continuar investigando sobre el manejo del ictus agudo.
Ventricular aneurysm represents a rare complication of transmural acute myocardial infarction, although other cardiac, congenital, or metabolic diseases may also predispose to such condition. ...Ventricular expansion includes all the cardiac layers, usually with a large segment involved. Adverse events include recurrent angina, reduced ventricular stroke volume with congestive heart failure, mitral regurgitation, thromboembolism, and ventricular arrhythmias. Multimodality imaging is paramount to provide comprehensive assessment, allowing for appropriate therapeutic decision-making. When indicated, surgical intervention remains the gold standard, although additional therapy (heart failure, anticoagulation, and advanced antiarrhythmic treatment) might be required. However, the STICH (Surgical Treatment for Ischemic Heart Failure) trial did not show any advantage from adding surgical ventricular reconstruction to coronary artery bypass surgery in terms of survival, rehospitalization or symptoms, compared with revascularization alone. Finally, implantable cardiac defibrillator may reduce the risk of fatal arrhythmias.
Ventricular septal rupture remains a dreadful complication of acute myocardial infarction. Although less commonly observed than during the prethrombolytic era, the condition remains complex and is ...often associated with refractory cardiogenic shock and death. Corrective surgery, although superior to medical treatment, has been associated with high perioperative morbidity and mortality. Transcatheter closure techniques are less invasive to surgery and offer a valuable alternative, particularly in patients with cardiogenic shock. In these patients, percutaneous mechanical circulatory support represents a novel opportunity for immediate stabilization and preserved end-organ function. Multimodality imaging can identify favorable septal anatomy for the most appropriate type of repair. The heart team approach will define optimal timing for surgery vs percutaneous repair. Emerging concepts are proposed for a deferred treatment approach, including orthotropic heart transplantation in ideal candidates. Finally, for futile situations, palliative care experts and a medical ethics team will provide the best options for end-of-life clinical decision making.
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