The role of insulin receptor substrate 2 in hypothalamic and β cell function

Insulin receptor substrate 2 (Irs2) plays complex roles in energy homeostasis. We generated mice lacking Irs2 in β cells and a population of hypothalamic neurons (RIPCreIrs2KO), in all neurons (NesCreIrs2KO), and in proopiomelanocortin neurons (POMCCreIrs2KO) to determine the role of Irs2 in the CNS and β cell. RIPCreIrs2KO mice displayed impaired glucose tolerance and reduced β cell mass. Overt diabetes did not ensue, because β cells escaping Cre-mediated recombination progressively populated islets. RIPCreIrs2KO and NesCreIrs2KO mice displayed hyperphagia, obesity, and increased body length, which suggests altered melanocortin action. POMCCreIrs2KO mice did not display this phenotype. RIPCreIrs2KO and NesCreIrs2KO mice retained leptin sensitivity, which suggests that CNS Irs2 pathways are not required for leptin action. NesCreIrs2KO and POMCCreIrs2KO mice did not display reduced β cell mass, but NesCreIrs2KO mice displayed mild abnormalities of glucose homeostasis. RIPCre neurons did not express POMC or neuropeptide Y. Insulin and a melanocortin agonist depolarized RIPCre neurons, whereas leptin was ineffective. Insulin hyperpolarized and leptin depolarized POMC neurons. Our findings demonstrate a critical role for IRS2 in β cell and hypothalamic function and provide insights into the role of RIPCre neurons, a distinct hypothalamic neuronal population, in growth and energy homeostasis

The role of insulin receptor substrate 2 in hypothalamic and beta cell function

Insulin receptor substrate 2 (Irs2) plays complex roles in energy homeostasis. We generated mice lacking Irs2 in beta cells and a population of hypothalamic neurons (RIPCreIrs2KO), in all neurons (NesCreIrs2KO), and in proopiomelanocortin neurons (POMCCreIrs2KO) to determine the role of Irs2 in the CNS and beta cell. RIPCreIrs2KO mice displayed impaired glucose tolerance and reduced P cell mass. Overt diabetes did not ensue, because beta cells escaping Cre-mediated recombination progressively populated islets. RIPCreIrs2KO and NesCreIrs2KO mice displayed hyperphagia, obesity, and increased body length, which suggests altered melanocortin action. POMCCreIrs2KO mice did not display this phenotype. RIPCreIrs2KO and NesCreIrs2KO mice retained leptin sensitivity, which suggests that CNS Irs2 pathways are not required for leptin action. NesCreIrs2KO and POMCCreIrs2KO mice did not display reduced beta cell mass, but NesCreIrs2KO mice displayed mild abnormalities of glucose homeostasis. RIPCre neurons did not express POMC or neuropeptide Y. Insulin and a melanocortin agonist depolarized RIPCre neurons, whereas leptin was ineffective. Insulin hyperpolarized and leptin depolarized POMC neurons. Our findings demonstrate a critical role for IRS2 in beta cell and hypothalamic function and provide insights into the role of RIPCre neurons, a distinct hypothalamic neuronal population, in growth and energy homeostasis

Challenges in the delivery of e-government through kiosks

Kiosks are increasingly being heralded as a technology through which governments, government departments and local authorities or municipalities can engage with citizens. In particular, they have attractions in their potential to bridge the digital divide. There is some evidence to suggest that the citizen uptake of kiosks and indeed other channels for e-government, such as web sites, is slow, although studies on the use of kiosks for health information provision offer some interesting perspectives on user behaviour with kiosk technology. This article argues that the delivery of e-government through kiosks presents a number of strategic challenges, which will need to be negotiated over the next few years in order that kiosk applications are successful in enhancing accessibility to and engagement with e-government. The article suggests that this involves consideration of: the applications to be delivered through a kiosk; one stop shop service and knowledge architectures; mechanisms for citizen identification; and, the integration of kiosks within the total interface between public bodies and their communities. The article concludes by outlining development and research agendas in each of these areas.</p

Measurement of Forward Jets Produced in High-Transverse-Momentum Hadron-Proton Collisions

A measurement of charged-particle production is reported for the forward region in events triggered by high-transverse-momentum (p⊥) jets and single particles. The momentum distributions of forward-going particles are observed to scale in a simple p⊥-dependent longitudinal variable. Forward-going (beam) jets are observed to be tilted away from the original direction by an amount which agrees with muon-pair data when interpreted in a parton (quantum-chromodynamics) model

Jets Produced in π^-, π^+, and Proton Interactions at 200 GeV on Hydrogen and Aluminum Targets

This paper presents results from an experiment on the production of jets (groups of particles) with high p_⊥ produced in 200-GeV/c interactions. Results are presented on the comparison of jet cross sections on aluminum and hydrogen targets. The jet fragmentation distributions are also examined. Both the cross section and the jet structure are found to depend strongly on the beam and target types

Observation of the Production of Jets of Particles at High Transverse Momentum and Comparison with Inclusive Single-Particle Reactions

Data are presented on production by 200-GeV/c hadrons incident on beryllium of both single particles and jets (groups of particles) with high p_T (transverse momentum). The experiment was performed in a wide-aperture multiparticle spectrometer at Fermilab. The jet and single-particle cross sections have a similar shape from p_T=3 to 5 GeV/c but the jet cross section is over two orders of magnitude larger. The distributions of charged-particle momenta show striking similarities to those observed in lepton-induced processes

Experimental Tests of Quantum Chromodynamics in High-p_⊥ Jet Production in 200-GeV/c Hadron-Proton Collisions

Data on inclusive jet production in the transverse-momentum (p_⊥) range 0-8 GeV/c for 200-GeV/c p, π^-, π^+, K^-, K^+, and p incident on a hydrogen target are presented. The jet cross section is fully corrected for losses and biases, and compared with the predictions of a model based on quantum chromodynamics. Both the absolute cross section and the inclusive charged-particle distributions inside and outside the jet are in qualitative agreement with the model

Supporting perinatal anxiety in the digital age; a qualitative exploration of stressors and support strategies

Background The period surrounding childbirth is one of profound change, which can often be experienced as stressful and overwhelming. Indeed, around 20% of women may experience significant levels of anxiety in the perinatal period. However, most women experiencing perinatal anxiety (PNA) go unrecognised and untreated. The Internet offers a potentially scalable solution to improve access to support, however a dearth of research in this area means that work is needed to better understand women’s experience of PNA, so that potential targets for intervention can be identified and possible barriers to support overcome. This study aimed to qualitatively explore women’s experience of anxiety triggers and support in the perinatal period; and gain insight into what online support is acceptable for women with PNA. Methods Women who were either pregnant or within one-year postpartum were invited to participate in focus groups across the UK. Focus groups were used to allow a diversity of perspectives to be heard, while simultaneously promoting the identification and prioritisation of important support needs and solutions. Interviews were transcribed and thematically analysed. Results Five key themes emerged in relation to women’s experience with PNA: holding unrealistic expectations of birth and motherhood; stigma; the importance of peer support; uncertainty and poor maternal confidence; and a lack of mental health support and knowledge. Perinatal women felt under-supported and poorly prepared for motherhood. A mismatch between their expectations and the reality of their experience, alongside a pressure to be the ‘perfect mum’ was the primary source of their anxiety. Furthermore, stigma associated with PNA may have exacerbated these issues and led to help-seeking avoidance. Overall, women felt these issues could be addressed via online support, through the delivery of more realistic information, providing psychoeducation about PNA symptoms and management, and the inclusion of authentic peer experiences. Thus, delivering evidence-based information and interventions online may provide a solution that is acceptable to this cohort. Conclusions This work provides unique insight into potential sources of anxiety for women in the perinatal period, while also offering potential internet-based support solutions that are likely to be acceptable and helpful for women with PNA

Social, environmental and psychological factors associated with objective physical activity levels in the over 65s

Objective: To assess physical activity levels objectively using accelerometers in community dwelling over 65 s and to examine associations with health, social, environmental and psychological factors. Design: Cross sectional survey. Setting: 17 general practices in Scotland, United Kingdom. Participants: Random sampling of over 65 s registered with the practices in four strata young-old (65–80 years), old-old (over 80 years), more affluent and less affluent groups. Main Outcome Measures: Accelerometry counts of activity per day. Associations between activity and Theory of Planned Behaviour variables, the physical environment, health, wellbeing and demographic variables were examined with multiple regression analysis and multilevel modelling. Results: 547 older people (mean (SD) age 79(8) years, 54% female) were analysed representing 94% of those surveyed. Accelerometry counts were highest in the affluent younger group, followed by the deprived younger group, with lowest levels in the deprived over 80 s group. Multiple regression analysis showed that lower age, higher perceived behavioural control, the physical function subscale of SF-36, and having someone nearby to turn to were all independently associated with higher physical activity levels (R2 = 0.32). In addition, hours of sunshine were independently significantly associated with greater physical activity in a multilevel model. Conclusions: Other than age and hours of sunlight, the variables identified are modifiable, and provide a strong basis for the future development of novel multidimensional interventions aimed at increasing activity participation in later life.Publisher PDFPeer reviewe