Conversations Matter: Initiating a Serious Illness Conversation

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The potential role of kelp forests on iodine speciation in coastal seawater

Funding: FCK would like to thank the TOTAL Foundation (Paris) and the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland) for their support. MASTS is funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions. JG acknowledges support from an SDSU Research Foundation Summer Undergraduate Research Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Successful Modified Therapy in a Patient With Probable Infection-Associated Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare, hyperinflammatory syndrome characterized by clinical signs and symptoms of extreme inflammation. In adults, HLH is typically a complication of infections, autoimmune diseases, and malignancies. While the disease is often fatal, classic management of HLH revolves around early diagnosis and initiation of protocolized therapy. We present a case of a previously healthy 56-year-old female who developed distributive shock requiring intubation, vasopressors, and continuous venovenous hemofiltration. In the setting of multiple infectious syndromes, severe cytopenias, and rising direct hyperbilirubinemia, her diagnosis of HLH was confirmed. Therapy was initiated with dexamethasone and two doses of reduced-intensity etoposide based on the patient's clinical course. Over the next few weeks, she continued to improve on dexamethasone monotherapy and has maintained remission up to the present with complete resolution of her cytopenias and return of baseline renal function. Our case highlights the variability in the management of probable infection-associated HLH (IHLH) with a good patient outcome. We demonstrate the potential to treat IHLH with partial protocols and minimal chemotherapeutics

Pyrrolo[2,3D]Pyrimidine Compounds

Described herein is pyrrolo{2,3-d}pyrimidine compounds, their use as Janus Kinase (JAK) inhibitors, pharmaceutical compositions containing this compounds, and methods for the preparation of these compounds

The influence of marine algae on iodine speciation in the coastaocean

Funding Information: This work was supported in part by grant CHE-1664657 from the National Science Foundation to CJC and FCK, the TOTAL Foundation (Paris) and the UK Natural Environment Research Council grants (NE/D521522/1, NE/ J023094/1, Oceans 2025 / WP 4.5) to FCK. We are also grateful for funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland). We thank Dr. M. L. Carter, SIO for help with collection of water samples at Scripps Pier, César O. Almeda-Jáuregui, CICESE for Ocean Data View plots and Dr. Avery Tatters, USC for the initial culture of Lingulodinium polyedra. A fellowship from the Hanse-Wissenschaftskolleg to CJC is also gratefully acknowledged.Peer reviewedPublisher PD

Estimating physical activity from self-reported behaviours in large-scale population studies using network harmonisation: findings from UK Biobank and associations with disease outcomes

Abstract: Background: UK Biobank is a large prospective cohort study containing accelerometer-based physical activity data with strong validity collected from 100,000 participants approximately 5 years after baseline. In contrast, the main cohort has multiple self-reported physical behaviours from > 500,000 participants with longer follow-up time, offering several epidemiological advantages. However, questionnaire methods typically suffer from greater measurement error, and at present there is no tested method for combining these diverse self-reported data to more comprehensively assess the overall dose of physical activity. This study aimed to use the accelerometry sub-cohort to calibrate the self-reported behavioural variables to produce a harmonised estimate of physical activity energy expenditure, and subsequently examine its reliability, validity, and associations with disease outcomes. Methods: We calibrated 14 self-reported behavioural variables from the UK Biobank main cohort using the wrist accelerometry sub-cohort (n = 93,425), and used published equations to estimate physical activity energy expenditure (PAEESR). For comparison, we estimated physical activity based on the scoring criteria of the International Physical Activity Questionnaire, and by summing variables for occupational and leisure-time physical activity with no calibration. Test-retest reliability was assessed using data from the UK Biobank repeat assessment (n = 18,905) collected a mean of 4.3 years after baseline. Validity was assessed in an independent validation study (n = 98) with estimates based on doubly labelled water (PAEEDLW). In the main UK Biobank cohort (n = 374,352), Cox regression was used to estimate associations between PAEESR and fatal and non-fatal outcomes including all-cause, cardiovascular diseases, respiratory diseases, and cancers. Results: PAEESR explained 27% variance in gold-standard PAEEDLW estimates, with no mean bias. However, error was strongly correlated with PAEEDLW (r = −.98; p < 0.001), and PAEESR had narrower range than the criterion. Test-retest reliability (Λ = .67) and relative validity (Spearman = .52) of PAEESR outperformed two common approaches for processing self-report data with no calibration. Predictive validity was demonstrated by associations with morbidity and mortality, e.g. 14% (95%CI: 11–17%) lower mortality for individuals meeting lower physical activity guidelines. Conclusions: The PAEESR variable has good reliability and validity for ranking individuals, with no mean bias but correlated error at individual-level. PAEESR outperformed uncalibrated estimates and showed stronger inverse associations with disease outcomes

An integrated multi-study analysis of intra-subject variability in cerebrospinal fluid amyloid-β concentrations collected by lumbar puncture and indwelling lumbar catheter

INTRODUCTION: Amyloid-β (Aβ) has been investigated as a diagnostic biomarker and therapeutic drug target. Recent studies found that cerebrospinal fluid (CSF) Aβ fluctuates over time, including as a diurnal pattern, and increases in absolute concentration with serial collection. It is currently unknown what effect differences in CSF collection methodology have on Aβ variability. In this study, we sought to determine the effect of different collection methodologies on the stability of CSF Aβ concentrations over time. METHODS: Grouped analysis of CSF Aβ levels from multiple industry and academic groups collected by either lumbar puncture (n=83) or indwelling lumbar catheter (n=178). Participants were either placebo or untreated subjects from clinical drug trials or observational studies. Participants had CSF collected by lumbar puncture or lumbar catheter for quantitation of Aβ concentration by enzyme linked immunosorbent assay. Data from all sponsors was converted to percent of the mean for Aβ40 and Aβ42 for comparison. Repeated measures analysis of variance was performed to assess for factors affecting the linear rise of Aβ concentrations over time. RESULTS: Analysis of studies collecting CSF via lumbar catheter revealed tremendous inter-subject variability of Aβ40 and Aβ42 as well as an Aβ diurnal pattern in all of the sponsors' studies. In contrast, Aβ concentrations from CSF samples collected at two time points by lumbar puncture showed no significant differences. Repeated measures analysis of variance found that only time and draw frequency were significantly associated with the slope of linear rise in Aβ40 and Aβ42 concentrations during the first 6 hours of collection. CONCLUSIONS: Based on our findings, we recommend minimizing the frequency of CSF draws in studies measuring Aβ levels and keeping the frequency standardized between experimental groups. The Aβ diurnal pattern was noted in all sponsors' studies and was not an artifact of study design. Averaging Aβ concentrations at each time point is recommended to minimize the effect of individual variability. Indwelling lumbar catheters are an invaluable research tool for following changes in CSF Aβ over 24-48 hours, but factors affecting Aβ concentration such as linear rise and diurnal variation need to be accounted for in planning study designs

Project overview and update on WEAVE: the next generation wide-field spectroscopy facility for the William Herschel Telescope

We present an overview of and status report on the WEAVE next-generation spectroscopy facility for the William Herschel Telescope (WHT). WEAVE principally targets optical ground-based follow up of upcoming ground-based (LOFAR) and space-based (Gaia) surveys. WEAVE is a multi-object and multi-IFU facility utilizing a new 2-degree prime focus field of view at the WHT, with a buffered pick-and-place positioner system hosting 1000 multi-object (MOS) fibres, 20 integral field units, or a single large IFU for each observation. The fibres are fed to a single spectrograph, with a pair of 8k(spectral) x 6k (spatial) pixel cameras, located within the WHT GHRIL enclosure on the telescope Nasmyth platform, supporting observations at R~5000 over the full 370-1000nm wavelength range in a single exposure, or a high resolution mode with limited coverage in each arm at R~20000. The project is now in the final design and early procurement phase, with commissioning at the telescope expected in 2017.Comment: 11 pages, 11 Figures, Summary of a presentation to Astronomical Telescopes and Instrumentation 201