A novel myeloid leukemia suppressor locus at human chromosome 5q13.3

Molecular mechanisms that underlie preleukemic myelodysplasia (MDS) and acute myelogenous leukemia (AML) are poorly understood. In MDS or AML with a refractory clinical course, more than 30% of patients have acquired interstitial or complete deletions of chromosome 5. The 5q13.3 chromosomal segment is commonly lost as the result of 5q deletion. Reciprocal and unbalanced translocations of 5q13.3 can also occur as sole anomalies associated with refractory AML or MDS. This study addresses the hypothesis that a critical gene at 5q13.3 functions either as a classical tumor suppressor or as a chromosomal translocation partner and contributes to leukemogenesis. ^ Previous studies from our laboratory delineated a critical region of loss to a 2.5–3.0Mb interval at 5q13.3 between microsatellite markers D5S672 and GATA-P18104. The critical region of loss was later resolved to an interval of approximately 2Mb between the markers D5S672 and D5S2029. I, then generated a long range physical map of yeast artificial chromosomes (YACs) and developed novel sequence tagged sites (STS). To enhance the resolution of this map, bacterial artificial chromosomes (BACs) were used to construct a triply linked contig across a 1 Mb interval. These BACs were used as probes for fluorescent in situ hybridization (FISH) on an AML cell line to define the 5q13.3 critical region. A 200kb BAC, 484a9, spans the translocation breakpoint in this cell line. A novel gene, SSDP2 (single stranded DNA binding protein), is disrupted at the breakpoint because its first four exons are encoded within 140kb of BAC 484a9. This finding suggests that SSDP2 is the critical gene at 5q13.3. ^ In addition, I made an observation that deletions of chromosome 5q13 co-segregate with loss of the chromosome 17p. In some cases the deletions result from unbalanced translocations between 5q13 and 17p13. It was confirmed that the TP53 gene is deleted in patients with 17p loss, and the remaining allele harbors somatic mutation. Thus, the genetic basis for the aggressive clinical course in AML and MDS may be caused by functional cooperation between deletion or disruption of the 5q13.3 critical gene and inactivation of TP53. ^

News media coverage of policies surrounding the HPV vaccine before and after Texas Governor Rick Perry's executive order, February 2006-February 2008

Objective. In June 2006, the first vaccine for human papillomavirus (HPV) was approved by the FDA and shortly after approval, the Advisory Committee on Immunization Practices (ACIP) voted to recommend the HPV vaccine for young girls. As a result of ACIP recommendations, state legislators introduced bills to mandate the vaccine. Policies related to public health issues, such as vaccination mandates, are often influenced by news coverage of these issues. News media, particularly in times of controversies, reinforce specific messages and plays an essential role in framing issues for the public. The objective of this study is to examine the quality, content, and scope of policies for the HPV vaccine before and after Texas Governor Rick Perry issued an executive order mandating the vaccine for middle school girls.^ Methods. The Lexis-Nexis database was used to identify 335 articles on HPV vaccination mandate policies that were published in U.S. newspapers from February 1, 2006 to February 2, 2008. The coding instrument captured information about article type, main news story concern, general information about HPV, HPV vaccine mandate policies, arguments for and against HPV vaccination mandates, arguments for and against the HPV vaccine, and sources of information.^ Results. Most news articles (82.4%) occurred after Governor Rick Perry issued an executive order mandating the HPV vaccine. Most articles mentioned that HPV is sexually transmitted (90.7%) and linked HPV infection to cervical cancer (96.1%). Only 63.9% of the articles reported that the HPV vaccine protects against types of HPV that cause cervical cancer and 18.8% of the articles reported that the vaccine protects against genital warts. Only 18.2% of the news articles presented a balanced argument regarding mandatory HPV vaccinations, and only 39.4% of the news articles presented a balanced argument for the HPV vaccine.^ Conclusions. Our study revealed that news coverage regarding mandating the HPV vaccine and issues related to the vaccine itself is biased, unbalanced, and incomplete. Since the public pays a great deal of attention to health in the media, it is essential that news stories are balanced, complete, and accurate. In order to ensure that future vaccination mandates are not covered in the same way the HPV vaccination was, public health officials, health care providers and scientists should work effectively with the media to ensure that balanced information is provided.^

The determinants of improvements in health outcomes and of cost reduction in hospital inpatient care

This study aims to address two research questions. First, ‘Can we identify factors that are determinants both of improved health outcomes and of reduced costs for hospitalized patients with one of six common diagnoses?’ Second, ‘Can we identify other factors that are determinants of improved health outcomes for such hospitalized patients but which are not associated with costs?’ The Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database from 2003 to 2006 was employed in this study. The total study sample consisted of hospitals which had at least 30 patients each year for the given diagnosis: 954 hospitals for acute myocardial infarction (AMI), 1552 hospitals for congestive heart failure (CHF), 1120 hospitals for stroke (STR), 1283 hospitals for gastrointestinal hemorrhage (GIH), 979 hospitals for hip fracture (HIP), and 1716 hospitals for pneumonia (PNE). This study used simultaneous equations models to investigate the determinants of improvement in health outcomes and of cost reduction in hospital inpatient care for these six common diagnoses. In addition, the study used instrumental variables and two-stage least squares random effect model for unbalanced panel data estimation. The study concluded that a few factors were determinants of high quality and low cost. Specifically, high specialty was the determinant of high quality and low costs for CHF patients; small hospital size was the determinant of high quality and low costs for AMI patients. Furthermore, CHF patients who were treated in Midwest, South, and West region hospitals had better health outcomes and lower hospital costs than patients who were treated in Northeast region hospitals. Gastrointestinal hemorrhage and pneumonia patients who were treated in South region hospitals also had better health outcomes and lower hospital costs than patients who were treated in Northeast region hospitals. This study found that six non-cost factors were related to health outcomes for a few diagnoses: hospital volume, percentage emergency room admissions for a given diagnosis, hospital competition, specialty, bed size, and hospital region.^

A Bayesian approach to estimating the intraclass correlation coefficient

A Bayesian approach to estimating the intraclass correlation coefficient was used for this research project. The background of the intraclass correlation coefficient, a summary of its standard estimators, and a review of basic Bayesian terminology and methodology were presented. The conditional posterior density of the intraclass correlation coefficient was then derived and estimation procedures related to this derivation were shown in detail. Three examples of applications of the conditional posterior density to specific data sets were also included. Two sets of simulation experiments were performed to compare the mean and mode of the conditional posterior density of the intraclass correlation coefficient to more traditional estimators. Non-Bayesian methods of estimation used were: the methods of analysis of variance and maximum likelihood for balanced data; and the methods of MIVQUE (Minimum Variance Quadratic Unbiased Estimation) and maximum likelihood for unbalanced data. The overall conclusion of this research project was that Bayesian estimates of the intraclass correlation coefficient can be appropriate, useful and practical alternatives to traditional methods of estimation. ^