Results of the MAJORANA DEMONSTRATOR's Search for Double-Beta Decay of 76Ge to Excited States of 76Se

The MAJORANA DEMONSTRATOR is searching for double-beta decay of 76Ge to excited states (E.S.) in 76Se using a modular array of high purity Germanium detectors. 76Ge can decay into three E.S.s of 76Se. The E.S. decays have a clear event signature consisting of a ββ-decay with the prompt emission of one or two γ-rays, resulting in with high probability in a multi-site event. The granularity of the DEMONSTRATOR detector array enables powerful discrimination of this event signature from backgrounds. Using 21.3 kg-y of isotopic exposure, the DEMONSTRATOR has set world leading limits for each E.S. decay, with 90% CL lower half-life limits in the range of (0.56 2.1) ⋅ 1024 y. In particular, for the 2v transition to the first 0+ E.S. of 76Se, a lower half-life limit of 0.68 ⋅ 1024 at 90% CL was achieved

ADC Nonlinearity Correction for the Majorana Demonstrator

Imperfections in analog-to-digital conversion (ADC) cannot be ignored when signal digitization requirements demand both wide dynamic range and high resolution, as is the case for the Majorana Demonstrator 76Ge neutrinoless double-beta decay search. Enabling the experiment's high-resolution spectral analysis and efficient pulse shape discrimination required careful measurement and correction of ADC nonlinearities. A simple measurement protocol was developed that did not require sophisticated equipment or lengthy data-taking campaigns. A slope-dependent hysteresis was observed and characterized. A correction applied to digitized waveforms prior to signal processing reduced the differential and integral nonlinearities by an order of magnitude, eliminating these as dominant contributions to the systematic energy uncertainty at the double-beta decay Q value

Differences in school factors associated with adolescent HPV vaccination initiation and completion coverage in three Australian states.

BackgroundSchools are the primary setting for the delivery of adolescent HPV vaccination in Australia. Although this strategy has achieved generally high vaccination coverage, gaps persist for reasons that are mostly unknown. This study sought to identify school-level correlates of low vaccination course initiation and completion in New South Wales, Tasmania, and Western Australia to inform initiatives to increase uptake.MethodsInitiation was defined as the number of first doses given in a school in 2016 divided by vaccine-eligible student enrolments. Completion was the number of third doses given in a school in 2015-2016 divided by the number of first doses. Low initiation and completion were defined as coverage ≤ 25thpercentile of all reporting schools. We investigated correlations between covariates using Spearman's rank correlation coefficients. Due to multicollinearity, we used univariable logistic regression to investigate associations between school characteristics and low coverage.ResultsMedian initiation was 84.7% (IQR: 75.0%-90.4%) across 1,286 schools and median completion was 93.8% (IQR: 86.0%-97.3%) across 1,295 schools. There were strong correlations between a number of school characteristics, particularly higher Indigenous student enrolments and lower attendance, increasing remoteness, higher postcode socioeconomic disadvantage, and smaller school size. Characteristics most strongly associated with low initiation in univariate analyses were small school size, location in Tasmania, and schools catering for special educational needs. Low completion was most strongly associated with schools in Tasmania and Western Australia, remote location, small size, high proportion of Indigenous student enrolments, and low attendance rates.ConclusionThis study provides indicative evidence that characteristics of schools and school populations are associated with the likelihood of low initiation and completion of the HPV vaccination course. The findings will guide further research and help target initiatives to improve vaccination uptake in schools with profiles associated with lower coverage

Origins of the Tumor Microenvironment: Quantitative Assessment of Adipose-Derived and Bone Marrow–Derived Stroma

To meet the requirements for rapid tumor growth, a complex array of non-neoplastic cells are recruited to the tumor microenvironment. These cells facilitate tumor development by providing matrices, cytokines, growth factors, as well as vascular networks for nutrient and waste exchange, however their precise origins remain unclear. Through multicolored tissue transplant procedures; we have quantitatively determined the contribution of bone marrow-derived and adipose-derived cells to stromal populations within syngeneic ovarian and breast murine tumors. Our results indicate that subpopulations of tumor-associated fibroblasts (TAFs) are recruited from two distinct sources. The majority of fibroblast specific protein (FSP) positive and fibroblast activation protein (FAP) positive TAFs originate from mesenchymal stem/stromal cells (MSC) located in bone marrow sources, whereas most vascular and fibrovascular stroma (pericytes, α-SMA+ myofibroblasts, and endothelial cells) originates from neighboring adipose tissue. These results highlight the capacity for tumors to utilize multiple sources of structural cells in a systematic and discriminative manner

Clinical capabilities of graduates of an outcomes-based integrated medical program

<p>Abstract</p> <p>Background</p> <p>The University of New South Wales (UNSW) Faculty of Medicine replaced its old content-based curriculum with an innovative new 6-year undergraduate entry outcomes-based integrated program in 2004. This paper is an initial evaluation of the perceived and assessed clinical capabilities of recent graduates of the new outcomes-based integrated medical program compared to benchmarks from traditional content-based or process-based programs.</p> <p>Method</p> <p>Self-perceived capability in a range of clinical tasks and assessment of medical education as preparation for hospital practice were evaluated in recent graduates after 3 months working as junior doctors. Responses of the 2009 graduates of the UNSW’s new outcomes-based integrated medical education program were compared to those of the 2007 graduates of UNSW’s previous content-based program, to published data from other Australian medical schools, and to hospital-based supervisor evaluations of their clinical competence.</p> <p>Results</p> <p>Three months into internship, graduates from UNSW’s new outcomes-based integrated program rated themselves to have good clinical and procedural skills, with ratings that indicated significantly greater capability than graduates of the previous UNSW content-based program. New program graduates rated themselves significantly more prepared for hospital practice in the confidence (reflective practice), prevention (social aspects of health), interpersonal skills (communication), and collaboration (teamwork) subscales than old program students, and significantly better or equivalent to published benchmarks of graduates from other Australian medical schools. Clinical supervisors rated new program graduates highly capable for teamwork, reflective practice and communication.</p> <p>Conclusions</p> <p>Medical students from an outcomes-based integrated program graduate with excellent self-rated and supervisor-evaluated capabilities in a range of clinically-relevant outcomes. The program-wide curriculum reform at UNSW has had a major impact in developing capabilities in new graduates that are important for 21^st century medical practice.</p

Common variation near ROBO2 is associated with expressive vocabulary in infancy

Twin studies suggest that expressive vocabulary at ~24 months is modestly heritable. However, the genes influencing this early linguistic phenotype are unknown. Here we conduct a genome-wide screen and follow-up study of expressive vocabulary in toddlers of European descent from up to four studies of the EArly Genetics and Lifecourse Epidemiology consortium, analysing an early (15–18 months, ‘one-word stage’, NTotal=8,889) and a later (24–30 months, ‘two-word stage’, NTotal=10,819) phase of language acquisition. For the early phase, one single-nucleotide polymorphism (rs7642482) at 3p12.3 near ​ROBO2, encoding a conserved axon-binding receptor, reaches the genome-wide significance level (P=1.3 × 10−8) in the combined sample. This association links language-related common genetic variation in the general population to a potential autism susceptibility locus and a linkage region for dyslexia, speech-sound disorder and reading. The contribution of common genetic influences is, although modest, supported by genome-wide complex trait analysis (meta-GCTA h215–18-months=0.13, meta-GCTA h224–30-months=0.14) and in concordance with additional twin analysis (5,733 pairs of European descent, h224-months=0.20)

How Large Is the Metabolome? A Critical Analysis of Data Exchange Practices in Chemistry

Calculating the metabolome size of species by genome-guided reconstruction of metabolic pathways misses all products from orphan genes and from enzymes lacking annotated genes. Hence, metabolomes need to be determined experimentally. Annotations by mass spectrometry would greatly benefit if peer-reviewed public databases could be queried to compile target lists of structures that already have been reported for a given species. We detail current obstacles to compile such a knowledge base of metabolites.As an example, results are presented for rice. Two rice (oryza sativa) subspecies have been fully sequenced, oryza japonica and oryza indica. Several major small molecule databases were compared for listing known rice metabolites comprising PubChem, Chemical Abstracts, Beilstein, Patent databases, Dictionary of Natural Products, SetupX/BinBase, KNApSAcK DB, and finally those databases which were obtained by computational approaches, i.e. RiceCyc, KEGG, and Reactome. More than 5,000 small molecules were retrieved when searching these databases. Unfortunately, most often, genuine rice metabolites were retrieved together with non-metabolite database entries such as pesticides. Overlaps from database compound lists were very difficult to compare because structures were either not encoded in machine-readable format or because compound identifiers were not cross-referenced between databases.We conclude that present databases are not capable of comprehensively retrieving all known metabolites. Metabolome lists are yet mostly restricted to genome-reconstructed pathways. We suggest that providers of (bio)chemical databases enrich their database identifiers to PubChem IDs and InChIKeys to enable cross-database queries. In addition, peer-reviewed journal repositories need to mandate submission of structures and spectra in machine readable format to allow automated semantic annotation of articles containing chemical structures. Such changes in publication standards and database architectures will enable researchers to compile current knowledge about the metabolome of species, which may extend to derived information such as spectral libraries, organ-specific metabolites, and cross-study comparisons

Galanin Transgenic Mice with Elevated Circulating Galanin Levels Alleviate Demyelination in a Cuprizone-Induced MS Mouse Model

Multiple Sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS) with a presumed autoimmune etiology. Approved treatments for MS are immunoregulatory and are able to reduce the inflammatory components of the disease. However, these treatments do not suppress progressive clinical disability. Approaches that directly protect myelin-producing oligodendrocytes and enhance remyelination are likely to improve long-term outcomes and reduce the rate of axonal damage. Galanin (GAL) is a bioactive neuropeptide that is widely distributed throughout the nervous system and has diverse neuromodulatory effects. In this study, using the cuprizone (CPZ) demyelination model of MS, we demonstrate that GAL has pronounced neuroprotective effects with respect to demyelination and remyelination. Using our GAL transgenic mouse (GAL-Tg), we identified a novel attenuation of OLs against CPZ induced demyelination, which was exerted independently of progenitor cells. Alleviation of myelin breakdown in the GAL-Tg mice was observed to be significant. Furthermore, we observed changes in the expression of the GAL receptor GalR1 during the demyelination and remyelination processes. Our data strongly indicate that GAL has the capacity to influence the outcome of primary insults that directly target OLs, as opposed to cases where immune activation is the primary pathogenic event. Taken together, these results suggest that GAL is a promising next-generation target for the treatment of MS

Individual Differences in Sound-in-Noise Perception Are Related to the Strength of Short-Latency Neural Responses to Noise

Important sounds can be easily missed or misidentified in the presence of extraneous noise. We describe an auditory illusion in which a continuous ongoing tone becomes inaudible during a brief, non-masking noise burst more than one octave away, which is unexpected given the frequency resolution of human hearing. Participants strongly susceptible to this illusory discontinuity did not perceive illusory auditory continuity (in which a sound subjectively continues during a burst of masking noise) when the noises were short, yet did so at longer noise durations. Participants who were not prone to illusory discontinuity showed robust early electroencephalographic responses at 40–66 ms after noise burst onset, whereas those prone to the illusion lacked these early responses. These data suggest that short-latency neural responses to auditory scene components reflect subsequent individual differences in the parsing of auditory scenes