Working with cancer: health and employment among cancer survivors.

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Available online 4 August 2015PURPOSE: Cancer affects a growing proportion of US workers. Factors contributing to whether they continue or return to work after cancer diagnosis include: age, physical and mental health, health insurance, education, and cancer site. The purpose of this study was to assess the complex relationships between health indicators and employment status for adult cancer survivors. METHODS: We analyzed pooled data from the 1997-2012 US National Health Interview Survey (NHIS). Our sample included adults with a self-reported physician diagnosis of cancer (n = 24,810) and adults with no cancer history (n = 382,837). Using structural equation modeling (SEM), we evaluated the relationship between sociodemographic factors, cancer site, and physical and mental health indicators on the overall health and employment status among adults with a cancer history. RESULTS: The overall model for cancer survivors fit the data well (χ(2) (374) = 3654.7, P < .001; comparative fit index = 0.98; root mean square error of approximation = 0.04). Although black cancer survivors were less likely to report good-to-excellent health, along with Hispanic survivors, they were more likely to continue to work after diagnosis compared with their white counterparts. Health insurance status and educational level were strongly and positively associated with health status and current employment. Age and time since diagnosis were not significantly associated with health status or employment, but there were significant differences by cancer site. CONCLUSIONS: A proportion of cancer survivors may continue to work because of employment-based health insurance despite reporting poor health and significant physical and mental health limitations. Acute and long-term health and social support are essential for the continued productive employment and quality of life of all cancer survivors.The work was supported in part by a National Cancer Institute (NCI) fellowship at the National Institutes of Health (1F31CA153937); the National Institute for Occupational Safety and Health (NIOSH R01 OH03915); and the European Regional Development Fund Programme and European Social Fund Convergence Programme for Cornwall and the Isles of Scilly (the University of Exeter Medical School)

Working with cancer: Health and employment among cancer survivors

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Purpose: Cancer affects a growing proportion of US workers. Factors contributing to whether they continue or return to work after cancer diagnosis include: age, physical and mental health, health insurance, education, and cancer site. The purpose of this study was to assess the complex relationships between health indicators and employment status for adult cancer survivors. Methods: We analyzed pooled data from the 1997-2012 US National Health Interview Survey (NHIS). Our sample included adults with a self-reported physician diagnosis of cancer (n = 24,810) and adults with no cancer history (n = 382,837). Using structural equation modeling (SEM), we evaluated the relationship between sociodemographic factors, cancer site, and physical and mental health indicators on the overall health and employment status among adults with a cancer history. Results: The overall model for cancer survivors fit the data well (χ2 (374) = 3654.7, P < .001; comparative fit index = 0.98; root mean square error of approximation = 0.04). Although black cancer survivors were less likely to report good-to-excellent health, along with Hispanic survivors, they were more likely to continue to work after diagnosis compared with their white counterparts. Health insurance status and educational level were strongly and positively associated with health status and current employment. Age and time since diagnosis were not significantly associated with health status or employment, but there were significant differences by cancer site. Conclusions: A proportion of cancer survivors may continue to work because of employment-based health insurance despite reporting poor health and significant physical and mental health limitations. Acute and long-term health and social support are essential for the continued productive employment and quality of life of all cancer survivors.The work was supported in part by a National Cancer Institute (NCI) fellowship at the National Institutes of Health (1F31CA153937); the National Institute for Occupational Safety and Health (NIOSH R01 OH03915); and the European Regional Development Fund Programme and European Social Fund Convergence Programme for Cornwall and the Isles of Scilly (the University of Exeter Medical School)

Health status of older US workers and nonworkers, National Health Interview Survey, 1997-2011.

This is the final version of the article. Available from the publisher via the DOI in this record.INTRODUCTION: Many US workers are increasingly delaying retirement from work, which may be leading to an increase in chronic disease at the workplace. We examined the association of older adults' health status with their employment/occupation and other characteristics. METHODS: National Health Interview Survey data from 1997 through 2011 were pooled for adults aged 65 or older (n = 83,338; mean age, 74.6 y). Multivariable logistic regression modeling was used to estimate the association of socioeconomic factors and health behaviors with 4 health status measures: 1) self-rated health (fair/poor vs good/very good/excellent); 2) multimorbidity (≤1 vs ≥2 chronic conditions); 3) multiple functional limitations (≤1 vs ≥2); and 4) Health and Activities Limitation Index (HALex) (below vs above 20th percentile). Analyses were stratified by sex and age (young-old vs old-old) where interactions with occupation were significant. RESULTS: Employed older adults had better health outcomes than unemployed older adults. Physically demanding occupations had the lowest risk of poor health outcomes, suggesting a stronger healthy worker effect: service workers were at lowest risk of multiple functional limitations (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.71-0.95); and blue-collar workers were at lowest risk of multimorbidity (OR, 0.84; 95% CI, 0.74-0.97) and multiple functional limitation (OR, 0.84; 95% CI, 0.72-0.98). Hispanics were more likely than non-Hispanic whites to report fair/poor health (OR, 1.62; 95% CI, 1.52-1.73) and lowest HALex quintile (OR, 1.21; 95% CI, 1.13-1.30); however, they were less likely to report multimorbidity (OR, 0.78; 95% CI, 0.73-0.83) or multiple functional limitations (OR, 0.82; 95% CI, 0.77-0.88). CONCLUSION: A strong association exists between employment and health status in older adults beyond what can be explained by socioeconomic factors (eg, education, income) or health behaviors (eg, smoking). Disability accommodations in the workplace could encourage employment among older adults with limitations.Funding sources included the National Institute for Occupational Safety and Health (grant no. R01OH03915), the National Institute on Aging (grant no. F30AG040886), and the European Regional Development Fund and European Social Fund to the European Centre for Environment and Human Health (University of Exeter Medical School)

Simulation Modelling in Ophthalmology : Application to Cost Effectiveness of Ranibizumab and Aflibercept for the Treatment of Wet Age-Related Macular Degeneration in the United Kingdom

Previously developed models in ophthalmology have generally used a Markovian structure. There are a number of limitations with this approach, most notably the ability to base patient outcomes on best-corrected visual acuity (BCVA) in both eyes, which may be overcome using a different modelling structure. Simulation modelling allows for this to be modelled more precisely, and therefore may provide more accurate and relevant estimates of the cost effectiveness of ophthalmology interventions

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0→D*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4  fb-1 collected at the Υ(4S) resonance during 1999–2000, we have reconstructed 38 candidate signal events in the mode B0→D*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0→D*+D*-)=[8.3±1.6(stat)±1.2(syst)]×10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at √s=10.6 GeV

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qq̅ continuum events near the Υ(4S) resonance are presented. Using 20.8 fb-1 of data on the Υ(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(B⃗Ds+X)=(10.93±0.19±0.58±2.73)% and B(B⃗Ds*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+→φπ+ branching fraction uncertainty. The production cross sections σ(e+e-→Ds+X)×B(Ds+→φπ+)=7.55±0.20±0.34pb and σ(e+e-→Ds*±X)×B(Ds+→φπ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the Υ(4S) mass. The branching fractions ΣB(B⃗Ds(*)+D(*))=(5.07±0.14±0.30±1.27)% and ΣB(B⃗Ds*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Plasticity of BRCA2 Function in Homologous Recombination: Genetic Interactions of the PALB2 and DNA Binding Domains

The breast cancer suppressor BRCA2 is essential for the maintenance of genomic integrity in mammalian cells through its role in DNA repair by homologous recombination (HR). Human BRCA2 is 3,418 amino acids and is comprised of multiple domains that interact with the RAD51 recombinase and other proteins as well as with DNA. To gain insight into the cellular function of BRCA2 in HR, we created fusions consisting of various BRCA2 domains and also introduced mutations into these domains to disrupt specific protein and DNA interactions. We find that a BRCA2 fusion peptide deleted for the DNA binding domain and active in HR is completely dependent on interaction with the PALB2 tumor suppressor for activity. Conversely, a BRCA2 fusion peptide deleted for the PALB2 binding domain is dependent on an intact DNA binding domain, providing a role for this conserved domain in vivo; mutagenesis suggests that both single-stranded and double-stranded DNA binding activities in the DNA binding domain are required for its activity. Given that PALB2 itself binds DNA, these results suggest alternative mechanisms to deliver RAD51 to DNA. In addition, the BRCA2 C terminus contains both RAD51-dependent and -independent activities which are essential to HR in some contexts. Finally, binding the small peptide DSS1 is essential for activity when its binding domain is present, but not when it is absent. Our results reveal functional redundancy within the BRCA2 protein and emphasize the plasticity of this large protein built for optimal HR function in mammalian cells. The occurrence of disease-causing mutations throughout BRCA2 suggests sub-optimal HR from a variety of domain modulations

LEDGF/p75-Independent HIV-1 Replication Demonstrates a Role for HRP-2 and Remains Sensitive to Inhibition by LEDGINs

Lens epithelium–derived growth factor (LEDGF/p75) is a cellular cofactor of HIV-1 integrase (IN) that interacts with IN through its IN binding domain (IBD) and tethers the viral pre-integration complex to the host cell chromatin. Here we report the generation of a human somatic LEDGF/p75 knockout cell line that allows the study of spreading HIV-1 infection in the absence of LEDGF/p75. By homologous recombination the exons encoding the LEDGF/p75 IBD (exons 11 to 14) were knocked out. In the absence of LEDGF/p75 replication of laboratory HIV-1 strains was severely delayed while clinical HIV-1 isolates were replication-defective. The residual replication was predominantly mediated by the Hepatoma-derived growth factor related protein 2 (HRP-2), the only cellular protein besides LEDGF/p75 that contains an IBD. Importantly, the recently described IN-LEDGF/p75 inhibitors (LEDGINs) remained active even in the absence of LEDGF/p75 by blocking the interaction with the IBD of HRP-2. These results further support the potential of LEDGINs as allosteric integrase inhibitors