Search

Background Adrenomedullin (AM) is a vasodilator peptide produced by endothelial and smooth muscle cells in the systemic and pulmonary circulation. It promotes angiogenesis and alveolar growth and has protective effects in the cardiovascular and respiratory systems. Adrenomedullin's role in human pulmonary vascular and alveolar development is unknown. Objective To test the hypothesis that AM is expressed during normal human lung development and that its expression changes with advancing gestational age by investigating the messenger RNA and protein expression of AM and its receptor components, calcitonin-receptorlike receptor (CRLR), receptor activity–modifying protein (RAMP)2, and RAMP3 in human fetal lung from 10 to 24 weeks of gestation. Methods The gene expression of AM, CRLR, RAMP2, and RAMP3 was measured with real-time reverse-transcription polymerase chain reaction. Adrenomedullin protein expression was measured with Western blot. Immunohistochemical analyses of sections of lung tissue were performed. Statistical analysis was performed using linear regression and one-way analysis of variance followed by the Tukey range test. Results Adrenomedullin, CRLR, RAMP2, and RAMP3 transcripts were expressed in the midgestation human fetal lung. The gene expression of AM, CRLR, and RAMP2 increased with increasing gestational age, whereas the gene expression of RAMP3 decreased. Adrenomedullin protein expression increased with increasing gestational age. Conclusion Adrenomedullin is expressed in the midgestation human fetal lung and its gene and protein expression increased with increasing gestational age, suggesting a role for AM in human lung development. Supporting this conclusion, the AM1 receptor components CRLR and RAMP2 gene expression also increased with increasing gestational age. Conversely, the expression of RAMP3, a structural component of the AM2 receptor, decreased with increasing gestational age, suggesting different functions for the AM receptors in human fetal lung, as it has been demonstrated in animal models. This speculation requires further investigation.

The National Institute of Standards and Technology (NIST) conducted an extensive investigation of the collapse of the three tall World Trade Center (WTC) buildings. A central part of this investigation was the reconstruction and understanding of the initiation and spread of the fires. This paper describes the reconstruction of the fires, the thermal environment they created within the buildings, and the raising of the temperatures of the structural components. NIST analyzed thousands of documents, interviews, photographs, and videos to obtain information on the layout of the floors and the progress of the fires. Experiments provided information on the factors likely to have determined the fire growth. Simulations using the Fire Dynamics Simulator gave good agreement with the fire spread as observed at the windows. Imposition of the probable thermal environment on the structural steel produced maps of the probable temperature profile of the steel as the fires progressed. For WTC 1 and WTC 2, even in the vicinity of the fires, it was unlikely that the columns and floor trusses with intact insulation heated to temperatures where significant loss of strength occurred. This was in part due to the short time between aircraft impact and building collapse. There were regions of the towers in which the loss of structural strength of floors and columns, whose insulation had been damaged by aircraft impact, was likely. For WTC 7, even though the insulation was intact, the long periods of heating resulted in floor components whose temperatures exceeded 600°C, but columns did not exceed 300°C.

The incidence of colorectal cancer (CRC) among Hispanics in the state of New Mexico has increased in the past decade while that among whites has declined significantly. Using the 2006 New Mexico Behavioral Risk Factor Sur- veillance System (BRFSS) survey, we compared CRC screening among Hispanics and whites by gender to examine the influence of demographic, socioeconomic, preventive health, and clinical measures on the utilization of CRC screening. Although we found no ethnic differences in the prevalence of current breast, cervical and cancer screening, Hispanics were less likely to be current with CRC screening than whites. These differences wereobserved acrossa range of socioeconomic and other explanatory measures and in both genders. Hispanics also had a higher prevalence of CRC- related risk factors than whites, including inactivity, obesity, and diabetes, and ranked lower for most socioeconomic measures. Adjusting for healthcare coverage, education, and income in logistic regression models eliminated the Hispanic- white differences in CRC screening among men, and sub- stantially reduced but did not eliminate screening differences among women. Innovative methods are needed to reach Hispanics to raise awareness of and participation in CRC screening. Because many CRC risk factors are potentially modifiable, appropriate cultural and linguistic interventions tailored to specific Hispanic subgroups and aimed at pro- moting CRC screening and reducing CRC risk factors may decrease ethnic disparities in CRC incidence.

BACKGROUND Emerging evidence indicates that testosterone (T), and not dihydrotestosterone (DHT), is the most relevant androgen that promotes carcinogenesis in the prostate. Steroid 5-alpha reductase type II (SRD5A2) catalyzes the irreversible conversion of T to DHT in male reproductive organs. Because the SRD5A2 gene is highly polymorphic at codon 89, two SRD5A2 isoforms are expressed that differ in Km and Vmax values. The more common and rapid catalytic isoform contains a valine residue at position 89; the slower-catalytic variant contains leucine at this position. METHODS Thirty-three men with early onset prostate cancer (PCa) were genotyped for the SRD5A2 V89L substitution and other polymorphisms in genes encoding receptors or enzymes that play important roles in pathways of steroid metabolism to ascertain if they were associated with standard clinical measures of disease progression at the time of diagnosis. RESULTS The expression of at least one SRD5A2 leucine allele in young men with PCa was associated with more significant disease at the time of presentation, as was defined by pretreatment PSA level, clinical staging and Gleason score when compared with affected subjects harboring the more common SRD5A2 valine variant. A dosage effect of a single leucine allele was evident in heterozygotes, as values of their clinical and pathological variables were consistently situated between the extremes of the homozygous V or L phenotypes. CONCLUSION The SRD5A2 leucine isoform appears to be acting in a dose-dependent manner as a significant disease-modifying factor in young men diagnosed with PCa. Prostate © 2008 Wiley-Liss, Inc.

Purpose Adolescents with cancer may access oncologic care from pediatric or adult medical centers, given overlapping age eligibility. However, some recent data suggest a benefit to adolescents with certain cancers when treated at pediatric centers or on pediatric protocols. We used a population-based registry to determine the site of care of children, adolescents, and young adults (age 0 to 24 years) with newly diagnosed cancer. Patients and Methods From the Utah Cancer Registry 1994 to 2000, new malignant cases in patients aged 0 to 24 years were chosen; data including diagnosis, home ZIP code and sites of oncologic care were abstracted. Distance between home ZIP code and Primary Children's Medical Center (PCMC; Salt Lake City, Utah), the state's sole site of pediatric oncology care, was determined. Results Sixty-six percent of Utah 15- to 19-year-olds with cancer were never seen by a PCMC oncologist. Even among this narrow age range, utilization of the pediatric center dropped with each additional year of age. Not unexpectedly, few of those with epithelial malignancies in this age group were seen at PCMC. But surprisingly, 47% of the older adolescents with leukemia, 66% with brain tumors, and 71% with lymphoma never saw a pediatric oncologist. After consideration of age and diagnosis, distance the patient lived from PCMC had a negligible effect on the likelihood of an adolescent being seen there. Conclusion The referral of adolescents with cancer to a pediatric oncology center diminishes greatly with age, and is moderately influenced by diagnosis and minimally by distance from center. Further study should investigate reasons for referral patterns, and impact on outcomes.

Lynch Syndrome (LS), an inherited genetic syndrome, predisposes to cancers such as colorectal and endometrial. However, the risk for endometrial cancer (EC) in women not affected by LS, but with a family history of cancer, is currently unknown. We examined the association between a family history of cancer and the risk for EC in non-LS patients.This population-based case-control study included 519 EC cases and 1015 age-matched controls and took place in Alberta, Canada between 2002 and 2006. Information about risk factors, including family history of cancer in first and second degree relatives, was ascertained via in-person interviews. Microsatellite instability (MSI) status of tumor tissue was assessed to determine involvement of DNA mismatch repair (MMR) genes.A first or second degree family history of uterine cancer was modestly associated with the risk for overall EC [odds ratio (OR), 1.3; 95% confidence interval (CI), 0.9, 1.9], and the risks were similar for MSI+cancer (OR=1.5, 95%CI=0.7, 3.3) and MSI- cancer (OR=1.3, 95%CI=0.8, 2.4). Although consistent, these associations were modest and not significant. In contrast, the risk for MSI+cancer was elevated with a reported family history of colorectal cancer (OR=1.4, 95%CI=1.0, 2.2), but not for MSI- cancer.A family history of uterine cancer may be modestly associated with EC risk in non-LS patients regardless of MSI status, suggesting that risk was not related to inherited defects in the MMR gene pathway. These results provide preliminary support for an EC-specific genetic syndrome.

We investigated comorbidities and endometrial cancer survival by ethnicity because Hispanic whites (HWs) have worse survival than non-Hispanic whites (NHWs).An endometrial cancer cohort (1992-2004) established with the Surveillance, Epidemiology and End Results-Medicare-linked database (n = 3,286) was followed through 2007. Endometrial cancer-specific and other cause mortality were evaluated with multivariate hazard ratios (mHRs).HWs were more likely than NHWs to have regional/distant disease (31.7 vs. 24.8 %), diabetes (31.7 vs. 11.0 %), and hypertension (49.4 vs. 37.6 %). HWs had poorer endometrial cancer-specific survival than NHWs (age-adjusted HR = 1.28; 95% CI 1.01-1.61), but not after adjustment for tumor characteristics and treatment (mHR = 1.02; 95% CI 0.81-1.29). In contrast, even after adjustment for cancer-related factors, other cause mortality in HWs was elevated (mHR = 1.27; 95% CI 1.01-1.59), but not after further adjustment for comorbid conditions (mHR = 1.07; 95% CI 0.85-1.35).Comorbidities, particularly diabetes, were more common in HWs than in NHWs and impacted other cause mortality. Improving diabetes management may be an effective means of improving other cause mortality. This may be particularly true for HWs, given their particularly high prevalence of diabetes.

This paper considers door assemblies that separate a fire environment from a protected space. It analyzes three methods of “feeling a door” on the protected side that can assist in determining the existence of a direct fire threat on the other side. These methods are: 1) feeling the door surface to determine whether or not it is at an elevated temperature; 2) feeling, smelling and visual inspection of the door edges to determine possible smoke flows from an adjacent fire environment; and 3) feeling the door-knob to determine whether or not it is at an elevated temperature. It is determined that a practical and effective strategy can be developed which uses all three methods to establish the existence of a fire threat without direct exposure to the fire environment. Of all methods discussed, the most reliable single indicator involves touching the base of the door-knob.

This paper presents the findings of the NIST World Trade Center Investigation describing the occupant evacuation of WTC 1 and WTC 2 on September 11, 2001. The egress system, including stairwells and elevators, is described along with the evacuation procedures. The population in WTC 1 and WTC 2 on September 11, 2001 at 8:46 a.m. is enumerated and described, where the background of the population was relevant to the subsequent evacuation, including training, experience, mobility status, among others. The progress of the evacuation of both towers is described in a quasi-chronological manner. A decedent analysis explores where occupants were located when each tower was attacked. Multiple regression models were built to explore the sources of evacuation initiation delay (why people did not immediately start to leave the building), as well as stairwell evacuation time (how long the average occupant spent in the stairwells per floor). Issues identified as contributing to either slowing or aiding the evacuation process were explored. Egress simulations provided context for estimating how long WTC 1 and WTC 2 would have taken to evacuate with different populations, using three different models, and subject to different assumptions of damage to the building.

Background Imatinib is a highly effective treatment for chronic myeloid leukemia. It was approved by the Food and Drug Administration in 2001 and thereafter rapidly became front-line therapy. This study characterized the prevailing chronic myeloid leukemia therapies in the United States and assessed the impact of imatinib on chronic myeloid leukemia survival and mortality rates in the general population. Methods Investigators with the National Cancer Institute's Patterns of Care study reviewed medical records and queried physicians regarding therapy for 423 patients with chronic myeloid leukemia diagnosed in 2003 who were randomly selected from cancer registries in the Surveillance, Epidemiology, and End Results Program. Characteristics associated with the receipt of imatinib were documented, as were survival differences between those who received imatinib and those who did not. Population-based data were used to assess chronic myeloid leukemia survival and mortality rates in time periods before and after the introduction of imatinib. Results Imatinib was administered to 76% of patients in the Patterns of Care study. Imatinib use was inversely associated with age: 90%, 75%, and 46% for patients ages 20 to 59 years, 60 to 79 years, and 80 or more years, respectively. Elderly patients who received imatinib survived significantly longer than those who did not. After adjusting for age, imatinib use did not vary significantly by race/ethnicity, socioeconomic status, urban/rural residence, presence of comorbid conditions, or insurance status. Overall, chronic myeloid leukemia survival in the Surveillance, Epidemiology, and End Results population improved, and mortality in the United States declined dramatically during the period when imatinib became widely available; these improvements diminished with increasing age. Conclusion Age disparities in treatment with imatinib likely contributed to worse survival for many elderly patients with chronic myeloid leukemia.

A first order model and computer program implementing previously developed procedures for estimating the speed, depth, and temperature of a fire produced gravity wave front in a corridor have been developed. The program has been incorporated into FPETOOL and adjustments made to accommodated fires that occur in the corridor or in a room adjacent to the corridor. Comparisons to test results are presented and show reasonable correlation. A users' guide is included.

Despite the problems of life in an ever-changing world, there is strong evidence that the future of the United States can be bright and that it can continue to offer leadership to the non-Communist and third-world nations. The population will continue to increase but at a more moderate rate. The size of the workforce will increase as more women take jobs. Pollution controls will become more effective and shortages will develop as controls are placed on nonrenewable resources. Environmental control and stewardship of resources will be recognized, but will not overcome the basic concern for economic survival and social need. Land use will continue to be a problem. A greater respect will be developed for ecology and for land as a critical resource; for the need of a strong economic base and the continuing need for leadership in the face of the growing needs and concerns of people.

The Central Area of Chicago presents a unique opportunity to carry out a carefully planned rapid transit system. The Chicago Urban Transportation District — formed to design and construct the Central Area Transit Project — subscribes to sound land-use policies and is actively working with the City and the private sector to encourage development of land areas adjacent to the proposed transit facilities to their highest and best use. In 1975, partially in response to the need to update the original transit plan, especially in the areas of land use and travel behavior and patterns, the District began a project specific transit planning effort called the Transportation Engineering Program (TEP). The TEP provides assistance in staging and sequencing the Core System, planning, and close coordination with other transportation planning.

Monolayers of adherent mononuclear leukocytes prepared from normal subjects and asthmatic children whose bronchodilator therapy did not include sympathomimetic drugs respond to relatively low concentrations of isoproterenol (ISO) and prostaglandin E 1 with increased intracellular cyclic adenosine monophosphate (cAMP) levels. The magnitude of in vitro responses to ISO is decreased by previous contact of the cells with ISO or other, orally effective, adrenergic drugs. The desensitization is rapid, concentration- and time-dependent, and is readily reversible after removal of the desensitizing drug. The phenomenon exhibits pharmacologic specificity. Cells in which the response to restimulation with ISO was decreased exhibited full sensitivity to prostaglandin E 1 . No differences in these behaviors were detected in cells from normal or asthmatic subjects. The results suggest that earlier observations reporting decreased responses to beta adrenergic stimulation in asthmatics may have been due to the treatment of these patients with sympathomimetic agents and not caused by a disease-related beta adrenergic receptor dysfunction.

Potential fire intensity and fire spread are acknowledged to be important considerations in designing buildings. Most investigations in this area have attempted to relate fire intensity to fuel load. The author submits that room geometry and influence fire intensity and that architectural layouts around room openings may influence fire spread by means of convestion.

The author develops a mode of radiant energy transfer for rectangular surfaces, regardless of size, and presents it in terms of configuration factor developed from graphic presentations that avoid cumbersome mathematics.

The author has derived a flow diagram of fire development in order to point out areas where current technology can be applied to the fire problem as well as areas where further research is required.

(1948). The effect of variation of rate on the recall by radio listeners of “straight” newscasts. Speech Monographs: Vol. 15, No. 2, pp. 173-180.