Global parameter search reveals design principles of the mammalian circadian clock

Background: Virtually all living organisms have evolved a circadian (~24 hour) clock that controls physiological and behavioural processes with exquisite precision throughout the day/night cycle. The suprachiasmatic nucleus (SCN), which generates these ~24 h rhythms in mammals, consists of several thousand neurons. Each neuron contains a gene-regulatory network generating molecular oscillations, and the individual neuron oscillations are synchronised by intercellular coupling, presumably via neurotransmitters. Although this basic mechanism is currently accepted and has been recapitulated in mathematical models, several fundamental questions about the design principles of the SCN remain little understood. For example, a remarkable property of the SCN is that the phase of the SCN rhythm resets rapidly after a 'jet lag' type experiment, i.e. when the light/ dark (LD) cycle is abruptly advanced or delayed by several hours. Results: Here, we describe an extensive parameter optimization of a previously constructed simplified model of the SCN in order to further understand its design principles. By examining the top 50 solutions from the parameter optimization, we show that the neurotransmitters' role in generating the molecular circadian rhythms is extremely important. In addition, we show that when a neurotransmitter drives the rhythm of a system of coupled damped oscillators, it exhibits very robust synchronization and is much more easily entrained to light/dark cycles. We were also able to recreate in our simulations the fast rhythm resetting seen after a 'jet lag' type experiment. Conclusion: Our work shows that a careful exploration of parameter space for even an extremely simplified model of the mammalian clock can reveal unexpected behaviours and non-trivial predictions. Our results suggest that the neurotransmitter feedback loop plays a crucial role in the robustness and phase resetting properties of the mammalian clock, even at the single neuron level

Impacts of organic and conventional crop management on diversity and activity of free-living nitrogen fixing bacteria and total bacteria are subsidiary to temporal effects

A three year field study (2007-2009) of the diversity and numbers of the total and metabolically active free-living diazotophic bacteria and total bacterial communities in organic and conventionally managed agricultural soil was conducted at the Nafferton Factorial Systems Comparison (NFSC) study, in northeast England. The result demonstrated that there was no consistent effect of either organic or conventional soil management across the three years on the diversity or quantity of either diazotrophic or total bacterial communities. However, ordination analyses carried out on data from each individual year showed that factors associated with the different fertility management measures including availability of nitrogen species, organic carbon and pH, did exert significant effects on the structure of both diazotrophic and total bacterial communities. It appeared that the dominant drivers of qualitative and quantitative changes in both communities were annual and seasonal effects. Moreover, regression analyses showed activity of both communities was significantly affected by soil temperature and climatic conditions. The diazotrophic community showed no significant change in diversity across the three years, however, the total bacterial community significantly increased in diversity year on year. Diversity was always greatest during March for both diazotrophic and total bacterial communities. Quantitative analyses using qPCR of each community indicated that metabolically active diazotrophs were highest in year 1 but the population significantly declined in year 2 before recovering somewhat in the final year. The total bacterial population in contrast increased significantly each year. Seasonal effects were less consistent in this quantitative study

Can Broader Diffusion of Value-Based Insurance Design Increase Benefits from US Health Care without Increasing Costs? Evidence from a Computer Simulation Model

Using a computer simulation based on US data, R. Scott Braithwaite and colleagues calculate the benefits of value-based insurance design, in which patients pay less for highly cost-effective services

Crack formation and prevention in colloidal drops

Crack formation is a frequent result of residual stress release from colloidal films made by the evaporation of colloidal droplets containing nanoparticles. Crack prevention is a significant task in industrial applications such as painting and inkjet printing with colloidal nanoparticles. Here, we illustrate how colloidal drops evaporate and how crack generation is dependent on the particle size and initial volume fraction, through direct visualization of the individual colloids with confocal laser microscopy. To prevent crack formation, we suggest use of a versatile method to control the colloid-polymer interactions by mixing a nonadsorbing polymer with the colloidal suspension, which is known to drive gelation of the particles with short-range attraction. Gelation-driven crack prevention is a feasible and simple method to obtain crack-free, uniform coatings through drying-mediated assembly of colloidal nanoparticlesopen0

Risk-taking attitudes and their association with process and outcomes of cardiac care: a cohort study

<p>Abstract</p> <p>Background</p> <p>Prior research reveals that processes and outcomes of cardiac care differ across sociodemographic strata. One potential contributing factor to such differences is the personality traits of individuals within these strata. We examined the association between risk-taking attitudes and cardiac patients' clinical and demographic characteristics, the likelihood of undergoing invasive cardiac procedures and survival.</p> <p>Methods</p> <p>We studied a large inception cohort of patients who underwent cardiac catheterization between July 1998 and December 2001. Detailed clinical and demographic data were collected at time of cardiac catheterization and through a mailed survey one year post-catheterization. The survey included three general risk attitude items from the Jackson Personality Inventory. Patients' (n = 6294) attitudes toward risk were categorized as risk-prone versus non-risk-prone and were assessed for associations with baseline clinical and demographic characteristics, treatment received (i.e., medical therapy, coronary artery bypass graft (CABG) surgery, percutaneous coronary intervention (PCI)), and survival (to December 2005).</p> <p>Results</p> <p>2827 patients (45%) were categorized as risk-prone. Having risk-prone attitudes was associated with younger age (p < .001), male sex (p < .001), current smoking (p < .001) and higher household income (p < .001). Risk-prone patients were more likely to have CABG surgery in unadjusted (Odds Ratio [OR] = 1.21; 95% CI 1.08–1.36) and adjusted (OR = 1.18; 95% CI 1.02–1.36) models, but were no more likely to have PCI or any revascularization. Having risk-prone attitudes was associated with better survival in an unadjusted survival analysis (Hazard Ratio [HR] = 0.78 (95% CI 0.66–0.93), but not in a risk-adjusted analysis (HR = 0.92, 95% CI 0.77–1.10).</p> <p>Conclusion</p> <p>These exploratory findings suggest that patient attitudes toward risk taking may <b>contribute to </b>some of the documented differences in use of invasive cardiac procedures. An awareness of these associations could help healthcare providers as they counsel patients regarding cardiac care decisions.</p

Prokineticin 2 Regulates the Electrical Activity of Rat Suprachiasmatic Nuclei Neurons

Neuropeptide signaling plays roles in coordinating cellular activities and maintaining robust oscillations within the mammalian suprachiasmatic nucleus (SCN). Prokineticin2 (PK2) is a signaling molecule from the SCN and involves in the generation of circadian locomotor activity. Prokineticin receptor 2 (PKR2), a receptor for PK2, has been shown to be expressed in the SCN. However, very little is known about the cellular action of PK2 within the SCN. In the present study, we investigated the effect of PK2 on spontaneous firing and miniature inhibitory postsynaptic currents (mIPSCs) using whole cell patch-clamp recording in the SCN slices. PK2 dose-dependently increased spontaneous firing rates in most neurons from the dorsal SCN. PK2 acted postsynaptically to reduce γ-aminobutyric acid (GABA)-ergic function within the SCN, and PK2 reduced the amplitude but not frequency of mIPSCs. Furthermore, PK2 also suppressed exogenous GABA-induced currents. And the inhibitory effect of PK2 required PKC activation in the postsynaptic cells. Our data suggest that PK2 could alter cellular activities within the SCN and may influence behavioral and physiological rhythms

Clients’ satisfaction with quality of childbirth services: A comparative study between public and private facilities in Limuru Sub-County, Kiambu, Kenya

Background: This study intended to compare the clients’ satisfaction with the quality of childbirth services in a private and public facility amongst mothers who have delivered within the last twenty four to seventy hours. Methods: This was a cross-sectional comparative research design with both quantitative and qualitative data collection and analysis methods. Data were collected through a focused group discussion guide and structured questionnaire collecting information on clients’ satisfaction with quality of childbirth services. The study was conducted amongst women of reproductive age (WRA) between 15-49 years in Tigoni District hospital (public hospital) and Limuru Nursing home (private hospital). For quantitative data we conducted descriptive analysis and Mann-Whitney test using SPSS version 20.0 while qualitative data was manually analyzed manually using thematic analysis. Results: A higher proportion of clients from private facility 98.1% were attended within 0-30 minutes of arrival to the facility as compared to 87% from public facility. The overall mean score showed that the respondents in public facility gave to satisfaction with the services was 4.46 out of a maximum of 5.00 score while private facility gave 4.60. The level of satisfaction amongst respondents in the public facility on pain relief after delivery was statistically significantly higher than the respondents in private facilities (U=8132.50, p<0.001) while the level of satisfaction amongst respondents in the public facility on functional equipment was statistically significantly higher than the respondents in private facilities (U=9206.50, p=0.001). Moreover, level of satisfaction with the way staff responded to questions and concerns during labour and delivery was statistically significantly higher than the respondents in private facilities (U=9964.50, p=0.022). Conclusion: In overall, majority of clients from both public and private facilities expressed satisfaction with quality of services from admission till discharge in both public and private facilities and were willing to recommend other to come and deliver in the respective facilities

Scaffolding teacher learning: Examining teacher practice and the professional development process of teachers with culturally and linguistically diverse (CLD) learners.

Teachers work in complex and demanding times with an increasing number of students from culturally and linguistically diverse backgrounds (CLD) in classrooms. These students are over represented in statistics of under achievement. All teachers are teachers of academic language, and while no child is born with school language as a first language, for some students the match between home and school is more closely aligned than for other students. Teachers are expected to be culturally responsive, ensuring the languages and culture of students is visible in the classroom environment and the classroom curriculum. Despite the increasing knowledge about the specific strategies and approaches that will most effectively support CLD students in classrooms, the teaching of CLD students within mainstream contexts remains far from ideal. Teachers need support to access the principles of effective teaching of CLD learners that are available, and importantly to transfer the knowledge into classroom practice. Professional development and learning is linked to improved teacher practice and student learning outcomes. When teachers have opportunities to be engaged in successful elements of in-depth professional learning such as in-class modelling, observation and feedback, and co-construction of teaching and planning they are able to demonstrate improved pedagogical content knowledge. Their beliefs may also need to be challenged. The study was conducted in two schools in a large city in New Zealand where I am employed as an ESOL and literacy adviser. Using an action research method I was able to examine how a professional development and learning process shaped my own knowledge and practice as well as teacher knowledge and practice. The study fills a research space to gain insights into the effective professional learning processes that impact on teacher strategies and approaches with their CLD learners A central tenet of this research is that teachers can improve their practice of teaching CLD students and they can specifically learn strategies and approaches that are considered effective for them