Haplotype differences for copy number variants in the 22q11.23 region among human populations: a pigmentation-based model for selective pressure.

Two gene clusters are tightly linked in a narrow region of chromosome 22q11.23: the macrophage migration inhibitory factor (MIF) gene family and the glutathione S-transferase theta class. Within 120 kb in this region, two 30-kb deletions reach high frequencies in human populations. This gives rise to four haplotypic arrangements, which modulate the number of genes in both families. The variable patterns of linkage disequilibrium (LD) between these copy number variants (CNVs) in diverse human populations remain poorly understood. We analyzed 2469 individuals belonging to 27 human populations with different ethnic origins. Then we correlated the genetic variability of 22q11.23 CNVs with environmental variables. We confirmed an increasing strength of LD from Africa to Asia and to Europe. Further, we highlighted strongly significant correlations between the frequency of one of the haplotypes and pigmentation-related variables: skin color (R2=0.675, P<0.001), distance from the equator (R2=0.454, P<0.001), UVA radiation (R2=0.439, P<0.001), and UVB radiation (R2=0.313, P=0.002). The fact that all MIF-related genes are retained on this haplotype and the evidences gleaned from experimental systems seem to agree with the role of MIF-related genes in melanogenesis. As such, we propose a model that explains the geographic and ethnic distribution of 22q11.23 CNVs among human populations, assuming that MIF-related gene dosage could be associated with adaptation to low UV radiatio

Cancer effects of formaldehyde: a proposal for an indoor air guideline value

Formaldehyde is a ubiquitous indoor air pollutant that is classified as “Carcinogenic to humans (Group 1)” (IARC, Formaldehyde, 2-butoxyethanol and 1-tert-butoxypropanol-2-ol. IARC monographs on the evaluation of carcinogenic risks to humans, vol 88. World Health Organization, Lyon, pp 39–325, 2006). For nasal cancer in rats, the exposure–response relationship is highly non-linear, supporting a no-observed-adverse-effect level (NOAEL) that allows setting a guideline value. Epidemiological studies reported no increased incidence of nasopharyngeal cancer in humans below a mean level of 1 ppm and peak levels below 4 ppm, consistent with results from rat studies. Rat studies indicate that cytotoxicity-induced cell proliferation (NOAEL at 1 ppm) is a key mechanism in development of nasal cancer. However, the linear unit risk approach that is based on conservative (“worst-case”) considerations is also used for risk characterization of formaldehyde exposures. Lymphohematopoietic malignancies are not observed consistently in animal studies and if caused by formaldehyde in humans, they are high-dose phenomenons with non-linear exposure–response relationships. Apparently, these diseases are not reported in epidemiological studies at peak exposures below 2 ppm and average exposures below 0.5 ppm. At the similar airborne exposure levels in rodents, the nasal cancer effect is much more prominent than lymphohematopoietic malignancies. Thus, prevention of nasal cancer is considered to prevent lymphohematopoietic malignancies. Departing from the rat studies, the guideline value of the WHO (Air quality guidelines for Europe, 2nd edn. World Health Organization, Regional Office for Europe, Copenhagen, pp 87–91, 2000), 0.08 ppm (0.1 mg m−3) formaldehyde, is considered preventive of carcinogenic effects in compliance with epidemiological findings

Electroweak parameters of the z0 resonance and the standard model

Contains fulltext : 124399.pdf (publisher's version ) (Open Access

Economic analysis of two-stage septic revision after total hip arthroplasty: What are the relevant costs for the hospital's orthopedic department?

© 2016 Kasch et al. Background: The number of septic total hip arthroplasty (THA) revisions is increasing continuously, placing a growing financial burden on hospitals. Orthopedic departments performing septic THA revisions have no basis for decision making regarding resource allocation as the costs of this procedure for the departments are unknown. It is widely assumed that septic THA procedures can only be performed at a loss for the department. Therefore, the purpose of this study was to investigate whether this assumption is true by performing a detailed analysis of the costs and revenues for two-stage septic THA revision. Methods: Patients who underwent revision THA for septic loosening in two sessions from January 2009 through March 2012 were included in this retrospective, consecutive cost study from the orthopedic department's point of view. We analyzed variable and case-fixed costs for septic revision THA with special regard to implantation and explantation stay. By using marginal costing approach we neglected hospital-fixed costs. Outcome measures include reimbursement and daily contribution margins. Results: The average direct costs (reimbursement) incurred for septic two-stage revision THA was €10,828 (€24,201). The difference in cost and contribution margins per day was significant (p &lt; .001 and p = 0.019) for ex- and implantation (€4147 vs. €6680 and €429 vs. €306) while length of stay and reimbursement were comparable. Conclusions: This is the first detailed analysis of the hospital department's cost for septic revision THA performed in two sessions. Disregarding hospital-fixed costs the included variable and case fixed-costs were covered by revenues. This study provides cost data, which will be guidance for health care decision makers