Soluble pre-fibrillar tau and β-amyloid species emerge in early human Alzheimer’s disease and track disease progression and cognitive decline

Acknowledgments We would like to gratefully acknowledge all donors and their families for the tissue provided for this study. Human tissue samples were supplied by the Brains for Dementia Research programme, jointly funded by Alzheimer’s Research UK, the Alzheimer’s Society and the Medical Research Council, and sourced from the MRC London Neurodegenerative Diseases Brain Bank, the Manchester Brain Bank, the South West Dementia Brain Bank (SWDBB), the Newcastle Brain Tissue Resource and the Oxford Brain Bank. The Newcastle Brain Tissue Resource and Oxford Brain Bank are also supported by the National Institute for Health Research (NIHR) Units. The South West Dementia Brain Bank (SWDBB) receives additional support from BRACE (Bristol Research into Alzheimer’s and Care of the Elderly). Alz-50, CP13, MC-1 and PHF-1 antibodies were gifted from Dr. Peter Davies and brain lystates from BACE1−/−mice were obtained from Prof Mike Ashford. The work presented here was funded by Alzheimer’s Research UK (Grant refs: ARUKPPG2014A-21 and ARUK-NSG2015-1 to BP and DK and NIH/NIA grants NIH/NINDS R01 NS082730 and R01 AG044372 to NK)Peer reviewedPublisher PD

Measurements of the Diffuse Ultraviolet Background and the Terrestrial Airglow with the Space Telescope Imaging Spectrograph

Far-UV observations in and near the Hubble Deep Fields demonstrate that the Space Telescope Imaging Spectrograph (STIS) can potentially obtain unique and precise measurements of the diffuse far-ultraviolet background. Although STIS is not the ideal instrument for such measurements, high-resolution images allow Galactic and extragalactic objects to be masked to very faint magnitudes, thus ensuring a measurement of the truly diffuse UV signal. The programs we have analyzed were not designed for this scientific purpose, but would be sufficient to obtain a very sensitive measurement if it were not for a weak but larger-than-expected signal from airglow in the STIS 1450-1900 A bandpass. Our analysis shows that STIS far-UV crystal quartz observations taken near the limb during orbital day can detect a faint airglow signal, most likely from NI\1493, that is comparable to the dark rate and inseparable from the far-UV background. Discarding all but the night data from these datasets gives a diffuse far-ultraviolet background measurement of 501 +/- 103 ph/cm2/sec/ster/A, along a line of sight with very low Galactic neutral hydrogen column (N_HI = 1.5E20 cm-2) and extinction (E(B-V)=0.01 mag). This result is in good agreement with earlier measurements of the far-UV background, and should not include any significant contribution from airglow. We present our findings as a warning to other groups who may use the STIS far-UV camera to observe faint extended targets, and to demonstrate how this measurement may be properly obtained with STIS.Comment: 7 pages, Latex. 4 figures. Uses corrected version of emulateapj.sty and apjfonts.sty (included). Accepted for publication in A

Temporal genetic patterns of diversity and structure evidence chaotic genetic patchiness in a spiny lobster

Population structure of many marine organisms is spatially patchy and varies within and between years, a phenomenon defined as chaotic genetic patchiness. This results from the combination of planktonic larval dispersal and environmental stochasticity. Additionally, in species with bi-partite life, postsettlement selection can magnify these genetic differences. The high fecundity (up to 500,000 eggs annually) and protracted larval duration (12–24 months) and dispersal of the southern rock lobster, Jasus edwardsii, make it a good test species for chaotic genetic patchiness and selection during early benthic life. Here, we used double digest restriction site-associated DNA sequencing (ddRADseq) to investigate chaotic genetic patchiness and postsettlement selection in this species. We assessed differences in genetic structure and diversity of recently settled pueruli across four settlement years and between two sites in southeast Australia separated by approximately 1,000 km. Postsettlement selection was investigated by identifying loci under putative positive selection between recently settled pueruli and postpueruli and quantifying differences in the magnitude and strength of the selection at each year and site. Genetic differences within and among sites through time in neutral SNP markers indicated chaotic genetic patchiness. Recently settled puerulus at the southernmost site exhibited lower genetic diversity during years of low puerulus catches, further supporting this hypothesis. Finally, analyses of outlier SNPs detected fluctuations in the magnitude and strength of the markers putatively under positive selection over space and time. One locus under putative positive selection was consistent at both locations during the same years, suggesting the existence of weak postsettlement selection

Analysis of Learning Outcomes in LGBTQ+ Medical School Curriculum

Introduction. Lesbian, gay, bisexual, transgender, and queer (LGBTQ+) youth are at increased risk for negative health outcomes and experience increased barriers to health care.https://scholarworks.uvm.edu/comphp_gallery/1088/thumbnail.jp

Emission Line Galaxies in the STIS Parallel Survey I: Observations and Data Analysis

In the first three years of operation STIS obtained slitless spectra of approximately 2500 fields in parallel to prime HST observations as part of the STIS Parallel Survey (SPS). The archive contains almost 300 fields at high galactic latitude (|b|>30) with spectroscopic exposure times greater than 3000 seconds. This sample contains 220 fields (excluding special regions and requiring a consistent grating angle) observed between 6 June 1997 and 21 September 2000, with a total survey area of about 160 square arcminutes. At this depth, the SPS detects an average of one emission line galaxy per three fields. We present the analysis of these data, and the identification of 131 low to intermediate redshift galaxies detected by optical emission lines. The sample contains 78 objects with emission lines that we infer to be redshifted [OII]3727 emission at 0.43<z<1.7. The comoving number density of these objects is comparable to that of H-alpha emitting galaxies in the NICMOS parallel observations. One quasar and three probable Seyfert galaxies are detected. Many of the emission-line objects show morphologies suggestive of mergers or interactions. The reduced data are available upon request from the authors.Comment: 58 preprint pages, including 26 figures; accepted for publication in ApJ

Factors that impact on recruitment to randomised trials in health care: a qualitative evidence synthesis

BACKGROUND: Randomised trials (also referred to as 'randomised controlled trials' or 'trials') are the optimal way to minimise bias in evaluating the effects of competing treatments, therapies and innovations in health care. It is important to achieve the required sample size for a trial, otherwise trialists may not be able to draw conclusive results leading to research waste and raising ethical questions about trial participation. The reasons why potential participants may accept or decline participation are multifaceted. Yet, the evidence of effectiveness of interventions to improve recruitment to trials is not substantial and fails to recognise these individual decision-making processes. It is important to synthesise the experiences and perceptions of those invited to participate in randomised trials to better inform recruitment strategies. OBJECTIVES: To explore potential trial participants' views and experiences of the recruitment process for participation. The specific objectives are to describe potential participants' perceptions and experiences of accepting or declining to participate in trials, to explore barriers and facilitators to trial participation, and to explore to what extent barriers and facilitators identified are addressed by strategies to improve recruitment evaluated in previous reviews of the effects of interventions including a Cochrane Methodology Review. SEARCH METHODS: We searched the Cochrane Library, Medline, Embase, CINAHL, Epistemonikos, LILACS, PsycINFO, ORRCA, and grey literature sources. We ran the most recent set of searches for which the results were incorporated into the review in July 2017. SELECTION CRITERIA: We included qualitative and mixed-methods studies (with an identifiable qualitative component) that explored potential trial participants' experiences and perceptions of being invited to participate in a trial. We excluded studies that focused only on recruiters' perspectives, and trials solely involving children under 18 years, or adults who were assessed as having impaired mental capacity. DATA COLLECTION AND ANALYSIS: Five review authors independently assessed the titles, abstracts and full texts identified by the search. We used the CART (completeness, accuracy, relevance, timeliness) criteria to exclude studies that had limited focus on the phenomenon of interest. We used QSR NVivo to extract and manage the data. We assessed methodological limitations using the Critical Skills Appraisal Programme (CASP) tool. We used thematic synthesis to analyse and synthesise the evidence. This provided analytical themes and a conceptual model. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. Our findings were integrated with two previous intervention effectiveness reviews by juxtaposing the quantitative and qualitative findings in a matrix. MAIN RESULTS: We included 29 studies (published in 30 papers) in our synthesis. Twenty-two key findings were produced under three broad themes (with six subthemes) to capture the experience of being invited to participate in a trial and making the decision whether to participate. Most of these findings had moderate to high confidence. We identified factors from the trial itself that influenced participation. These included how trial information was communicated, and elements of the trial such as the time commitment that might be considered burdensome. The second theme related to personal factors such as how other people can influence the individual's decision; and how a personal understanding of potential harms and benefits could impact on the decision. Finally, the potential benefits of participation were found to be key to the decision to participate, namely personal benefits such as access to new treatments, but also the chance to make a difference and help others. The conceptual model we developed presents the decision-making process as a gauge and the factors that influence whether the person will, or will not, take part. AUTHORS' CONCLUSIONS: This qualitative evidence synthesis has provided comprehensive insight into the complexity of factors that influence a person's decision whether to participate in a trial. We developed key questions that trialists can ask when developing their recruitment strategy. In addition, our conceptual model emphasises the need for participant-centred approaches to recruitment. We demonstrated moderate to high level confidence in our findings, which in some way can be attributed to the large volume of highly relevant studies in this field. We recommend that these insights be used to direct or influence or underpin future recruitment strategies that are developed in a participant-driven way that ultimately improves trial conduct and reduces research waste

Advancing our understanding of the connectivity, evolution and management of marine lobsters through genetics

The genomic revolution has provided powerful insights into the biology and ecology of many non-model organisms. Genetic tools have been increasingly applied to marine lobster research in recent years and have improved our understanding of species delimitation and population connectivity. High resolution genomic markers are just beginning to be applied to lobsters and are now starting to revolutionise our understanding of fine spatial and temporal scales of population connectivity and adaptation to environmental conditions. Lobsters play an important role in the ecosystem and many species are commercially exploited but many aspects of their biology is still largely unknown. Genetics is a powerful tool that can further contribute to our understanding of their ecology and evolution and assist management. Here we illustrate how recent genetic advancements are (1) leading to a step change in our understanding of evolution and adaptation, (2) elucidating factors driving connectivity and recruitment, (3) revealing insights into ecological processes and can (4) potentially revolutionise management of this commercially important group. We discuss how improvements in sequencing technologies and statistical methods for genetic data analyses combined with increased sampling efforts and careful sampling design have transformed our understanding of lobsters biology in recent years. We also highlight possible future directions in the application of genomic tools to lobster research that can aid management, in particular, the close-kin-mark-recapture method. Finally, we identify gaps and challenges in lobster research, such as the lack of any reference genomes and predictions on how lobsters will respond to future environmental conditions

UVUDF: Ultraviolet Imaging of the Hubble Ultradeep Field with Wide-field Camera 3

We present an overview of a 90-orbit Hubble Space Telescope treasury program to obtain near ultraviolet imaging of the Hubble Ultra Deep Field using the Wide Field Camera 3 UVIS detector with the F225W, F275W, and F336W filters. This survey is designed to: (i) Investigate the episode of peak star formation activity in galaxies at 1<z<2.5; (ii) Probe the evolution of massive galaxies by resolving sub-galactic units (clumps); (iii) Examine the escape fraction of ionizing radiation from galaxies at z~2-3; (iv) Greatly improve the reliability of photometric redshift estimates; and (v) Measure the star formation rate efficiency of neutral atomic-dominated hydrogen gas at z~1-3. In this overview paper, we describe the survey details and data reduction challenges, including both the necessity of specialized calibrations and the effects of charge transfer inefficiency. We provide a stark demonstration of the effects of charge transfer inefficiency on resultant data products, which when uncorrected, result in uncertain photometry, elongation of morphology in the readout direction, and loss of faint sources far from the readout. We agree with the STScI recommendation that future UVIS observations that require very sensitive measurements use the instrument's capability to add background light through a "post-flash". Preliminary results on number counts of UV-selected galaxies and morphology of galaxies at z~1 are presented. We find that the number density of UV dropouts at redshifts 1.7, 2.1, and 2.7 is largely consistent with the number predicted by published luminosity functions. We also confirm that the image mosaics have sufficient sensitivity and resolution to support the analysis of the evolution of star-forming clumps, reaching 28-29th magnitude depth at 5 sigma in a 0.2 arcsecond radius aperture depending on filter and observing epoch.Comment: Accepted A

Factors that impact on recruitment to randomised trials in health care : a qualitative evidence synthesis (Review)

Peer reviewedPublisher PD