Towards a Conceptualization of Sociomaterial Entanglement

In knowledge representation, socio-technical systems can be modeled as multiagent systems in which the local knowledge of each individual agent can be seen as a context. In this paper we propose formal ontologies as a means to describe the assumptions driving the construction of contexts as local theories and to enable interoperability among them. In particular, we present two alternative conceptualizations of the notion of sociomateriality (and entanglement), which is central in the recent debates on socio-technical systems in the social sciences, namely critical and agential realism. We thus start by providing a model of entanglement according to the critical realist view, representing it as a property of objects that are essentially dependent on different modules of an already given ontology. We refine then our treatment by proposing a taxonomy of sociomaterial entanglements that distinguishes between ontological and epistemological entanglement. In the final section, we discuss the second perspective, which is more challenging form the point of view of knowledge representation, and we show that the very distinction of information into modules can be at least in principle built out of the assumption of an entangled reality

Effect of atorvastatin on glycaemia progression in patients with diabetes:an analysis from the Collaborative Atorvastatin in Diabetes Trial (CARDS)

AIMS/HYPOTHESIS: In an individual-level analysis we examined the effect of atorvastatin on glycaemia progression in type 2 diabetes and whether glycaemia effects reduce the prevention of cardiovascular disease (CVD) with atorvastatin. METHODS: The study population comprised 2,739 people taking part in the Collaborative Atorvastatin Diabetes Study (CARDS) who were randomised to receive atorvastatin 10 mg or placebo and who had post-randomisation HbA(1c) data. This secondary analysis used Cox regression to estimate the effect of atorvastatin on glycaemia progression, defined as an increase in HbA(1c) of ≥0.5% (5.5 mmol/mol) or intensification of diabetes therapy. Mixed models were used to estimate the effect of atorvastatin on HbA(1c) as a continuous endpoint. RESULTS: Glycaemia progression occurred in 73.6% of participants allocated placebo and 78.1% of those allocated atorvastatin (HR 1.18 [95% CI 1.08, 1.29], p < 0.001) by the end of follow-up. The HR was 1.22 (95% CI 1.19, 1.35) in men and 1.11 (95% CI 0.95, 1.29) in women (p = 0.098 for the sex interaction). A similar effect was seen in on-treatment analyses: HR 1.20 (95% CI 1.07, 1.35), p = 0.001. The net mean treatment effect on HbA(1c) was 0.14% (95% CI 0.08, 0.21) (1.5 mmol/mol). The effect did not increase through time. Diabetes treatment intensification alone did not differ with statin allocation. Neither baseline nor 1-year-attained HbA(1c) predicted subsequent CVD, and the atorvastatin effect on CVD did not vary by HbA(1c) change (interaction p value 0.229). CONCLUSIONS/INTERPRETATION: The effect of atorvastatin 10 mg on glycaemia progression among those with diabetes is statistically significant but very small, is not significantly different between sexes, does not increase with duration of statin and does not have an impact on the magnitude of CVD risk reduction with atorvastatin. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-015-3802-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users

On the Cognition of States of Affairs

The theory of speech acts put forward by Adolf Reinach in his "The A Priori Foundations of the Civil Law" of 1913 rests on a systematic account of the ontological structures associated with various different sorts of language use. One of the most original features of Reinach's account lies in hIs demonstration of how the ontological structure of, say, an action of promising or of commanding, may be modified in different ways, yielding different sorts of non-standard instances of the corresponding speech act varieties. The present paper is an attempt to apply this idea of standard and modified instances of ontological structures to the realm of judgement and cognition, and thereby to develop a Reinachian theory of how intentionality is mediated through language in acts of thinking and speaking

Calciphylaxis in chronic, non-dialysis-dependent renal disease

BACKGROUND: Calciphylaxis cutis is characterized by media calcification of arteries and, most prominently, of cutaneous and subcutaneous arterioles occurring in renal insufficiency patients. CASE REPORT: A 53-year-old woman with chronic cardiac and renal failure complained of painful crural, non-varicosis ulcers. She was hospitalized in an immobilized condition due to both the crural ulcerations and the existing heart-failure state (NYHA III-IV) having pleural and pericardial effusions, atrial fibrillation and weight loss of 30 kg over the past year. Despite normalization of calcium-phosphorus balance and improvement of renal function, the clinical course of crural ulcerations deteriorated during the following 3 months. After failure of surgical debridements, multiple courses of sterile-maggot therapy were introduced at a late stage to stabilize the wounds. The patient died of recurrent wound infections and sepsis paralleled by exacerbations of renal malfunction. CONCLUSIONS: The role of renal disease in vascular complications is discussed. Sterile-maggot debridement may constitute a therapy for the ulcerated calciphylaxis at an earlier stage, i.e. when first ulcerations appear

TMEM16F activation by Ca2+ triggers plasma membrane expansion and directs PD-1 trafficking

TMEM16F is a Ca2+ -gated ion channel that is required for Ca2+ -activated phosphatidylserine exposure on the surface of many eukaryotic cells. TMEM16F is widely expressed and has roles in platelet activation during blood clotting, bone formation and T cell activation. By combining microscopy and patch clamp recording we demonstrate that activation of TMEM16F by Ca2+ ionophores in Jurkat T cells triggers large-scale surface membrane expansion in parallel with phospholipid scrambling. With continued ionophore application,TMEM16F-expressing cells then undergo extensive shedding of ectosomes. The T cell co-receptor PD-1 is selectively incorporated into ectosomes. This selectivity depends on its transmembrane sequence. Surprisingly, cells lacking TMEM16F not only fail to expand surface membrane in response to elevated cytoplasmic Ca2+, but instead undergo rapid massive endocytosis with PD-1 internalisation. These results establish a new role for TMEM16F as a regulator of Ca2+ activated membrane trafficking

Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths

Background: Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes. Methods: In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality. Results: Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses). Conclusions: Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. © 2011 Yende et al

The effect of prior statin use on 30-day mortality for patients hospitalized with community-acquired pneumonia

BACKGROUND: Recent studies suggest that HMG-CoA reductase inhibitors ("statins") may have beneficial effects for patients at risk for some types of infections. We examined the effect of prior outpatient use of statins on mortality for patients hospitalized with community-acquired pneumonia. METHODS: A retrospective cohort study conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had a chest x-ray consistent with, and had a discharge ICD-9 diagnosis of pneumonia. Subjects were excluded if they were "comfort measures only" or transferred from another acute care hospital. Subjects were considered to be on a medication if they were taking it at the time of presentation. RESULTS: Data was abstracted on 787 subjects at the two hospitals. Mortality was 9.2% at 30-days and 13.6% at 90-days. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk based on the pneumonia severity index. In the multivariable regression analysis, after adjusting for potential confounders including a propensity score, the use of statins at presentation (odds ratio 0.36, 95% confidence interval 0.14–0.92) was associated with decreased 30-day mortality. DISCUSSION: Prior outpatient statin use was associated with decreased mortality in patients hospitalized with community-acquired pneumonia despite their use being associated with comorbid illnesses likely to contribute to increased mortality. Confirmatory studies are needed, as well as research to determine the mechanism(s) of this protective effect

Quality of care in elder emergency department patients with pneumonia: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>The goals of the study were to assess the relationship between age and processes of care in emergency department (ED) patients admitted with pneumonia and to identify independent predictors of failure to meet recommended quality care measures.</p> <p>Methods</p> <p>This was a prospective cohort study of a pre-existing database undertaken at a university hospital ED in the Midwest. ED patients ≥18 years of age requiring admission for pneumonia, with no documented use of antibiotics in the 24 hours prior to ED presentation were included. Compliance with Pneumonia National Quality Measures was assessed including ED antibiotic administration, antibiotics within 4 hours, oxygenation assessment, and obtaining of blood cultures. Odds ratios were calculated for elders and non-elders. Logistic regression was used to identify independent predictors of process failure.</p> <p>Results</p> <p>One thousand, three hundred seventy patients met inclusion criteria, of which 560 were aged ≥65 years. In multiple variable logistic regression analysis, age ≥65 years was independently associated with receiving antibiotics in the ED (odds ratio [OR] = 2.03, 95% CI 1.28–3.21) and assessment of oxygenation (OR = 2.10, 95% CI, 1.18–3.32). Age had no significant impact on odds of receiving antibiotics within four hours of presentation (OR 1.10, 95% CI 0.84–1.43) or having blood cultures drawn (OR 1.02, 95%CI 0.78–1.32). Certain other patient characteristics were also independently associated with process failure.</p> <p>Conclusion</p> <p>Elderly patients admitted from the ED with pneumonia are more likely to receive antibiotics while in the ED and to have oxygenation assessed in the ED than younger patients. The independent association of certain patient characteristics with process failure provides an opportunity to further increase compliance with recommended quality measures in admitted patients diagnosed with pneumonia.</p

Estimating the Extent of Vaccine-Derived Poliovirus Infection

BACKGROUND: Eight outbreaks of paralytic polio attributable to circulating vaccine-derived poliovirus (cVDPV) have highlighted the risks associated with oral poliovirus vaccine (OPV) use in areas of low vaccination coverage and poor hygiene. As the Polio Eradication Initiative enters its final stages, it is important to consider the extent to which these viruses spread under different conditions, so that appropriate strategies can be devised to prevent or respond to future cVDPV outbreaks. METHODS AND FINDINGS: This paper examines epidemiological (temporal, geographic, age, vaccine history, social group, ascertainment), and virological (type, genetic diversity, virulence) parameters in order to infer the numbers of individuals likely to have been infected in each of these cVDPV outbreaks, and in association with single acute flaccid paralysis (AFP) cases attributable to VDPVs. Although only 114 virologically-confirmed paralytic cases were identified in the eight cVDPV outbreaks, it is likely that a minimum of hundreds of thousands, and more likely several million individuals were infected during these events, and that many thousands more have been infected by VDPV lineages within outbreaks which have escaped detection. CONCLUSIONS: Our estimates of the extent of cVDPV circulation suggest widespread transmission in some countries, as might be expected from endemic wild poliovirus transmission in these same settings. These methods for inferring extent of infection will be useful in the context of identifying future surveillance needs, planning for OPV cessation and preparing outbreak response plans

Prior outpatient antibiotic use as predictor for microbial aetiology of community-acquired pneumonia: hospital-based study

Objective: The causative micro-organism in community-acquired pneumonia (CAP) is often difficult to predict. Different studies have examined chronic morbidity and clinical symptoms as predictors for microbial aetiology of pneumonia. The aim of our study was to assess whether prior outpatient antimicrobial treatment is predictive for determining the microbial aetiology of CAP. Methods: This was a hospital-based prospective observational study including all patients admitted with CAP between 1 October 2004 and 1 August 2006. Microbial investigations included sputum, blood culture, sputum PCR, antigen testing and serology. Exposure to antimicrobial drugs prior to hospital admission was ascertained through community pharmacy dispensing records. Multivariate logistic regression analysis was conducted to assess whether prior outpatient antimicrobial treatment is a predictor of microbial aetiology. Patient demographics, co-morbidities and pneumonia severity were considered to be other potential predictors. Results: Overall, 201 patients were included in the study. The microbial aetiology was determined in 64% of the patients. The five most prevalent pathogens were Streptococcus pneumoniae, Heamophilus influenzae, Legionella spp., Mycoplasma pneumoniae and Influenza virus A+B. Forty-seven of the patients (23%) had received initial antimicrobial treatment as outpatients. Multivariate analyses revealed that initial outpatient beta-lactam treatment was associated with a threefold increased chance of finding atypical pathogens and a threefold decreased probability of pneumococcal infection; the corresponding odds ratios were 3.51 (95% CI 1.25-9.99) and 0.30 (95% CI 0.10-0.90), respectively. Patients who received macrolides prior to hospitalisation had an increased probability of viral pneumonia. Conclusion: Prior outpatient antimicrobial therapy has a predictive value in the diagnostic workup aimed at identifying the causative pathogen and planning corresponding antimicrobial treatment in patients hospitalised for pneumonia