Leveraging Epidemiology to Improve Risk Assessment.

The field of environmental public health is at an important crossroad. Our current biomonitoring efforts document widespread exposure to a host of chemicals for which toxicity information is lacking. At the same time, advances in the fields of genomics, proteomics, metabolomics, genetics and epigenetics are yielding volumes of data at a rapid pace. Our ability to detect chemicals in biological and environmental media has far outpaced our ability to interpret their health relevance, and as a result, the environmental risk paradigm, in its current state, is antiquated and ill-equipped to make the best use of these new data. In light of new scientific developments and the pressing need to characterize the public health burdens of chemicals, it is imperative to reinvigorate the use of environmental epidemiology in chemical risk assessment. Two case studies of chemical assessments from the Environmental Protection Agency Integrated Risk Information System database are presented to illustrate opportunities where epidemiologic data could have been used in place of experimental animal data in dose-response assessment, or where different approaches, techniques, or studies could have been employed to better utilize existing epidemiologic evidence. Based on the case studies and what can be learned from recent scientific advances and improved approaches to utilizing human data for dose-response estimation, recommendations are provided for the disciplines of epidemiology and risk assessment for enhancing the role of epidemiologic data in hazard identification and dose-response assessment

The State, the UDHR, and the Social Construction of Family in Human Rights: The Case of the Scarborough 11

The Universal Declaration of Human Rights (UDHR) (UN 1947:34) declares in Article 16(3) that “the family is the natural and fundamental group unit of society and is entitled to the full protection by society and the state.” However, the UDHR does not define family, but rather presumes it is defined by traditional heteronormative marriage in a nuclear family. The failure of the UDHR to consider a more expansive view of family leaves the definition of family centrally in the hands of the state, and affects the ability of all but traditional nuclear family forms to access other human rights. We add to the scholarship on the role of the state in defining and maintaining family and family inequality through an examination of the case of the Scarborough 11, an intentional family sued by the city of Hartford, CT for violations of residential zoning ordinance based on family. This case challenges hegemonic constructions of family and illustrates the limits of the UDHR to protect all families. The case demonstrates the importance of the related questions: 1) how legal definitions of family create the capacity for local residents to understand non-nuclear families living among them, 2) whether the end-goal of this problem should be to expand the state’s definition of family or remove that power from the state in total (a question of reform vs. abolition) and, 3) what might a case concerning white middle-class professionals’ struggles to thrive tell us about boundary maintenance and the struggles of the poor to survive

"Come i secchi nel pozzo". Scienza ed etica negli scritti contro la vivisezione delle femministe britanniche (1870-1910)

Il saggio ripercorre le riflessioni teoriche delle femministe britanniche su scienza ed etica in relazione al dibattito sulla vivisezion

Behavioral Responses of Pacific Lamprey to Alarm Cues

Pacific lamprey (Entosphenus tridentatus), an anadromous ectoparasite, faces several challenges during adult migration to spawning grounds. Developingmethods to address these challenges is critical to the success of ongoing conservation efforts. The challenges are diverse, and include anthropogenic alterations to the ecosystem resulting in loss of habitat, impassable barriers such as dams, climate change impacts, and altered predator fields. We conducted a behavioral study to understand how adult migrating Pacific lamprey respond to potential alarm cues: White Sturgeon (Acipenser transmontanus), human saliva, decayed Pacific lamprey, and river otter (Lontra canadensis). Research has shown that some species of lamprey can be guided to a location using odors and similar cues may be useful as a management tool for Pacific lamprey. Experiments were conducted over 2 nights and measured the number of entries (count) and duration of time spent (occupancy) by adult lamprey in each arm of a two-choice maze. During the first night, no odor was added to test for selection bias between arms. During the second night odor was added to one arm of the maze. Contrary to expectations, lamprey were significantly attracted to the river otter odor in both count and occupancy. No significant differences were found in the response of lamprey to the other three odors. Results from this study indicate that Pacific lamprey do respond to some odors; however, additional tests are necessary to better identify the types of odors and concentrations that elicit a repeatable response

Story in health and social care

This paper offers a brief consideration of how narrative, in the form of people‟s own stories, potentially figures in health and social care provision as part of the impulse towards patient-centred care. The rise of the epistemological legitimacy of patients‟ stories is sketched here. The paper draws upon relevant literature and original writing to consider the ways in which stories can mislead as well as illuminate the process of making individual treatment care plans

Pancreatic β-Cell Death in Response to Pro-Inflammatory Cytokines Is Distinct from Genuine Apoptosis

A reduction in functional β-cell mass leads to both major forms of diabetes; pro-inflammatory cytokines, such as interleukin-1beta (IL-1β) and gamma-interferon (γ-IFN), activate signaling pathways that direct pancreatic β-cell death and dysfunction. However, the molecular mechanism of β-cell death in this context is not well understood. In this report, we tested the hypothesis that individual cellular death pathways display characteristic phenotypes that allow them to be distinguished by the precise biochemical and metabolic responses that occur during stimulus-specific initiation. Using 832/13 and INS-1E rat insulinoma cells and isolated rat islets, we provide evidence that apoptosis is unlikely to be the primary pathway underlying β-cell death in response to IL-1β+γ-IFN. This conclusion was reached via the experimental results of several different interdisciplinary strategies, which included: 1) tandem mass spectrometry to delineate the metabolic differences between IL-1β+γ-IFN exposure versus apoptotic induction by camptothecin and 2) pharmacological and molecular interference with either NF-κB activity or apoptosome formation. These approaches provided clear distinctions in cell death pathways initiated by pro-inflammatory cytokines and bona fide inducers of apoptosis. Collectively, the results reported herein demonstrate that pancreatic β-cells undergo apoptosis in response to camptothecin or staurosporine, but not pro-inflammatory cytokines. DOI: 10.1371/journal.pone.002248

Amphotericin forms an extramembranous and fungicidal sterol sponge.

For over 50 years, amphotericin has remained the powerful but highly toxic last line of defense in treating life-threatening fungal infections in humans with minimal development of microbial resistance. Understanding how this small molecule kills yeast is thus critical for guiding development of derivatives with an improved therapeutic index and other resistance-refractory antimicrobial agents. In the widely accepted ion channel model for its mechanism of cytocidal action, amphotericin forms aggregates inside lipid bilayers that permeabilize and kill cells. In contrast, we report that amphotericin exists primarily in the form of large, extramembranous aggregates that kill yeast by extracting ergosterol from lipid bilayers. These findings reveal that extraction of a polyfunctional lipid underlies the resistance-refractory antimicrobial action of amphotericin and suggests a roadmap for separating its cytocidal and membrane-permeabilizing activities. This new mechanistic understanding is also guiding development of what are to our knowledge the first derivatives of amphotericin that kill yeast but not human cells

Quiescent Radio Emission from Southern Late-type M Dwarfs and a Spectacular Radio Flare from the M8 Dwarf DENIS 1048-3956

We report the results of a radio monitoring program conducted at the Australia Telescope Compact Array to search for quiescent and flaring emission from seven nearby Southern late-type M and L dwarfs. Two late-type M dwarfs, the M7 V LHS 3003 and the M8 V DENIS 1048-3956, were detected in quiescent emission at 4.80 GHz. The observed emission is consistent with optically thin gyrosynchrotron emission from mildly relativistic (~1-10 keV) electrons with source densities n_e ~ 10 G magnetic fields. DENIS 1048-3956 was also detected in two spectacular, short-lived flares, one at 4.80 GHz (peak f_nu = 6.0+/-0.8 mJy) and one at 8.64 GHz (peak f_nu = 29.6+/-1.0 mJy) approximately 10 minutes later. The high brightness temperature (T_B >~ 10^13 K), short emission period (~4-5 minutes), high circular polarization (~100%), and apparently narrow spectral bandwidth of these events imply a coherent emission process in a region of high electron density (n_e ~ 10^11-10^12 cm^-3) and magnetic field strength (B ~ 1 kG). If the two flare events are related, the apparent frequency drift in the emission suggests that the emitting source either moved into regions of higher electron or magnetic flux density; or was compressed, e.g., by twisting field lines or gas motions. The quiescent fluxes from the radio-emitting M dwarfs violate the Gudel-Benz empirical radio/X-ray relations, confirming a trend previously noted by Berger et al. (abridged)Comment: 28 pages, 8 figures, accepted for publication in Ap

Methodology for studying Relative Energy Deficiency in Sport (REDs) : A narrative review by a subgroup of the International Olympic Committee (IOC) consensus on REDs

In the past decade, the study of relationships among nutrition, exercise and the effects on health and athletic performance, has substantially increased. The 2014 introduction of Relative Energy Deficiency in Sport (REDs) prompted sports scientists and clinicians to investigate these relationships in more populations and with more outcomes than had been previously pursued in mostly white, adolescent or young adult, female athletes. Much of the existing physiology and concepts, however, are either based on or extrapolated from limited studies, and the comparison of studies is hindered by the lack of standardised protocols. In this review, we have evaluated and outlined current best practice methodologies to study REDs in an attempt to guide future research. This includes an agreement on the definition of key terms, a summary of study designs with appropriate applications, descriptions of best practices for blood collection and assessment and a description of methods used to assess specific REDs sequelae, stratified as either Preferred, Used and Recommended or Potential. Researchers can use the compiled information herein when planning studies to more consistently select the proper tools to investigate their domain of interest. Thus, the goal of this review is to standardise REDs research methods to strengthen future studies and improve REDs prevention, diagnosis and care