Examining the effects of gestational exposure to perfluorooctanoic acid on the developing and differentiating mammary gland, their consequences, and the possible modes of action by which they are mediated

Perfluorooctanoic acid (PFOA) is a persistent industrial compound, which is commonly detected in human and wildlife sera. Low-dose prenatal PFOA exposure negatively affects postnatal growth and survival with little prenatal effect, indicating the potential for PFOA to alter lactation in the nursing dam. These studies aim to understand the impact PFOA has on development and differentiation of the mammary gland (MG). To address this, timed-pregnant CD-1 mice were gestationally exposed to 0 or 5 mg PFOA/kg body weight. PFOA-treated dams exhibited significant histopathologic delays in MG lactational differentiation and alterations in milk protein gene expression, and their exposed female offspring displayed stunted mammary epithelial branching and growth. The roles of timing and route of exposure were then addressed by cross-fostering litters, and the 5 mg/kg dose, under either lactational- or intrauterine-only exposures, was determined sufficient to delay MG development as early as postnatal day (PND) 1, with effects persisting beyond PND63. The consequences to F1 lactational function and subsequent development of F2 offspring were investigated, and F1 dams exhibited delayed lactational differentiation, though no effect of early-life exposure on milk production or F2 offspring body weight was detected. Finally, the potential mode of action for the effects of PFOA on the MG was investigated, by treating pregnant wild-type (WT) and peroxisome proliferator-activated receptor alpha (PPARα) knock-out (KO) mice similarly with PFOA. At weaning, PFOA treatment caused diminished lactational differentiation in WT, but not KO dams. In offspring, however, effects of PFOA exposure were apparent in both strains at weaning, suggesting a non-PPARα mode of action may be responsible for offspring MG effects. In total, these studies defined a window of MG sensitivity in late fetal and early neonatal life, as well as the persistence of MG effects beyond the age at which serum PFOA concentrations reach background levels. This suggests a permanent, non-PPARα mediated effect in the offspring, though without clear functional consequences. The characterization of MG effects in light of PFOA dosimetry data, as well as the discovery that MG effects are not strictly controlled by PPARα, will greatly assist in the regulation of this compound

Discovery of a Classic FR-II Broad Absorption Line Quasar from the FIRST Survey

We have discovered a remarkable quasar, FIRST J101614.3+520916, whose optical spectrum shows unambiguous broad absorption features while its double-lobed radio morphology and luminosity clearly indicate a classic Fanaroff-Riley Type II radio source. Its radio luminosity places it at the extreme of the recently established class of radio-loud broad absorption line quasars (Becker et al. 1997, 2000; Brotherton et al. 1998). Because of its hybrid nature, we speculate that FIRST J101614.3+520916 is a typical FR-II quasar which has been rejuvenated as a broad absorption line (BAL) quasar with a Compact Steep Spectrum core. The direction of the jet axis of FIRST J101614.3+520916 can be estimated from its radio structure and optical brightness, indicating that we are viewing the system at a viewing angle of > 40 degrees. The position angles of the radio jet and optical polarization are not well-aligned, differing by 20 to 30 degrees. When combined with the evidence presented by Becker et al. (2000) for a sample of 29 BAL quasars showing that at least some BAL quasars are viewed along the jet axis, the implication is that no preferred viewing orientation is necessary to observe BAL systems in a quasar's spectrum. This, and the probable young nature of compact steep spectrum sources, leads naturally to the alternate hypothesis that BALs are an early stage in the lives of quasars.Comment: 14 pages, 6 postscript figures; accepted for publication in the Astrophysical Journa

What Determines the Depth of BALs? Keck HIRES Observations of BALQSO 1603+300

We find that the depth and shape of the broad absorption lines (BALs) in BALQSO 1603+3002 are determined largely by the fraction of the emitting source which is covered by the BAL flow. In addition, the observed depth of the BALs is poorly correlated with their real optical depth. The implication of this result is that abundance studies based on direct extraction of column densities from the depth of the absorption troughs are unreliable. Our conclusion is based on analysis of unblended absorption features of two lines from the same ion (in this case the Si IV doublet), which allows unambiguous separation of covering factor and optical depth effects. The complex morphology of the covering factor as a function of velocity suggests that the BALs are produced by several physically separated outflows. The covering factor is ion dependent in both depth and velocity width. We also find evidence that in BALQSO 1603+3002 the flow does not cover the broad emission line region.Comment: 13 pages, 2 figures, accepted for publication in Ap

Keck Hires Observations of the QSO First J104459.6+365605: Evidence for a Large Scale Outflow

This paper presents an analysis of a Keck HIRES spectrum of the QSO FIRST J104459.6+365605. The line of sight towards the QSO contains two clusters of outflowing clouds that give rise to broad blue shifted absorption lines. The outflow velocities of the clouds range from -200 to -1200 km/s and from -3400 to -5200 km/s, respectively. The width of the individual absorption lines ranges from 50 to more than 1000 km/s. The most prominent absorption lines are those of Mg II, Mg I, and Fe II. The low ionization absorption lines occur at the same velocities as the most saturated Mg II lines, showing that the Fe II, Mg I and Mg II line forming regions must be closely associated. Many absorption lines from excited states of Fe II are present, allowing a determination of the population of several low lying energy levels. From this we determine an electron density in the Fe II line forming regions of 4000 per cubic cm. Modelling the ionization state of the absorbing gas with this value of the electron density as a constraint, we find that the distance between the Fe II and Mg I line forming region and the continuum source is of order 700 parsec. From the correspondence in velocity between the Fe II, Mg I and Mg II lines we infer that the Mg II lines must be formed at the same distance. The Mg II absorption fulfills the criteria for Broad Absorption Lines defined by Weymann et al. (1991). This large distance is surprising, since BALs are generally thought to be formed in outflows at a much smaller distance from the nucleus.Comment: 34 pages, 11 figures. Accepted by The Astrophysical Journa

Discrimination, labour markets and the Labour Market Prospects of Older Workers: What Can a Legal Case Teach us?

As governments become increasingly concerned about the fiscal implications of the ageing population, labour market policies have sought to encourage mature workers to remain in the labour force. The ‘human capital’ discourses motivating these policies rest on the assumption that older workers armed with motivation and vocational skills will be able to return to fulfilling work. This paper uses the post-redundancy recruitment experiences of former Ansett Airlines flight attendants to develop a critique of these expectations. It suggests that policies to increase older workers’ labour market participation will not succeed while persistent socially constructed age- and gender- typing shape labour demand. The conclusion argues for policies sensitive to the institutional structures that shape employer preferences, the competitive rationality of discriminatory practices, and the irresolvable tension between workers’ human rights and employers’ property rights

Gestational and Chronic Low-Dose PFOA Exposures and Mammary Gland Growth and Differentiation in Three Generations of CD-1 Mice

Background: Prenatal exposure to perfluorooctanoic acid (PFOA), a ubiquitous industrial surfactant, has been reported to delay mammary gland development in female mouse offspring (F1) and the treated lactating dam (P0) after gestational treatments at 3 and 5 mg PFOA/kg/day

The structural response of the cornea to changes in stromal hydration

The primary aim of this study was to quantify the relationship between corneal structure and hydration in humans and pigs. X-ray scattering data were collected from human and porcine corneas equilibrated with polyethylene glycol (PEG) to varying levels of hydration, to obtain measurements of collagen fibril diameter, interfibrillar spacing and intermolecular spacing. Both species showed a strong positive linear correlation between hydration and interfibrillar spacing2 and a non-linear, bi-phasic relationship between hydration and fibril diameter, whereby fibril diameter increased up to approximately physiological hydration, H = 3.0, with little change thereafter. Above H = 3.0, porcine corneas exhibited a larger fibril diameter than human corneas (p < 0.001). Intermolecular spacing also varied with hydration in a bi-phasic manner but reached a maximum value at a lower hydration (H = 1.5) than fibril diameter. Human corneas displayed a higher intermolecular spacing than porcine corneas at all hydrations (p < 0.0001). Human and porcine corneas required a similar PEG concentration to reach physiological hydration, suggesting that the total fixed charge that gives rise to the swelling pressure is the same. The difference in their structural responses to hydration can be explained by variations in molecular crosslinking and intra/interfibrillar water partitioning

The lay health worker-patient relationship in promoting pulmonary rehabilitation (PR) in COPD: What makes it work?

Lay health workers (LHWs) can improve access to services and adherence to treatment, as well as promoting self-care and prevention. Their effect in promoting uptake and adherence in pulmonary rehabilitation (PR) for chronic obstructive pulmonary disease (COPD) has not been tested. PR is the most effective treatment for the symptoms and disability of COPD, but this effectiveness is undermined by poor rates of completion. Trained LHWs with COPD, who also have first-hand experience of PR, are well placed to help overcome the documented barriers to its completion. The relationship between LHWs and patients may be one of the keys to their effectiveness but it has been little explored. Semi-structured qualitative interviews were used with the aim of examining the LHW-patient partnership in a feasibility study of trained PR-experienced LHWs used to support COPD patients referred to PR. Twelve volunteers with COPD who completed LHW training supported 66 patients referred for PR. All 12 of these LHWs gave end-of-study interviews, 21 COPD patients supported by LHWs were also interviewed. Patients reported that the LHWs were keen to share their experiences of PR, and that this had a positive impact. The enthusiasm of the LHWs for PR was striking. The common bond between LHWs and patients of having COPD together with the LHWs positive, first-hand experience of PR were dominant and recurring themes in their relationship.This article presents independent research funded by the NIHR under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG0214-30052). SL receives additional funding from the South African Medical Research Council. SJCT was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) North Thames at Bart’s Health NHS Trust

The FIRST Bright Quasar Survey. II. 60 Nights and 1200 Spectra Later

We have used the VLA FIRST survey and the APM catalog of the POSS-I plates as the basis for constructing a new radio-selected sample of optically bright quasars. This is the first radio-selected sample that is competitive in size with current optically selected quasar surveys. Using only two basic criteria, radio-optical positional coincidence and optical morphology, quasars and BL Lacs can be identified with 60% selection efficiency; the efficiency increases to 70% for objects fainter than magnitude 17. We show that a more sophisticated selection scheme can predict with better than 85% reliability which candidates will turn out to be quasars. This paper presents the second installment of the FIRST Bright Quasar Survey with a catalog of 636 quasars distributed over 2682 square degrees. The quasar sample is characterized and all spectra are displayed. The FBQS detects both radio-loud and radio-quiet quasars out to a redshift z>3. We find a large population of objects of intermediate radio-loudness; there is no evidence in our sample for a bimodal distribution of radio characteristics. The sample includes ~29 broad absorption line quasars, both high and low ionization, and a number of new objects with remarkable optical spectra.Comment: 41 pages plus 39 gifs which contain all quasar spectra. Accepted for publication in the Astrophysical Journal Supplement Serie