Cre/lox generation of a novel whole-body Kiss1r KO mouse line recapitulates a hypogonadal, obese, and metabolically-impaired phenotype.

Kisspeptin and its receptor, Kiss1r, act centrally to stimulate reproduction. Recent evidence indicates that kisspeptin is also important for body weight and metabolism, as whole-body Kiss1r KO mice, developed with gene trap technology, display obesity and reduced metabolism. Kiss1r is expressed in brain and multiple peripheral tissues, but it is unknown which is responsible for the metabolic phenotype. Here, we sought to confirm that 1) the metabolic phenotype of the gene trap Kiss1r KOs is due to disruption of kisspeptin signaling and not off-target effects of viral mutagenesis, and 2) the Kiss1r flox line is suitable for creating conditional KOs to study the metabolic phenotype. We used Cre/lox technology (Zp3-Cre/Kiss1r flox) to develop a new global Kiss1r KO ("Kiss1r gKO") to compare with the original gene trap KO phenotype. We confirmed that deleting exon 2 of Kiss1r from the entire body induces hypogonadism in both sexes. Moreover, global deletion of Kiss1r induced obesity in females, but not males, along with increased adiposity and impaired glucose tolerance, similar to the gene trap Kiss1r KOs. Likewise, Kiss1r gKO females had decreased VO2 and VCO2, likely underlying their obesity. These findings support that our previous results in gene trap Kiss1r KOs are due to disrupted kisspeptin signaling, and further highlight a role for Kiss1r signaling in energy expenditure and metabolism besides controlling reproduction. Moreover, given Kiss1r expression in multiple cell-types, our findings indicate that the Kiss1r flox line is viable for future investigations to isolate specific target cells of kisspeptin's metabolic effects

A feasibility study of a microgravity enhancement system for Space Station Freedom

The current low frequency microgravity requirements for Space Station Freedom (SSF) call for a level of less than 1 micro-g over 50 percent of all the laboratory racks for continuous periods of 30 days for at least 180 days per year. While this requirement is attainable for some of the laboratory modules for the Permanently Manned Configuration (PMC), it can not be met for the Man-Tended Configuration (MTC). In addition, many experiments would prefer even lower acceleration levels. To improve the microgravity environment, the Microgravity Enhancement System (MESYS) will apply a continuous thrust to SSF, to negate the disturbing gravity gradient and drag forces. The MESYS consists of a sensor, throttle-able thrusters and a control system. Both a proof mass system and accelerometer were evaluated for use as the sensor. The net result of the MESYS will be to shift the microgravity contours from the center of mass to a chosen location. Results indicate the MESYS is not feasible for MTC since it will require 5,073 kg of hydrazine fuel and 7,660 watts of power for 30 days of operation during average atmospheric conditions. For PMC, the MESYS is much more practical since only 4,008 kg of fuel and 5,640 watts of power are required

The relationship between engineering bachelor qualifications and occupational status in Australia

Internationally, the importance of science, technology, engineering and mathematics (STEM) for innovation and competition drives concerns about the adequacy of national STEM workforces. Data from the UK, USA and Australia suggest that, even immediately post-graduation, a significant proportion of engineering bachelor graduates do not work in engineering roles. Using the 2011 Australian census data, we present an investigation into the relationship between educational qualifications and occupational status of Australian engineering bachelor graduates, and how this status varies specifically with graduate age. We consider the implications of these findings and present recommendations for the recruitment and education of Australian engineering undergraduates. We conclude that engineering students would be better informed about, and equipped for, the world of post-graduation work if they were exposed to the likely options for their career trajectory. Likewise, secondary school students and others considering engineering undergraduate study would be more honestly advised if they were informed about the full range of career possibilities for engineering graduates and the probability that they are just as likely to work out of engineering as in it

Effects of Selective Deletion of Tyrosine Hydroxylase from Kisspeptin Cells on Puberty and Reproduction in Male and Female Mice.

The neuropeptide kisspeptin, encoded by Kiss1, regulates reproduction by stimulating GnRH secretion. Kiss1-syntheizing neurons reside primarily in the hypothalamic anteroventral periventricular (AVPV/PeN) and arcuate (ARC) nuclei. AVPV/PeN Kiss1 neurons are sexually dimorphic, with females expressing more Kiss1 than males, and participate in estradiol (E2)-induced positive feedback control of GnRH secretion. In mice, most AVPV/PeN Kiss1 cells coexpress tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis (in this case, dopamine). Dopamine treatment can inhibit GnRH neurons, but the function of dopamine signaling arising specifically from AVPV/PeN Kiss1 cells is unknown. We generated a novel TH flox mouse and used Cre-Lox technology to selectively ablate TH specifically from Kiss1 cells. We then examined the effects of selective TH knock-out on puberty and reproduction in both sexes. In control mice, 90% of AVPV/PeN Kiss1 neurons coexpressed TH, whereas in mice lacking TH exclusively in Kiss1 cells (termed Kiss THKOs), TH was successfully absent from virtually all Kiss1 cells. Despite this absence of TH, both female and male Kiss THKOs displayed normal body weights, puberty onset, and basal gonadotropin levels in adulthood, although testosterone (T) was significantly elevated in adult male Kiss THKOs. The E2-induced LH surge was unaffected in Kiss THKO females, and neuronal activation status of kisspeptin and GnRH cells was also normal. Supporting this, fertility and fecundity were normal in Kiss THKOs of both sexes. Thus, despite high colocalization of TH and Kiss1 in the AVPV/PeN, dopamine produced in these cells is not required for puberty or reproduction, and its function remains unknown

Masculinity at work: The experiences of men in female dominated occupations

This paper presents the findings of a research project on the implications of men's non-traditional career choices for their experiences within the organization and for gender identity. The research is based on 40 in-depth interviews with male workers from four occupational groups: librarian-ship, cabin crew, nurses and primary school teachers. Results suggest a typology of male workers in female dominated occupations: seekers (who actively seek the career), finders (who find the occupation in the process of making general career decisions) and settlers (who settle into the career after periods of time in mainly male dominated occupations). Men benefit from their minority status through assumptions of enhanced leadership (the assumed authority effect), by being given differential treatment (the special consideration effect) and being associated with a more careerist attitude to work (the career effect). At the same time, they feel comfortable working with women (the zone of comfort effect). Despite this comfort, men adopt a variety of strategies to re-establish a masculinity that has been undermined by the 'feminine' nature of their work. These include re-labeling, status enhancement and distancing from the feminine. The dynamics of maintaining and reproducing masculinities within the non-traditional work setting are discussed in the light of recent theorising around gender, masculinity and work

Feeding back surveillance data to prevent hospital-acquired infections.

We describe the Centers for Disease Control and Prevention's National Nosocomial Infections Surveillance system. Elements of the system critical for successful reduction of nosocomial infection rates include voluntary participation and confidentiality; standard definitions and protocols; identification of populations at high risk; site-specific, risk- adjusted infection rates comparable across institutions; adequate numbers of trained infection control professionals; dissemination of data to health-care providers; and a link between monitored rates and prevention efforts

Imager Evaluation of Diabetic Retinopathy at the Time of Imaging in a Telemedicine Program

Objective: To evaluate the ability of certified retinal imagers to identify presence versus absence of sight-threatening diabetic retinopathy (stDR) (moderate nonproliferative diabetic retinopathy or worse or diabetic macular edema) at the time of retinal imaging in a telemedicine program. Research Design and Methods: Diabetic patients in a primary care setting or specialty diabetes clinic received Joslin Vision Network protocol retinal imaging as part of their care. Trained nonphysician imagers graded the presence versus absence of stDR at the time of imaging. These gradings were compared with masked gradings of certified readers. Results: Of 158 patients (316 eyes) imaged, all cases of stDR (42 eyes [13%]) were identified by the imagers at the time of imaging. Six eyes with mild nonproliferative diabetic retinopathy were graded by the imagers to have stDR (sensitivity 1.00, 95% CI 0.90–1.00; specificity 0.97, 0.94–0.99). Conclusions: Appropriately trained imagers can accurately identify stDR at the time of imaging

The appropriation of hegemonic masculinity within selected research on men's health

Connell's hegemonic masculinity thesis (HMT) has occupied a relatively dominant position within contemporary research exploring the lives of men. Messerschmidt has conducted a review of recent literature that purports to use HMT, he describes in detail some of the ways Connell's work has been appropriated. Taking Messerschmidt's lead, this paper explores a small selection of men's health research that employ HMT as a central organising theme. Such a narrow focus and limited sample enables the theoretical, conceptual and empirical contributions of engagements with Connell's work to be critically explored in detail. This paper provides colleagues with clear examples of ways in which reified and reductive account of masculinity, are still being reproduced in contemporary analyses of men's lives. In calling for researchers to critically reflect upon their usage of Connell's thesis in more detail, my aim is to increase the subtlety and sophistication of such works. A further hope is that by highlighting specific examples of the need to appraise the relevance and adequacy of HMT as a conceptual frame of lived experiences, we might encourage researchers to access the multitude of different theoretical positions that speak to the lives of men

A realistic evaluation : the case of protocol-based care

Background 'Protocol based care' was envisioned by policy makers as a mechanism for delivering on the service improvement agenda in England. Realistic evaluation is an increasingly popular approach, but few published examples exist, particularly in implementation research. To fill this gap, within this paper we describe the application of a realistic evaluation approach to the study of protocol-based care, whilst sharing findings of relevance about standardising care through the use of protocols, guidelines, and pathways. Methods Situated between positivism and relativism, realistic evaluation is concerned with the identification of underlying causal mechanisms, how they work, and under what conditions. Fundamentally it focuses attention on finding out what works, for whom, how, and in what circumstances. Results In this research, we were interested in understanding the relationships between the type and nature of particular approaches to protocol-based care (mechanisms), within different clinical settings (context), and what impacts this resulted in (outcomes). An evidence review using the principles of realist synthesis resulted in a number of propositions, i.e., context, mechanism, and outcome threads (CMOs). These propositions were then 'tested' through multiple case studies, using multiple methods including non-participant observation, interviews, and document analysis through an iterative analysis process. The initial propositions (conjectured CMOs) only partially corresponded to the findings that emerged during analysis. From the iterative analysis process of scrutinising mechanisms, context, and outcomes we were able to draw out some theoretically generalisable features about what works, for whom, how, and what circumstances in relation to the use of standardised care approaches (refined CMOs). Conclusions As one of the first studies to apply realistic evaluation in implementation research, it was a good fit, particularly given the growing emphasis on understanding how context influences evidence-based practice. The strengths and limitations of the approach are considered, including how to operationalise it and some of the challenges. This approach provided a useful interpretive framework with which to make sense of the multiple factors that were simultaneously at play and being observed through various data sources, and for developing explanatory theory about using standardised care approaches in practice