Invasive Haemophilus influenzae Disease in Adults ≥65 Years, United States, 2011.

BackgroundSince the introduction of the Haemophilus influenzae serotype b vaccine, H influenzae epidemiology has shifted. In the United States, the largest burden of disease is now in adults aged ≥65 years. However, few data exist on risk factors for disease severity and outcome in this age group.MethodsA retrospective case-series review of invasive H influenzae infections in patients aged ≥65 years was conducted for hospitalized cases reported to Active Bacterial Core surveillance in 2011.ResultsThere were 299 hospitalized cases included in the analysis. The majority of cases were caused by nontypeable H influenzae, and the overall case fatality ratio (CFR) was 19.5%. Three or more underlying conditions were present in 63% of cases; 94% of cases had at least 1. Patients with chronic heart conditions (congestive heart failure, coronary artery disease, and/or atrial fibrillation) (odds ratio [OR], 3.27; 95% confidence interval [CI], 1.65-6.46), patients from private residences (OR, 8.75; 95% CI, 2.13-35.95), and patients who were not resuscitate status (OR, 2.72; 95% CI, 1.31-5.66) were more likely to be admitted to the intensive care unit (ICU). Intensive care unit admission (OR, 3.75; 95% CI, 1.71-8.22) and do not resuscitate status (OR, 12.94; 95% CI, 4.84-34.55) were significantly associated with death.ConclusionsWithin this age group, burden of disease and CFR both increased significantly as age increased. Using ICU admission as a proxy for disease severity, our findings suggest several conditions increased risk of disease severity and patients with severe disease were more likely to die. Further research is needed to determine the most effective approach to prevent H influenzae disease and mortality in older adults

The effect of d-cycloserine on brain processing of breathlessness over pulmonary rehabilitation: an experimental medicine study

Research questionPulmonary rehabilitation is the best treatment for chronic breathlessness in COPD but there remains an unmet need to improve efficacy. Pulmonary rehabilitation has strong parallels with exposure-based cognitive behavioural therapies (CBT), both clinically and in terms of brain activity patterns. The partial N-methyl-d-aspartate (NMDA)-receptor agonistd-cycloserine has shown promising results in enhancing efficacy of CBT, thus we hypothesised that it would similarly augment the effects of pulmonary rehabilitation in the brain. Positive findings would support further development in phase 3 clinical trials.Methods72 participants with mild-to-moderate COPD were recruited to a double-blind pre-registered (ClinicalTrials.govidentifier:NCT01985750) experimental medicine study running parallel to a pulmonary rehabilitation course. Participants were randomised to 250 mgd-cycloserine or placebo, administered immediately prior to the first four sessions of pulmonary rehabilitation. Primary outcome measures were differences betweend-cycloserine and placebo in brain activity in the anterior insula, posterior insula, anterior cingulate cortices, amygdala and hippocampus following completion of pulmonary rehabilitation. Secondary outcomes included the same measures at an intermediate time point and voxel-wise difference across wider brain regions. An exploratory analysis determined the interaction with breathlessness anxiety.ResultsNo difference betweend-cycloserine and placebo groups was observed across the primary or secondary outcome measures.d-cycloserine was shown instead to interact with changes in breathlessness anxiety to dampen reactivity to breathlessness cues. Questionnaire and measures of respiratory function showed no group difference. This is the first study testing brain-active drugs in pulmonary rehabilitation. Rigorous trial methodology and validated surrogate end-points maximised statistical power.ConclusionAlthough increasing evidence supports therapeutic modulation of NMDA pathways to treat symptoms, we conclude that a phase 3 clinical trial ofd-cycloserine would not be worthwhile

Predicted Coverage and Immuno-Safety of a Recombinant C-Repeat Region Based Streptococcus pyogenes Vaccine Candidate

The C-terminal region of the M-protein of Streptococcus pyogenes is a major target for vaccine development. The major feature is the C-repeat region, consisting of 35-42 amino acid repeat units that display high but not perfect identity. SV1 is a S. pyogenes vaccine candidate that incorporates five 14mer amino acid sequences (called J14i variants) from differing C-repeat units in a single recombinant construct. Here we show that the J14i variants chosen for inclusion in SV1 are the most common variants in a dataset of 176 unique M-proteins. Murine antibodies raised against SV1 were shown to bind to each of the J14i variants present in SV1, as well as variants not present in the vaccine. Antibodies raised to the individual J14i variants were also shown to bind to multiple but different combinations of J14i variants, supporting the underlying rationale for the design of SV1. A Lewis Rat Model of valvulitis was then used to assess the capacity of SV1 to induce deleterious immune response associated with rheumatic heart disease. In this model, both SV1 and the M5 positive control protein were immunogenic. Neither of these antibodies were cross-reactive with cardiac myosin or collagen. Splenic T cells from SV1/CFA and SV1/alum immunized rats did not proliferate in response to cardiac myosin or collagen. Subsequent histological examination of heart tissue showed that 4 of 5 mice from the M5/CFA group had valvulitis and inflammatory cell infiltration into valvular tissue, whereas mice immunised with SV1/CFA, SV1/alum showed no sign of valvulitis. These results suggest that SV1 is a safe vaccine candidate that will elicit antibodies that recognise the vast majority of circulating GAS M-types

Film as architectural theory

Publications on architectural theory have predominantly taken on the form of text-based books, monographs, and articles. With the rise of transdisciplinary and practice-based research in architecture, new opportunities are opening up for other forms of architectural theory, such as film-based mediums, which promise to expand and alter the convention of the written practice of theory. Two possible types of filmic theory are presented here. One follows the method of ethnographic documentary filmmaking inspired by Sarah Pinkfilm-based mediums, which promise to expand and alter thellows the line of art house filmmaking inspired by Kathryn Rameyyn Rameyg inspired by Sarah Pinkfilm-based mediums, which promise to expand ae to expand ad mediums, which promise to expand a convention of the written practice of theory. or constructing knowledge, new discourses on filmic theory can be opened up. It is argued here that film as architectural theory is part of this new discourse, broadening the audience’u engagement with architecture through not only “readership” but also “viewership.

It's about time: A synthesis of changing phenology in the Gulf of Maine ecosystem

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Staudinger, M. D., Mills, K. E., Stamieszkin, K., Record, N. R., Hudak, C. A., Allyn, A., Diamond, A., Friedland, K. D., Golet, W., Henderson, M. E., Hernandez, C. M., Huntington, T. G., Ji, R., Johnson, C. L., Johnson, D. S., Jordaan, A., Kocik, J., Li, Y., Liebman, M., Nichols, O. C., Pendleton, D., Richards, R. A., Robben, T., Thomas, A. C., Walsh, H. J., & Yakola, K. It's about time: A synthesis of changing phenology in the Gulf of Maine ecosystem. Fisheries Oceanography, 28(5), (2019): 532-566, doi: 10.1111/fog.12429.The timing of recurring biological and seasonal environmental events is changing on a global scale relative to temperature and other climate drivers. This study considers the Gulf of Maine ecosystem, a region of high social and ecological importance in the Northwest Atlantic Ocean and synthesizes current knowledge of (a) key seasonal processes, patterns, and events; (b) direct evidence for shifts in timing; (c) implications of phenological responses for linked ecological‐human systems; and (d) potential phenology‐focused adaptation strategies and actions. Twenty studies demonstrated shifts in timing of regional marine organisms and seasonal environmental events. The most common response was earlier timing, observed in spring onset, spring and winter hydrology, zooplankton abundance, occurrence of several larval fishes, and diadromous fish migrations. Later timing was documented for fall onset, reproduction and fledging in Atlantic puffins, spring and fall phytoplankton blooms, and occurrence of additional larval fishes. Changes in event duration generally increased and were detected in zooplankton peak abundance, early life history periods of macro‐invertebrates, and lobster fishery landings. Reduced duration was observed in winter–spring ice‐affected stream flows. Two studies projected phenological changes, both finding diapause duration would decrease in zooplankton under future climate scenarios. Phenological responses were species‐specific and varied depending on the environmental driver, spatial, and temporal scales evaluated. Overall, a wide range of baseline phenology and relevant modeling studies exist, yet surprisingly few document long‐term shifts. Results reveal a need for increased emphasis on phenological shifts in the Gulf of Maine and identify opportunities for future research and consideration of phenological changes in adaptation efforts.This work was supported by the Department of the Interior Northeast Climate Adaptation Science Center (G14AC00441) for MDS, AJ, and KY; the National Science Foundation's Coastal SEES Program (OCE‐1325484) for KEM, ACT, MEH, and AA; the National Aeronautics and Space Administration (NNX16 AG59G) for ACT, KEM, NRR, and KSS; the USGS Climate Research and Development Program for TGH; National Science & Engineering Research Council of Canada, University of New Brunswick, Environment Canada, Sir James Dunn Wildlife Research Centre, and New Brunswick Wildlife Trust Fund for AD. We also thank the Regional Association for Research on the Gulf of Maine for support, and the Gulf of Maine Research Institute for hosting and providing in kind resources for a two day in‐person workshop in August 2016. We greatly appreciate contributions from K. Alexander, G. Calandrino, C. Feurt, I. Mlsna, N. Rebuck, J. Seavey, and J. Sun for helping shape the initial scope of the manuscript. We thank J. Weltzin and two anonymous reviewers for their constructive comments. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the views of the Northeast Climate Adaptation Science Center, U.S. Geological Survey, National Oceanographic and Atmospheric Administration, Fisheries and Oceans Canada or the US Environmental Protection Agency. This manuscript is submitted for publication with the understanding that the United States Government is authorized to reproduce and distribute reprints for Governmental purposes. None of the authors have conflicts of interest to declare in association with the contents of this manuscript

Thoracic CT findings of novel influenza A (H1N1) infection in immunocompromised patients

The goal of this study is to describe the spectrum of initial and follow-up CT findings of novel influenza A (H1N1) infection in a series of immunocompromised patients. Eight immunocompromised patients with documented novel influenza A (H1N1) had CT imaging at our institution between May 2009 and August 2009. A total of 20 CTs (initial and follow-up) were reviewed for the presence, severity, and distribution of the following: ground glass opacity, consolidation, interlobular septal thickening, mosaic perfusion, airway wall thickening, airway dilatation, nodules, cysts, pleural effusion, pericardial effusion, lymphadenopathy, and air trapping. The most common findings were airway thickening/dilatation, peribronchial ground glass opacity, centrilobular nodules, and tree-in-bud opacities. Peripheral consolidation involving the lower lobes was also a common pattern. Findings frequently involved all lobes and were closely associated with either large or small airways. Two patients presented with atypical CT findings including focal lobar consolidation and patchy lower lobe consolidation with soft tissue centrilobular nodules. Most survivors showed near complete resolution of findings within 35 days. CT scans in immunocompromised patients with novel influenza H1N1 commonly show a strong airway predominance of findings or peripheral areas of consolidation involving the lower lobes. A subset of patients with novel influenza A (H1N1) will show findings not typical of viral infection

The effect of D-cycloserine on brain processing of breathlessness over pulmonary rehabilitation - an experimental medicine study

Research Question: Pulmonary rehabilitation is the best treatment for chronic breathlessness in COPD but there remains an unmet need to improve efficacy. Pulmonary rehabilitation has strong parallels with exposure-based cognitive behavioural therapies (CBT), both clinically and in terms of brain activity patterns. The partial NMDA-receptor agonist, D-cycloserine has shown promising results in enhancing efficacy of CBT, thus we hypothesised that it would similarly augment the effects of pulmonary rehabilitation in the brain. Positive findings would support further development in phase 3 clinical trials. Methods: 72 participants with mild-to-moderate COPD were recruited to a doubleblind pre-registered (ID: NCT01985750) experimental medicine study running parallel to a pulmonary rehabilitation course. Participants were randomised to 250mg Dcycloserine or placebo, administered immediately prior to the first four sessions of pulmonary rehabilitation. Primary outcome measures were differences between Dcycloserine and placebo in brain activity in the anterior insula, posterior insula, anterior cingulate cortices, amygdala and hippocampus following completion of pulmonary rehabilitation. Secondary outcomes included the same measures at an intermediate time point and voxel-wise difference across wider brain regions. An exploratory analysis determined the interaction with breathlessness-anxiety. Results: No difference between D-cycloserine and placebo groups was observed across the primary or secondary outcome measures. D-cycloserine was shown instead to interact with changes in breathlessness anxiety to dampen reactivity to breathlessness cues. Questionnaire and measures of respiratory function showed no group difference. This is the first study testing brain-active drugs in pulmonary rehabilitation. Rigorous trial methodology and validated surrogate end-points maximised statistical power. Conclusion: Although increasing evidence supports therapeutic modulation of NMDA pathways to treat symptoms, we conclude that a phase 3 clinical trial of D- cycloserine would not be worthwhile

Metacognitive monitoring and control processes in children with autism spectrum disorder: Diminished judgement of confidence accuracy

Metacognition consists of monitoring processes (the ability to accurately represent one’s own mental states) and control processes (the ability to control one’s cognitive processes effectively). Both processes play vital roles in self-regulated learning. However, currently it is unclear whether these processes are impaired in individuals with autism spectrum disorders (ASDs). This study aimed to assess metacognition in thirty-two children with ASD, and 30 IQ-/age-matched neurotypical children, using a judgment of confidence task. It was found that children with ASD showed diminished accuracy in their judgments of confidence, indicating metacognitive monitoring impairments in ASD. Children with ASD also used monitoring to influence control processes significantly less than neurotypical children, despite little evidence of impairments in overall control ability

Reliability of multi-site UK Biobank MRI brain phenotypes for the assessment of neuropsychiatric complications of SARS-CoV-2 infection: The COVID-CNS travelling heads study.

Funder: National Institute for Health Research (NIHR)INTRODUCTION: Magnetic resonance imaging (MRI) of the brain could be a key diagnostic and research tool for understanding the neuropsychiatric complications of COVID-19. For maximum impact, multi-modal MRI protocols will be needed to measure the effects of SARS-CoV-2 infection on the brain by diverse potentially pathogenic mechanisms, and with high reliability across multiple sites and scanner manufacturers. Here we describe the development of such a protocol, based upon the UK Biobank, and its validation with a travelling heads study. A multi-modal brain MRI protocol comprising sequences for T1-weighted MRI, T2-FLAIR, diffusion MRI (dMRI), resting-state functional MRI (fMRI), susceptibility-weighted imaging (swMRI), and arterial spin labelling (ASL), was defined in close approximation to prior UK Biobank (UKB) and C-MORE protocols for Siemens 3T systems. We iteratively defined a comparable set of sequences for General Electric (GE) 3T systems. To assess multi-site feasibility and between-site variability of this protocol, N = 8 healthy participants were each scanned at 4 UK sites: 3 using Siemens PRISMA scanners (Cambridge, Liverpool, Oxford) and 1 using a GE scanner (King's College London). Over 2,000 Imaging Derived Phenotypes (IDPs), measuring both data quality and regional image properties of interest, were automatically estimated by customised UKB image processing pipelines (S2 File). Components of variance and intra-class correlations (ICCs) were estimated for each IDP by linear mixed effects models and benchmarked by comparison to repeated measurements of the same IDPs from UKB participants. Intra-class correlations for many IDPs indicated good-to-excellent between-site reliability. Considering only data from the Siemens sites, between-site reliability generally matched the high levels of test-retest reliability of the same IDPs estimated in repeated, within-site, within-subject scans from UK Biobank. Inclusion of the GE site resulted in good-to-excellent reliability for many IDPs, although there were significant between-site differences in mean and scaling, and reduced ICCs, for some classes of IDP, especially T1 contrast and some dMRI-derived measures. We also identified high reliability of quantitative susceptibility mapping (QSM) IDPs derived from swMRI images, multi-network ICA-based IDPs from resting-state fMRI, and olfactory bulb structure IDPs from T1, T2-FLAIR and dMRI data. CONCLUSION: These results give confidence that large, multi-site MRI datasets can be collected reliably at different sites across the diverse range of MRI modalities and IDPs that could be mechanistically informative in COVID brain research. We discuss limitations of the study and strategies for further harmonisation of data collected from sites using scanners supplied by different manufacturers. These acquisition and analysis protocols are now in use for MRI assessments of post-COVID patients (N = 700) as part of the ongoing COVID-CNS study

Contributions of a global network of tree diversity experiments to sustainable forest plantations

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