Assessing the Environmental Protection Agency's guidelines for cumulative risk assessment: Are they suitable for state agencies and EPA regional offices?

In the field of health risk analysis, cumulative risk assessment (CRA) is a necessary, although undeniably more complex approach to understanding the mixture of stressors, whether chemical or psychosocial, that exist in our environment, in all the pathways through which the chemicals may evolve—air, soil, or water, as well as the accumulation of these exposures over time. Related, or attached to the developing awareness of scientists understanding this mix of combined health effects is the burgeoning of the environmental justice movement, in which educated community advocates and even affected community members have called attention to evidence of a higher pollution burden in minority and/or lower SES communities. The intention of this paper is to 1) examine the development and understanding of CRA, primarily by the U.S. Environmental Protection Agency; 2) to assess several states agencies and some EPA regional offices' interpretation of CRA, again based primarily on EPA guidance, and 3) to analyze how CRA might be refined in its implementation—giving some cues as to how the EPA may more effectively interact with communities interested in CRA.^

THE MULTIPLE LOCATION TIME WEIGHTED INDEX: USING PATIENT ACTIVITY SPACES TO CALCULATE PRIMARY CARE SERVICE AREAS

Geographic health planning analyses, such as service area calculations, are hampered by a lack of patient-specific geographic data. Using the limited patient address information in patient management systems, planners analyze patient origin based on home address. But activity space research done sparingly in public health and extensively in non-health related arenas uses multiple addresses per person when analyzing accessibility. Also, health care access research has shown that there are many non-geographic factors that influence choice of provider. Most planning methods, however, overlook non-geographic factors influencing choice of provider, and the limited data mean the analyses can only be related to home address. This research attempted to determine to what extent geography plays a part in patient choice of provider and to determine if activity space data can be used to calculate service areas for primary care providers. During Spring 2008, a convenience sample of 384 patients of a locally-funded Community Health Center in Houston, Texas, completed a survey that asked about what factors are important when he or she selects a health care provider. A subset of this group (336) also completed an activity space log that captured location and time data on the places where the patient regularly goes. Survey results indicate that for this patient population, geography plays a role in their choice of health care provider, but it is not the most important reason for choosing a provider. Other factors for choosing a health care provider such as the provider offering “free or low cost visits”, meeting “all of the patient’s health care needs”, and seeing “the patient quickly” were all ranked higher than geographic reasons. Analysis of the patient activity locations shows that activity spaces can be used to create service areas for a single primary care provider. Weighted activity-space-based service areas have the potential to include more patients in the service area since more than one location per patient is used. Further analysis of the logs shows that a reduced set of locations by time and type could be used for this methodology, facilitating ongoing data collection for activity-space-based planning efforts.

Absolute quantitative real-time polymerase chain reaction for the measurement of human papillomavirus E7 mRNA in cervical cytobrush specimens.

BACKGROUND: Few reports of the utilization of an accurate, cost-effective means for measuring HPV oncogene transcripts have been published. Several papers have reported the use of relative quantitation or more expensive Taqman methods. Here, we report a method of absolute quantitative real-time PCR utilizing SYBR-green fluorescence for the measurement of HPV E7 expression in cervical cytobrush specimens. RESULTS: The construction of a standard curve based on the serial dilution of an E7-containing plasmid was the key for being able to accurately compare measurements between cervical samples. The assay was highly reproducible with an overall coefficient of variation of 10.4%. CONCLUSION: The use of highly reproducible and accurate SYBR-based real-time polymerase chain reaction (PCR) assays instead of performing Taqman-type assays allows low-cost, high-throughput analysis of viral mRNA expression. The development of such assays will help in refining the current screening programs for HPV-related carcinomas.

Health-related quality of life and survival in liver transplant candidates.

Health-related quality of life (HRQOL) is an important measure of the effects of chronic liver disease in affected patients that helps guide interventions to improve well-being. However, the relationship between HRQOL and survival in liver transplant candidates remains unclear. We examined whether the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the Short Form 36 (SF-36) Health Survey were associated with survival in liver transplant candidates. We administered the SF-36 questionnaire (version 2.0) to patients in the Pulmonary Vascular Complications of Liver Disease study, a multicenter prospective cohort of patients evaluated for liver transplantation in 7 academic centers in the United States between 2003 and 2006. Cox proportional hazards models were used with death as the primary outcome and adjustment for liver transplantation as a time-varying covariate. The mean age of the 252 participants was 54 +/- 10 years, 64% were male, and 94% were white. During the 422 person years of follow-up, 147 patients (58%) were listed, 75 patients (30%) underwent transplantation, 49 patients (19%) died, and 3 patients were lost to follow-up. Lower baseline PCS scores were associated with an increased mortality rate despite adjustments for age, gender, Model for End-Stage Liver Disease score, and liver transplantation (P for the trend = 0.0001). The MCS score was not associated with mortality (P for the trend = 0.53). In conclusion, PCS significantly predicts survival in liver transplant candidates, and interventions directed toward improving the physical status may be helpful in improving outcomes in liver transplant candidates.

EFFECT OF ANCHORING ON PERCEIVED AMNIOCENTESIS RELATED MISCARRIAGE RISK WITHIN A LATINA POPULATION

Most recognized pregnancies are completed without difficulty, yet there is always a 3-5% background risk to have a child with a birth defect. Amniocentesis, the most common type of prenatal diagnostic test, is used to detect chromosomal abnormalities, such as Down syndrome. Amniocentesis is associated with a risk of complications that can lead to a miscarriage, which is typically quoted to be between 1 in 300 and 1 in 500. Amniocentesis uptake rates are typically lowest within the Latina community, and although the factors related to this have been studied before, no specific conclusions have been reached. The general population has a difficult time interpreting risks, as individuals vary in numeracy skills as well as personal factors that can influence risk perception. A recent study by Nuccio (2010) investigated the effect of anchoring, where a patient’s prior knowledge about a subject affects her risk perception, and how it relates to the uptake of amniocentesis within a diverse population in Houston, TX. The effect of anchoring on perceived amniocentesis-related miscarriage risk within the Latina population has not been previously examined. A two-part questionnaire was completed by 96 Latinas receiving prenatal genetic counseling due to an increased risk to have a baby with a chromosome abnormality at various clinics in Houston, TX. The genetic counselor involved in the session completed a separate survey. This population was largely unfamiliar with surveys, risk figures, and prenatal testing. Only one individual was able to quantify the risk associated with amniocentesis prior to the genetic counseling. While the majority of women felt that the risk association with amniocentesis is very low to average, only 7 individuals pursued diagnostic testing through amniocentesis. Most women did not feel like the information gained from an amniocentesis would change the management of their pregnancy and/or they did not believe that their baby had a problem. Women, regardless of ethnicity, deserve individualized genetic counseling sessions that cater to their needs and desires regarding their prenatal care.

What's Working in Family-Based Services--or, What's Left to Believe in During a Time of Such Doubt?

This article is a qualitative, personal report from the field, designed to highlight current developments in family-based theory and practice that bring hopefulness to workers and clients. The author, an experienced human services consultant and family therapist, draws from his recent experience in a number of states to identify exemplars of practice in the following areas: integrative theory building, functional family assessment, systems change in regard to inter-agency coordination and foster care, community building in low income neighborhoods, developing humility as helpers, and addressing issues of hope and spirituality with clients and with co-workers. Given the turbulent and hostile political environment for family-based services, this article challenges us to remember that effectiveness in helping others is directly related to our feelings of hopefulness about ourselves and our world.

A urokinase receptor promoter element (-152/-135) bound with an AP-2-alpha-related protein and SP1 is required for the induction of gene expression by PMA and SRC

The urokinase-type plasminogen activator receptor (u-PAR) promotes extracellular matrix degradation, invasion and metastasis. A first objective of this dissertation was to identify cis-elements and trans-acting factors activating u-PAR gene expression through a previously footprinted (–148/–124) promoter region. Mobility shifting experiments on nuclear extracts of a high u-PAR-expressing colon cancer cell line (RKO) indicated Sp1, Sp3 and a factor similar to, but distinct from, AP-2α bound to an oligonucleotide spanning –152/–135. Mutations preventing the binding of the AP-2α-related factor reduced u-PAR promoter activity. In RKO, the expression of a dominant negative AP-2 (AP-2αB) diminished u-PAR promoter activity, protein and u-PAR mediated laminin degradation. Conversely, u-PAR promoter activity in low u-PAR-expressing GEO cells was increased by AP-2αA expression. PMA treatment, which induces u-PAR expression, caused an increased amount of the AP-2α-related factor-containing complex in GEO, and mutations preventing AP-2α-like and Sp1/Sp3 binding reduced the u-PAR promoter stimulation by PMA. In resected colon cancers, u-PAR protein amounts were related to the amount of the AP-2α-related factor-containing complex. In conclusion, constitutive and PMA- inducible u-PAR gene expression and -proteolysis are mediated partly through transactivation via a promoter sequence (–152/435) bound with an AP-2α-related factor and Sp1/Sp3. ^ A second interest of this dissertation was to determine if a constitutively active Src regulates the transcription of the u-PAR gene, since c-src expression increases invasion in colon cancer. Increased u-PAR protein and laminin degradation paralleling elevated Src activity was evident in SW480 colon cancer cells stably expressing a constitutively active Src (Y- c-src527F). Nuclear run-on experiments indicated that this was due largely to transcriptional activation. While transient transfection of SW480 cells with Y-c-src527F induced a u-PAR-CAT-reporter, mutations preventing Sp1-binding to promoter region –152/435 abolished this induction. Mobility shift assays revealed increased Sp1 binding to region –152/135 with nuclear extracts of Src-transfected SW480 cells. Finally, the amounts of endogenous u-PAR in resected colon cancers significantly correlated with Src-activity. These data suggest that u-PAR gene expression and proteolysis are regulated by Src, this requiring the promoter region (–152/–135) bound with Sp1, thus, demonstrating for the first time that transcription factor Sp1 is a downstream effector of Src. ^

ALTERATIONS IN HYPOTHALAMIC CONTENT OF LUTEINIZING HORMONE RELEASING HORMONE AND PITUITARY RESPONSIVENESS ASSOCIATED WITH TESTICULAR REGRESSION INDUCED BY PINEAL RELATED TREATMENTS IN THE GOLDEN HAMSTER

The adult male golden hamster, when exposed to blinding (BL), short photoperiod (SP), or daily melatonin injections (MEL) demonstrates dramatic reproductive collapse. This collapse can be blocked by removal of the pineal gland prior to treatment. Reproductive collapse is characterized by a dramatic decrease in both testicular weight and serum gonadotropin titers. The present study was designed to examine the interactions of the hypothalamus and pituitary gland during testicular regression, and to specifically compare and contrast changes caused by the three commonly employed methods of inducing testicular regression (BL,SP,MEL). Hypothalamic LHRH content was altered by all three treatments. There was an initial increase in content of LHRH that occurred concomitantly with the decreased serum gonadotropin titers, followed by a precipitous decline in LHRH content which reflected the rapid increases in both serum LH and FSH which occur during spontaneous testicular recrudescence. In vitro pituitary responsiveness was altered by all three treatments: there was a decline in basal and maximally stimulatable release of both LH and FSH which paralleled the fall of serum gonadotropins. During recrudescence both basal and maximal release dramatically increased in a manner comparable to serum hormone levels. While all three treatments were equally effective in their ability to induce changes at all levels of the endocrine system, there were important temporal differences in the effects of the various treatments. Melatonin injections induced the most rapid changes in endocrine parameters, followed by exposure to short photoperiod. Blinding required the most time to induce the same changes. This study has demonstrated that pineal-mediated testicular regression is a process which involves dynamic changes in multiply-dependent endocrine relationships, and proper evaluation of these changes must be performed with specific temporal events in mind. ^

Is sensitization to stimulants time dependent and mediated via NMDA receptors?

Chronic administration of psychomotor stimulants has been reported to produce behavioral sensitization to its effects on motor activity. This adaptation may be related to the pathophysiology of recurrent psychiatric disorders. Since disturbances in circadian rhythms are also found in many of these disorders, the relationship between sensitization and chronobiological factors became of interest. Therefore, a computerized monitoring system investigated the following: whether repeated exposure to methylphenidate (MPD) and amphetamine (AMP) could produce sensitization to its locomotor effects in the rat; whether sensitization to MPD and AMP was dependent on the circadian time of drug administration; whether the baseline levels of locomotor activity would be effected by repeated exposure to MPD and AMP; whether the expression of a sensitized response could be affected by the photoperiod; and whether MK-801, a non-competitive NMDA antagonist, could disrupt the development of sensitization to MPD. Dawley rats were housed in test cages and motor activity was recorded continuously for 16 days. The first 2 days served as baseline for each rat, and on day 3 each rat received a saline injection. The locomotor response to 0.6, 2.5, or 10 mg/kg of MPD was tested on day 4, followed by five days of single injections of 2.5 mg/kg MPD (days 5–9). After five days without injection (days 10–14) rats were re-challenged (day 15) with the same doses they received on day 4. There were three separate dose groups ran at four different times of administration, 08:00, 14:00, 20:00, or 02:00 (i.e. 12 groups). The same protocol was conducted with AMP with the doses of 0.3, 0.6, and 1.2 mg/kg given on day 4 and 15, and 0.6 mg/kg AMP as the repeated dose on days 5 to 9. In the second set of experiments only sensitization to MPD was investigated. The expression of the sensitized response was dose-dependent and mainly observed with challenge of the lower dose groups. The development of sensitization to MPD and ANT was differentially time-dependent. For MPD, the most robust sensitization occurred during the light phase, with no sensitization during the middle of the dark phase. (Abstract shortened by UMI.) ^

Hypertension control and related variables among urban and rural adults in Taiwan

Literature on hypertension treatment has demonstrated that a healthy life style is one of the best strategies for hypertension control. In exploring the mechanisms of behavioral change for hypertension control, a comprehensive study based on the Transtheoretical Model was carried out in Taiwan during the summer of 2000 with a sample of 350 hypertensive adults living in Taipei urban and rural areas. ^ The relationships among stages of change, processes of change and demographic factors were analyzed for six health behaviors—low fat food consumption, alcohol use, smoking, physical activity, weight control, and routine blood pressure checkups. In addition, differences were assessed between urban and rural populations in changing their behavior for hypertension control. ^ The results showed that rural populations had more difficulties than urban populations in avoiding smoking and engaging in physical activity, and the processes of change being used by urban populations were significantly greater than rural populations. The study findings support a strong association between processes and stages of change. ^ Individuals who use more processes of change will be more inclined to move from precontemplation stage to maintenance stage. Counterconditioning, which is the substitution of alternatives for the problem behaviors, in this study, significantly helped people to change diet, engage in physical activity, and check blood pressure regularly. For example, counterconditioning is eating more vegetables instead of meat, or engaging in physical activity as a time to relax rather than another task to accomplish. ^ In addition, self-reevaluation was the most important process for helping people to engage in physical activity; and social liberation was the most important process for changing diet behavior. The findings in this study may be applied to improve health behaviors among rural populations with low income and low education; however, at the same time, the obesity problems among urban populations should be prevented to control hypertension in Taiwan. ^

Exploring parents' memories of their child's death related sensory experiences as a dimension of grieving

Little is known about how dying children and their parents experience death. Dying children have reported death related sensory experiences (DRSEs), defined as seeing or hearing someone or something not visible or audible to others, associated with dying. Although parents report that they and the dying child benefit from these experiences, healthcare providers often unknowingly dismiss them. The aims of this phenomenological inquiry were to describe children's DRSEs and their meaning from the parents' perspectives. Four fathers and six mothers of African American, Caucasian, or Hispanic ethnicity, all Christian, ranging in age from 35 to 59 years, whose child died 23 to 52 months prior and was treated at a children's cancer center, were interviewed in the home or hospital setting of their choice. Children's ages at the time of their death ranged from 4 to 13 years. A modification of van Kaarn's phenomenological method of analysis was used to analyze data. Themes emerging from the data for the first aim were: perceiving someone or something from a spiritual realm others could not, expressing awareness tempered by parental reactions, and embracing transcendence. Themes emerging from the data for the second aim were: spiritual beings prepared child; child revealed reality, preparing parents; and child transcended wholly, easing parents' grief. Post-interview surveys revealed that parents found participating in this study a "very positive" or "positive" experience, particularly being able to tell the story of their child. Children's DRSEs have clinical implications for all who provide care near the end of life. Informing parents of DRSEs, cautioning that not all dying children express them, may help parents to anticipate this phenomenon, which may decrease anxiety when their child expresses them, increasing the opportunity for open dialogue between parent and child about dying and death, and decrease regrets associated with being unreceptive to their child's expressions of death awareness. Validating a child's DRSE can have profound effects on bereaved parents. Examining DRSEs from the child's perspective and the influence of informing parents of DRSEs on the dying experience of the child and the parental grieving process are recommended. ^

The multiple location time weighted index: Using patient activity spaces to calculate primary care service areas

Geographic health planning analyses, such as service area calculations, are hampered by a lack of patient-specific geographic data. Using the limited patient address information in patient management systems, planners analyze patient origin based on home address. But activity space research done sparingly in public health and extensively in non-health related arenas uses multiple addresses per person when analyzing accessibility. Also, health care access research has shown that there are many non-geographic factors that influence choice of provider. Most planning methods, however, overlook non-geographic factors influencing choice of provider, and the limited data mean the analyses can only be related to home address. This research attempted to determine to what extent geography plays a part in patient choice of provider and to determine if activity space data can be used to calculate service areas for primary care providers. ^ During Spring 2008, a convenience sample of 384 patients of a locally-funded Community Health Center in Houston, Texas, completed a survey that asked about what factors are important when he or she selects a health care provider. A subset of this group (336) also completed an activity space log that captured location and time data on the places where the patient regularly goes. ^ Survey results indicate that for this patient population, geography plays a role in their choice of health care provider, but it is not the most important reason for choosing a provider. Other factors for choosing a health care provider such as the provider offering "free or low cost visits", meeting "all of the patient's health care needs", and seeing "the patient quickly" were all ranked higher than geographic reasons. ^ Analysis of the patient activity locations shows that activity spaces can be used to create service areas for a single primary care provider. Weighted activity-space-based service areas have the potential to include more patients in the service area since more than one location per patient is used. Further analysis of the logs shows that a reduced set of locations by time and type could be used for this methodology, facilitating ongoing data collection for activity-space-based planning efforts. ^

If we call them, will they change? Feasibility of a telephone adaptation of motivational interviewing aimed at parents to reduce television time among 2nd and 4th grade children

Television viewing is a sedentary behavior that is modifiable. Reducing media-related behaviors via parent-focused interventions may hold promise for decreasing childhood obesity. This feasibility study examines a novel parent-centered brief telephone-delivered Motivational Enhancement Interview (MEI) to encourage parents of 2nd and 4th graders to set a rules limiting TV time or remove the TV from the child's bedroom. This quasi-experimental sub-study was part of the larger CATCH: En Vivo pilot study conducted in a Hispanic population in the Texas Rio Grande Valley. Parents in the MEI condition were contacted via telephone and encouraged to meet the American Academy of Pediatrics (AAP) recommended 2 hours per day or less of TV. Unconditional logistic regression was used to analyze the data. At post-test, 85% of parents of 4th graders in the MEI group (compared to 71% at pre-test) reported having a rule limiting TV time. The adjusted odds ratio for the MEI group compared to the control group was 3.88, 95% CI (0.72-20.99). At pre-test, 63.16% of 2nd graders had a television in their bedrooms. The 2nd grade MEI intervention reduced that number to 41.03% (OR=0.25, 95%CI (0.08-0.82)). This first look at using MEI to target parents of children to modify TV behavior presents evidence on a promising strategy for modifying children's home media environment and warrants further investigation. ^

Factors affecting ozone related asthma responses among middle school students with asthma

Outdoor environmental risk factors for asthma have been extensively researched, even though the majority of a person's daily activity occurs indoors. There is limited evidence linking personal exposure concentrations of ozone, pollen, mold, temperature, and humidity to childhood asthma. ^ The current study consisted of a secondary, more complex analysis of the data from the Houston Air Toxics and Asthma in Children (ATAC) Study to further investigate the association of personal ozone exposure on asthma outcome variability among middle school children with asthma. The ATAC Study primarily investigated the association between selected oxygenated air toxics and indicators of asthma variability (PEFR, FEV1, asthma symptoms, and rescue medication usage) among 30 labile and persistent Houston middle-school children with diagnosed asthma. This panel study used a repeated measurements design of four separate 10-day sampling periods that extended over a 20 month period. The secondary analysis included aggregate regression models that were constructed with two different estimates of ozone exposure (daily maximum hourly outdoor concentration and daily maximum hourly personal exposure), with three different estimates of personal environmental temperature and humidity exposures (daily average, intraday difference, and interday difference), and for thee different time periods [same day of exposure (lag 0), one day after initial exposure (lag 1), and two days after initial exposure (lag 2)]. ^ Overall, the models using daily maximum hourly personal ozone exposures in combination with intraday and interday personal temperature and humidity differences produced more significant plausible associations than models using daily maximum hourly personal ozone exposures with personal average temperature and humidity exposures. Significant associations were identified between daily maximum hourly personal ozone exposure and clinical indicators of asthma variability. The increasing effect on rescue medication usage from daily maximum hourly personal ozone exposure were identified as soon as the same day of exposure (lag 0; p=0.0072), and the same effects were delayed until the second next day (lag 2; p= 0.0026). The increasing effect on asthma symptoms were identified on the second next day after initial exposure (lag 2; p= 0.0024). There was a consistent inverse relationship between personal relative humidity exposure and indicators of asthma variability. Decreasing effects on daily FEV1 variability from personal relative humidity exposure were identified on the same day of exposure (lag 0; p= 0.034), increasing effects on morning PEFR were identified on the next day after initial exposure (lag 1; p= 0.0001), and decreasing effects on overnight PEFR variability were identified on the second next day after the initial exposure (lag 2; p= 0.007). With the conclusion of this research, there are opportunities for future similar studies in the preventive management of asthma in children living in high-ozone areas.^

Factors related to employment among chronically mentally ill patients

A descriptive study of demographic and psychosocial factors believed to be associated with employment was carried out through face-to-face interviews with 417 chronically mentally-ill patients. Subjects had been hospitalized a minimum of two times for psychiatric treatment, had been discharged from at least one of these hospitalizations in the two years prior to the study, and were currently residing within a specific community mental health center catchment area in Texas. The study group ranged in age from 16 to 68 years and over one-half had chart diagnoses of schizophrenia.^ A structured interview was developed which addressed current employment status, length of current employment, job title of current or last job, and detailed work history for the prior five years. Four measures of social support were included in the interview. Each subject was asked to identify one recent work and one recent non-work situation which had been stressful or very demanding. A coping questionnaire was verbally administered to measure the ways in which subjects had coped with these specific stressful situations.^ Analysis of results revealed that 27 percent of the sample was gainfully employed at time of interview. Differences between the employed and unemployed groups were analyzed by t-test an chi square. The employed demonstrated significantly more weeks of employment in the prior five years than the unemployed. The current jobs of the employed required a significantly higher relationship to "things" or inanimate objects than the last jobs of the unemployed. Subjects diagnosed as schizophrenic were significantly less likely to be employed than subjects with other diagnoses.^ Employed subjects scored significantly higher on three of four measures of social support than unemployed subjects, including reported frequency of social group attendance and/or meetings with mental health professionals. Problem-focused coping was used significantly more by the employed than by the unemployed to deal with stressful situations in the work, but not the non-work, context. ^