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CCAAT/enhancer-binding protein-beta (C/EBPbeta) is a mediator of cell survival and tumorigenesis. When C/EBPbeta(-/-) mice are treated with carcinogens that produce oncogenic Ras mutations in keratinocytes, they respond with abnormally elevated keratinocyte apoptosis and a block in skin tumorigenesis. Although this aberrant carcinogen-induced apoptosis results from abnormal upregulation of p53, it is not known whether upregulated p53 results from oncogenic Ras and its ability to induce p19(Arf) and/or activate DNA-damage response pathways or from direct carcinogen-induced DNA damage. We report that p19(Arf) is dramatically elevated in C/EBPbeta(-/-) epidermis and that C/EBPbeta represses a p19(Arf) promoter reporter. To determine whether p19(Arf) is responsible for the proapoptotic phenotype in C/EBPbeta(-/-) mice, C/EBPbeta(-/-);p19(Arf-/-) mice were generated. C/EBPbeta(-/-);p19(Arf-/-) mice responded to carcinogen treatment with increased p53 and apoptosis, indicating p19(Arf) is not essential. To ascertain whether oncogenic Ras activation induces aberrant p53 and apoptosis in C/EBPbeta(-/-) epidermis, we generated K14-ER:Ras;C/EBPbeta(-/-) mice. Oncogenic Ras activation induced by 4-hydroxytamoxifen did not produce increased p53 or apoptosis. Finally, when C/EBPbeta(-/-) mice were treated with differing types of DNA-damaging agents, including alkylating chemotherapeutic agents, they displayed aberrant levels of p53 and apoptosis. These results indicate that C/EBPbeta represses p53 to promote cell survival downstream of DNA damage and suggest that inhibition of C/EBPbeta may be a target for cancer cotherapy to increase the efficacy of alkylating chemotherapeutic agents.

The study was designed to provide evidence of a cascade effect linking socioeconomic position to anthropometric indicators of cardiovascular disease (CVD) risk through effects on psychosocial stress, psychological distress and health-related behaviours, and consider implications for disease prevention and health promotion.A cross-sectional stratified two-stage probability sample of occupied housing units in three areas of Detroit, Michigan, was used in the study. 919 adults agedor =25 years completed the survey (mean age 46.3; 53% annual household income$20 000; 57% non-Hispanic black, 22% Latino, 19% non-Hispanic white). Variables included self-report (eg, psychosocial stress, depressive symptoms, health behaviours) and anthropometric measurements (eg, waist circumference, height, weight). The main outcome variables were depressive symptoms, smoking status, physical activity, body mass index and waist circumference.Income was inversely associated with depressive symptoms, likelihood of current smoking, physical inactivity and waist circumference. These relationships were partly or fully mediated by psychosocial stress. A suppressor effect of current smoking on the relationship between depressive symptoms and waist circumference was found. Independent effects of psychosocial stress and psychological distress on current smoking and waist circumference were found, above and beyond the mediated pathways.The results suggest that relatively modest improvements in the income of economically disadvantaged people can set in motion a cascade of effects, simultaneously reducing exposure to stressful life conditions, improving mental well-being, increasing health-promoting behaviours and reducing anthropometric risks associated with CVD. Such interventions offer important opportunities to improve population health and reduce health disparities.

The present study examined the role of self-reported helping behavior in attenuating the helper's depression following spousal loss. Using archival data from the Changing Lives of Older Couples sample (N = 289), the study shows that among bereaved participants who had experienced high loss-related grief, helping behavior (providing instrumental support to others) was associated with an accelerated decline in depressive symptoms for the helper from 6 months to 18 months following spousal loss. This relationship between giving help and recovery from depression was independent of support received, as well as measured health, and interpersonal and demographic factors. Implications of these results for theoretical approaches to the study of close relationships and well-being are discussed.

This paper examines the interface between work stress and nonwork stress and how it relates to health. Results indicate that the way people feel at work is largely a function of conditions at work. Similarly, the way people feel outside of work is largely a function of things that occur outside the job. Both work and nonwork stress are independently associated with physical and mental health, although the relationship between nonwork stress and health is slightly stronger. Excessive demands or stresses in one domain can interfere with life in the other. Such conflict operates equally in both directions. When present it can be an added source of stress and adversely affect health. Taken together these findings suggest that the stress people experience at work is not simply a reflection of their "personal problems." This has implications for the design of health promotion and stress prevention programs in the workplace.

5-Azacytidine (5-aza), a chemical that is incorporated into DNA and RNA with consequent alterations in the expression of mammalian genes, was administered to pregnant Sprague-Dawley rats on single days during gestation. Doses of 0.5, 1, and 2 mg/kg were given by intraperitoneal injection on d 9, 10, 11, or 12. Dams were killed on d 20 of gestation and fetuses were examined for both external and skeletal defects. 5-Azacytidine affected development on all days tested. The compound was embryolethal, caused reductions in fetal weight, and had profound effects on morphological development. Digit and limb anomalies, exencephaly, micrognathia, gastroschisis, and various rib defects were observed and related to the day of exposure.

The spatial segregation of the U.S. population by socioeconomic position and especially race-ethnicity suggests that the social contexts or “neighborhoods” in which people live may substantially contribute to social disparities in hypertension. The Chicago Community Adult Health Study did face-to-face interviews, including direct measurement of blood pressure, with a representative probability sample of adults in Chicago. These data were used to estimate socioeconomic and racial-ethnic disparities in the prevalence, awareness, treatment, and control of hypertension, and to analyze how these disparities are related to the areas in which people live. Hypertension was significantly negatively associated with neighborhood affluence/gentrification, and adjustments for context eliminated the highly significant disparity between blacks/African-Americans and whites, and reduced the significant educational disparity by 10–15% to borderline statistical significance. Awareness of hypertension was significantly higher in more disadvantaged neighborhoods and in places with higher concentrations of blacks (and lower concentrations of Hispanics and immigrants). Adjustment for context completely eliminated blacks’ greater awareness, but slightly accentuated the lesser awareness of Hispanics and the greater levels of awareness among the less educated. There was no consistent evidence of either social disparities in or contextual associations with treatment of hypertension, given awareness. Among those on medication, blacks were only 40–50% as likely as whites to have their hypertension controlled, but context played little or no role in either the level of or disparities in control of hypertension. In sum, residential contexts potentially play a large role in accounting for racial-ethnic, and to a lesser degree, socioeconomic disparities in hypertension prevalence and, in a different way, awareness, but not in treatment or control of diagnosed hypertension.

There is an ongoing need for empirically based treatments for child sexual abuse (CSA) that are time-efficient and cost-effective. This article describes a modification of cognitive processing therapy for child sexual abuse (CPT-SA) that increases the therapy's usability by reducing the number of individual therapy sessions required. The modifications are based on the developing literature on stage-based approaches to the treatment of CSA and incorporate dialectical behavior therapy skills training into the treatment protocol. Initial pilot data (N = 6) on modified CPT-SA suggests the therapy may be effective for the treatment of posttraumatic stress disorder (PTSD) and depression.

Fluorescence is a tool widely employed in biological assays. Fluorescent semiconducting nanocrystals, quantum dots (QDs), are beginning to find their way into the tool box of many biologist, chemist and biochemist. These quantum dots are an attractive alternative to the traditional organic dyes due to their broad excitation spectra, narrow emission spectra and photostability. Quantum dots were used to detect and monitor the progession of viral glycoproteins, F (fusion) and G (attachment), from Respiratory Syncytial Virus (RSV) in HEp-2 cells. Additionally, oligo-Qdot RNA probes have been developed for identification and detection of mRNA of the N(nucleocapsid) protein for RSV. The use of quantum dot-FISH probes provides another confirmatory route to diagnostics as well as a new class of probes for monitoring the flux and fate of viral RNA RSV is the most common cause of lower respiratory tract infection in children worldwide and the most common cause of hospitalization of infants in the US. Antiviral therapy is available for treatment of RSV but is only effective if given within the first 48 hours of infection. Existing test methods require a virus level of at least 1000-fold of the amount needed for infection of most children and require several days to weeks to obtain results. The use of quantum dots may provide an early, rapid method for detection and provide insight into the trafficking of viral proteins during the course of infection.

The Healthy Environments Partnership (HEP) is a community-based participatory research effort investigating variations in cardiovascular disease risk, and the contributions of social and physical environments to those variations, among non-Hispanic black, non Hispanic white, and Hispanic residents in three areas of Detroit, Michigan. Initiated in October 2000 as a part of the National Institute of Environmental Health Sciences’ Health Disparities Initiative, HEP is affiliated with the Detroit Community–Academic Urban Research Center. The study is guided by a conceptual model that considers race based residential segregation and associated concentrations of poverty and wealth to be fundamental factors influencing multiple, more proximate predictors of cardiovascular risk. Within this model, physical and social environments are identified as intermediate factors that mediate relationships between fundamental factors and more proximate factors such as physical activity and dietary practices that ultimately influence anthropomorphic and physiologic indicators of cardiovascular risk. The study design and data collection methods were jointly developed and implemented by a research team based in community-based organizations, health service organizations, and academic institutions. These efforts include collecting and analyzing airborne particulate matter over a 3-year period; census and administrative data; neighborhood observation checklist data to assess aspects of the physical and social environment; household survey data including information on perceived stressors, access to social support, and health related behaviors; and anthropometric, biomarker, and selfreport data as indicators of cardiovascular health. Through these collaborative efforts, HEP seeks to contribute to an understanding of factors that contribute to racial and socioeconomic health inequities, and develop a foundation for efforts to eliminate these disparities in Detroit. Key words: community-based participatory research partnerships, racial segregation and cardiovascular disease, social and physical environments and cardiovascular disease.

The popularity of direct or systematic social observation as a method to evaluate the mechanisms by which neighborhood environments impact health and contribute to health disparities is growing. The development of measures with adequate inter-rater and test-retest reliability is essential for this research. In this paper, based on our experiences conducting direct observation of neighborhoods in Detroit, MI, we describe strategies to promote high inter-rater and test-retest reliability and methods to evaluate reliability. We then present the results and discuss implications for future research efforts using direct observation in four areas: methods to evaluate reliability, instrument content and design, observer training, and data collection.

Background. The role that human metapneumovirus (hMPV) plays in the etiology of upper respiratory tract infections (URIs) in children over a period of many years has not been evaluated previously. Methods. By use of real-time reverse-transcriptase polymerase chain reaction, we retrospectively tested nasal wash (NW) specimens for hMPV that had been obtained from a cohort of 1532 infants and children with URIs who were prospectively followed for an average of 2.4 years during the period from 1982 to 2001. Virus genes were sequenced, and prospectively collected clinical data were analyzed. Results. There were 2710 visits for URIs for which routine cultures did not reveal a viral etiology. Archival NW specimens from 2384 of these visits were available. hMPV RNA was detected in 118 (5%) of 2384 specimens. The mean age of the children with hMPV infection was 20 months, and 78% of illnesses occurred from December through May. Acute otitis media (AOM) was detected in 50% of these children. hMPV circulated each year, but the numbers of isolates detected varied by year. Reinfections with both homologous and heterologous strains occurred. Four distinct genetic lineages were present over the 20 years of surveillance, with several different lineages circulating during some seasons. Conclusions. hMPV was detected in a substantial number of children with URIs and concomitant AOM.

We report the use of quantum dots (QDs) to identify the presence and monitor the progression of respiratory syncytial virus (RSV) infection over time by labeling the F and G proteins. In addition, co-localization of these viral proteins was shown using confocal microscopy. The implications of these results are that QDs may provide a method for early, rapid detection of viral infection and open the door for future studies of the intricate spatial features cell trafficking of viral proteins.

Fluorescence is a tool widely employed in biological assays. Fluorescent semiconducting nanocrystals, quantum dots (QDs), are beginning to find their way into the tool box of many biologist, chemist and biochemist. These quantum dots are an attractive alternative to the traditional organic dyes due to their broad excitation spectra, narrow emission spectra and photostability. Non-specific binding is a frequently encountered problem with fluorescent labeling in biological assays. In these studies various cell lines were examined for non-specific binding to quantum dots. Evidence suggests that non-specific binding is related to cell type and, may be significantly reduced by functionalizing quantum dots with polyethyleneglycol ligands (PEG). In addition quantum dots were used to detect and monitor the progession of the viral glycoproteins ,F (fusion) and G (attachment), from Respiratory Syncytial Virus (RSV) in HEp-2 cells. RSV is the most common cause of lower respiratory tract infection in children worldwide and the most common cause of hospitalization of infants in the US. Antiviral therapy is available for treatment of RSV but is only effective if given within the first 48 hours of infection. Existing test methods require a virus level of at least 1000-fold of the amount needed for infection of most children and require several days to weeks to obtain results. The use of quantum dots may provide an early, rapid method for detection and provide insight into the trafficking of viral proteins during the course of infection.

Ferrer, Palmer, and Burge1 make an important contribution toward reorienting family medicine and the primary care disciplines to understand the health and illness of individuals as members of populations in a multilevel context. It is critical that the health care professions, especially those engaged in primary care, think about and act on broader, often nonbiomedical, determinants of population health while also attending to needs of patients for individualized health care. The authors credit George Engel for having initially championed a multilevel perspective as an antidote to the biomedical reductionism that then and still now has dominated the biomedical sciences.2 This perspective emphasizes social and physical-chemical-biological environmental contexts. These contexts begin with the immediate or proximal family and social networks, then extend to the household, neighborhood, and broader environments in which people live and work. They include the broader metropolitan, regional, state, national, and international contexts in which all are embedded. These social contexts may be determinants of the health of individuals that are equal to or more important than biological (including genetic) processes and biomedical treatments operative at the level of the individuals. In the end, we must understand the interactions and relationships among all of these levels. Attending to those levels above the individual leads to a focus on the health of populations (and individuals only as a component of those populations). Sir Geoffrey Rose had the key insight that the determinants of variations in the health of populations across time and space might be quite different from the determinants of differences in health between individuals within populations.3 For example, interindividual differences in cardiovascular health within populations may be a function of individual characteristics, such as body mass, blood pressure, and lipids, or they may be a function of individual behaviors, such as smoking, eating, drinking, and physical activity. In contrast, differences in health between populations are often determined by broader social and cultural factors, (ranging from socioeconomic conditions to regulation and taxation of cigarettes, food, and pollutants, to the cultural and familial influences on health behavior). These population or macro-level factors are likely responsible for the major shifts in population health over time, for example: the rise and decline of cardiovascular disease and major cancers in developed countries during the twentieth century, or the current obesity epidemic. Because they affect so many members of a population for sustained periods, interventions that focus on these broader determinants may be more effective than individualized treatments or prevention approaches.4 Ferrer and colleagues endeavor to advance understanding and appreciation of these supraindividual determinants of population health by estimating with hierarchical linear models the proportions of general health status that “can be attributed to” individual-, family-, and community-level determinants of the physical components summary scale (PCS) and mental components summary scale (MCS) of the SF-12 in the Community Tracking Study (CTS). As the CTS included only 60 rather large communities or metropolitan areas, only 1% of the variance was accounted for at the community level. This is, however, probably a considerable underestimate, as the authors suggest, relative both to the individual-level and the family-level variation on which they focus. A more precise and narrow definition of other relevant social contexts could have yielded rather different results. Across a wide range of family types and across both physical and mental health scores on the CTS, between 13% and 25% of the variance is “attributable to” the family level, as opposed to the individual level (ie, lies between families rather than within families). Adjustment for age and family income reduces the between-family variance by 23% to 60% (of the 13% to 25% total), depending on family configuration. As the authors note, analyses based on partitioning variability can shed only limited light on the causal importance of factors defined above the level of individuals, because small estimates of between-group variance may coexist with strong effects of specific group-level variables. Nevertheless, illustrating between-group (in this case between-family) variance is a first step in the recognition and investigation of these higher level effects. The authors go one step further in estimating how between-family variance changes as individual-level factors (eg, age), and family-level factors (income) are added to the models. The extent to which an individual-level factor such as age accounts for between-group (in this case between-family) variability will depend on the nature and strength of its association with the outcome and the extent to which age is differentially distributed across families. In the models presented by Ferrer et al, age appears to be more strongly related to the outcomes studied in the married-with-no-kids group than in the other groups studied. There may also be more age variation across families in the married-with-no-kids group, and these factors could explain the greater reduction in between-family variance found after age adjustment. In any case, age is merely a confounder of between-family differences in the analyses presented by Ferrer et al. A more interesting question is what family-level factors explain between-family differences. The authors investigate family income as one possible family-level influence of health and find that family income generally explains an important proportion of between-family variance, especially for physical health outcomes. Family income may be an important determinant of family effects through its impact on housing location and quality, nutrition, exposure to stressful or toxic environments, or medical care. It may also be a marker or proxy for a variety of other social and environmental characteristics that differ across families and are likely to be important to health. The authors discuss a number of ways in which family-level factors and processes could affect health. Understanding these family influences will require further specification and empirical testing of the role of these different processes. It is also important to recognize that families themselves are situated within broader contexts. Specifying and studying these broader contexts are major challenges, as illustrated by the limitations that Ferrer et al allude to in their analyses of between-community variability. As cautiously noted by the authors, much better specified measures and analyses are needed to understand the sources of these variations (at the level of individuals, families, and broader social conditions or contexts) and hence to find appropriate interventions in social policy as well as medical practice for improving the health of the population of individuals and families in the United States and the wider world. By moving beyond purely individual-level analyses, Ferrer and colleagues importantly sensitize health care professionals to recognize and attempt to influence variations in population health at the level of families and broader social contexts, as well as at the level of individual cases. The tradition of community-oriented primary care provides one example of how such a multilevel approach to medical care5 may be possible.

Objective We examined the association between depressive symptoms and all-cause mortality in a population sample. Published findings on the relation between depressive symptoms and mortality risk point to an inconsistent association and one that is likely influenced by health status. Few studies have assessed this relation in randomly selected population samples. Methods Participants were 3617 noninstitutionalized adults, age 25 years or older, from the Americans' Changing Lives Study, an ongoing longitudinal study of a nationally representative sample. Depressive symptoms were measured by the 11-item version of the Center for Epidemiological Studies Depression Scale (CES-D). Cox proportional hazards models estimated the relative risk of mortality as a function of the CES-D scores at baseline. Results In 7.5 years of follow-up, 542 deaths occurred. Each 1-standard unit increase on the CES-D predicted a 21% increased risk of all-cause mortality, adjusting for age, gender, and race (hazard ratio = 1.21, 95% confidence interval = 1.08 to 1.36, p = .001). This association was weakened somewhat following adjustment for education, income, body mass index, smoking and alcohol consumption (hazard ratio = 1.13, 95% confidence interval = 0.99 to 1.28, p = .06). However, control for self-reported functional limitations or chronic health conditions at baseline effectively eliminated the relationship. Analyses limited to participants with good to excellent health or no functional impairments at baseline showed no association between depressive symptoms and subsequent mortality risk. Secondary analyses showed no association between depressive symptoms and cardiovascular mortality. Conclusions These findings from a randomly selected, nationally representative sample do not support the hypothesis that depressive symptoms are independently related to mortality in the general population, after adequate adjustment for the confounding effects of physical health status.

Based on recent applications of attachment theory to religion, the authors predicted that the loss of a spouse would cause widowed individuals to increase the importance of their religious/spiritual beliefs. This hypothesis was examined using the Changing Lives of Older Couples sample from which preloss measures of religiosity were available for widowed individuals and matched controls. A total of 103 widowed individuals provided follow-up data, including reports of religious beliefs and grief, at 6 months, 24 months, and 48 months after the loss. Results indicated that widowed individuals were more likely than controls to increase their religious/spiritual beliefs. This increase was associated with decreased grief but did not influence other indicators of adjustment such as depression. Finally, insecure individuals were most likely to benefit from increasing the importance of their beliefs. Results are discussed in terms of the potential value of applying psychological theory to the study of religion.

As part of a larger elastic numerical modeling project, we have been investigating how energy reflected from steeply dipping interfaces is recorded using typical multicomponent acquisition geometries. Specifically, we have been interpreting how rcflection events from the flanks of salt dome structures are distributed on 3C and 4C phones for vertical seismic profiles (VSPs) and ocean bottom seismic (OBS) or land surface surveys. The ultimate goal of this investigation is to improve the structural imaging of steeply dipping interfaces and eventually to evaluate the usc of the recorded elastic wavefield for fluid description near these interfaces. In the current work, we focus on a common assumption used when processing converted wave reflection seismic data that most PP energy is recorded on the vertical geophone and/or the hydrophone and that most PS energy is recorded on the horizontal geophones. This is a useful assumption when it is valid, because it eliminates the need for separation of the recorded wavefield into P and S wavetypes. Using two elastic models and different acquisition geometries, we examine the validity of this assumption in the presence of steeply dipping interfaces and discuss the implications for converted-wave and vector imaging of salt flanks.

background. Hidradenomas are adnexal tumors that may grow to be very large and frequently recur after excision. Malignant transformation and metastatic spread can occur and histologic distinction of benign from malignant hidradenomas can be very difficult. Some tumors with bland histology have demonstrated aggressive behavior. objective. To decide the benefits of management with Mohs micrographic surgery of large hidradenomas. methods. The literature was reviewed, including both the clinical course of the tumor and histologic features. The case of our report was interpreted in light of the review. results. Three stages of Mohs surgery were required for complete removal of the hidradenoma. The patient remains free of recurrence. conclusions. This report highlights the difficulties in distinguishing benign from malignant hidradenomas and emphasizes the benefits of Mohs surgery for large or recurrent tumors.

The development of social epidemiology and medical sociology over the last half of the 20th century, in which Leo Reeder played a central role, transformed scientific and popular understanding of the nature and causes of physical health and illness. Viewed in the early 1950s as shaped almost entirely by biological processes and medical care, physical health and illness are now understood to be as much or more a function of social, psychological, and behavioral factors. Utilizing a stress and adaptation conceptual framework, social epidemiology has identified a broad range of psychosocial risk factors for health, most notably: (1) social relationships and support; (2) acute or event-based stress; (3) chronic stress in work and life; and (4) psychological dispositions such as anger/hostility, lack of self-efficacy/control, and negative affect/hopelessness/pessimism, with new risk factors continuing to be identified. However, proliferation of risk factors must be balanced by conceptual integration and causal understanding of the relationships among them, their causes, and consequences. One source of such integration and understanding has been the rediscovery of large and persistent socioeconomic and racial-ethnic disparities in health. Socioeconomic position and race/ethnicity shape individuals' exposure to and experience of virtually all known psychosocial, and well as many environmental and biomedical, risk factors, and these risk factors help to explain the size and persistence of social disparities in health. Improving the socioeconomic position of a broad range of disadvantaged socioeconomic and racial-ethnic strata constitutes a major avenue for reducing exposure to and experience of deleterious risk factors for health, and hence for improving the health of these groups and the overall population. This in turn requires better understanding of the macrosocial forces that influence the socioeconomic position of individuals.

Cutaneous spindle cell squamous cell carcinoma (SSCC) is a challenging diagnosis since it may be difficult to distinguish from spindle cell melanoma, leiomyosarcoma and atypical fibroxanthoma. Furthermore, it may be difficult to demonstrate epithelial differentiation by a traditional immunohistochemical panel. We performed an expanded immunohistochemical evaluation of ultrastructurally documented SSCC to assess its utility in diagnosing this entity.We identified 16 cases of SSCC that were composed predominantly of spindle-shaped cells and with ultrastructural evidence of epithelial differentiation (i.e. at least rudimentary cell junctions). Immunohistochemical analysis using antibodies to a variety of cytokeratins (AE1/3, K903, CK5/6) and S-100 protein was performed. The extent of immunostaining was graded on a scale of 0 to 4+ (0: no staining; 1+:or =25%; 2+: 26-50%; 3+: 51-75%; 4+:75%).Of the 16 cases, 6 expressed AE1/3 (38%), 8 expressed K903 (50%) and 11 (69%) expressed CK5/6. Six cases were positive for all three CK markers and two cases were positive for both K903 and CK5/6 but negative for AE1/3. Three cases (19%) stained for CK5/6 without any staining for AE1/3 or K903. Five cases (31%) were negative for all epithelial markers. The extent of CK5/6 staining was either similar to or greater than K903 staining in 7 of 8 cases that stained with both markers. All 16 cases were negative for S-100 protein.Including CK5/6 in the initial battery of immunostains performed on a cutaneous spindle cell neoplasm can help demonstrate epithelial differentiation in SSCC, even in the absence of AE1/3 or K903 staining. However, some cases of cutaneous SSCC can only be confirmed ultrastructurally, as up to one-third may not show evidence of epithelial differentiation using an expanded immunohistochemical panel.

In a zero-gravity environment, astronauts exhibit Bone Mineral Density (BMD) loss in their spine and lower extremities with no net changes in the upper extremities [1]. Astronauts use their upper extremities for locomotion in flight by pushing off of the walls of the spacecraft, but since their lower extremities are not supporting their mass, as in gravitational loading, there is significant BMD loss in these areas.

In the early 1990s, it was suggested that the central neuronal network responsible for breathing relies on pacemaker cells to promote its rhythmic activity.1,2,3These pacemaker neurons were shown to be concentrated in the region of the pre-Botzinger complex and are critical components of the network generating respiratory rhythm.3,4Previous studies of this neuronal population have been done primarily in fresh tissue slices in vitro which have a limited survival (less than 48 hours) and, due to thickness of the slice, offer poor accessibility to neurons of interest. Tissue culture of the isolated pre-Botzinger complex may offer some advantages in this respect, but it is not known whether the isolated pre-Botzinger network would maintain its functional properties. Therefore, we evaluated the viability of the stationary explant of the cultured pre-Botzinger region (“island”). We hypothesized that the pacemaker network would maintain functional activity for extended periods in culture due to the network robust functional properties.

Biochemical research has identified many failures in reproductive processes with specific nutrient deficits, xenobiotics and some infectious illnesses. This has led to some effective safeguards. During meiosis and fertilization, as genetic material divides and rearranges, it is exposed and open to mutation. A nutritionally unfavourable environment is a major risk factor. At stages of rapid cell division, differentiation and organisation, as in the embryo and later in the fetal brain, the child's survival, completeness and future health and ability are at stake. From months before conception, reproduction needs preparing for, especially with today's environmental pollution, even entering the foodchain. Care from before conception can contribute not only to the child's healthy basis for life, full development of brain, eyesight and other complex attributes, but also to the health of at least the subsequent generation. Since the female baby's oocytes are being formed while she is still in the womb, the grandmother's nutritional status, around the time of conceiving a daughter, can permanently affect a grandchild. Recent insights into evolution, particularly of the brain, give us fresh indications of dietary needs to fulfil human potential for health and acuity. Despite the hazards, nature is remarkably successful. This paper is not designed to alarm but to help attainment of full genetic potential. With healthy parents serious malformations are a low percentage. The numbers of babies with avoidable disorders, however, calls urgently for action, especially in our own inner cities and in developing countries where there is inadequate nutrition. Action will more than justify itself, including financially. It will reward handsomely.

Although a number of authors have proposed that older volunteers should benefit in terms of better health and well-being, few researchers have examined the issue empirically to see whether this is true. The purpose of this article is to build on this literature by empirically examining the association between volunteering and mortality among older adults.Using data from a nationally representative sample, we use Cox proportional hazards regression to estimate the effects of volunteering on the rate of mortality among persons aged 65 and older.We find that volunteering has a protective effect on mortality among those who volunteered for one organization or for forty hours or less over the past year. We further find that the protective effects of volunteering are strongest for respondents who report low levels of informal social interaction and who do not live alone.We discuss the possibility that the curvilinear relationship we observe between volunteering and mortality is due to a combination of factors, including self-identity, role strain, and meaningfulness. Other research using more precise data is needed to determine whether these ideas are supportable.

Despite considerable evidence documenting a strong and persistent relationship between socioeconomic position and mortality, recent research suggests that this association may be weaker among women. In our examination of gender differences in the socioeconomic gradient in mortality, we argue that this inconsistency arises from the failure to consider the ways in which gender is a fundamental constituent of socioeconomic position. The data used are from the Panel Study of Income Dynamics. Respondents, including all household heads and their partners, aged 29 years and older in 1972 (N = 5,665; 56% female), were followed until 1991, death, or attrition. Discrete time event history analysis was used to examine the predictors of death between 1972 and 1991. Of the key socioeconomic predictors, years of education was measured at baseline, while earned income was a time-varying covariate. We find no gender differences in the effect of respondents' own socioeconomic positions on their mortality risk. However, increasing spousal income raises men's odds of dying, while the opposite is true for women. Our results raise questions about the prevailing view that the socioeconomic gradient in mortality is weaker among women. Moreover, gender differences in the effects of spousal earnings on mortality risk suggest that their labor market rewards have fundamentally different meanings for women and men.

Cyclin-dependent kinases (Cdks) and their cyclin partners regulate mammalian cell proliferation and withdrawal from the cell cycle and, as such, control differentiation in many tissues. Studies were undertaken to examine the roles of cell cycle proteins in differentiating cytotrophoblasts. Cyclin E gene and protein expression was down-regulated after 24 h in cultured trophoblasts. Cdk2-associated kinase activity was decreased after 96 h in culture as was the amount of cyclin E in complexes with Cdk2; however, levels of the Cdk inhibitor, p27Kip1, were significantly increased. In freshly isolated trophoblasts and in 24-h cultures, the retinoblastoma gene product (pRb) was found in both the active and inactive forms, yet only hypophosphorylated, active pRb was present in syncytiotrophoblast. Thus, inactivation of Cdk2 through cyclin E down-regulation and increased p27Kip1 expression leads to an accumulation of active pRb in syncytiotrophoblast. Prevention of entry into S phase by hypophosphorylated pRb may allow trophoblasts to respond to signals that potentiate differentiation. Our studies suggest that regulation of G1-phase Cdk activity may be involved in the terminal differentiation process of cytotrophoblasts.

OBJECTIVES: The aim of this study was to examine relationships between income and mortality, focusing on the predictive utility of single-year and multiyear measures of income, the shape of the income gradient in mortality, trends in this gradient over time, the impact of income change on mortality, and the joint effects of income and age, race, and sex on mortality risk. METHODS: Data were taken from the Panel Study of Income Dynamics for the years 1968 through 1989. Fourteen 10-year panels were constructed in which predictors were measured over the first 5 years and vital status over the subsequent 5 years. The panels were pooled and logistic regression was used in the analysis. RESULTS: Income level was a strong predictor of mortality, especially for persons under the age of 65 years. Persistent low income was particularly consequential for mortality. Income instability was also important among middle-income individuals. Single-year and multiyear income measures had comparable predictive power. All effects persisted after adjustment for education and initial health status. CONCLUSIONS: The issues of low income and income instability should be addressed in population health policy.

Despite the general persistence and even increase of strong socioeconomic status (SES) differentials in health in the United States, research suggests that SES differentials in health may diminish or become nonexistent at older ages. However, most research has used only limited measures of SES (e.g. education, income), and has not thoroughly investigated intra-elderly age differences in this trend. The current study investigates how SES differentials in health vary by age in the United States, using fairly detailed age categories (through ages 85+), and 2 alternative indicators (home ownership and liquid assets) of a major additional dimension of SES, financial assets, which may be especially important at older ages. We address (a) how strongly financial assets are associated with health, considered both alone and net of education and income; (b) if the health effects of financial assets vary by age; and, more specifically, (c) if their effects are especially pronounced in older age, again considered both alone and net of or relative to education and income. Results show that financial assets, especially liquid assets, considered both alone and net of education and income, are associated with health throughout adulthood and old age, at least until ages 85+. Furthermore, financial assets remain associated with health until quite late in life and become more important relative to education and income at older ages for some measures of health.

Purpose : Psychological flexibility involves mindful awareness of our thoughts and feelings without allowing them to prohibit acting consistently with our values and may have important implications for patient-centered clinical care. Although psychological flexibility appears quite relevant to the training and development of health care providers, prior research has not evaluated measures of psychological flexibility in medical learners. Therefore, we investigated the validity of our learners’ responses to three measures related to psychological flexibility. Methods : Fourth-year medical students and residents ( n =275) completed three measures of overlapping aspects of psychological flexibility: (1) Acceptance and Action Questionnaire-II (AAQ-II); (2) Cognitive Fusion Questionnaire (CFQ); and (3) Mindful Attention and Awareness Questionnaire (MAAS). We evaluated five aspects of construct validity: content, response process, internal structure, relationship with other variables, and consequences. Results : We found good internal consistency for responses on the AAQ ( α =0.93), MAAS ( α =0.92), and CFQ ( α =0.95). Factor analyses demonstrated a reasonable fit to previously published factor structures. As expected, scores on all three measures were moderately correlated with one another and with a measure of life satisfaction ( p

Corrigendum: Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors

The way health varies with age is importantly stratified by socioeconomic status (SES)--specifically, education and income. Prior theory and cross-sectional data suggest that among higher SES persons the onset of health problems is usually postponed until rather late in life, while health declines are prevalent in lower SES groups by middle age. Thus, SES differences in health are small in early adulthood, but increase with age until relatively late in life, when they diminish due to selection or greater equalization of health risks and protections. The present paper strengthens our causal and interpretive understanding of these phenomena by showing: (1) that results previously reported for indices of SES hold separately for education and income; (2) that the interaction between age and SES (i.e., education or income) in predicting health can be substantially explained by the greater exposure of lower SES persons to a wide range of psychosocial risk factors to health, especially in middle and early old age, and, to a lesser degree, the greater impact of these risk factors on health with age; and (3) that results (1) and (2) generally hold in short-term longitudinal as well as in cross-sectional data. Implications for science and policy in the areas of aging, health, and social stratification are discussed.

There is inconsistency in the literature on the relationship between age and depressive symptoms. Although a careful review shows that some of this inconsistency can be reconciled by recognizing the nonlinear relationship (Newmann, 1989), 2 additional issues remain unclear. One is that most previous studies used depression screening scales that contain somatic items that could introduce an age bias. The other is that most previous studies combined samples of men and women even though there is evidence that the sex difference in depressive symptoms varies with age. These 2 issues are addressed in this article, using analyzed data from 2 large national surveys. There is a consistent, but quite modest, nonlinear association between age, somatic, and nonsomatic depressive symptoms in both surveys. There is no significant sex difference in the age curves.

We have developed a method for using short (30-42 base pair) synthetic oligonucleotide DNA probes in Northern blot assays. The method involves labeling the probes to high specific activity, very stringent hybridization and wash conditions, and the presence of several inhibitors of nonspecific binding in the hybridization buffer. We have tested this method with several probes obtained from local and commercial sources. The results with every probe used were high signal-to-noise ratios in an exposure time range of 30 min to 7 days.

A little over a decade ago, I wrote one of the numerous papers of the 1970s analyzing the perceived “crisis” of social psychology of that time (House, 1977). My particular diagnosis of that crisis was that it reflected the division of social psychology into three increasingly isolated domains or faces: (1) psychological social psychology, (2) symbolic interactionism, and (3) what I termed psychological sociology or what is more often labelled as the study of social structure and personality. I saw the solution to the crisis in greater unification of, or at least interchange between, the three faces and their disparate substantive and methodological concerns, though I had only tentative ideas on how that might be achieved, and was uncertain that it could be. Much of what I wrote ten years ago remains valid in my view, but I also have revised or extended my thinking on some issues.

Further analyses have been made on readings of two scripts by six talkers [T. H. Crystal and A. S. House, J. Acoust. Soc. Am. 72, 705-716 (1982); 84, 1932-1935 (1988); 83, 1553-1573 (1988)]. Durations of syllables and stress groups are compared to earlier data and various pertinent published reports, and are used to evaluate reports of articulation rate variability. The average durations of syllables of different complexity have a quasilinear dependency on the number of phones in the syllable, where the linear factor and the vowel durations are functions of stress. The duration of stress groups has a quasilinear dependency on the number of syllables and the number of phones. It was found that variability of articulation rate, measured as the average syllable duration for interpause intervals (runs), is not random, but is the natural consequence of the content of the run. Durations of comparable runs of different talkers are highly correlated. Major determinants of average syllable duration are the average number of phones per syllable and the proportion of either + stress phones or + stress syllables in the run.