Improved performance of the LHCb Outer Tracker in LHC Run 2

The LHCb Outer Tracker is a gaseous detector covering an area of $5\times 6 m^2$ with 12 double layers of straw tubes. The performance of the detector is presented based on data of the LHC Run 2 running period from 2015 and 2016. Occupancies and operational experience for data collected in $p p$, pPb and PbPb collisions are described. An updated study of the ageing effects is presented showing no signs of gain deterioration or other radiation damage effects. In addition several improvements with respect to LHC Run 1 data taking are introduced. A novel real-time calibration of the time-alignment of the detector and the alignment of the single monolayers composing detector modules are presented, improving the drift-time and position resolution of the detector by 20\%. Finally, a potential use of the improved resolution for the timing of charged tracks is described, showing the possibility to identify low-momentum hadrons with their time-of-flight.Comment: 29 pages, 20 figures, minor changes to match the published versio

Stalking influenza by vaccination with pre-fusion headless HA mini-stem.

Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies indudced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity

ABO-incompatible kidney transplantation in perspective of deceased donor transplantation and induction strategies:a propensity-matched analysis

BACKGROUND: Kidney transplant candidates are blood group incompatible with roughly one out of three potential living donors. We compared outcomes after ABO-incompatible (ABOi) kidney transplantation with matched ABO-compatible (ABOc) living and deceased donor transplantation and analyzed different induction regimens. METHODS: We performed a retrospective study with propensity matching and compared patient and death-censored graft survival after ABOi versus ABOc living donor and deceased donor kidney transplantation in a nationwide registry from 2006 till 2019. RESULTS: 296 ABOi were compared to 1184 center and propensity matched ABOc living donor and 1184 deceased donor recipients (matching: recipient age, sex, blood group and PRA). Patient survival was better compared to deceased donor (hazard ratio (HR) for death of HR 0.69 [0.49-0.96], and not-significantly different from ABOc living donor recipients (HR 1.28 [0.90-1.81]). Rate of graft failure was higher compared to ABOc living donor transplantation (HR 2.63 [1.72-4.01]). Rejection occurred in 47% of 140 rituximab versus 22% of 50 rituximab/basiliximab, and 4% of 92 alemtuzumab treated recipients (p <0.001). CONCLUSIONS: ABOi kidney transplantation is superior to deceased donor transplantation. Rejection rate and graft failure are higher compared to matched ABOc living donor transplantation, underscoring the need for further studies into risk stratification and induction therapy

Pathological and Biological Differences Between Screen-Detected and Interval Ductal Carcinoma in situ of the Breast

Background: The incidence of ductal carcinoma in situ (DCIS) has risen dramatically with the introduction of screening mammography. The aim was to evaluate differences in pathological and biological characteristics between patients with screen-detected and interval DCIS. Methods: From January 1992 to December 2001, 128 consecutive patients had been treated for pure DCIS at our institute. From these, 102 had been attending the Dutch breast cancer screening program. Sufficient paraffin-embedded tissue was available in 74 out of the 102 cases to evaluate biological marker expression (Her2/neu, ER, PR, p53 and cyclin D1) on tissue microarrays (TMA group). Differences in clinicopathological characteristics and marker expression between screen-detected and interval patients were evaluated. Screen-detected DCIS was classified as DCIS detected by screening mammography, when the two-year earlier examination failed to reveal an abnormality. Interval patients were classified as patients with DCIS detected within the two-year interval between two subsequent screening rounds. Results: Screen-detected DCIS was related with linear branching and coarse granular microcalcifications on mammography (p < .001) and with high-grade DCIS according to the Van Nuys classification (p = .025). In univariate analysis, screen-detected DCIS was related with Her2/neu overexpression (odds ratio [OR] = 6.5; 95%CI 1.3-31.0; p = .020), and interval DCIS was associated with low-grade (Van Nuys, OR = 7.3; 95% CI 1.6-33.3; p = .010) and PR positivity (OR = 0.3; 95%CI 0.1-1.0; p = .042). The multivariate analysis displayed an independent relation of Her2/neu overexpression with screen-detected DCIS (OR = 12.8; 95%CI 1.6-104.0; p = .018). Conclusions: These findings suggest that screen-detected DCIS is biologically more aggressive than interval DCIS and should not be regarded as overdiagnosis

The ANTARES Optical Beacon System

ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It consists of a three dimensional array of photomultiplier tubes that can detect the Cherenkov light induced by charged particles produced in the interactions of neutrinos with the surrounding medium. High angular resolution can be achieved, in particular when a muon is produced, provided that the Cherenkov photons are detected with sufficient timing precision. Considerations of the intrinsic time uncertainties stemming from the transit time spread in the photomultiplier tubes and the mechanism of transmission of light in sea water lead to the conclusion that a relative time accuracy of the order of 0.5 ns is desirable. Accordingly, different time calibration systems have been developed for the ANTARES telescope. In this article, a system based on Optical Beacons, a set of external and well-controlled pulsed light sources located throughout the detector, is described. This calibration system takes into account the optical properties of sea water, which is used as the detection volume of the ANTARES telescope. The design, tests, construction and first results of the two types of beacons, LED and laser-based, are presented.Comment: 21 pages, 18 figures, submitted to Nucl. Instr. and Meth. Phys. Res.

Nature and mental health: An ecosystem service perspective

This is the final version. Available on open access from American Association for the Advancement of Science via the DOI in this recordData and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.A growing body of empirical evidence is revealing the value of nature experience for mental health. With rapid urbanization and declines in human contact with nature globally, crucial decisions must be made about how to preserve and enhance opportunities for nature experience. Here, we first provide points of consensus across the natural, social, and health sciences on the impacts of nature experience on cognitive functioning, emotional well-being, and other dimensions of mental health. We then show how ecosystem service assessments can be expanded to include mental health, and provide a heuristic, conceptual model for doing so.Doug Walker Endowed ProfessorshipCraig McKibben and Sarah MernerJohn MillerMarianne and Marcus Wallenberg FoundationWinslow FoundationGeorge Rudolf Fellowship FundVictoria and David Rogers FundMr. & Mrs. Dean A. McGee Fun

Social network and dominance hierarchy analyses at Chimpanzee Sanctuary Northwest

Different aspects of sociality bear considerable weight on the individual- and group-level welfare of captive nonhuman primates. Social Network Analysis (SNA) is a useful tool for gaining a holistic understanding of the dynamic social relationships of captive primate groups. Gaining a greater understanding of captive chimpanzees through investigations of centrality, preferred and avoided relationships, dominance hierarchy, and social network diagrams can be useful in advising current management practices in sanctuaries and other captive settings. In this study, we investigated the dyadic social relationships, group-level social networks, and dominance hierarchy of seven chimpanzees (Pan troglodytes) at Chimpanzee Sanctuary Northwest. We used focal-animal and instantaneous scan sampling to collect 106.75 total hours of associative, affiliative, and agonistic data from June to September 2016. We analyzed our data using SOCPROG to derive dominance hierarchies and network statistics, and we diagrammed the group\u27s social networks in NetDraw. Three individuals were most central in the grooming network, while two others had little connection. Through agonistic networks, we found that group members reciprocally exhibited agonism, and the group\u27s dominance hierarchy was statistically non-linear. One chimpanzee emerged as the most dominant through agonism but was least connected to other group members across affiliative networks. Our results indicate that the conventional methods used to calculate individuals\u27 dominance rank may be inadequate to wholly depict a group\u27s social relationships in captive sanctuary populations. Our results have an applied component that can aid sanctuary staff in a variety of ways to best ensure the improvement of group welfare

Prerequisites for effective adenovirus mediated gene therapy of colorectal liver metastases in the rat using an intracellular neutralizing antibody fragment to p21-Ras

Ras mutations are present in 40–50% of colorectal cancers. Inactivating this oncogene may therefore reduce proliferation capacity. In order to target ras we studied the transduction efficacy and anti tumour activity of an adenoviral vector expressing an intracellular, neutralizing single chain antibody to p21-ras (Y28). In in vitro studies transfection levels of the K-ras mutated rat colon carcinoma cell line CC531 were studied using the LacZ marker gene. In our in vivo liver metastases model different routes of administration were evaluated to determine which regimen resulted in the best transfection levels and tumour responses: intravenous injection, intratumoural injection, isolated liver perfusion, or hepatic artery infusion. CC531 cells are readily transfected in vitro, resulting in significant inhibition of tumour cell proliferation by the Y28 construct. Intravenous injection did not result in any measurable transfection. Intratumoural injection resulted only in the transfection of tumour cells along the needle track. IHP as well as single HAI achieved low transfection levels of tumour tissue. Expression of Y28 was demonstrated in tumours after IT injection, HAI and IHP. Whereas, repeated HAI's clearly achieved expression in and around tumour associated vessels. Only five times repeated HAI's with Y28 resulted in a tumour response: in all animals tumour growth was inhibited, and in three rats out of eight a complete regression of the liver tumours was observed

SUrgical versus PERcutaneous Bypass: SUPERB-trial; Heparin-bonded endoluminal versus surgical femoro-popliteal bypass: study protocol for a randomized controlled trial

Contains fulltext : 96315.pdf (publisher's version ) (Open Access)BACKGROUND: Endovascular treatment options for the superficial femoral artery are evolving rapidly. For long lesions, the venous femoropopliteal bypass considered to be superior above the prosthetic bypass. An endoluminal bypass, however, may provide equal patency rates compared to the prosthetic above knee bypass. The introduction of heparin-bonded endografts may further improve patency rates. The SUrgical versus PERcutaneous Bypass (SuperB) study is designed to assess whether a heparin-bonded endoluminal bypass provides equal patency rates compared to the venous bypass and to prove that it is associated with improved quality of life, related to a decreased complication rate, or not. METHODS/DESIGN: Two-hundred-twenty-two patients with peripheral arterial occlusive disease, category 3-6 according to Rutherford, will be randomized in two treatment arms; 1. the surgical femoro-popliteal bypass, venous whenever possible, and 2. the heparin-bonded endoluminal bypass. The power analysis was based on a non-inferiority principle, with an effect size of 90% and 10% margins (alpha 5%, power 80%). Patients will be recruited from 5 teaching hospitals in the Netherlands during a 2-year period. The primary endpoint is primary patency and quality of life evaluated by the RAND-36 questionnaire and the Walking Impairment Questionnaire. Secondary endpoints include secondary patency, freedom-from-TLR and complications. DISCUSSION: The SuperB trial is a multicentre randomized controlled trial designed to show non-inferiority in patency rates of the heparin-bonded endograft compared to the surgical bypass for treatment of long SFA lesions, and to prove a better quality of life using the heparin bonded-endograft compared to surgically treatment, related to a reduction in complications. TRIAL REGISTRATION: Clinicaltrials: NCT01220245