Working time society consensus statements: Prescriptive rule sets and risk management-based approaches for the management of fatigue-related risk in working time arrangements

Traditionally, working time arrangements to limit fatigue-related risk have taken a prescriptive approach, which sets maximum shift durations in order to prevent excessive buildup of fatigue (and the associated increased risk) within shifts and sets minimum break durations to allow adequate time for rest and recovery within and/or between shifts. Prescriptive rule sets can be successful when, from a fatigue-related risk standpoint, they classify safe work hours as permitted and unsafe work hours as not permitted. However, prescriptive rule sets ignore important aspects of the biological factors (such as the interaction between circadian and homeostatic processes) that drive fatigue, which are critical modulators of the relationship between work hours and fatigue-related risk. As such, in around-the-clock operations when people must work outside of normal daytime hours, the relationship between regulatory compliance and safety tends to break down, and thus these rule sets become less effective. To address this issue, risk management-based approaches have been designed to regulate the procedures associated with managing fatigue-related risk. These risk management-based approaches are suitable for nighttime operations and a variety of other non-standard work schedules, and can be tailored to the particular job or industry. Although the purpose of these fatigue risk management approaches is to curb fatigue risk, fatigue risk cannot be measured directly. Thus, the goal is not on regulating fatigue risk per se, but rather to put in place procedures that serve to address fatigue before, during, and after potential fatigue-related incidents. Examples include predictive mathematical modeling of fatigue for work scheduling, proactive fatigue monitoring in the workplace, and reactive post-incident follow-up. With different risks and different needs across industries, there is no “one size fits all” approach to managing fatiguerelated risk. However, hybrid strategies combining prescriptive rule sets and risk managementbased approaches can create the flexibility necessary to reduce fatigue-related risk based on the specific needs of different work environments while maintaining appropriate regulatory oversight. © 2019 National Institute of Occupational Safety and Health

Netrin-1 as a potential target for metastatic cancer: focus on colorectal cancer

Despite advanced screening technology and cancer treatments available today, metastasis remains an ongoing major cause of cancer-related deaths worldwide. Typically, colorectal cancer is one of the cancers treatable by surgery in conjunction with chemotherapy when it is detected at an early stage. However, it still ranks as the second highest modality and mortality of cancer types in western countries, and this is mostly due to a recurrence of metastatic colorectal cancer post-resection of the primary malignancy. Colorectal cancer metastases predominantly occur in the liver and lung, and yet the molecular mechanisms that regulate these organ-specific colorectal cancer metastases are largely unknown. Therefore, the identification of any critical molecule, which triggers malignancy in colorectal cancer, would be an excellent target for treatment. Netrin-1 was initially discovered as a chemotropic neuronal guidance molecule, and has been marked as a regulator for many cancers including colorectal cancer. Here, we summarise key findings of the role of netrin-1 intrinsic to colorectal cancer cells, extrinsic to the tumour microenvironment and angiogenesis, and consequently, we evaluate netrin-1 as a potential target molecule for metastasis

Correlates of Executive Dysfunction in HIV

Despite advancements in combination antiretroviral therapy rates of mild neurocognitive impairment remain elevated amongst persons living with HIV (PLWH). Concomitant with the greater rate of survival into old age PLWH show accelerated cognitive Aging in multiple domains. Executive function is among the domains where early onset of decline is most evident. This chapter will discuss what are known correlates of executive dysfunction in PLWH in this era of antiretroviral therapy. The goal of this chapter is to expand on what is known regarding HIV disease severity and executive dysfunction to provide a more nuanced look at how other central and peripheral biomarkers, psychosocial and behavioral risk factors relate to deficits in inhibition, updating and working memory, cognitive set-shifting, and mental flexibility