A Homological Approach to Belief Propagation and Bethe Approximations

We introduce a differential complex of local observables given a decomposition of a global set of random variables into subsets. Its boundary operator allows us to define a transport equation equivalent to Belief Propagation. This definition reveals a set of conserved quantities under Belief Propagation and gives new insight on the relationship of its equilibria with the critical points of Bethe free energy.Comment: 14 pages, submitted for the 2019 Geometric Science of Information colloquiu

Software development cultures and cooperation problems: a field study of the early stages of development of software for a scientific community

In earlier work, I identified a particular class of end-user developers, who include scientists and whom I term 'professional end-user developers', as being of especial interest. Here, I extend this work by articulating a culture of professional end-user development, and illustrating by means of a field-study how the influence of this culture causes cooperation problems in an inter-disciplinary team developing a software system for a scientific community. My analysis of the field study data is informed by some recent literature on multi-national work cultures. Whilst acknowledging that viewing a scientific development through a lens of software development culture does not give a full picture, I argue that it nonetheless provides deep insights

Outcome-related metabolomic patterns from 1H/31P NMR after mild hypothermia treatments of oxygen–glucose deprivation in a neonatal brain slice model of asphyxia

Human clinical trials using 72 hours of mild hypothermia (32°C–34°C) after neonatal asphyxia have found substantially improved neurologic outcomes. As temperature changes differently modulate numerous metabolite fluxes and concentrations, we hypothesized that 1H/31P nuclear magnetic resonance (NMR) spectroscopy of intracellular metabolites can distinguish different insults, treatments, and recovery stages. Three groups of superfused neonatal rat brain slices underwent 45 minutes oxygen–glucose deprivation (OGD) and then were: treated for 3 hours with mild hypothermia (32°C) that began with OGD, or similarly treated with hypothermia after a 15-minute delay, or not treated (normothermic control group, 37°C). Hypothermia was followed by 3 hours of normothermic recovery. Slices collected at different predetermined times were processed, respectively, for 14.1 Tesla NMR analysis, enzyme-linked immunosorbent assay (ELISA) cell-death quantification, and superoxide production. Forty-nine NMR-observable metabolites underwent a multivariate analysis. Separated clustering in scores plots was found for treatment and outcome groups. Final ATP (adenosine triphosphate) levels, severely decreased at normothermia, were restored equally by immediate and delayed hypothermia. Cell death was decreased by immediate hypothermia, but was equally substantially greater with normothermia and delayed hypothermia. Potentially important biomarkers in the 1H spectra included PCr-1H (phosphocreatine in the 1H spectrum), ATP-1H (adenosine triphosphate in the 1H spectrum), and ADP-1H (adenosine diphosphate in the 1H spectrum). The findings suggest a potential role for metabolomic monitoring during therapeutic hypothermia

Noninvasive cardiac output and blood pressure monitoring cannot replace an invasive monitoring system in critically ill patients

Background: Monitoring of cardiac output and blood pressure are standard procedures in critical care medicine. Traditionally, invasive techniques like pulmonary artery catheter (PAC) and arterial catheters are widely used. Invasiveness bears many risks of deleterious complications. Therefore, a noninvasive reliable cardiac output (CO) and blood pressure monitoring system could improve the safety of cardiac monitoring. The aim of the present study was to compare a noninvasive versus a standard invasive cardiovascular monitoring system. Methods: Nexfin HD is a continuous noninvasive blood pressure and cardiac output monitor system and is based on the development of the pulsatile unloading of the finger arterial walls using an inflatable finger cuff. During continuous BP measurement CO is calculated. We included 10 patients with standard invasive cardiac monitoring system (pulmonary artery catheter and arterial catheter) comparing invasively obtained data to the data collected noninvasively using the Nexfin HD. Results: Correlation between mean arterial pressure measured with the standard arterial monitoring system and the Nexfin HD was r2 = 0.67 with a bias of -2 mmHg and two standard deviations of ± 16 mmHg. Correlation between CO derived from PAC and the Nexfin HD was r2 = 0.83 with a bias of 0.23 l/min and two standard deviations of ± 2.1 l/min; the percentage error was 29%. Conclusion: Although the noninvasive CO measurement appears promising, the noninvasive blood pressure assessment is clearly less reliable than the invasively measured blood pressure. Therefore, according to the present data application of the Nexfin HD monitoring system in the ICU cannot be recommended generally. Whether such a tool might be reliable in certain critically ill patients remains to be determined

Effects of deletion of the Streptococcus pneumoniae lipoprotein diacylglyceryl transferase gene lgt on ABC transporter function and on growth in vivo

Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the corresponding gene potentially allows the characterisation of the overall importance of lipoproteins for specific bacterial functions. We have used a Δlgt mutant strain of Streptococcus pneumoniae to investigate the effects of loss of lipoprotein attachment on cation acquisition, growth in media containing specific carbon sources, and virulence in different infection models. Immunoblots of triton X-114 extracts, flow cytometry and immuno-fluorescence microscopy confirmed the Δlgt mutant had markedly reduced lipoprotein expression on the cell surface. The Δlgt mutant had reduced growth in cation depleted medium, increased sensitivity to oxidative stress, reduced zinc uptake, and reduced intracellular levels of several cations. Doubling time of the Δlgt mutant was also increased slightly when grown in medium with glucose, raffinose and maltotriose as sole carbon sources. These multiple defects in cation and sugar ABC transporter function for the Δlgt mutant were associated with only slightly delayed growth in complete medium. However the Δlgt mutant had significantly reduced growth in blood or bronchoalveolar lavage fluid and a marked impairment in virulence in mouse models of nasopharyngeal colonisation, sepsis and pneumonia. These data suggest that for S. pneumoniae loss of surface localisation of lipoproteins has widespread effects on ABC transporter functions that collectively prevent the Δlgt mutant from establishing invasive infection

Crisis discharges and readmission risk in acute psychiatric male inpatients

<p>Abstract</p> <p>Background</p> <p>Severe pressures on beds in psychiatric services have led to the implementation of an early ("crisis") discharge policy in the Western Cape, South Africa. The study examined the effect of this policy and length of hospital stay (LOS) on readmission rates in one psychiatric hospital in South Africa.</p> <p>Methods</p> <p>Discharge summaries of adult male patients (<it>n </it>= 438) admitted to Stikland Psychiatric Hospital during 2004 were retrospectively examined. Each patient's clinical course was then analysed for the period between January 1^st, 2004, and August 31^st, 2006.</p> <p>Results</p> <p>Although shorter LOS was associated with decreased readmission rates, the effect of crisis discharges was far more powerful. Patients discharged as usual had a far lower risk of readmission than those discharged due to bed pressures (i.e. crisis discharge).</p> <p>Conclusion</p> <p>Increased risks associated with the early discharge policy necessitate the urgent review of the current management of bed shortages in this inpatient facility. The strengthening of community initiatives, particularly assertive outreach could be a way forward.</p

Identification of Yeast Transcriptional Regulation Networks Using Multivariate Random Forests

The recent availability of whole-genome scale data sets that investigate complementary and diverse aspects of transcriptional regulation has spawned an increased need for new and effective computational approaches to analyze and integrate these large scale assays. Here, we propose a novel algorithm, based on random forest methodology, to relate gene expression (as derived from expression microarrays) to sequence features residing in gene promoters (as derived from DNA motif data) and transcription factor binding to gene promoters (as derived from tiling microarrays). We extend the random forest approach to model a multivariate response as represented, for example, by time-course gene expression measures. An analysis of the multivariate random forest output reveals complex regulatory networks, which consist of cohesive, condition-dependent regulatory cliques. Each regulatory clique features homogeneous gene expression profiles and common motifs or synergistic motif groups. We apply our method to several yeast physiological processes: cell cycle, sporulation, and various stress conditions. Our technique displays excellent performance with regard to identifying known regulatory motifs, including high order interactions. In addition, we present evidence of the existence of an alternative MCB-binding pathway, which we confirm using data from two independent cell cycle studies and two other physioloigical processes. Finally, we have uncovered elaborate transcription regulation refinement mechanisms involving PAC and mRRPE motifs that govern essential rRNA processing. These include intriguing instances of differing motif dosages and differing combinatorial motif control that promote regulatory specificity in rRNA metabolism under differing physiological processes

Anosmia, ageusia, and other COVID-19-like symptoms in association with a positive SARS-CoV-2 test, across six national digital surveillance platforms: an observational study.

Background: Multiple voluntary surveillance platforms were developed across the world in response to the COVID-19 pandemic, providing a real-time understanding of population-based COVID-19 epidemiology. During this time, testing criteria broadened and health-care policies matured. We aimed to test whether there were consistent associations of symptoms with SARS-CoV-2 test status across three surveillance platforms in three countries (two platforms per country), during periods of testing and policy changes. Methods: For this observational study, we used data of observations from three volunteer COVID-19 digital surveillance platforms (Carnegie Mellon University and University of Maryland Facebook COVID-19 Symptom Survey, ZOE COVID Symptom Study app, and the Corona Israel study) targeting communities in three countries (Israel, the UK, and the USA; two platforms per country). The study population included adult respondents (age 18–100 years at baseline) who were not health-care workers. We did logistic regression of self-reported symptoms on self-reported SARS-CoV-2 test status (positive or negative), adjusted for age and sex, in each of the study cohorts. We compared odds ratios (ORs) across platforms and countries, and we did meta-analyses assuming a random effects model. We also evaluated testing policy changes, COVID-19 incidence, and time scales of duration of symptoms and symptom-to-test time. Findings: Between April 1 and July 31, 2020, 514 459 tests from over 10 million respondents were recorded in the six surveillance platform datasets. Anosmia–ageusia was the strongest, most consistent symptom associated with a positive COVID-19 test (robust aggregated rank one, meta-analysed random effects OR 16·96, 95% CI 13·13–21·92). Fever (rank two, 6·45, 4·25–9·81), shortness of breath (rank three, 4·69, 3·14–7·01), and cough (rank four, 4·29, 3·13–5·88) were also highly associated with test positivity. The association of symptoms with test status varied by duration of illness, timing of the test, and broader test criteria, as well as over time, by country, and by platform. Interpretation: The strong association of anosmia–ageusia with self-reported positive SARS-CoV-2 test was consistently observed, supporting its validity as a reliable COVID-19 signal, regardless of the participatory surveillance platform, country, phase of illness, or testing policy. These findings show that associations between COVID-19 symptoms and test positivity ranked similarly in a wide range of scenarios. Anosmia, fever, and respiratory symptoms consistently had the strongest effect estimates and were the most appropriate empirical signals for symptom-based public health surveillance in areas with insufficient testing or benchmarking capacity. Collaborative syndromic surveillance could enhance real-time epidemiological investigations and public health utility globally. Funding: National Institutes of Health, National Institute for Health Research, Alzheimer's Society, Wellcome Trust, and Massachusetts Consortium on Pathogen Readiness

Relating Differently to Intrusive Images: The Impact of Mindfulness Based Cognitive Therapy (MBCT) on Intrusive Images in Patients With Severe Health Anxiety (Hypochondriasis).

Recurrent distressing intrusive images are a common experience in hypochondriasis. The aim of the current study was to assess the impact of Mindfulness-Based Cognitive Therapy (MBCT) for hypochondriasis on the occurrence and nature of distressing intrusive imagery in hypochondriasis. A semi-structured interview was used to assess intrusive imagery, and an adapted version of the Southampton Mindfulness Questionnaire (SMQ) was used to assess participants’ relationship with their intrusive images. A consecutive series of participants (N = 20) who were receiving MBCT for hypochondriasis as part of an ongoing research program were assessed prior to participating in an 8-week MBCT intervention, immediately following the intervention, and at three month follow-up. As compared to the baseline assessment, the frequency of intrusive images, the distress associated with them, and the intrusiveness of the images were all significantly reduced at the post-MBCT assessment. Participants’ adapted SMQ scores were significantly increased following the MBCT intervention, suggesting that participants’ relationship with their intrusive images had changed in that they had developed a more ‘mindful’ and compassionate response to the images when they did occur. Effect sizes from pre- to post-intervention were medium to large (Cohen’s d = 0.75 - 1.50). All treatment gains were maintained at 3 month follow-up. Results suggest that MBCT may be an effective intervention for addressing intrusive imagery in hypochondriasis