The Role of the Hypothalamus-Pituitary-Gonadal Axis in Breast Cancer: a candidate gene approach

This chapter provides a general overview of breast cancer, including the possible role of genetic and exogenous factors and an overview of the role of hormones in carcinogenesis of the breast. Variability in susceptibility to the disease, timing of development, as well as tumor characteristics upon presentation and outcome of breast cancer, are likely to be affected by differences in both genetic and exogenous factors. The role of polymorphic variation in genes involved in hormonal control of carcinogenesis will be introduced. Breast cancer is the most frequently occurring malignancy in women, affecting women of all ages. More than 1 million new cases are diagnosed each year, accounting for almost one third of incident cases of cancer in women in Western industrialized countries . The cumulative lifetime risk, documented between 2000 and 2002, for women in the USA is 13% (1:8), while in The Netherlands the approximate lifetime risk is currently about 11% (1:9) (www.kankerregistratie.nl). In total over 400,000 women die each year worldwide of breast cancer (www.iarc.fr), making it the leading cause of death among women 35 to 55 years of age (3). Important aims of breast cancer research are prevention, early detection and reduction of mortality. Both basic molecular biological research and epidemiological investigations can help to achieve these goals by identification of women at risk, development of techniques for early diagnosis, prediction of outcome and response to therapy and finally optimization of targeted therapies resulting in tailoredtreatment. In essence, breast cancer, like all cancers, is a genetic disease resulting from an accumulation of somatic mutations and/ or altered expression of genes. In addition, breast cancer is a complex, multifactorial disease in which environmental factors and individual genetic background, including germline mutations and polymorphisms, may influence susceptibility, prognosis and response to treatment

A Revitalized Role for Library Media Specialists in School Reading Programs

At 8:00 a.m., while children are arriving at school, Mrs.Beasley, the elementary school library media specialist, is busy shelving the books returned yesterday. She has new books to catalog, newspaper and magazines to display and audio visual equipment to distribute to teachers. Before she completes any of this, her first group of children arrives for their regularly scheduled 30 minutes library visit. Mrs. Beasley attempts to help a few children in their selection of appropriate books, but finds that she spends most of her time checking books in and out. To Mrs. Beasley\u27s dismay, there is little time to share her love of books and reading with the children who visit her at the library. As this class leaves, another group of children arrives at the library, and the same scenario continues throughout the day

Stochastic atmospheric assistance and the use of emergency staging sites by migrants

Numerous animals move vast distances through media with stochastic dynamic properties. Avian migrants must cope with variable wind speeds and directions en route, which potentially jeopardize fine-tuned migration routes and itineraries. We show how unpredictable winds affect flight times and the use of an intermediate staging site by red knots (Calidris canutus canutus) migrating from west Africa to the central north Siberian breeding areas via the German Wadden Sea. A dynamic migration model incorporating wind conditions during flight shows that flight durations between Mauritania and the Wadden Sea vary between 2 and 8 days. The number of birds counted at the only known intermediate staging site on the French Atlantic coast was strongly positively correlated with simulated flight times. In addition, particularly light-weight birds occurred at this location. These independent results support the idea that stochastic wind conditions are the main driver of the use of this intermediate stopover site as an emergency staging area. Because of the ubiquity of stochastically varying media, we expect such emergency habitats to exist in many other migratory systems, both airborne and oceanic. Our model provides a tool to quantify the effect of winds and currents en route

Variability in the area, energy and time costs of wintering waders responding to disturbance

Birds’ responses to human disturbance are interesting due to their similarities to anti-predator behaviour, and understanding this behaviour has practical applications for conservation management by informing measures such as buffer zones to protect priority species. To understand better the costs of disturbance and whether it will impact on population size, studies should quantify time-related responses as well as the more commonly reported flight initiation distance (FID). Using waders wintering on an estuarine area, we experimentally disturbed foraging birds on the Wash Embayment, UK, by walking towards them and recording their responses (FID, alert time, time spent in flight, time taken to resume feeding, and total feeding time lost). We present data for 10 species of conservation concern: Curlew Numenius arquata, Oystercatcher Haematopus ostralegus, Bar-tailed Godwit Limosa lapponica, Grey Plover Pluvialis squatarola, Redshank Tringa totanus, Knot Calidris canutus, Turnstone Arenaria interpres, Ringed Plover Charadrius hiaticula, Sanderling Calidris alba and Dunlin Calidris alpina. Larger species responded more strongly, response magnitude was greater under milder environmental conditions, and responses varied over both small and large spatial scales. The energetic costs of individual responses, however, were low relative to daily requirements and disturbance events were unlikely to be frequent enough to seriously limit foraging time. We suggest, therefore, that wintering wader populations on the Wash are not currently significantly negatively impacted by human disturbance during the intertidal foraging period. This is also likely to be the case at other estuarine sites with comparable access levels, visitor patterns, invertebrate food availability and environmental conditions

Joint optimization of customer segmentation and marketing policy to maximize long-term profitability

With the advent of one-to-one marketing media, e.g. targeted direct mail or internet marketing, the opportunities to develop targeted marketing campaigns are enhanced in such a way that it is now both organizationally and economically feasible to profitably support a substantially larger number of marketing segments. However, the problem of what segments to distinguish, and what actions to take towards the different segments increases substantially in such an environment. A systematic analytic procedure optimizing both steps would be very welcome.In this study, we present a joint optimization approach addressing two issues: (1) the segmentation of customers into homogeneous groups of customers, (2) determining the optimal policy (i.e., what action to take from a set of available actions) towards each segment. We implement this joint optimization framework in a direct-mail setting for a charitable organization. Many previous studies in this area highlighted the importance of the following variables: R(ecency), F(requency), and M(onetary value). We use these variables to segment customers. In a second step, we determine which marketing policy is optimal using markov decision processes, following similar previous applications. The attractiveness of this stochastic dynamic programming procedure is based on the long-run maximization of expected average profit. Our contribution lies in the combination of both steps into one optimization framework to obtain an optimal allocation of marketing expenditures. Moreover, we control segment stability and policy performance by a bootstrap procedure. Our framework is illustrated by a real-life application. The results show that the proposed model outperforms a CHAID segmentation

Highly Pathogenic Avian Influenza Virus H5N1 Infection in a Long-Distance Migrant Shorebird under Migratory and Non-Migratory States

Corticosterone regulates physiological changes preparing wild birds for migration. It also modulates the immune system and may lead to increased susceptibility to infection, with implications for the spread of pathogens, including highly pathogenic avian influenza virus (HPAIV) H5N1. The red knot (Calidris canutus islandica) displays migratory changes in captivity and was used as a model to assess the effect of high plasma concentration of corticosterone on HPAIV H5N1 infection. We inoculated knots during pre-migration (N = 6), fueling (N = 5), migration (N = 9) and post-migration periods (N = 6). Knots from all groups shed similar viral titers for up to 5 days post-inoculation (dpi), peaking at 1 to 3 dpi. Lesions of acute encephalitis, associated with virus replication in neurons, were seen in 1 to 2 knots per group, leading to neurological disease and death at 5 to 11 dpi. Therefore, the risk of HPAIV H5N1 infection in wild birds and of potential transmission between wild birds and poultry may be similar at different times of the year, irrespective of wild birds' migratory status. However, in knots inoculated during the migration period, viral shedding levels positively correlated with pre-inoculation plasma concentration of corticosterone. Of these, knots that did not become productively infected had lower plasma concentration of corticosterone. Conversely, elevated plasma concentration of corticosterone did not result in an increased probability to develop clinical disease. These results suggest that birds with elevated plasma concentration of corticosterone at the time of migration (ready to migrate) may be more susceptible to acquisition of infection and shed higher viral titers—before the onset of clinical disease—than birds with low concentration of corticosterone (not ready for take-off). Yet, they may not be more prone to the development of clinical disease. Therefore, assuming no effect of sub-clinical infection on the likelihood of migratory take-off, this may favor the spread of HPAIV H5N1 by migratory birds over long distances

Migration route, stopping sites, and non-breeding destinations of adult Black-tailed Godwits breeding in southwest Fryslân, The Netherlands

In this paper, we extend our understanding of the migration of Black-tailed Godwits (Limosa limosa limosa) by describing: (1) the orientation and geographic locations of individual migratory routes and (2) the spatial distribution of godwits across seasons and years. We accomplish this using satellite-tracking data from 36 adult godwits breeding in the 200-ha Haanmeer polder in The Netherlands, from 2015 to 2018. During both southward and northward migration, godwits used a narrow migratory corridor along which most individuals made stops within a network of sites, especially the Bay of Biscay, France and Doñana, Spain. Most sites were used consistently by the same individuals across years. However, sites in Morocco were used during northward migration by 75% of individuals, but not revisited by the same individual across years. After southward migration, a small proportion (15%) of godwits spent the entire non-breeding period north of the Sahara, but most (85%) crossed the Sahara and spent at least part of the non-breeding season among seven coastal sites in West Africa and one site in the Inner Niger Delta. Although site-use patterns varied among individuals, individuals showed high site fidelity and were consistent in the number of sites they used from year to year. The considerable differences in the spatial distribution of individuals that breed within a kilometre of one another raise questions about the causes and consequences of individual migratory differences. We discuss that full annual cycle tracking of juveniles from birth to adulthood is needed to understand the source of these individual differences. Our results on the spatial distribution of godwits throughout their annual cycle lay an important foundation of information that can be used to help conserve this declining species