On the gradient of the yield plateau in structural carbon steels

New design methodologies are being developed to allow stocky steel members to attain and exceed the full plastic condition. For theoretical validation, such methods require a characterisation of the uniaxial stress-strain behaviour of structural steel beyond an idealised elastic-plastic representation. However, the strain hardening properties of carbon steels are not currently guaranteed by the standards or by any steel manufacturer. Assumptions must thus be made on what values of these properties are appropriate, often based on limited information in the form of individual stress-strain curves. There is very little consistency in the choices made. This paper first illustrates, using an example elastic-plastic finite element calculation, that a stocky tubular structure can attain the full plastic condition at slendernesses comparable with those defined in current standards and supported by experiment when using only a very modest level of strain hardening, initiated at first yield. It is then hypothesised that the yield plateau in the stress-strain curve for structural carbon steels, classically treated as flat and with zero tangent modulus, actually has a small but statistically significant positive finite gradient. Finally, a robust set of linear regression analyses of yield plateau gradients extracted from 225 tensile tests appears to support this hypothesis, finding that the plateau gradient is of the order of 0.3% of the initial elastic modulus, consistent with what the finite element example suggests is sufficient to reproduce the full plastic condition at experimentally-supported slendernesses

International variation in prescribing antihypertensive drugs: Its extent and possible explanations

BACKGROUND: Inexpensive antihypertensive drugs are at least as effective and safe as more expensive drugs. Overuse of newer, more expensive antihypertensive drugs is a poor use of resources. The potential savings are substantial, but vary across countries, in large part due to differences in prescribing patterns. We wanted to describe prescribing patterns of antihypertensive drugs in ten countries and explore possible reasons for inter-country variation. METHODS: National prescribing profiles were determined based on information on sales and indications for prescribing. We sent a questionnaire to academics and drug regulatory agencies in Canada, France, Germany, UK, US and the Nordic countries, asking about explanations for differences in prescribing patterns in their country compared with the other countries. We also conducted telephone interviews with medical directors of drug companies in the UK and Norway, the countries with the largest differences in prescribing patterns. RESULTS: There is considerable variation in prescribing patterns. In the UK thiazides account for 25% of consumption, while the corresponding figure for Norway is 6%. In Norway alpha-blocking agents account for 8% of consumption, which is more than twice the percentage found in any of the other countries. Suggested factors to explain inter-country variation included reimbursement policies, traditions, opinion leaders with conflicts of interests, domestic pharmaceutical production, and clinical practice guidelines. The medical directors also suggested hypotheses that: Norwegian physicians are early adopters of new interventions while the British are more conservative; there are many clinical trials conducted in Norway involving many general practitioners; there is higher cost-awareness among physicians in the UK, in part due to fund holding; and there are publicly funded pharmaceutical advisors in the UK. CONCLUSION: Two compelling explanations the variation in prescribing that warrant further investigation are the promotion of less-expensive drugs by pharmaceutical advisors in UK and the promotion of more expensive drugs through "seeding trials" in Norway

Temperature- and thickness-dependent elastic moduli of polymer thin films

The mechanical properties of polymer ultrathin films are usually different from those of their counterparts in bulk. Understanding the effect of thickness on the mechanical properties of these films is crucial for their applications. However, it is a great challenge to measure their elastic modulus experimentally with in situ heating. In this study, a thermodynamic model for temperature- (T) and thickness (h)-dependent elastic moduli of polymer thin films Ef(T,h) is developed with verification by the reported experimental data on polystyrene (PS) thin films. For the PS thin films on a passivated substrate, Ef(T,h) decreases with the decreasing film thickness, when h is less than 60 nm at ambient temperature. However, the onset thickness (h*), at which thickness Ef(T,h) deviates from the bulk value, can be modulated by T. h* becomes larger at higher T because of the depression of the quenching depth, which determines the thickness of the surface layer δ

Area-level deprivation and adiposity in children: is the relationship linear?

OBJECTIVE: It has been suggested that childhood obesity is inversely associated with deprivation, such that the prevalence is higher in more deprived groups. However, comparatively few studies actually use an area-level measure of deprivation, limiting the scope to assess trends in the association with obesity for this indicator. Furthermore, most assume a linear relationship. Therefore, the aim of this study was to investigate associations between area-level deprivation and three measures of adiposity in children: body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). DESIGN: This is a cross-sectional study in which data were collected on three occasions a year apart (2005-2007). SUBJECTS: Data were available for 13,333 children, typically aged 11-12 years, from 37 schools and 542 lower super-output areas (LSOAs). MEASURES: Stature, mass and WC. Obesity was defined as a BMI and WC exceeding the 95th centile according to British reference data. WHtR exceeding 0.5 defined obesity. The Index of Multiple Deprivation affecting children (IDACI) was used to determine area-level deprivation. RESULTS: Considerable differences in the prevalence of obesity exist between the three different measures. However, for all measures of adiposity the highest probability of being classified as obese is in the middle of the IDACI range. This relationship is more marked in girls, such that the probability of being obese for girls living in areas at the two extremes of deprivation is around half that at the peak, occurring in the middle. CONCLUSION: These data confirm the high prevalence of obesity in children and suggest that the relationship between obesity and residential area-level deprivation is not linear. This is contrary to the 'deprivation theory' and questions the current understanding and interpretation of the relationship between obesity and deprivation in children. These results could help make informed decisions at the local level

Water dispersible microbicidal cellulose acetate phthalate film

BACKGROUND: Cellulose acetate phthalate (CAP) has been used for several decades in the pharmaceutical industry for enteric film coating of oral tablets and capsules. Micronized CAP, available commercially as "Aquateric" and containing additional ingredients required for micronization, used for tablet coating from water dispersions, was shown to adsorb and inactivate the human immunodeficiency virus (HIV-1), herpesviruses (HSV) and other sexually transmitted disease (STD) pathogens. Earlier studies indicate that a gel formulation of micronized CAP has a potential as a topical microbicide for prevention of STDs including the acquired immunodeficiency syndrome (AIDS). The objective of endeavors described here was to develop a water dispersible CAP film amenable to inexpensive industrial mass production. METHODS: CAP and hydroxypropyl cellulose (HPC) were dissolved in different organic solvent mixtures, poured into dishes, and the solvents evaporated. Graded quantities of a resulting selected film were mixed for 5 min at 37°C with HIV-1, HSV and other STD pathogens, respectively. Residual infectivity of the treated viruses and bacteria was determined. RESULTS: The prerequisites for producing CAP films which are soft, flexible and dispersible in water, resulting in smooth gels, are combining CAP with HPC (other cellulose derivatives are unsuitable), and casting from organic solvent mixtures containing ≈50 to ≈65% ethanol (EtOH). The films are ≈100 µ thick and have a textured surface with alternating protrusions and depressions revealed by scanning electron microscopy. The films, before complete conversion into a gel, rapidly inactivated HIV-1 and HSV and reduced the infectivity of non-viral STD pathogens >1,000-fold. CONCLUSIONS: Soft pliable CAP-HPC composite films can be generated by casting from organic solvent mixtures containing EtOH. The films rapidly reduce the infectivity of several STD pathogens, including HIV-1. They are converted into gels and thus do not have to be removed following application and use. In addition to their potential as topical microbicides, the films have promise for mucosal delivery of pharmaceuticals other than CAP

A four-helix bundle stores copper for methane oxidation

Methane-oxidising bacteria (methanotrophs) require large quantities of copper for the membrane-bound (particulate) methane monooxygenase (pMMO). Certain methanotrophs are also able to switch to using the iron-containing soluble MMO (sMMO) to catalyse methane oxidation, with this switchover regulated by copper. MMOs are Nature’s primary biological mechanism for suppressing atmospheric levels of methane, a potent greenhouse gas. Furthermore, methanotrophs and MMOs have enormous potential in bioremediation and for biotransformations producing bulk and fine chemicals, and in bioenergy, particularly considering increased methane availability from renewable sources and hydraulic fracturing of shale rock. We have discovered and characterised a novel copper storage protein (Csp1) from the methanotroph Methylosinus trichosporium OB3b that is exported from the cytosol, and stores copper for pMMO. Csp1 is a tetramer of 4-helix bundles with each monomer binding up to 13 Cu(I) ions in a previously unseen manner via mainly Cys residues that point into the core of the bundle. Csp1 is the first example of a protein that stores a metal within an established protein-folding motif. This work provides a detailed insight into how methanotrophs accumulate copper for the oxidation of methane. Understanding this process is essential if the wide-ranging biotechnological applications of methanotrophs are to be realised. Cytosolic homologues of Csp1 are present in diverse bacteria thus challenging the dogma that such organisms do not use copper in this location

Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways

To achieve its precise neural connectivity, the developing mammalian nervous system undergoes extensive activity-dependent synapse remodeling. Recently microglial cells have been shown to be responsible for a portion of synaptic remodeling, but the remaining mechanisms remain mysterious. Here we report a new role for astrocytes in actively engulfing CNS synapses. This process helps to mediate synapse elimination, requires the Megf10 and Mertk phagocytic pathways, and is strongly dependent on neuronal activity. Developing mice deficient in both astrocyte pathways fail to normally refine their retinogeniculate connections and retain excess functional synapses. Lastly, we show that in the adult mouse brain, astrocytes continuously engulf both excitatory and inhibitory synapses. These studies reveal a novel role for astrocytes in mediating synapse elimination in the developing and adult brain, identify Megf10 and Mertk as critical players in the synapse remodeling underlying neural circuit refinement, and have important implications for understanding learning and memory as well as neurological disease processes

Analysis of four studies in a comparative framework reveals: health linkage consent rates on British cohort studies higher than on UK household panel surveys

Background: A number of cohort studies and longitudinal household panel studies in Great Britain have asked for consent to link survey data to administrative health data. We explore commonalities and differences in the process of collecting consent, achieved consent rates and biases in consent with respect to socio-demographic, socio-economic and health characteristics. We hypothesise that British cohort studies which are rooted within the health sciences achieve higher consent rates than the UK household longitudinal studies which are rooted within the social sciences. By contrast, the lack of a specific health focus in household panel studies means there may be less selectivity in consent, in particular, with respect to health characteristics. Methods: Survey designs and protocols for collecting informed consent to health record linkage on two British cohort studies and two UK household panel studies are systematically compared. Multivariate statistical analysis is then performed on information from one cohort and two household panel studies that share a great deal of the data linkage protocol but vary according to study branding, survey design and study population. Results: We find that consent is higher in the British cohort studies than in the UK household panel studies, and is higher the more health-focused the study is. There are no systematic patterns of consent bias across the studies and where effects exist within a study or study type they tend to be small. Minority ethnic groups will be underrepresented in record linkage studies on the basis of all three studies. Conclusions: Systematic analysis of three studies in a comparative framework suggests that the factors associated with consent are idiosyncratic to the study. Analysis of linked health data is needed to establish whether selectivity in consent means the resulting research databases suffer from any biases that ought to be considered

Area deprivation and its association with health in a cross-sectional study: are the results biased by recent migration?

<p>Abstract</p> <p>Background</p> <p>The association between area deprivation and health has mostly been examined in cross-sectional studies or prospective studies with short follow-up. These studies have rarely taken migration into account. This is a possible source of misclassification of exposure, i.e. an unknown number of study participants are attributed an exposure of area deprivation that they may have experienced too short for it to have any influence. The aim of this article was to examine to what extent associations between area deprivation and health outcomes were biased by recent migration.</p> <p>Methods</p> <p>Based on data from the Oslo Health Study, a cross-sectional study conducted in 2000 in Oslo, Norway, we used six health outcomes (self rated health, mental health, coronary heart disease, chronic obstructive pulmonary disease, smoking and exercise) and considered migration nine years prior to the study conduct. Migration into Oslo, between the areas of Oslo, and the changes in area deprivation during the period were taken into account. Associations were investigated by multilevel logistic regression analyses.</p> <p>Results</p> <p>After adjustment for individual socio-demographic variables we found significant associations between area deprivation and all health outcomes. Accounting for migration into Oslo and between areas of Oslo did not change these associations much. However, the people who migrated into Oslo were younger and had lower prevalences of unfavourable health outcomes than those who were already living in Oslo. But since they were evenly distributed across the area deprivation quintiles, they had little influence on the associations between area deprivation and health. Evidence of selective migration within Oslo was weak, as both moving up and down in the deprivation hierarchy was associated with significantly worse health than not moving.</p> <p>Conclusion</p> <p>We have documented significant associations between area deprivation and health outcomes in Oslo after adjustment for socio-demographic variables in a cross-sectional study. These associations were weakly biased by recent migration. From our results it still appears that migration prior to study conduct may be relevant to investigate even within a relatively short period of time, whereas changes in area deprivation during such a period is of limited interest.</p

A study of the diagnostic accuracy of the PHQ-9 in primary care elderly

<p>Abstract</p> <p>Background</p> <p>The diagnostic accuracy of the Patient Health Questionnaire-9 (PHQ-9) for assessment of depression in elderly persons in primary care settings in the United States has not been previously addressed. Thus, the purpose of this study was to evaluate the test performance of the PHQ-9 for detecting major and minor depression in elderly patients in primary care.</p> <p>Methods</p> <p>A prospective study of diagnostic accuracy was conducted in two primary care, university-based clinics in the Pacific Northwest of the United States. Seventy-one patients aged 65 years or older participated; all completed the PHQ-9 and the 15-item Geriatric Depression Scale (GDS) and underwent the Structured Clinical Interview for Depression (SCID). Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, and likelihood ratios (LRs) were calculated for the PHQ-9, the PHQ-2, and the 15-item GDS for major depression alone and the combination of major plus minor depression.</p> <p>Results</p> <p>Two thirds of participants were female, with a mean age of 78 and two chronic health conditions. Twelve percent met SCID criteria for major depression and 13% minor depression. The PHQ-9 had an area under the curve (AUC) of 0.87 (95% confidence interval [CI], 0.74-1.00) for major depression, while the PHQ-2 and the 15-item GDS each had an AUC of 0.81 (95% CI for PHQ-2, 0.64-0.98, and for 15-item GDS, 0.70-0.91; <it>P </it>= 0.551). For major and minor depression combined, the AUC for the PHQ-9 was 0.85 (95% CI, 0.73-0.96), for the PHQ-2, 0.80 (95% CI, 0.68-0.93), and for the 15-item GDS, 0.71 (95% CI, 0.55-0.87; <it>P </it>= 0.187).</p> <p>Conclusions</p> <p>Based on AUC values, the PHQ-9 performs comparably to the PHQ-2 and the 15-item GDS in identifying depression among primary care elderly.</p