Common variants in signaling transcription-factor-binding sites drive phenotypic variability in red blood cell traits

Genome-wide association studies identify genomic variants associated with human traits and diseases. Most trait-associated variants are located within cell-type-specific enhancers, but the molecular mechanisms governing phenotypic variation are less well understood. Here, we show that many enhancer variants associated with red blood cell (RBC) traits map to enhancers that are co-bound by lineage-specific master transcription factors (MTFs) and signaling transcription factors (STFs) responsive to extracellular signals. The majority of enhancer variants reside on STF and not MTF motifs, perturbing DNA binding by various STFs (BMP/TGF-β-directed SMADs or WNT-induced TCFs) and affecting target gene expression. Analyses of engineered human blood cells and expression quantitative trait loci verify that disrupted STF binding leads to altered gene expression. Our results propose that the majority of the RBC-trait-associated variants that reside on transcription-factor-binding sequences fall in STF target sequences, suggesting that the phenotypic variation of RBC traits could stem from altered responsiveness to extracellular stimuli

Nurse staffing, direct nursing care hours and patient mortality in Taiwan: the longitudinal analysis of hospital nurse staffing and patient outcome study

<p>Abstract</p> <p>Background</p> <p>Studies over the past decades have shown an association between nurse staffing and patient outcomes, however, most of these studies were conducted in the West. Accordingly, the purpose of this study aimed to provide an overview of the research/evidence base which has clarified the relationship between nurse staffing and patient mortality of acute care hospital wards under a universal health insurance system and attempted to provide explanations for some of the phenomena that are unique in Taiwan.</p> <p>Methods</p> <p>Through stratified random sampling, a total of 108 wards selected from 32 hospitals in Taiwan were collected over a consecutive seven month period. The mixed effect logit model was used to explore the relationship between nurse staffing and patient mortality.</p> <p>Results</p> <p>The medians of direct-nursing-care-hour, and nurse manpower were 2.52 h, and 378 persons, respectively. The OR for death between the long direct-nursing-care-hour (> median) group and the short direct-nursing-care-hour (≦median) group was 0.393 (95% CI = [0.245, 0.617]). The OR for death between the high (> median) and the low (≦median) nurse manpower groups was 0.589 (95% CI = [0.381, 0.911]).</p> <p>Conclusions</p> <p>Findings from this study demonstrate an association of nurse staffing and patient mortality and are consistent with findings from similar studies. These findings have policy implications for strengthening the nursing profession, nurse staffing, and the hospital quality associated with nursing. Additional research is necessary to demonstrate adequate nurse staffing ratios of different wards in Taiwan.</p

Performance evaluation of inpatient service in Beijing: a horizontal comparison with risk adjustment based on Diagnosis Related Groups

<p>Abstract</p> <p>Background</p> <p>The medical performance evaluation, which provides a basis for rational decision-making, is an important part of medical service research. Current progress with health services reform in China is far from satisfactory, without sufficient regulation. To achieve better progress, an effective tool for evaluating medical performance needs to be established. In view of this, this study attempted to develop such a tool appropriate for the Chinese context.</p> <p>Methods</p> <p>Data was collected from the front pages of medical records (FPMR) of all large general public hospitals (21 hospitals) in the third and fourth quarter of 2007. Locally developed Diagnosis Related Groups (DRGs) were introduced as a tool for risk adjustment and performance evaluation indicators were established: Charge Efficiency Index (CEI), Time Efficiency Index (TEI) and inpatient mortality of low-risk group cases (IMLRG), to reflect respectively work efficiency and medical service quality. Using these indicators, the inpatient services' performance was horizontally compared among hospitals. Case-mix Index (CMI) was used to adjust efficiency indices and then produce adjusted CEI (aCEI) and adjusted TEI (aTEI). Poisson distribution analysis was used to test the statistical significance of the IMLRG differences between different hospitals.</p> <p>Results</p> <p>Using the aCEI, aTEI and IMLRG scores for the 21 hospitals, Hospital A and C had relatively good overall performance because their medical charges were lower, LOS shorter and IMLRG smaller. The performance of Hospital P and Q was the worst due to their relatively high charge level, long LOS and high IMLRG. Various performance problems also existed in the other hospitals.</p> <p>Conclusion</p> <p>It is possible to develop an accurate and easy to run performance evaluation system using Case-Mix as the tool for risk adjustment, choosing indicators close to consumers and managers, and utilizing routine report forms as the basic information source. To keep such a system running effectively, it is necessary to improve the reliability of clinical information and the risk-adjustment ability of Case-Mix.</p

Human Papillomavirus (HPV) 16 E6 Variants in Tonsillar Cancer in Comparison to Those in Cervical Cancer in Stockholm, Sweden

Background: Human papillomavirus (HPV), especially HPV16, is associated with the development of both cervical and tonsillar cancer and intratype variants in the amino acid sequence of the HPV16 E6 oncoprotein have been demonstrated to be associated with viral persistence and cancer lesions. For this reason the presence of HPV16 E6 variants in tonsillar squamous cell carcinoma (TSCC) in cervical cancer (CC), as well as in cervical samples (CS), were explored. Methods: HPV16 E6 was sequenced in 108 TSCC and 52 CC samples from patients diagnosed 2000–2008 in the County of Stockholm, and in 51 CS from young women attending a youth health center in Stockholm. Results: The rare E6 variant R10G was relatively frequent (19%) in TSCC, absent in CC and infrequent (4%) in CS, while the well-known L83V variant was common in TSCC (40%), CC (31%), and CS (29%). The difference for R10G was significant between TSCC and CC (p = 0.0003), as well as between TSCC and CS (p = 0.009). The HPV16 European phylogenetic lineage and its derivatives dominated in all samples (.90%). Conclusion: The relatively high frequency of the R10G variant in TSCC, as compared to what has been found in CC both in the present study as well as in several other studies in different countries, may indicate a difference between TSCC and CC with regard to tumor induction and development. Alternatively, there could be differences with regard to the oral an

Interaction between polymorphisms of the Human Leukocyte Antigen and HPV-16 Variants on the risk of invasive cervical cancer

<p>Abstract</p> <p>Background</p> <p>Persistent infection with oncogenic types of human papillomavirus (HPV) is the major risk factor for invasive cervical cancer (ICC), and non-European variants of HPV-16 are associated with an increased risk of persistence and ICC. HLA class II polymorphisms are also associated with genetic susceptibility to ICC. Our aim is to verify if these associations are influenced by HPV-16 variability.</p> <p>Methods</p> <p>We characterized HPV-16 variants by PCR in 107 ICC cases, which were typed for <it>HLA-DQA1</it>, <it>DRB1 </it>and <it>DQB1 </it>genes and compared to 257 controls. We measured the magnitude of associations by logistic regression analysis.</p> <p>Results</p> <p>European (E), Asian-American (AA) and African (Af) variants were identified. Here we show that inverse association between <it>DQB1*05 </it>(adjusted odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.39–1.12]) and HPV-16 positive ICC in our previous report was mostly attributable to AA variant carriers (OR = 0.27; 95%CI: 0.10–0.75). We observed similar proportions of <it>HLA DRB1*1302 </it>carriers in E-P positive cases and controls, but interestingly, this allele was not found in AA cases (p = 0.03, Fisher exact test). A positive association with <it>DRB1*15 </it>was observed in both groups of women harboring either E (OR = 2.99; 95% CI: 1.13–7.86) or AA variants (OR = 2.34; 95% CI: 1.00–5.46). There was an inverse association between <it>DRB1*04 </it>and ICC among women with HPV-16 carrying the 350T [83L] single nucleotide polymorphism in the <it>E6 </it>gene (OR = 0.27; 95% CI: 0.08–0.96). An inverse association between <it>DQB1*05 </it>and cases carrying 350G (83V) variants was also found (OR = 0.37; 95% CI: 0.15–0.89).</p> <p>Conclusion</p> <p>Our results suggest that the association between HLA polymorphism and risk of ICC might be influenced by the distribution of HPV-16 variants.</p

Institutional risk factors for norovirus outbreaks in Hong Kong elderly homes: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Most of the institutional outbreaks of norovirus in Hong Kong occur in elderly homes, the proportion being 69% in 2006. Residents in elderly homes are a special population seriously affected by norovirus infections, it is necessary to investigate the risk factors of the norovirus outbreaks in Hong Kong elderly homes at the facility level.</p> <p>Methods</p> <p>A cohort of 748 elderly homes was followed up from January 2005 to December 2007; each elderly home was treated as one observation unit and the outcome event was the norovirus outbreak. Cox regression models were fitted to estimate the rate ratio (RR) and 95% confidence interval (CI) for the potential risk factors.</p> <p>Results</p> <p>A total of 276 norovirus outbreaks were confirmed during the study period; the outbreak rate was 12.2 (95% CI: 9.9-14.6) per 100 home-years; elderly homes with a larger capacity (RR = 1.4, 95% CI: 1.3-1.5 (per 30-resident increment)), a higher staff-to-resident ratio (RR = 1.2, 95% CI: 1.1-1.3 (per 1/30 increment) and better wheelchair accessibility (RR = 2.0, 95% CI: 1.3-3.2) were found to have an elevated norovirus outbreak rate in Hong Kong elderly homes; Elderly homes with partitions between beds had a lower rate of norovirus outbreaks (RR = 0.6, 95% CI: 0.4-0.8).</p> <p>Conclusions</p> <p>Elderly home capacity, staff-to-resident ratio and wheelchair accessibility were risk factors for norovirus outbreaks in Hong Kong elderly homes. Partitions between beds were a protective factor of norovirus outbreaks. These results should be considered in the infection control in Hong Kong elderly homes.</p

A Review of the fossil record of turtles of the clade Baenidae

The fossil record of the turtle clade Baenidae ranges from the Early Cretaceous (Aptian—Albian) to the Eocene. The group is present throughout North America during the Early Cretaceous, but is restricted to the western portions of the continents in the Late Cretaceous and Paleogene. No credible remains of the clade have been reported outside of North America to date. Baenids were warmadapted freshwater aquatic turtles that supported high levels of diversity at times through niche partitioning, particularly by adapting to a broad range of dietary preferences ranging from omnivorous to molluscivorous. Current phylogenies place Baenidae near the split of crown-group Testudines. Within Baenidae three more inclusive, named clades are recognized: Baenodda, Palatobaeninae and Eubaeninae. A taxonomic review of the group concludes that of 49 named taxa, 30 are nomina valida, 12 are nomina invalida and 7 are nomina dubia