Although the nature of firefighting involves particular health hazards, previous mortality and morbidity studies of firemen have produced inconsistent evidence for an increased risk of mortality from cardiovascular disease, respiratory disease, cancer (Hunter, 1907(Hunter, -1908Hunter and Rogers, 1920;Hunter, 1927; The Actuarial Society of America and the Association of Life Insurance Medical Directors, 1929;Jenkins, 1930;Whitney, 1934;Registrar General, 1938;Dublin and Vane, 1947; Commonwealth of Massachusetts, 1952;Registrar General, 1957; Mastromatteo, 1959;Guralnick, 1963;Guthrie, 1970;Registrar General, 1971; Committee on Biological Effects of Atmospheric Pollutants, 1972;Peters et al., 1974;Balanof, 1976;Milham, 1976

Mitochondria play an important role in numerous diseases as well as normative aging. Severe reduction in mitochondrial function contributes to childhood disorders such as Leigh Syndrome, whereas mild disruption can extend the lifespan of model organisms. The Caenorhabditis elegans isp-1 gene encodes the Rieske iron-sulfur protein subunit of cytochrome c oxidoreductase (complex III of the electron transport chain). The partial loss of function allele, isp-1(qm150), leads to several pleiotropic phenotypes. To better understand the molecular mechanisms of ISP-1 function, we sought to identify genetic suppressors of the delayed development of isp-1(qm150) animals. Here we report a series of intragenic suppressors, all located within a highly conserved six amino acid tether region of ISP-1. These intragenic mutations suppress all of the evaluated isp-1(qm150) phenotypes, including developmental rate, pharyngeal pumping rate, brood size, body movement, activation of the mitochondrial unfolded protein response reporter, CO 2 production, mitochondrial oxidative phosphorylation, and lifespan extension. Furthermore, analogous mutations show a similar effect when engineered into the budding yeast Rieske iron-sulfur protein Rip1, revealing remarkable conservation of the structure-function relationship of these residues across highly divergent species. The focus on a single subunit as causal both in generation and in suppression of diverse pleiotropic phenotypes points to a common underlying molecular mechanism, for which we propose a "spring-loaded" model. These observations provide insights into how gating and control processes influence the function of ISP-1 in mediating pleiotropic phenotypes including developmental rate, movement, sensitivity to stress, and longevity.itochondria are sites for adenosine 5′-triphosphate (ATP) production by oxidative phosphorylation, cellular calcium buffering, iron-sulfur cluster biogenesis, reactive oxygen species (ROS) formation, and regulation of apoptosis. Although inherited defects in mitochondrial function are most often associated with severe childhood disorders, a large number of age-related diseases such as heart disease, cancer, diabetes, obesity, and neurodegeneration have also been linked to mitochondrial dysfunction (1, 2).In Caenorhabditis elegans, multiple studies have demonstrated that reduced electron transport chain activity (ETC) can lead to increased lifespan. These include mutations in the coenzyme Q biosynthetic gene clk-1, the pyrophosphokinase gene tpk-1, and the Rieske iron-sulfur protein isp-1 (3-7). Following RNAi knockdown of ETC components, several other proteins have been implicated in lifespan extension, including HIF-1, GCN-2, CEP-1, CEH-23, TAF-4, AHA-1, CEH-18, JUN-1, NHR-27, and NHR-49 (8-12). In addition, it was proposed that the mitochondrial unfolded protein response (mtUPR) directly mediated lifespan extension from ETC inhibition (13); however, more recent work has suggested that induction of the mtUPR is neither necessary nor sufficient to extend li...

This paper analyses the performance of state enterprises in Bulgaria during 1992-94. Consistent with the literature on other transitional economies, this paper finds that one key factor underlying (the lack of) enterprise adjustment in Bulgaria during this period was the availability of financing. Empirically, the (lack of) past adjustment and the softness of finance are the best predictors of current adjustment. Many state enterprises, mostly smaller ones, appear to have adjusted to the new economic structure, partly in response to tighter budget constraints. However, a number of large, hard-core lossmaking state enterprises did not adjust, due primarily to the soft budget constraints that they faced. These enterprises crowded out profitable enterprises, both public and private, through their large financing requirements, adversely affecting economic growth. Moreover, continued bank financing of these large loss-makers decapitalized the banking system, and budgetary financing of their losses, largely through tax arrears, has undermined fiscal policy. This lack of enterprise adjustment and the resulting financial indiscipline lies at the core of the macroeconomic difficulties that Bulgaria has recently faced. Copyright The European Bank for Reconstruction and Development, 1997.

The purpose of this review was to identify instruments designed to predict future child maltreatment and to evaluate their predictive accuracy. A number of electronic databases were searched to identify published studies. Only studies that had utilized a prospective methodology and tested at least one standardized instrument designed to identify families during the antenatal or postnatal periods who are at increased risk of maltreatment were included in the review. Eight studies were included that had prospectively tested a standardized instrument to predict child maltreatment during the antenatal or postnatal periods. Only six of the included studies followed up the entire sample, and of these only two did not provide an intervention for some or all of the high-risk group. While many of the included instruments obtained sensitivity and specificity above 80%, only two of the included instruments combined specificity over 80% with a positive predictive value above 25%. Currently available instruments have limited accuracy, suggesting that they should only be used to focus non-punitive interventions. These findings, in conjunction with other issues such as the stigma attached to the use of such instruments and difficulties in their application within a clinical and research context, suggest the need for a new approach to the identification of parents in need of higher levels of intervention.