Sick-leave track record and other potential predictors of a disability pension. A population based study of 8,218 men and women followed for 16 years

<p>Abstract</p> <p>Background</p> <p>A number of previous studies have investigated various predictors for being granted a disability pension. The aim of this study was to test the efficacy of sick-leave track record as a predictor of being granted a disability pension in a large dataset based on subjects sampled from the general population and followed for a long time.</p> <p>Methods</p> <p>Data from five ongoing population-based Swedish studies was used, supplemented with data on all compensated sick leave periods, disability pensions granted, and vital status, obtained from official registers. The data set included 8,218 men and women followed for 16 years, generated 109,369 person years of observation and 97,160 sickness spells. Various measures of days of sick leave during follow up were used as independent variables and disability pension grant was used as outcome.</p> <p>Results</p> <p>There was a strong relationship between individual sickness spell duration and annual cumulative days of sick leave on the one hand and being granted a disability pension on the other, among both men and women, after adjustment for the effects of marital status, education, household size, smoking habits, geographical area and calendar time period, a proxy for position in the business cycle. The interval between sickness spells showed a corresponding inverse relationship. Of all the variables studied, the number of days of sick leave per year was the most powerful predictor of a disability pension. For both men and women 245 annual sick leave days were needed to reach a 50% probability of transition to disability. The independent variables, taken together, explained 96% of the variation in disability pension grantings.</p> <p>Conclusion</p> <p>The sick-leave track record was the most important predictor of the probability of being granted a disability pension in this study, even when the influences of other variables affecting the outcome were taken into account.</p

The role of the tissue microenvironment in the regulation of cancer cell motility and invasion

During malignant neoplastic progression the cells undergo genetic and epigenetic cancer-specific alterations that finally lead to a loss of tissue homeostasis and restructuring of the microenvironment. The invasion of cancer cells through connective tissue is a crucial prerequisite for metastasis formation. Although cell invasion is foremost a mechanical process, cancer research has focused largely on gene regulation and signaling that underlie uncontrolled cell growth. More recently, the genes and signals involved in the invasion and transendothelial migration of cancer cells, such as the role of adhesion molecules and matrix degrading enzymes, have become the focus of research. In this review we discuss how the structural and biomechanical properties of extracellular matrix and surrounding cells such as endothelial cells influence cancer cell motility and invasion. We conclude that the microenvironment is a critical determinant of the migration strategy and the efficiency of cancer cell invasion

The mTOR Signalling Pathway in Human Cancer

The conserved serine/threonine kinase mTOR (the mammalian target of rapamycin), a downstream effector of the PI3K/AKT pathway, forms two distinct multiprotein complexes: mTORC1 and mTORC2. mTORC1 is sensitive to rapamycin, activates S6K1 and 4EBP1, which are involved in mRNA translation. It is activated by diverse stimuli, such as growth factors, nutrients, energy and stress signals, and essential signalling pathways, such as PI3K, MAPK and AMPK, in order to control cell growth, proliferation and survival. mTORC2 is considered resistant to rapamycin and is generally insensitive to nutrients and energy signals. It activates PKC-α and AKT and regulates the actin cytoskeleton. Deregulation of multiple elements of the mTOR pathway (PI3K amplification/mutation, PTEN loss of function, AKT overexpression, and S6K1, 4EBP1 and eIF4E overexpression) has been reported in many types of cancers, particularly in melanoma, where alterations in major components of the mTOR pathway were reported to have significant effects on tumour progression. Therefore, mTOR is an appealing therapeutic target and mTOR inhibitors, including the rapamycin analogues deforolimus, everolimus and temsirolimus, are submitted to clinical trials for treating multiple cancers, alone or in combination with inhibitors of other pathways. Importantly, temsirolimus and everolimus were recently approved by the FDA for the treatment of renal cell carcinoma, PNET and giant cell astrocytoma. Small molecules that inhibit mTOR kinase activity and dual PI3K-mTOR inhibitors are also being developed. In this review, we aim to survey relevant research, the molecular mechanisms of signalling, including upstream activation and downstream effectors, and the role of mTOR in cancer, mainly in melanoma

Individual Perceptions of the Criminal

This paper empirically examines perceptions of the criminal justice system held by young males using longitudinal survey data from the recent National Longitudinal Survey of Youth 1997 Cohort and the National Youth Survey. While beliefs about the probability of an arrest are positively correlated with local official arrest rates, they are largely idiosyncratic and unresponsive to information about the arrests of other random individuals and local neighborhood conditions. There is little support, therefore, for the `broken windows &apos; theory of Wilson and Kelling (1982). Yet, perceptions do respond to changes in an individual&apos;s own criminal and arrest history. Young males who engage in crime but are not arrested revise their perceived probability of arrest downward, while those who are arrested revise their probability upwards. Beliefs respond similarly to changes in a sibling&apos;s criminal and arrest history. The perceived probability of arrest is then linked to subsequent criminal behavior. Cross-sectionally, youth with a lower perceived probability of arrest are significantly more likely to engage in crime during subsequent periods. Following an arrest