Are Estimates of the Value of a Statistical Life Exaggerated?

The magnitude of the value of a statistical life (VSL) is critical to the evaluation of many health and safety initiatives. To date, the large and rigorous VSL research literature has not explicitly accommodated publication selectivity bias (i.e., the reduced probability that insignificant or negative VSL values are reported). This study demonstrates that doing so is essential. For studies that employ hedonic wage equations to estimate VSL, correction for selection bias reduces the average value of a statistical life by seventy to eighty percent. Our meta-regression analysis also identifies several sources for the wide heterogeneity found among reported VSL estimates.Value of statistical life; meta-regression analysis; selectivity bias

The importance of fungal pathogens and antifungal coatings in medical device infections

In recent years, increasing evidence has been collated on the contributions of fungal species, particularly Candida, to medical device infections. Fungal species can form biofilms by themselves or by participating in polymicrobial biofilms with bacteria. Thus, there is a clear need for effective preventative measures, such as thin coatings that can be applied onto medical devices to stop the attachment, proliferation, and formation of device-associated biofilms. However, fungi being eukaryotes, the challenge is greater than for bacterial infections because antifungal agents are often toxic towards eukaryotic host cells. Whilst there is extensive literature on antibacterial coatings, a far lesser body of literature exists on surfaces or coatings that prevent attachment and biofilm formation on medical devices by fungal pathogens. Here we review strategies for the design and fabrication of medical devices with antifungal surfaces. We also survey the microbiology literature on fundamental mechanisms by which fungi attach and spread on natural and synthetic surfaces. Research in this field requires close collaboration between biomaterials scientists, microbiologists and clinicians; we consider progress in the molecular understanding of fungal recognition of, and attachment to, suitable surfaces, and of ensuing metabolic changes, to be essential for designing rational approaches towards effective antifungal coatings, rather than empirical trial of coatings.Carla Giles, Stephanie J.Lamont-Friedrich, Thomas D.Michl, Hans J.Griesser, Bryan R.Coa

TCF21 hypermethylation regulates renal tumor cell clonogenic proliferation and migration

We recently identified hypermethylation at the gene promoter of transcription factor 21 (TCF21) in clear cell sarcoma of the kidney (CCSK), a rare pediatric renal tumor. TCF21 is a transcription factor involved in tubular epithelial development of the kidney and is a candidate tumor suppressor. As there are no in vitro models of CCSK, we employed a well-established clear cell renal cell carcinoma (ccRCC) cell line, 786-O, which also manifests high methylation at the TCF21 promoter, with consequent low TCF21 expression. The tumor suppressor function of TCF21 has not been functionally addressed in ccRCC cells; we aimed to explore the functional potential of TCF21 expression in ccRCC cells in vitro. 786-O clones stably transfected with either pBABE-TCF21-HA construct or pBABE vector alone were functionally analyzed. We found that ectopic expression of TCF21 in 786-O cells results in a trend toward decreased cell proliferation (not significant) and significantly decreased migration compared with mock-transfected 786-O cells. Although the number of colonies established in colony formation assays was not different between 786-O clones, colony size was significantly reduced in 786-O cells expressing TCF21. To investigate whether the changes in migration were due to epithelial-to-mesenchymal transition changes, we interrogated the expression of selected epithelial and mesenchymal markers. Although we observed upregulation of mRNA and protein levels of epithelial marker E-cadherin in clones overexpressing TCF21, this did not result in surface expression of E-cadherin as measured by fluorescence-activated cell sorting and immunofluorescence. Furthermore, mRNA expression of the mesenchymal markers vimentin (VIM) and SNAI1 was not significantly decreased in TCF21-expressing 786-O cells, while protein levels of VIM were markedly decreased. We conclude that re-expression of TCF21 in renal cancer cells that have silenced their endogenous TCF21 locus through hypermethylation results in reduced clonogenic proliferation, reduced migration, and reduced mesenchymal-like characteristics, suggesting a tumor suppressor function for transcription factor 21

Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture

A joint Fermi-GBM and Swift-BAT analysis of gravitational-wave candidates from the third gravitational-wave observing run

We present Fermi Gamma-ray Burst Monitor (Fermi-GBM) and Swift Burst Alert Telescope (Swift-BAT) searches for gamma-ray/X-ray counterparts to gravitational-wave (GW) candidate events identified during the third observing run of the Advanced LIGO and Advanced Virgo detectors. Using Fermi-GBM onboard triggers and subthreshold gamma-ray burst (GRB) candidates found in the Fermi-GBM ground analyses, the Targeted Search and the Untargeted Search, we investigate whether there are any coincident GRBs associated with the GWs. We also search the Swift-BAT rate data around the GW times to determine whether a GRB counterpart is present. No counterparts are found. Using both the Fermi-GBM Targeted Search and the Swift-BAT search, we calculate flux upper limits and present joint upper limits on the gamma-ray luminosity of each GW. Given these limits, we constrain theoretical models for the emission of gamma rays from binary black hole mergers

Effects of captopril and enalapril on renal function in elderly patients with chronic heart failure

OBJECTIVE: To compare the effects on renal function of captopril and enalapril in elderly patients with chronic heart failure. DESIGN: A multi-centre double-blind parallel-group comparison of the two angiotensin-converting enzyme (ACE) inhibitors, captopril (12.5 mg bid) and enalapril (2.5 mg bid). SUBJECTS: 80 elderly patients with chronic heart failure (41 in the captopril group, 39 in the enalapril group). MAIN OUTCOME MEASURES: The blood pressure and pulse rate response to the first dose of ACE inhibitor was assessed in all patients. Glomerular filtration rate (GFR) was measured radioisotopically by 99mTcDTPA or 51CrEDTA clearance after three and six months of each treatment. Subgroups were assessed for effective renal plasma flow (33 patients), exercise tolerance (25 patients) and by a symptom-oriented questionnaire (45 patients). RESULTS: No serious adverse effect on GFR was noticed. There was no significant difference between the two treatments in the mean baseline GFR or in changes from baseline at three and six months (captopril mean baseline GFR 49.6 ml min-1 1.76 m-2, enalapril 54.7 ml min-1 1.76 m-2; mean change (95% confidence interval) at three months captopril 12 ml min-1 (+3.0, +21.0), enalapril -2 ml min-1 (-13.0; +9.0); mean change at six months, captopril 3.7 ml min-1 (-6.7; +14.2), enalapril -6.0 ml min-1 (-21.0; +9.4). Significantly more patients given captopril had an improvement in GFR during the study period (26/31 compared with 20/31 enalapril-treated patients at three months, p = 0.0096, and 23/30 compared with 15/27 at six months, p = 0.021). There were no significant changes in effective renal plasma flow. Three patients treated with enalapril developed symptomatic hypotension within three days of starting treatment. Quality of life questionnaires revealed more gastrointestinal symptoms in the enalapril group (p = 0.039). CONCLUSIONS: Captopril seems marginally preferable to enalapril in the treatment of chronic heart failure in elderly patients

The construction of sex discriminant functions from a large collection of skulls of known sex

Abstract The suitability of the large collection of skulls of known sex (n?=357, n?=213), housed in the Department of Anthropology of the University of Coimbra, as a reference series for sex diagnosis from skulls, was investigated. This was done by calculating estimates for the maximum actual discriminatory value for samples being diagnosed. here called Dt max. The estimates for this statistic were found to be relatively low. Depending on the estimation procedure used, values of 1.68 and 1.64, were obtained, which correspond with theoretical percentages of correct classification of 79.8 and 79.3, respectively. An attempt was then made to investigate whether the low level of sexual dimorphism was due to heterogeneity in the series, which was therefore partitioned into Northern, Central and Southern groups according to place of birth. Only in the Southern group was the level of sexual dimorphism found to be slightly higher than in the whole series. The need for large well documented reference series for deriving techniques for sex determination from the skull and other skeletal elements is discussed and an extensive description of the methods emploved in this study is given

An acid test: Facile SI-ARGET-ATRP of methacrylic acid

Atom transfer radical polymerization (ATRP) of methacrylic acid (MAA) is challenging. Herein is reported a study of conditions for facile surface‐initiated ATRP by activator regenerated electron transfer (SI‐ARGET‐ATRP) growth of poly‐methacrylic acid (PMAA) chains from a plasma polymer surface bearing surface‐immobilized α‐bromoisobutyryl bromide, with no deoxygenation required. Factors that affect PMAA polymer growth off the surface under ARGET‐ATRP conditions are systematically investigated, such as monomer/catalyst ratio, solvent, and, most importantly, addition of salts and change of pH. While the concentrations of the copper catalyst and acid affect grafting, the most pronounced effect arises from the concentration of chloride ions. Adding 0.1 m NaCl and acidifying the reaction solution to pH 3 offers the best trade‐off between reaction rate and reproducibility; yielding ≈60 nm thick PMAA graft polymers in 1 h under ambient conditions. Using this easily scalable recipe and surface analysis, the grafted polymers are verified to be pure PMAA and the graft coatings to be homogenous across a substrate of 100 mm diameter.Thomas D. Michl, Dimitri Jung, Andrea Pertoldi, Anna Schulte, Piotr Mocny, Harm-Anton Klok, Holger Schönherr, Carla Giles, Hans J. Griesser, and Bryan R. Coa