Questions on causality and responsibility arising from an outbreak of Pseudomonas aeruginosa infections in Norway

In 2002, Norway experienced a large outbreak of Pseudomonas aeruginosa infections in hospitals with 231 confirmed cases. This fuelled intense public and professional debates on what were the causes and who were responsible. In epidemiology, other sciences, in philosophy and in law there is a long tradition of discussing the concept of causality. We use this outbreak as a case; apply various theories of causality from different disciplines to discuss the roles and responsibilities of some of the parties involved. Mackie's concept of INUS conditions, Hill's nine viewpoints to study association for claiming causation, deterministic and probabilistic ways of reasoning, all shed light on the issues of causality in this outbreak. Moreover, applying legal theories of causation (counterfactual reasoning and the "but-for" test and the NESS test) proved especially useful, but the case also illustrated the weaknesses of the various theories of causation

Capsular profiling of the Cronobacter genus and the association of specific Cronobacter sakazakii and C. malonaticus capsule types with neonatal meningitis and necrotizing enterocolitis

Background: Cronobacter sakazakii and C. malonaticus can cause serious diseases especially in infants where they are associated with rare but fatal neonatal infections such as meningitis and necrotising enterocolitis. Methods: This study used 104 whole genome sequenced strains, covering all seven species in the genus, to analyse capsule associated clusters of genes involved in the biosynthesis of the O-antigen, colanic acid, bacterial cellulose, enterobacterial common antigen (ECA), and a previously uncharacterised K-antigen. Results: Phylogeny of the gnd and galF genes flanking the O-antigen region enabled the defining of 38 subgroups which are potential serotypes. Two variants of the colanic acid synthesis gene cluster (CA1 and CA2) were found which differed with the absence of galE in CA2. Cellulose (bcs genes) were present in all species, but were absent in C. sakazakii sequence type (ST) 13 and clonal complex (CC) 100 strains. The ECA locus was found in all strains. The K-antigen capsular polysaccharide Region 1 (kpsEDCS) and Region 3 (kpsMT) genes were found in all Cronobacter strains. The highly variable Region 2 genes were assigned to 2 homology groups (K1 and K2). C. sakazakii and C. malonaticus isolates with capsular type [K2:CA2:Cell+] were associated with neonatal meningitis and necrotizing enterocolitis. Other capsular types were less associated with clinical infections. Conclusion: This study proposes a new capsular typing scheme which identifies a possible important virulence trait associated with severe neonatal infections. The various capsular polysaccharide structures warrant further investigation as they could be relevant to macrophage survival, desiccation resistance, environmental survival, and biofilm formation in the hospital environment, including neonatal enteral feeding tubes

The prevalence of common mental disorders and PTSD in the UK military: using data from a clinical interview-based study

<p>Abstract</p> <p>Background</p> <p>The mental health of the Armed Forces is an important issue of both academic and public interest. The aims of this study are to: a) assess the prevalence and risk factors for common mental disorders and post traumatic stress disorder (PTSD) symptoms, during the main fighting period of the Iraq War (TELIC 1) and later deployments to Iraq or elsewhere and enlistment status (regular or reserve), and b) compare the prevalence of depression, PTSD symptoms and suicidal ideation in regular and reserve UK Army personnel who deployed to Iraq with their US counterparts.</p> <p>Methods</p> <p>Participants were drawn from a large UK military health study using a standard two phase survey technique stratified by deployment status and engagement type. Participants undertook a structured telephone interview including the Patient Health Questionnaire (PHQ) and a short measure of PTSD (Primary Care PTSD, PC-PTSD). The response rate was 76% (821 participants).</p> <p>Results</p> <p>The weighted prevalence of common mental disorders and PTSD symptoms was 27.2% and 4.8%, respectively. The most common diagnoses were alcohol abuse (18.0%) and neurotic disorders (13.5%). There was no health effect of deploying for regular personnel, but an increased risk of PTSD for reservists who deployed to Iraq and other recent deployments compared to reservists who did not deploy. The prevalence of depression, PTSD symptoms and subjective poor health were similar between regular US and UK Iraq combatants.</p> <p>Conclusion</p> <p>The most common mental disorders in the UK military are alcohol abuse and neurotic disorders. The prevalence of PTSD symptoms remains low in the UK military, but reservists are at greater risk of psychiatric injury than regular personnel.</p

Effect of Vaccines and Antivirals during the Major 2009 A(H1N1) Pandemic Wave in Norway – And the Influence of Vaccination Timing

To evaluate the impact of mass vaccination with adjuvanted vaccines (eventually 40% population coverage) and antivirals during the 2009 influenza pandemic in Norway, we fitted an age-structured SEIR model using data on vaccinations and sales of antivirals in 2009/10 in Norway to Norwegian ILI surveillance data from 5 October 2009 to 4 January 2010. We estimate a clinical attack rate of approximately 30% (28.7–29.8%), with highest disease rates among children 0–14 years (43–44%). Vaccination started in week 43 and came too late to have a strong influence on the pandemic in Norway. Our results indicate that the countermeasures prevented approximately 11–12% of potential cases relative to an unmitigated pandemic. Vaccination was found responsible for roughly 3 in 4 of the avoided infections. An estimated 50% reduction in the clinical attack rate would have resulted from vaccination alone, had the campaign started 6 weeks earlier. Had vaccination been prioritized for children first, the intervention should have commenced approximately 5 weeks earlier in order to achieve the same 50% reduction. In comparison, we estimate that a non-adjuvanted vaccination program should have started 8 weeks earlier to lower the clinical attack rate by 50%

Poor reproducibility of compression elastography in the Achilles tendon: same day and consecutive day measurements.

OBJECTIVE To determine the reproducibility of compression elastography (CE) when measuring strain data, a measure of stiffness of the human Achilles tendon in vivo, over consecutive measures, consecutive days and when using different foot positions. MATERIALS AND METHODS Eight participants (4 males, 4 females; mean age 25.5 ± 2.51 years, range 21-30 years; height 173.6 ± 11.7 cm, range 156-189 cm) had five consecutive CE measurements taken on one day and a further five CE measures taken, one per day, at the same time of day, every day for a consecutive 5-day period. These 80 measurements were used to assess both the repeatability and reproducibility of the technique. Means, standard deviations, coefficient of variation (CV), Pearson correlation analysis (R) and intra-class correlation coefficients (ICC) were calculated. RESULTS For CE data, all CVs were above 53%, R values indicated no-to-weak correlations between measures at best (range 0.01-0.25), and ICC values were all classified in the poor category (range 0.00-0.11). CVs for length and diameter measures were acceptably low indicating a high level of reliability. CONCLUSIONS Given the wide variation obtained in the CE results, it was concluded that CE using this specific system has a low level of reproducibility for measuring the stiffness of the human Achilles tendon in vivo over consecutive days, consecutive measures and in different foot positions

Skeletal Muscle PGC-1α Is Required for Maintaining an Acute LPS-Induced TNFα Response

Many lifestyle-related diseases are associated with low-grade inflammation and peroxisome proliferator activated receptor γ coactivator (PGC)-1α has been suggested to be protective against low-grade inflammation. However, whether these anti-inflammatory properties affect acute inflammation is not known. The aim of the present study was therefore to investigate the role of muscle PGC-1α in acute inflammation. Quadriceps muscles were removed from 10-week old whole body PGC-1α knockout (KO), muscle specific PGC-1α KO (MKO) and muscle-specific PGC-1α overexpression mice (TG), 2 hours after an intraperitoneal injection of either 0.8 µg LPS/g body weight or saline. Basal TNFα mRNA content was lower in skeletal muscle of whole body PGC-1α KO mice and in accordance TG mice showed increased TNFα mRNA and protein level relative to WT, indicating a possible PGC-1α mediated regulation of TNFα. Basal p65 phosphorylation was increased in TG mice possibly explaining the elevated TNFα expression in these mice. Systemically, TG mice had reduced basal plasma TNFα levels compared with WT suggesting a protective effect against systemic low-grade inflammation in these animals. While TG mice reached similar TNFα levels as WT and showed more marked induction in plasma TNFα than WT after LPS injection, MKO PGC-1α mice had a reduced plasma TNFα and skeletal muscle TNFα mRNA response to LPS. In conclusion, the present findings suggest that PGC-1α enhances basal TNFα expression in skeletal muscle and indicate that PGC-1α does not exert anti-inflammatory effects during acute inflammation. Lack of skeletal muscle PGC-1α seems however to impair the acute TNFα response, which may reflect a phenotype more susceptible to infections as also observed in type 2 diabetes patients

Relationship between Plasmodium falciparum malaria prevalence, genetic diversity and endemic Burkitt lymphoma in Malawi

Endemic Burkitt lymphoma (eBL) has been linked to Plasmodium falciparum (Pf) malaria infection, but the contribution of infection with multiple Pf genotypes is uncertain. We studied 303 eBL (cases) and 274 non eBL-related cancers (controls) in Malawi using a sensitive and specific molecular-barcode array of 24 independently segregating Pf single nucleotide polymorphisms. Cases had a higher Pf malaria prevalence than controls (64.7% versus 45.3%; odds ratio [OR] 2.1, 95% confidence interval (CI): 1.5 to 3.1). Cases and controls were similar in terms of Pf density (4.9 versus 4.5 log copies, p = 0.28) and having ≥3 non-clonal calls (OR 2.7, 95% CI: 0.7-9.9, P = 0.14). However, cases were more likely to have a higher Pf genetic diversity score (153.9 versus 133.1, p = 0.036), which measures a combination of clonal and non-clonal calls, than controls. Further work is needed to evaluate the possible role of Pf genetic diversity in the pathogenesis of endemic BL

Two cases of "cannabis acute psychosis" following the administration of oral cannabis

BACKGROUND: Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users. CASE PRESENTATIONS: We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation) following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented. CONCLUSION: While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Array algorithms for H^2 and H^∞ estimation

Currently, the preferred method for implementing H^2 estimation algorithms is what is called the array form, and includes two main families: square-root array algorithms, that are typically more stable than conventional ones, and fast array algorithms, which, when the system is time-invariant, typically offer an order of magnitude reduction in the computational effort. Using our recent observation that H^∞ filtering coincides with Kalman filtering in Krein space, in this chapter we develop array algorithms for H^∞ filtering. These can be regarded as natural generalizations of their H^2 counterparts, and involve propagating the indefinite square roots of the quantities of interest. The H^∞ square-root and fast array algorithms both have the interesting feature that one does not need to explicitly check for the positivity conditions required for the existence of H^∞ filters. These conditions are built into the algorithms themselves so that an H^∞ estimator of the desired level exists if, and only if, the algorithms can be executed. However, since H^∞ square-root algorithms predominantly use J-unitary transformations, rather than the unitary transformations required in the H^2 case, further investigation is needed to determine the numerical behavior of such algorithms