Causality and Association: The Statistical and Legal Approaches

This paper discusses different needs and approaches to establishing ``causation'' that are relevant in legal cases involving statistical input based on epidemiological (or more generally observational or population-based) information. We distinguish between three versions of ``cause'': the first involves negligence in providing or allowing exposure, the second involves ``cause'' as it is shown through a scientifically proved increased risk of an outcome from the exposure in a population, and the third considers ``cause'' as it might apply to an individual plaintiff based on the first two. The population-oriented ``cause'' is that commonly addressed by statisticians, and we propose a variation on the Bradford Hill approach to testing such causality in an observational framework, and discuss how such a systematic series of tests might be considered in a legal context. We review some current legal approaches to using probabilistic statements, and link these with the scientific methodology as developed here. In particular, we provide an approach both to the idea of individual outcomes being caused on a balance of probabilities, and to the idea of material contribution to such outcomes. Statistical terminology and legal usage of terms such as ``proof on the balance of probabilities'' or ``causation'' can easily become confused, largely due to similar language describing dissimilar concepts; we conclude, however, that a careful analysis can identify and separate those areas in which a legal decision alone is required and those areas in which scientific approaches are useful.Comment: Published in at http://dx.doi.org/10.1214/07-STS234 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Temperature in nonequilibrium systems with conserved energy

We study a class of nonequilibrium lattice models which describe local redistributions of a globally conserved energy. A particular subclass can be solved analytically, allowing to define a temperature T_{th} along the same lines as in the equilibrium microcanonical ensemble. The fluctuation-dissipation relation is explicitely found to be linear, but its slope differs from the inverse temperature T_{th}^{-1}. A numerical renormalization group procedure suggests that, at a coarse-grained level, all models behave similarly, leading to a two-parameter description of their macroscopic properties.Comment: 4 pages, 1 figure, final versio

Creating Desirable Organizational Characteristics. How Organizations Create a Focus on

Abstract What are the factors that lead to desirable organizational characteristics? This article examines this question by proposing a model to explain the ability of some organizations to create a focus on results and high levels of managerial authority. The new public management literature points to these two organizational characteristics as key steps for improving public performance and providing results-based accountability. Employing a national survey of US state government health and human service agency managers we find that political support for the organization and purposeful reform efforts do lead to desirable organizational characteristics. In addition, strong internal communication fosters a focus on results, and organizational culture shapes the decision-making authority of managers

Challenges Encountered Using Ophthalmic Anesthetics in Space Medicine

On orbit, ophthalmic anesthetics are used for tonometry and off-nominal corneal examinations. Proparacaine has been flown traditionally. However, the manufacturers recently changed its storage requirements from room temperature storage to refrigerated storage to preserve stability and prolong the shelf-life. Since refrigeration on orbit is not readily available and there were stability concerns about flying proparacaine unrefrigerated, tetracaine was selected as an alternative ophthalmic anesthetic in 2013. We will discuss the challenges encountered flying and using these anesthetics on the International Space Station

Effects of Starch on Oral Health: Systematic Review to Inform WHO Guideline.

A systematic review was conducted to update evidence on the effect of total dietary starch and of replacing rapidly digestible starches (RDSs) with slowly digestible starches (SDSs) on oral health outcomes to inform updating of World Health Organization guidance on carbohydrate intake. Data sources included MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, LILACS, and Wanfang. Eligible studies were comparative and reported any intervention with a different starch content of diets or foods and data on oral health outcomes relating to dental caries, periodontal disease, or oral cancer. Studies that reported total dietary starch intake or change in starch intake were included or where comparisons or exposure included diets and foods that compared RDSs and/or SDSs. The review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) statement, and evidence was assessed with the GRADE Working Group guidelines. From 6,080 papers identified, 33 (28 studies) were included in the RDS versus SDS comparison: 15 (14 studies) assessed the relationship between SDS and/or RDS and dental caries; 16 (12 studies) considered oral cancer; and 2 studied periodontal disease. For total starch, 23 papers (22 studies) were included: 22 assessed the effects on dental caries, and 1 considered oral cancer. GRADE assessment indicated low-quality evidence, suggesting no association between total starch intake and caries risk but that RDS intake may significantly increase caries risk. Very low-quality evidence suggested no association between total starch and oral cancer risk, and low-quality evidence suggested that SDS decreases oral cancer risk. Data on RDS and oral cancer risk were inconclusive. Very low-quality data relating to periodontitis suggested a protective effect of whole grain starches (SDS). The best available evidence suggests that only RDS adversely affects oral health.World Health Organization (WHO) and Newcastle University

ActS activates peptidoglycan amidases during outer membrane stress in <i>Escherichia coli</i>

The integrity of the cell envelope of E. coli relies on the concerted activity of multi-protein machineries that synthesize the peptidoglycan (PG) and the outer membrane (OM). Our previous work found that the depletion of lipopolysaccharide (LPS) export to the OM induces an essential PG remodeling process involving LD-transpeptidases (LDTs), the glycosyltransferase function of PBP1B and the carboxypeptidase PBP6a. Consequently, cells with defective OM biogenesis lyse if they lack any of these PG enzymes. Here we report that the morphological defects, and lysis associated with a ldtF mutant with impaired LPS transport, are alleviated by the loss of the predicted OM-anchored lipoprotein ActS (formerly YgeR). We show that ActS is an inactive member of LytM-type peptidoglycan endopeptidases due to a degenerated catalytic domain. ActS is capable of activating all three main periplasmic peptidoglycan amidases, AmiA, AmiB, and AmiC, which were previously reported to be activated only by EnvC and/or NlpD. Our data also suggest that in vivo ActS preferentially activates AmiC and that its function is linked to cell envelope stress

Origin of non-exponential relaxation in a crystalline ionic conductor: a multi-dimensional 109Ag NMR study

The origin of the non-exponential relaxation of silver ions in the crystalline ion conductor Ag7P3S11 is analyzed by comparing appropriate two-time and three-time 109Ag NMR correlation functions. The non-exponentiality is due to a rate distribution, i.e., dynamic heterogeneities, rather than to an intrinsic non-exponentiality. Thus, the data give no evidence for the relevance of correlated back-and-forth jumps on the timescale of the silver relaxation.Comment: 4 pages, 3 figure

Interactions between microbial community structure and pathogen survival in soil

Manure and slurry are valuable resources that may enhance many soil properties. However, organic amendments can pose a significant health risk to both humans and livestock if not managed correctly due to pathogenic loads that may be carried within them. Therefore it is crucial to identify the factors that affect pathogen survival in soil, in order to gain maximum benefit from such resources, whilst minimising the threat to public and animal welfare. This research aimed to elucidate the impact of microbial community structure on pathogen decline following entry of such organisms into the soil. It was hypothesised that pathogen survival would be significantly influenced by both diversity and phenotypic configuration of the microbial community. This was experimentally investigated within three distinctly different biological contexts. Firstly, it was shown that the survival of Escherichia coli 0157 was significantly affected by the presence of an intact microbial community. Microcosms consisting of sterile and non-sterile sand and clay soils were inoculated with E. coli and destructively sampled over time. The pathogen remained stable at 4°C, irrespective of biological status. However at 18°C, the pathogen grew in sterile soil and declined in non-sterile soil. This result was attributed to microbial antagonism in non-sterile soil, which only became apparent at 18°C, due to increased metabolic activity of the native community. The next experiment was designed to investigate the impact of microbial diversity and community configuration on the survival of a suite of model pathogens. A gradient of community complexity was created by inoculation of gamma-irradiated soil mesocosms with a serial-dilution of a suspension of a field soil. Soils were incubated to allow biomass equilibration and the establishment of distinct community phenotypes. Sub-samples were then inoculated with Listeria, Salmonella and E. coli strains and survival was monitored over 160 days. Death rates were calculated and plotted as a function of dilution, which represented diversity, and of principal component (PC) scores from PLFA profiles, which represented the phenotypic community context. There was some evidence of a diversity effect as weak negative linear correlations were observed between death rate and dilution for S. Dublin and environmentally-persistent E. coli. However, a much stronger correlation was observed between death rate and certain PC scores for these organisms. No effect of diversity or phenotype was detected on either L. monocytogenes or E. coli 0157. These results suggest that pathogen survival was affected by diversity, but the phenotypic community context was apparently much more influential. Additionally, such community effects were specific to pathogen type. Pathogen survival was also investigated in the context of highly-contrasting communities within a range of naturally-derived field soils. PLFA analysis was used to determine phenotypic community structure and soils were also characterized for a range of physico-chemical properties. They were inoculated with Listeria, Salmonella and E. coli strains as above. Pathogen survival was monitored over 110 days and death rates were calculated. Physicochemical and biotic data, including PC scores derived from PLFA profiles, were used in stepwise regression analysis to determine the predominant factor influencing pathogen-specific death rates. PC scores were identified as the most significant factor in pathogen decay for all organisms tested, with the exception of an environmentally-persistent E. coli isolate. Overall, these results demonstrate the importance of soil biological quality, specifically the configuration of the microbial community, in pathogen suppression, and provide a possible means to assess the inherent potential of soils to regulate pathogen survival. This may lead to the identification of management strategies which will ultimately accelerate pathogen decay, and therefore improve the safety of agricultural practice.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Telescoped approach to aryl hydroxymethylation in the synthesis of a key pharmaceutical intermediate

An efficient synthetic approach leading to introduction of the hydroxymethyl group to an aryl moiety via combination of the Bouveault formylation and hydride reduction has been optimized using a rational, mechanistic-based approach. This approach enabled telescoping of the two steps into a single efficient process, readily amenable to scaleup