Quantifying HIV transmission flow between high-prevalence hotspots and surrounding communities: a population-based study in Rakai, Uganda

Background International and global organisations advocate targeting interventions to areas of high HIV prevalence (ie, hotspots). To better understand the potential benefits of geo-targeted control, we assessed the extent to which HIV hotspots along Lake Victoria sustain transmission in neighbouring populations in south-central Uganda. Methods We did a population-based survey in Rakai, Uganda, using data from the Rakai Community Cohort Study. The study surveyed all individuals aged 15–49 years in four high-prevalence Lake Victoria fishing communities and 36 neighbouring inland communities. Viral RNA was deep sequenced from participants infected with HIV who were antiretroviral therapy-naive during the observation period. Phylogenetic analysis was used to infer partial HIV transmission networks, including direction of transmission. Reconstructed networks were interpreted through data for current residence and migration history. HIV transmission flows within and between high-prevalence and low-prevalence areas were quantified adjusting for incomplete sampling of the population. Findings Between Aug 10, 2011, and Jan 30, 2015, data were collected for the Rakai Community Cohort Study. 25 882 individuals participated, including an estimated 75·7% of the lakeside population and 16·2% of the inland population in the Rakai region of Uganda. 5142 participants were HIV-positive (2703 [13·7%] in inland and 2439 [40·1%] in fishing communities). 3878 (75·4%) people who were HIV-positive did not report antiretroviral therapy use, of whom 2652 (68·4%) had virus deep-sequenced at sufficient quality for phylogenetic analysis. 446 transmission networks were reconstructed, including 293 linked pairs with inferred direction of transmission. Adjusting for incomplete sampling, an estimated 5·7% (95% credibility interval 4·4–7·3) of transmissions occurred within lakeside areas, 89·2% (86·0–91·8) within inland areas, 1·3% (0·6–2·6) from lakeside to inland areas, and 3·7% (2·3–5·8) from inland to lakeside areas. Interpretation Cross-community HIV transmissions between Lake Victoria hotspots and surrounding inland populations are infrequent and when they occur, virus more commonly flows into rather than out of hotspots. This result suggests that targeted interventions to these hotspots will not alone control the epidemic in inland populations, where most transmissions occur. Thus, geographical targeting of high prevalence areas might not be effective for broader epidemic control depending on underlying epidemic dynamics. Funding The Bill & Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute of Child Health and Development, the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases, the World Bank, the Doris Duke Charitable Foundation, the Johns Hopkins University Center for AIDS Research, and the President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention

Somatic mutations affect key pathways in lung adenocarcinoma

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well- classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers - including NF1, APC, RB1 and ATM - and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.National Human Genome Research InstituteWe thank A. Lash, M.F. Zakowski, M.G. Kris and V. Rusch for intellectual contributions, and many members of the Baylor Human Genome Sequencing Center, the Broad Institute of Harvard and MIT, and the Genome Center at Washington University for support. This work was funded by grants from the National Human Genome Research Institute to E.S.L., R.A.G. and R.K.W.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62885/1/nature07423.pd

Gamma-tracking and sensitivity to gamma-emitting backgrounds in SuperNEMO

International audienceSuperNEMO, successor to the NEMO3 experiment, is looking for the neutrinoless double beta decay. Its unique design, combining both tracking and calorimetry techniques, provides essential topological informations. Indeed, fully reconstructing the event kinematics allows a powerful background discrimination, would discriminate between the several hypothesized underlying mechanisms, but also gives access to a variety of event topologies which can be used to measure the different background contributions. The SuperNEMO software relies on a range of algorithms to ensure a faithful event reconstruction. The improved detector performance for γ detection coupled to new γ-reconstruction algorithms, based on geometrical and Time-of-Flight criteria, will not only improve the measurements of the γ-emitter backgrounds ((208)Tl, (214)Bi...) but also increase the sensitivity for the search of ββ-decays to the excited states

Reconstruction algorithm developments and study of the beam optics constraints at 4 TeV in the ATLAS/ALFA experiment

My summer student work was divided into two main projects. My first project consisted in implementing the fiber width measured from the data in the reconstruction algorithm in order to improve the detector resolution. I then performed some data analysis in order to measure the constraints on the beam optics at 4 TeV. Its main purpose was to check that the constraints deviations are the same as the 3.5 TeV run already analyzed

0νββ0 \nu \beta\beta sensitivity with the SuperNEMO demonstrator

International audienceThe SuperNEMO demonstrator 1 , which is the first module of the SuperNEMOexperiment, is looking for the neutrinoless double beta decay 0νββ in order tounveil the nature of the neutrino. Its unique design, combining both trackingand calorimetry techniques, provides essential topological information. Indeed,fully reconstructing the event kinematics gives access to a variety of eventtopologies which can be used to measure the different background contributionsas well as look for new processes such as the double beta decays to the excitedstates of the daughter nuclei. Using this information in a multivariate analysiscan improve the background discrimination power and further increase thedetector sensitivity. The commissioning of the demonstrator is ongoing and thedata taking should start in Summer 2017

Développement d'outils de reconstruction et sensibilité du démonstrateur SuperNEMO

SuperNEMO is an experiment looking for the neutrinoless double beta decay in an effort to unveil the Majorana nature of the neutrino. The first module, called the demonstrator, is under construction and commissioning in the Laboratoire Souterrain de Modane. Its unique design combines tracking and calorimetry techniques. The demonstrator can study 7 kg of ⁸²Se, shaped in thin source foils. These source foils are surrounded by a wire chamber, thus allowing a 3-dimensional reconstruction of the charged particles tracks. The individual particles energies are then measured by a segmented calorimeter, composed of plastic scintillators coupled with photomultipliers. A magnetic field can be applied to the tracking volume in order to identify the charge of the particles. SuperNEMO is thus able to perform a full reconstruction of the events kinematics and to identify the nature of the particles involved: electrons, positrons, α particles or γ particles. In practice, the particle and event reconstruction relies on a variety of algorithms, implemented in the dedicated SuperNEMO simulation and reconstruction software. The γ reconstruction is particularly challenging since γ particles do not leave tracks in the wire chamber and are only detected by the calorimeter, sometimes multiple times. Several γ reconstruction approaches were explored during this thesis. This work lead to the creation of a new algorithm optimizing the γ reconstruction efficiency and improving the γ energy reconstruction. Other programs allowing the particle identification and performing the topological measurements relevant to an event were also developed. The value of the magnetic field was optimized for the 0νββ decay search, based on Monte-Carlo simulations. The magnetic shieldings performances and their impact on the shape of the magnetic field were estimated with measurements performed on small scale magnetic coils. The SuperNEMO demonstrator is able to measure its own background contamination thanks to dedicated analysis channels. At the end of the first 2.5 years data taking phase, the main backgrounds target activities should be measured accurately. The ⁸²Se 2νββ half-life should be known with a 0.3 % total uncertainty. Unlike other double beta decay experiments relying solely on the two electrons energy sum, SuperNEMO has access to the full events kinematics and thus to more topological information. A multivariate analysis based on Boosted Decision Trees was shown to guarantee at least a 10 % increase of the sensitivity of the 0νββ decay search. After 2.5 years, and if no excess of 0νββ events is observed, the SuperNEMO demonstrator should be able to set a limit on the 0νββ half-life of T > 5.85 10²⁴ y, translating into a limit on the effective Majorana neutrino mass mββ 10²⁶ y or mββ 5.85 10²⁴ ans, équivalant à une limite supérieure sur la masse effective du neutrino mββ 10²⁶ ans et mββ < 40 − 110 meV

Développement d'outils de reconstruction et sensibilité du démonstrateur SuperNEMO

SuperNEMO is an experiment looking for the neutrinoless double beta decay in an effort to unveil the Majorana nature of the neutrino. The first module, called the demonstrator, is under construction and commissioning in the Laboratoire Souterrain de Modane. Its unique design combines tracking and calorimetry techniques. The demonstrator can study 7 kg of ⁸²Se, shaped in thin source foils. These source foils are surrounded by a wire chamber, thus allowing a 3-dimensional reconstruction of the charged particles tracks. The individual particles energies are then measured by a segmented calorimeter, composed of plastic scintillators coupled with photomultipliers. A magnetic field can be applied to the tracking volume in order to identify the charge of the particles. SuperNEMO is thus able to perform a full reconstruction of the events kinematics and to identify the nature of the particles involved: electrons, positrons, α particles or γ particles. In practice, the particle and event reconstruction relies on a variety of algorithms, implemented in the dedicated SuperNEMO simulation and reconstruction software. The γ reconstruction is particularly challenging since γ particles do not leave tracks in the wire chamber and are only detected by the calorimeter, sometimes multiple times. Several γ reconstruction approaches were explored during this thesis. This work lead to the creation of a new algorithm optimizing the γ reconstruction efficiency and improving the γ energy reconstruction. Other programs allowing the particle identification and performing the topological measurements relevant to an event were also developed. The value of the magnetic field was optimized for the 0νββ decay search, based on Monte-Carlo simulations. The magnetic shieldings performances and their impact on the shape of the magnetic field were estimated with measurements performed on small scale magnetic coils. The SuperNEMO demonstrator is able to measure its own background contamination thanks to dedicated analysis channels. At the end of the first 2.5 years data taking phase, the main backgrounds target activities should be measured accurately. The ⁸²Se 2νββ half-life should be known with a 0.3 % total uncertainty. Unlike other double beta decay experiments relying solely on the two electrons energy sum, SuperNEMO has access to the full events kinematics and thus to more topological information. A multivariate analysis based on Boosted Decision Trees was shown to guarantee at least a 10 % increase of the sensitivity of the 0νββ decay search. After 2.5 years, and if no excess of 0νββ events is observed, the SuperNEMO demonstrator should be able to set a limit on the 0νββ half-life of T > 5.85 10²⁴ y, translating into a limit on the effective Majorana neutrino mass mββ 10²⁶ y or mββ 5.85 10²⁴ ans, équivalant à une limite supérieure sur la masse effective du neutrino mββ 10²⁶ ans et mββ < 40 − 110 meV

Implementation of Feldman-Cousins corrections and oscillation calculations in the HPC environment for the NOvA Experiment

Analysis of neutrino oscillation data involves a combination of complex fitting procedures and statistical correction techniques that are used to determine the full three-flavor PMNS parameters and constraint contours. These techniques rely on computationally intensive “multi-universe” stochastic modeling. The process of calculating these contours and corrections can dominate final stages of the data analysis and become a bottleneck for examining the ef-fect of systematic variations on the final results. As part of the DOE SciDAC-4 sponsored research program, we present a new implementation of a neutrino oscillation fitting and framework to carry out calculations of Feldman-Cousins corrections. This implementation is specifically designed and optimized to operate on modern High-Performance Computing (HPC) facilities. We present the performance of the system in calculating allowed regions for the NOvA experiment based on 8.9 x 1020 and 6.9 x 1020 protons-on-target (POT) neutrino and antineutrino datasets, and compare the performance of this new implementation run at the NERSC supercomputing facility with that from methods used previously by the NOvA collaboration running on grid computing facilities

Implementation of Feldman-Cousins corrections and oscillation calculations in the HPC environment for the NOvA Experiment

Analysis of neutrino oscillation data involves a combination of complex fitting procedures and statistical correction techniques that are used to determine the full three-flavor PMNS parameters and constraint contours. These techniques rely on computationally intensive “multi-universe” stochastic modeling. The process of calculating these contours and corrections can dominate final stages of the data analysis and become a bottleneck for examining the ef-fect of systematic variations on the final results. As part of the DOE SciDAC-4 sponsored research program, we present a new implementation of a neutrino oscillation fitting and framework to carry out calculations of Feldman-Cousins corrections. This implementation is specifically designed and optimized to operate on modern High-Performance Computing (HPC) facilities. We present the performance of the system in calculating allowed regions for the NOvA experiment based on 8.9 x 1020 and 6.9 x 1020 protons-on-target (POT) neutrino and antineutrino datasets, and compare the performance of this new implementation run at the NERSC supercomputing facility with that from methods used previously by the NOvA collaboration running on grid computing facilities

Multi-Calorimetry in Light-based Neutrino Detectors

International audienceNeutrino detectors are among the largest photonics instruments built for fundamental research. Since its inception, neutrino detection has been inexorably linked to the challenging detection of scarce photons in huge instrumented volumes. Many discoveries in neutrino physics, including the neutrino itself, are inseparable from the evolution of the detector photonics interfaces, i.e. photo-sensors and readout electronics, to yield ever higher precision and richer detection information. The measurement of the energy of neutrinos, referred to as calorimetry, is pursued today to reach permille level systematics control precision, thus leading to further innovation in specialised photonics. This publication describes a novel articulation that detectors may be endowed with multiple photonics interfaces for simultaneous light detection to yield unprecedented high-precision calorimetry. This multi-calorimetry approach opens the novel notion of dual-calorimetry detectors as an evolution from the single-calorimetry setups used over several decades for most experiments so far. The dual-calorimetry design exploits unique response synergies between photon counting and photon-integration detection systems, including correlations and cancellations between calorimetric responses, to yield the unprecedented mitigation of the dominant response systematic effects today for the possible improved design of a new generation of neutrino experiments