Improving the performance of the single-dish Cherenkov telescope MAGIC through the use of signal timing

The Cherenkov light flashes produced by Extensive Air Showers are very short in time. A high bandwidth and fast digitizing readout, therefore, can minimize the influence of the background from the light of the night sky, and improve the performance in Cherenkov telescopes. The time structure of the Cherenkov image can further be used in single-dish Cherenkov telescopes as an additional parameter to reduce the background from unwanted hadronic showers. A description of an analysis method which makes use of the time information and the subsequent improvement on the performance of the MAGIC telescope (especially after the upgrade with an ultra fast 2 GSamples/s digitization system in February 2007) will be presented. The use of timing information in the analysis of the new MAGIC data reduces the background by a factor two, which in turn results in an enhancement of about a factor 1.4 of the flux sensitivity to point-like sources, as tested on observations of the Crab Nebula.

Optimized dark matter searches in deep observations of Segue 1 with MAGIC

We present the results of stereoscopic observations of the satellite galaxy Segue 1 with the MAGIC Telescopes, carried out between 2011 and 2013. With almost 160 hours of good-quality data, this is the deepest observational campaign on any dwarf galaxy performed so far in the very high energy range of the electromagnetic spectrum. We search this large data sample for signals of dark matter particles in the mass range between 100 GeV and 20 TeV. For this we use the full likelihood analysis method, which provides optimal sensitivity to characteristic gamma-ray spectral features, like those expected from dark matter annihilation or decay. In particular, we focus our search on gamma-rays produced from different final state Standard Model particles, annihilation with internal bremsstrahlung, monochromatic lines and box-shaped signals. Our results represent the most stringent constraints to the annihilation cross-section or decay lifetime obtained from observations of satellite galaxies, for masses above few hundred GeV. In particular, our strongest limit (95% confidence level) corresponds to a ~ 500 GeV dark matter particle annihilating into τ+τ−, and is of order langleσannvrangle simeq 1.2 × 10−24 cm3 s−1 a factor ~ 40 above the langleσannvrangle simeq thermal value.

Traumatisme isolé du thorax chez la personne âgée [Isolated chest trauma in elderly patients].

In elderly patients, a blunt trauma of the chest is associated with a significant risk of complications and mortality. The number of ribs fractures (≥ 4), the presence of bilateral rib fractures, of a pulmonary contusion, of existent comorbidities or acute extra-thoracic traumatic lesions, and lastly the severity of thoracic pain, are indeed important risk factors of complications and mortality. Their presence may require hospitalization of the patient. When complications do occur, they are represented by alveolar hypoventilation, pulmonary atelectasia and broncho-pulmonary infections. When hospitalization is required, it may allow for the specific treatment of thoracic pain, including locoregional anesthesia techniques.

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In the past 2 decades, there has been an increase in both basic science research detailing the anatomy and biomechanics of the native posterior cruciate ligament (PCL) and outcome studies evaluating manage- ment of the ruptured PCL. While the methodology of the latter continues to improve, results based on the current level of evidence must be interpreted cautiously (18). The focus of many recent studies has been double-bundle versus single-bundle reconstruction techniques. The theoretical advantage goes to double-bundle techniques, but a clinical difference in outcome has not been consistently demonstrated (8,17). Some biomechanical studies have reported improved control of posterior laxity with double-bundle reconstruc- tion; however, results appear to be more dependent on tunnel position and graft tensioning (13). In acute isolated symptomatic PCL injuries in which the posteromedial bundle and the meniscofemoral ligament remain intact, a single-bundle augmentation procedure may be the preferred surgical technique. In more complex PCL ruptures with associated injuries involving the posterolateral structures (PLS) or medial collateral ligament, more benefit may be derived from double-bundle reconstruction. Again, cadaveric testing of double-bundle PCL reconstruction has not consistently outperformed single-bundle techniques in combined PCL/PLS injury (3). Multi-ligamentous injuries are commonly associated with PCL rupture (15), and their management should be considered carefully in the decision to reconstruct one or both of the functionally dis- tinct PCL bundles. However, the technical complexity of double-bundle reconstruction, the longer surgical time required, as well as the inconclusive clinical outcome are all factors that must be weighed carefully.

Pulmonary valve stenosis due to undifferentiated pleomorphic sarcoma

Pulmonary artery sarcomas are uncommon intracardiac tumours with poor prognosis. We report the case of a 69-year-old woman in good health presenting with rapidly progressive dyspnoea and an unfamiliar systolic murmur. Echocardiography revealed pulmonary valve stenosis due to an obstructing mobile mass. Imaging studies confirmed the presence of a contrast-enhancing lesion adherent to the valve, extending into the pulmonary trunk and right ventricular outflow tract, and suggestive of malignancy. Endovascular biopsy was attempted with no success. Surgical resection with autologous graft valve replacement and pulmonary artery reconstruction was performed. Postoperative histological examination confirmed the diagnosis of an undifferentiated pleomorphic sarcoma. Pulmonary artery sarcoma should be considered as a rare differential diagnosis in patients presenting with dyspnoea and a crescendo-decrescendo systolic murmur increasing with inspiration. Echocardiography is a useful first diagnostic approach but multi-imaging assessment is almost always necessary for definite diagnosis. Our case provides insights into the challenges met by cardiologists, radiologists and cardiac surgeons in the management of such cases.

A retrospective study of deep sternal wound infections: clinical and microbiological characteristics, treatment, and risk factors for complications.

Deep sternal wound infection (DSWI) is a feared complication following cardiac surgery. This study describes clinical, microbiological, and treatment outcomes of DSWI and determines risk factors for complications. Of 55 patients with DSWI, 66% were male and mean age was 68.2years. Initial sternotomy was for coronary artery bypass graft in 49% of patients. Sternal debridement at mean 25.4±18.3days showed monomicrobial (94%), mainly Gram-positive infection. Secondary sternal wound infection (SSWI) occurred in 31% of patients, was mostly polymicrobial (71%), and was predominantly due to Gram-negative bacilli. Risk factors for SSWI were at least 1 revision surgery (odds ratio [OR] 4.8 [95% confidence interval {CI} 1.0-22.4], P=0.047), sternal closure by muscle flap (OR 4.6 [1.3-16.8], P=0.02), delayed sternal closure (mean 27 versus 14days, P=0.03), and use of vacuum-assisted closure device (100% versus 58%, P=0.008). Hospital stay was significantly longer in patients with SSWI (69days versus 48days, P=0.04).

Apical access and closure devices for transapical transcatheter heart valve procedures.

The majority of transcatheter aortic valve implantations, structural heart procedures and the newly developed transcatheter mitral valve repair and replacement are traditionally performed either through a transfemoral or a transapical access site, depending on the presence of severe peripheral vascular disease or anatomic limitations. The transapical approach, which carries specific advantages related to its antegrade nature and the short distance between the introduction site and the cardiac target, is traditionally performed through a left anterolateral mini-thoracotomy and requires rib retractors, soft tissue retractors and reinforced apical sutures to secure, at first, the left ventricular apex for the introduction of the stent-valve delivery systems and then to seal the access site at the end of the procedure. However, despite the advent of low-profile apical sheaths and newly designed delivery systems, the apical approach represents a challenge for the surgeon, as it has the risk of apical tear, life-threatening apical bleeding, myocardial damage, coronary damage and infections. Last but not least, the use of large-calibre stent-valve delivery systems and devices through standard mini-thoracotomies compromises any attempt to perform transapical transcatheter structural heart procedures entirely percutaneously, as happens with the transfemoral access site, or via a thoracoscopic or a miniaturised video-assisted percutaneous technique. During the past few years, prototypes of apical access and closure devices for transapical heart valve procedures have been developed and tested to make this standardised successful procedure easier. Some of them represent an important step towards the development of truly percutaneous transcatheter transapical heart valve procedures in the clinical setting.

De novo undifferentiated pleomorphic sarcoma arising from a renal allograft: A case report

To the best of our knowledge, this is the first report of an undifferentiated pleomorphic sarcoma arising from a renal graft. Transplantectomy was performed in a 47-year old woman presenting to the emergency room because of general weakness. Preoperative workup revealed a 5.5 cm malignant mass of the graft which was not present on routine ultrasound performed 12 months earlier. Following transplantectomy, local recurrence developed despite complete tumor resection and interruption of immunosuppression. Despite radiation therapy, the outcome was ultimately fatal. Genetic analysis revealed that the tumor had arisen from donor tissue. Annual ultrasound surveillance might not be enough effective to screen for these rare high grade neoplasms.

Postoperatorio del paciente pediátrico trasplantado renal

El trasplante renal es la modalidad de tratamiento sustitutivo que mejores resultados proporciona a niños afectos de insuficiencia renal crónica terminal, aunque no está exenta de una importante morbilidad y mortalidad. Se describen el protocolo para el postoperatorio adoptado en nuestro centro: monitorazación y soporte, variantes inmunopresoras, exploraciones complementarias, y las diversas complicaciones que pueden aparecer después del trasplante.

Mycoplasma hominis mediastinitis after acute aortic dissection repair.

We report a case of ascending aortic graft infection by an atypical bacteria, Mycoplasma hominis, with mediastinitis, a dreaded complication after cardiac surgery. A 55-year-old patient underwent ascending aorta replacement for acute type A dissection. He developed sternal instability and purulent discharge, requiring sternal wire removal and debridement. Cultures were initially sterile, but showed M. hominis infection after a significant delay and in specific culture media. The patient was treated with doxycycline and moxifloxacine. Cultures became negative and the sternum was closed on the 28th postoperative day after the first debridement. Recovery was favorable, with no signs of infection. Antibiotics were continued for one year. The patient is still asymptomatic 16 months after antibiotic interruption. Atypical organisms should be considered in the differential diagnosis of acute mediastinitis of unknown etiology after routine microbiological investigations.

The "Abdominal Circulatory Pump": An Auxiliary Heart during Exercise?

Apart from its role as a flow generator for ventilation the diaphragm has a circulatory role. The cyclical abdominal pressure variations from its contractions cause swings in venous return from the splanchnic venous circulation. During exercise the action of the abdominal muscles may enhance this circulatory function of the diaphragm. Eleven healthy subjects (25 ± 7 year, 70 ± 11 kg, 1.78 ± 0.1 m, 3 F) performed plantar flexion exercise at ~4 METs. Changes in body volume (ΔVb) and trunk volume (ΔVtr) were measured simultaneously by double body plethysmography. Volume of blood shifts between trunk and extremities (Vbs) was determined non-invasively as ΔVtr-ΔVb. Three types of breathing were studied: spontaneous (SE), rib cage (RCE, voluntary emphasized inspiratory rib cage breathing), and abdominal (ABE, voluntary active abdominal expiration breathing). During SE and RCE blood was displaced from the extremities into the trunk (on average 0.16 ± 0.33 L and 0.48 ± 0.55 L, p < 0.05 SE vs. RCE), while during ABE it was displaced from the trunk to the extremities (0.22 ± 0.20 L p < 0.001, p < 0.05 RCE and SE vs. ABE respectively). At baseline, Vbs swings (maximum to minimum amplitude) were bimodal and averaged 0.13 ± 0.08 L. During exercise, Vbs swings consistently increased (0.42 ± 0.34 L, 0.40 ± 0.26 L, 0.46 ± 0.21 L, for SE, RCE and ABE respectively, all p < 0.01 vs. baseline). It follows that during leg exercise significant bi-directional blood shifting occurs between the trunk and the extremities. The dynamics and partitioning of these blood shifts strongly depend on the relative predominance of the action of the diaphragm, the rib cage and the abdominal muscles. Depending on the partitioning between respiratory muscles for the act of breathing, the distribution of blood between trunk and extremities can vary by up to 1 L. We conclude that during exercise the abdominal muscles and the diaphragm might play a role of an "auxiliary heart."

From T cell “exhaustion” to anti-cancer immunity

The immune system has the potential to protect from malignant diseases for extended periods of time. Unfortunately, spontaneous immune responses are often inefficient. Significant effort is required to develop reliable, broadly applicable immunotherapies for cancer patients. A major innovation was transplantation with hematopoietic stem cells from genetically distinct donors for patients with hematologic malignancies. In this setting, donor T cells induce long-term remission by keeping cancer cells in check through powerful allogeneic graft-versus-leukemia effects. More recently, a long awaited breakthrough for patients with solid tissue cancers was achieved, by means of therapeutic blockade of T cell inhibitory receptors. In untreated cancer patients, T cells are dysfunctional and remain in a state of T cell "exhaustion". Nonetheless, they often retain a high potential for successful defense against cancer, indicating that many T cells are not entirely and irreversibly exhausted but can be mobilized to become highly functional. Novel antibody therapies that block inhibitory receptors can lead to strong activation of anti-tumor T cells, mediating clinically significant anti-cancer immunity for many years. Here we review these new treatments and the current knowledge on tumor antigen-specific T cells.

Enhancement of human adipose-derived stem cell expansion and stability for clinical use

Co-culture techniques associating both dermal fibroblasts and epidermal keratinocytes have shown to have better clinical outcome than keratinocyte culture alone for the treatment of severe burns. Since fat grafting has been shown to improve scar remodelling, new techniques such as cell-therapy-assisted surgical reconstruction with isolated and expanded autologous adipose-derived stem cells (ASCs) would be of benefit to increase graft acceptation. Therefore, integrating ASCs into standardized procedures for cultured skin grafting could be of benefit for the patient if cell quality and quantity could be maintained. The purpose of this study was to evaluate ASC processing from adult tissue with simple isolation (without enzymatic steps), expansion (low density of 325-3,000 cells/cm2) and storage conditions to assure methods to enhance the cellular resistance when transferred back to the patient. Co-culture with cell-banked skin progenitor cells (FE002-SK2) showed an increase of 40-50% ASCs yield at high passages alongside with a better preservation of morphology, proper adipogenic and osteogenic differentiation and efficient biocompatibility with 3D collagen scaffolds. ASCs can be considered as a valuable additional cell source to be delivered in biological bandages to the patient in a need of tissue reconstruction such as burn patients.

Immunotherapeutic targeting of LIGHT/LTβR/HVEM pathway fully recapitulates the reduced cytotoxic phenotype of LIGHT-deficient T cells.

Tumor necrosis factor (TNF)/TNF receptor (TNFR) superfamily members play essential roles in the development of the different phases of the immune response. Mouse LIGHT (TNFSF14) is a type II transmembrane protein with a C-terminus extracellular TNF homology domain (THD) that assembles in homotrimers and regulates the course of the immune responses by signaling through 2 receptors, the herpes virus entry mediator (HVEM, TNFSFR14) and the lymphotoxin β receptor (LTβR, TNFSFR3). LIGHT is a membrane-bound protein transiently expressed on activated T cells, natural killer (NK) cells and immature dendritic cells that can be proteolytically cleaved by a metalloprotease and released to the extracellular milieu. The immunotherapeutic potential of LIGHT blockade was evaluated in vivo. Administration of an antagonist of LIGHT interaction with its receptors attenuated the course of graft-versus-host reaction and recapitulated the reduced cytotoxic activity of LIGHT-deficient T cells adoptively transferred into non-irradiated semiallogeneic recipients. The lack of LIGHT expression on donor T cells or blockade of LIGHT interaction with its receptors slowed down the rate of T cell proliferation and decreased the frequency of precursor alloreactive T cells, retarding T cell differentiation toward effector T cells. The blockade of LIGHT/LTβR/HVEM pathway was associated with delayed downregulation of interleukin-7Rα and delayed upregulation of inducible costimulatory molecule expression on donor alloreactive CD8 T cells that are typical features of impaired T cell differentiation. These results expose the relevance of LIGHT/LTβR/HVEM interaction for the potential therapeutic control of the allogeneic immune responses mediated by alloreactive CD8 T cells that can contribute to prolong allograft survival.

Hints for a fast precessing relativistic radio jet in LS I + 61° 303

Here we discuss two consecutive MERLIN observations of the X-ray binary LS I +61° 303 . The first observation shows a double-sided jet extending up to about 200 AU on both sides of a central source. The jet shows a bent S-shaped structure similar to the one displayed by the well-known precessing jet of SS 433 . The precession suggested in the first MERLIN image becomes evident in the second one, showing a one-sided bent jet significantly rotated with respect to the jet of the day before. We conclude that the derived precession of the relativistic (beta=0.6) jet explains puzzling previous VLBI results. Moreover, the fact that the precession is fast could be the explanation of the never understood short term (days) variability of the associated gamma-ray source 2CG 135+01 / 3EG J0241+6103