Resuming Work After Cancer: A Prospective Study of Occupational Register Data

Introduction Long-term employment rates have been studied in cancer survivors, but little is known about the return to work of cancer patients. This study investigated return to work (RTW) within 2 years after the diagnosis of different types of cancer. Methods This prospective study investigated the associations of demographics (age, gender, socioeconomic status, and residential region) and occupational factors (occupation, duration of employment, and company size) of employees absent from work due to cancer with the time to partial RTW, defined as working at least 50% of the earnings before sickness absence. Likewise, the associations of demographics and occupational factors with full RTW at equal earnings as before sickness absence were investigated. Results The cohort included 5,234 employees who had been absent from work due to cancer between January 2004 and December 2006. The time to partial RTW was shortest among employees with skin cancer (median 55 days) and longest among employees with lung cancer (median 377 days). There were no significant associations between RTW and demographics. With regard to the occupational factors, employees in high occupational classes started working earlier than those in low occupational classes, but the time to full RTW did not differ significantly across occupational classes. Employees working in large companies returned to work earlier than those working in small companies. Conclusion RTW after different types of cancer depended on occupational factors rather than demographics

The Ups and Downs of Mutation Frequencies during Aging Can Account for the Apert Syndrome Paternal Age Effect

Apert syndrome is almost always caused by a spontaneous mutation of paternal origin in one of two nucleotides in the fibroblast growth factor receptor 2 gene (FGFR2). The incidence of this disease increases with the age of the father (paternal age effect), and this increase is greater than what would be expected based on the greater number of germ-line divisions in older men. We use a highly sensitive PCR assay to measure the frequencies of the two causal mutations in the sperm of over 300 normal donors with a wide range of ages. The mutation frequencies increase with the age of the sperm donors, and this increase is consistent with the increase in the incidence rate. In both the sperm data and the birth data, the increase is non-monotonic. Further, after normalizing for age, the two Apert syndrome mutation frequencies are correlated within individual sperm donors. We consider a mathematical model for germ-line mutation which reproduces many of the attributes of the data. This model, with other evidence, suggests that part of the increase in both the sperm data and the birth data is due to selection for mutated premeiotic cells. It is likely that a number of other genetic diseases have similar features

Parallel assessment of male reproductive function in workers and wild rats exposed to pesticides in banana plantations in Guadeloupe

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence that reproductive abnormalities are increasing in frequency in both human population and among wild fauna. This increase is probably related to exposure to toxic contaminants in the environment. The use of sentinel species to raise alarms relating to human reproductive health has been strongly recommended. However, no simultaneous studies at the same site have been carried out in recent decades to evaluate the utility of wild animals for monitoring human reproductive disorders. We carried out a joint study in Guadeloupe assessing the reproductive function of workers exposed to pesticides in banana plantations and of male wild rats living in these plantations.</p> <p>Methods</p> <p>A cross-sectional study was performed to assess semen quality and reproductive hormones in banana workers and in men working in non-agricultural sectors. These reproductive parameters were also assessed in wild rats captured in the plantations and were compared with those in rats from areas not directly polluted by humans.</p> <p>Results</p> <p>No significant difference in sperm characteristics and/or hormones was found between workers exposed and not exposed to pesticide. By contrast, rats captured in the banana plantations had lower testosterone levels and gonadosomatic indices than control rats.</p> <p>Conclusion</p> <p>Wild rats seem to be more sensitive than humans to the effects of pesticide exposure on reproductive health. We conclude that the concept of sentinel species must be carefully validated as the actual nature of exposure may varies between human and wild species as well as the vulnerable time period of exposure and various ecological factors.</p

Characterization of NF-κB reporter U937 cells and their application for the detection of inflammatory immune-complexes

Our study tested the hypothesis that immunoglobulins differ in their ability to activate the nuclear factor-κB pathway mediated cellular responses. These responses are modulated by several properties of the immune complex, including the ratio of antibody isotypes binding to antigen. Immunoassays allow the measurement of antigen specific antibodies belonging to distinct immunoglobulin classes and subclasses but not the net biological effect of the combination of these antibodies. We set out to develop a biosensor that is suitable for the detection and characterization of antigen specific serum antibodies. We genetically modified the monocytoid U937 cell line carrying Fc receptors with a plasmid encoding NF-κB promoter-driven GFP. This clone, U937-NF-κB, was characterized with respect to FcR expression and response to solid-phase immunoglobulins. Human IgG3, IgG4 and IgG1 induced GFP production in a time- and dose-dependent manner, in this order of efficacy, while IgG2 triggered no activation at the concentrations tested. IgA elicited no response alone but showed significant synergism with IgG3 and IgG4. We confirmed the importance of activation via FcγRI by direct stimulation with monoclonal antibody and by competition assays. We used citrullinated peptides and serum from rheumatoid arthritis patients to generate immune complexes and to study the activation of U937-NF-κB, observing again a synergistic effect between IgG and IgA. Our results show that immunoglobulins have distinct pro-inflammatory potential, and that U937-NF-κB is suitable for the estimation of biological effects of immune-complexes, offering insight into monocyte activation and pathogenesis of antibody mediated diseases

Spike-Timing Precision and Neuronal Synchrony Are Enhanced by an Interaction between Synaptic Inhibition and Membrane Oscillations in the Amygdala

The basolateral complex of the amygdala (BLA) is a critical component of the neural circuit regulating fear learning. During fear learning and recall, the amygdala and other brain regions, including the hippocampus and prefrontal cortex, exhibit phase-locked oscillations in the high delta/low theta frequency band (∼2–6 Hz) that have been shown to contribute to the learning process. Network oscillations are commonly generated by inhibitory synaptic input that coordinates action potentials in groups of neurons. In the rat BLA, principal neurons spontaneously receive synchronized, inhibitory input in the form of compound, rhythmic, inhibitory postsynaptic potentials (IPSPs), likely originating from burst-firing parvalbumin interneurons. Here we investigated the role of compound IPSPs in the rat and rhesus macaque BLA in regulating action potential synchrony and spike-timing precision. Furthermore, because principal neurons exhibit intrinsic oscillatory properties and resonance between 4 and 5 Hz, in the same frequency band observed during fear, we investigated whether compound IPSPs and intrinsic oscillations interact to promote rhythmic activity in the BLA at this frequency. Using whole-cell patch clamp in brain slices, we demonstrate that compound IPSPs, which occur spontaneously and are synchronized across principal neurons in both the rat and primate BLA, significantly improve spike-timing precision in BLA principal neurons for a window of ∼300 ms following each IPSP. We also show that compound IPSPs coordinate the firing of pairs of BLA principal neurons, and significantly improve spike synchrony for a window of ∼130 ms. Compound IPSPs enhance a 5 Hz calcium-dependent membrane potential oscillation (MPO) in these neurons, likely contributing to the improvement in spike-timing precision and synchronization of spiking. Activation of the cAMP-PKA signaling cascade enhanced the MPO, and inhibition of this cascade blocked the MPO. We discuss these results in the context of spike-timing dependent plasticity and modulation by neurotransmitters important for fear learning, such as dopamine

The role of economic evaluation in the decision-making process of family physicians: design and methods of a qualitative embedded multiple-case study

<p>Abstract</p> <p>Background</p> <p>A considerable amount of resource allocation decisions take place daily at the point of the clinical encounter; especially in primary care, where 80 percent of health problems are managed. Ignoring economic evaluation evidence in individual clinical decision-making may have a broad impact on the efficiency of health services. To date, almost all studies on the use of economic evaluation in decision-making used a quantitative approach, and few investigated decision-making at the clinical level. An important question is whether economic evaluations affect clinical practice. The project is an intervention research study designed to understand the role of economic evaluation in the decision-making process of family physicians (FPs). The contributions of the project will be from the perspective of Pierre Bourdieu's sociological theory.</p> <p>Methods/design</p> <p>A qualitative research strategy is proposed. We will conduct an embedded multiple-case study design. Ten case studies will be performed. The FPs will be the unit of analysis. The sampling strategies will be directed towards theoretical generalization. The 10 selected cases will be intended to reflect a diversity of FPs. There will be two embedded units of analysis: FPs (micro-level of analysis) and field of family medicine (macro-level of analysis). The division of the determinants of practice/behaviour into two groups, corresponding to the macro-structural level and the micro-individual level, is the basis for Bourdieu's mode of analysis. The sources of data collection for the micro-level analysis will be 10 life history interviews with FPs, documents and observational evidence. The sources of data collection for the macro-level analysis will be documents and 9 open-ended, focused interviews with key informants from medical associations and academic institutions. The analytic induction approach to data analysis will be used. A list of codes will be generated based on both the original framework and new themes introduced by the participants. We will conduct within-case and cross-case analyses of the data.</p> <p>Discussion</p> <p>The question of the role of economic evaluation in FPs' decision-making is of great interest to scientists, health care practitioners, managers and policy-makers, as well as to consultants, industry, and society. It is believed that the proposed research approach will make an original contribution to the development of knowledge, both empirical and theoretical.</p