The Role of Deontic Logic in the Specification of Information Systems

In this paper we discuss the role that deontic logic plays in the specification of information systems, either because constraints on the systems directly concern norms or, and even more importantly, system constraints are considered ideal but violable (so-called `soft¿ constraints).\ud To overcome the traditional problems with deontic logic (the so-called paradoxes), we first state the importance of distinguishing between ought-to-be and ought-to-do constraints and next focus on the most severe paradox, the so-called Chisholm paradox, involving contrary-to-duty norms. We present a multi-modal extension of standard deontic logic (SDL) to represent the ought-to-be version of the Chisholm set properly. For the ought-to-do variant we employ a reduction to dynamic logic, and show how the Chisholm set can be treated adequately in this setting. Finally we discuss a way of integrating both ought-to-be and ought-to-do reasoning, enabling one to draw conclusions from ought-to-be constraints to ought-to-do ones, and show by an example the use(fulness) of this

Calibrating the Performance of SNP Arrays for Whole-Genome Association Studies

To facilitate whole-genome association studies (WGAS), several high-density SNP genotyping arrays have been developed. Genetic coverage and statistical power are the primary benchmark metrics in evaluating the performance of SNP arrays. Ideally, such evaluations would be done on a SNP set and a cohort of individuals that are both independently sampled from the original SNPs and individuals used in developing the arrays. Without utilization of an independent test set, previous estimates of genetic coverage and statistical power may be subject to an overfitting bias. Additionally, the SNP arrays' statistical power in WGAS has not been systematically assessed on real traits. One robust setting for doing so is to evaluate statistical power on thousands of traits measured from a single set of individuals. In this study, 359 newly sampled Americans of European descent were genotyped using both Affymetrix 500K (Affx500K) and Illumina 650Y (Ilmn650K) SNP arrays. From these data, we were able to obtain estimates of genetic coverage, which are robust to overfitting, by constructing an independent test set from among these genotypes and individuals. Furthermore, we collected liver tissue RNA from the participants and profiled these samples on a comprehensive gene expression microarray. The RNA levels were used as a large-scale set of quantitative traits to calibrate the relative statistical power of the commercial arrays. Our genetic coverage estimates are lower than previous reports, providing evidence that previous estimates may be inflated due to overfitting. The Ilmn650K platform showed reasonable power (50% or greater) to detect SNPs associated with quantitative traits when the signal-to-noise ratio (SNR) is greater than or equal to 0.5 and the causal SNP's minor allele frequency (MAF) is greater than or equal to 20% (N = 359). In testing each of the more than 40,000 gene expression traits for association to each of the SNPs on the Ilmn650K and Affx500K arrays, we found that the Ilmn650K yielded 15% times more discoveries than the Affx500K at the same false discovery rate (FDR) level

MHC-based detection of antigen-specific CD8+ T cell responses

The hallmark of adaptive immunity is its ability to recognise a wide range of antigens and technologies that capture this diversity are therefore of substantial interest. New methods have recently been developed that allow the parallel analysis of T cell reactivity against vast numbers of different epitopes in limited biological material. These technologies are based on the joint binding of differentially labelled MHC multimers on the T cell surface, thereby providing each antigen-specific T cell population with a unique multicolour code. This strategy of ‘combinatorial encoding’ enables detection of many (at least 25) different T cell populations per sample and should be of broad value for both T cell epitope identification and immunomonitoring

Reduced haemodynamic response in the ageing visual cortex measured by absolute fNIRS

The effect of healthy ageing on visual cortical activation is still to be fully explored. This study aimed to elucidate whether the haemodynamic response (HDR) of the visual cortex altered as a result of ageing. Visually normal (healthy) participants were presented with a simple visual stimulus (reversing checkerboard). Full optometric screening was implemented to identify two age groups: younger adults (n = 12, mean age 21) and older adults (n = 13, mean age 71). Frequency-domain Multi-distance (FD-MD) functional Near-Infrared Spectroscopy (fNIRS) was used to measure absolute changes in oxygenated [HbO] and deoxygenated [HbR] haemoglobin concentrations in the occipital cortices. Utilising a slow event-related design, subjects viewed a full field reversing checkerboard with contrast and check size manipulations (15 and 30 minutes of arc, 50% and 100% contrast). Both groups showed the characteristic response of increased [HbO] and decreased [HbR] during stimulus presentation. However, older adults produced a more varied HDR and often had comparable levels of [HbO] and [HbR] during both stimulus presentation and baseline resting state. Younger adults had significantly greater concentrations of both [HbO] and [HbR] in every investigation regardless of the type of stimulus displayed (p<0.05). The average variance associated with this age-related effect for [HbO] was 88% and [HbR] 91%. Passive viewing of a visual stimulus, without any cognitive input, showed a marked age-related decline in the cortical HDR. Moreover, regardless of stimulus parameters such as check size, the HDR was characterised by age. In concurrence with present neuroimaging literature, we conclude that the visual HDR decreases as healthy ageing proceeds

Risk assessment of adding Gasodor S-Free to natural gas

Om te herkennen wanneer te veel aardgas vrijkomt, en zo explosies te voorkomen, wordt er een geurstof aan toegevoegd. De huidige geurstof (tetrahydrothiofeen) bevat zwavel. Om de uitstoot van zwavel naar het milieu verder te verminderen onderzoekt Gasunie Transport Services de mogelijkheid om een andere, zwavelvrije geurstof, toe te voegen: Gasodor S-Free. Vanwege het omvangrijke gebruik van aardgas is het van belang voldoende zicht te hebben op mogelijke risico's van dit product. Het RIVM heeft onvoldoende informatie kunnen vinden om vast te stellen of het gebruik van Gasodor S-Free als geurstof in aardgas veilig is. De zorg bestaat dat dit product allergische reacties kan veroorzaken als het wordt ingeademd. Het gebruik van Gasodor S-Free wordt afgeraden totdat meer duidelijk is over het mogelijke risico op allergische reacties. Het RIVM geeft aanbevelingen voor vervolgonderzoek om het risico op deze reacties beter te kunnen beoordelen. Gasodor S-Free is een mengsel van drie stoffen, voornamelijk ethylacrylaat en methylacrylaat (samen 95 procent of meer), en een kleine fractie 2-ethyl-3-methylpyrazine. Mogelijke gevolgen van de twee hoofdbestanddelen zijn op basis van de huidige kennis niet goed te beoordelen. Bekend is dat ethylacrylaat en methylacrylaat de luchtwegen kunnen irriteren, maar door de lage concentraties worden geen normen overschreden. Ook zijn ze niet kankerverwekkend. Het is bekend dat beide stoffen allergische reacties kunnen veroorzaken bij huidcontact. Vergelijkbare effecten zouden ook kunnen optreden als de stof wordt ingeademd, maar dit kan op basis van de beschikbare informatie niet worden beoordeeld. Over nadelige effecten van de derde stof (2-ethyl-3-methylpyrazine) is onvoldoende informatie beschikbaar om een uitspraak te kunnen doen over mogelijke effecten op mens en milieu.As natural gas is odourless, an odorant is added to detect the release of gas and prevent explosions. The odorant (tetrahydrothiophene) that is currently used contains sulphur. So as not to add to current levels of sulphur in the environment, Gasunie Transport Services has investigated the possibility of adding another sulphur-free fragrance: Gasodor S-Free. Because of the extensive use of natural gas, it is important that the potential risks of this product are thoroughly evaluated. RIVM has not been able to find sufficient information to determine whether the use of Gasodor S-Free as an odorant in natural gas is safe. There is a concern that this product can cause allergic reactions if inhaled. Any application of Gasodor S-Free, therefore, should be discouraged until the possible risk of allergic reactions has been clarified. RIVM provides recommendations about which investigations could be conducted to assess the risk of these reactions more comprehensively. Gasodor S-Free is a mixture of three substances, mainly ethyl acrylate and methyl acrylate (together 95 percent or more), and a small percent of 2-ethyl-3-methylpyrazine. The possible consequences of the two main components cannot be judged properly based on current knowledge. Ethyl acrylate and methyl acrylate are known to irritate the respiratory tract, but the low concentrations in intended use of Gasodor S-Free do not exceed standards. Nor are they carcinogenic. However, it is known that both substances can cause allergic contact dermatitis. Allergic effects could also occur if the substance is inhaled, but this cannot be evaluated based on the available information. There is also insufficient information available on the adverse effects of the third substance (2-ethyl-3-methylpyrazine) for an assessment of the possible effects on humans and the environment to be madeSod

The HLA class II allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients. Methods/Principal Findings: HLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7%) compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U.S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55). The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI 1.3-2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91) tended to have decreased diffusing capacities for carbon monoxide (DLCO) compared to the 184 disease subjects who lacked this allele (37.8±1.7% vs. 42.8±1.4%, p = 0.036). Conclusions/Significance: DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic implications, illustrate a specific chromosomal area for incremental, targeted genomic study, and may identify a distinct clinical phenotype among patients with this enigmatic, morbid lung disease

Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.

OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact. RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock

Further Insight into Mechanisms of Ventricular Tachycardia from the Clinical Electrophysiology Laboratory

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72003/1/j.1540-8167.1991.tb01319.x.pd

Detection of emphysema progression in alpha 1-antitrypsin deficiency using CT densitometry; Methodological advances

<p>Abstract</p> <p>Background</p> <p>Computer tomography (CT) densitometry is a potential tool for detecting the progression of emphysema but the optimum methodology is uncertain. The level of inspiration affects reproducibility but the ability to adjust for this variable is facilitated by whole lung scanning methods. However, emphysema is frequently localised to sub-regions of the lung and targeted densitometric sampling may be more informative than whole lung assessment.</p> <p>Methods</p> <p>Emphysema progression over a 2-year interval was assessed in 71 patients (alpha 1-antitrypsin deficiency with PiZ phenotype) with CT densitometry, using the 15^thpercentile point (Perc15) and voxel index (VI) -950 Hounsfield Units (HU) and -910 HU (VI -950 and -910) on whole lung, limited single slices, and apical, central and basal thirds. The relationship between whole lung densitometric progression (ΔCT) and change in CT-derived lung volume (ΔCT_Vol) was characterised, and adjustment for lung volume using statistical modelling was evaluated.</p> <p>Results</p> <p>CT densitometric progression was statistically significant for all methods. ΔCT correlated with ΔCT_Voland linear regression indicated that nearly one half of lung density loss was secondary to apparent hyperinflation. The most accurate measure was obtained using a random coefficient model to adjust for lung volume and the greatest progression was detected by targeted sampling of the middle third of the lung.</p> <p>Conclusion</p> <p>Progressive hyperinflation may contribute significantly to loss of lung density, but volume effects and absolute tissue loss can be identified by statistical modelling. Targeted sampling of the middle lung region using Perc15 appears to be the most robust measure of emphysema progression.</p