Analytical study of electro-osmosis modulated capillary peristaltic hemodynamics

A mathematical model is developed to analyse electro-kinetic effects on unsteady peristaltic transport of blood in cylindrical vessels of finite length. The Newtonian viscous model is adopted. The analysis is restricted under Debye-Hückel linearization (i.e. wall zeta potential less than or equal to 25mV is sufficiently small). The transformed, non-dimensional conservation equations are derived via lubrication theory and long wavelength and the resulting linearized boundary value problem is solved exactly. The case of a thin electric double layer (i.e. where only slip electro-osmotic velocity considered) is retrieved as a particular case of the present model. The response in pumping characteristics (axial velocity, pressure gradient or difference, volumetric flow rate, local wall shear stress) to the influence of electro-osmotic effect (inverse Debye length) and Helmholtz-Smoluchowski velocity is elaborated in detail. Visualization of trapping phenomenon is also included and the bolus dynamics evolution with electro-kinetic effects examined. A comparative study of train wave propagation and single wave propagation is presented under the effects of thickness of EDL and external electric field. The study is relevant to electrophoresis in haemotology, electrohydrodynamic therapy and biomimetic electro-osmotic pumps

Reviewing progress: 7 Year Trends in Characteristics of Adults and Children Enrolled at HIV Care and Treatment Clinics in the United Republic of Tanzania.

To evaluate the on-going scale-up of HIV programs, we assessed trends in patient characteristics at enrolment and ART initiation over 7 years of implementation. Data were from Optimal Models, a prospective open cohort study of HIV-infected (HIV+) adults (>=15 years) and children (<15 years) enrolled from January 2005 to December 2011 at 44 HIV clinics in 3 regions of mainland Tanzania (Kagera, Kigoma, Pwani) and Zanzibar. Comparative statistics for trends in characteristics of patients enrolled in 2005--2007, 2008--2009 and 2010--2011 were examined. Overall 62,801 HIV+ patients were enrolled: 58,102(92.5%) adults, (66.5% female); 4,699(7.5%) children.Among adults, pregnant women enrolment increased: 6.8%, 2005--2007; 12.1%, 2008--2009; 17.2%, 2010--2011; as did entry into care from prevention of mother-to-child HIV transmission (PMTCT) programs: 6.6%, 2005--2007; 9.5%, 2008--2009; 12.6%, 2010--2011. WHO stage IV at enrolment declined: 27.1%, 2005--2007; 20.2%, 2008--2009; 11.1% 2010--2011. Of the 42.5% and 29.5% with CD4+ data at enrolment and ART initiation respectively, median CD4+ count increased: 210cells/muL, 2005--2007; 262cells/muL, 2008--2009; 266cells/muL 2010--2011; but median CD4+ at ART initiation did not change (148cells/muL overall). Stavudine initiation declined: 84.9%, 2005--2007; 43.1%, 2008--2009; 19.7%, 2010--2011.Among children, median age (years) at enrolment decreased from 6.1(IQR:2.7-10.0) in 2005--2007 to 4.8(IQR:1.9-8.6) in 2008--2009, and 4.1(IQR:1.5-8.1) in 2010--2011 and children <24 months increased from 18.5% to 26.1% and 31.5% respectively. Entry from PMTCT was 7.0%, 2005--2007; 10.7%, 2008--2009; 15.0%, 2010--2011. WHO stage IV at enrolment declined from 22.9%, 2005--2007, to 18.3%, 2008--2009 to 13.9%, 2010--2011. Proportion initiating stavudine was 39.8% 2005--2007; 39.5%, 2008--2009; 26.1%, 2010--2011. Median age at ART initiation also declined significantly. Over time, the proportion of pregnant women and of adults and children enrolled from PMTCT programs increased. There was a decline in adults and children with advanced HIV disease at enrolment and initiation of stavudine. Pediatric age at enrolment and ART initiation declined. Results suggest HIV program maturation from an emergency response

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

&lt;p&gt;Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.&lt;/p&gt; &lt;p&gt;Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93–1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93–1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82–1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (&#60;2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76–1.10]).&lt;/p&gt; &lt;p&gt;Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).&lt;/p&gt

Responses of marine benthic microalgae to elevated CO<inf>2</inf>

Increasing anthropogenic CO2 emissions to the atmosphere are causing a rise in pCO2 concentrations in the ocean surface and lowering pH. To predict the effects of these changes, we need to improve our understanding of the responses of marine primary producers since these drive biogeochemical cycles and profoundly affect the structure and function of benthic habitats. The effects of increasing CO2 levels on the colonisation of artificial substrata by microalgal assemblages (periphyton) were examined across a CO2 gradient off the volcanic island of Vulcano (NE Sicily). We show that periphyton communities altered significantly as CO2 concentrations increased. CO2 enrichment caused significant increases in chlorophyll a concentrations and in diatom abundance although we did not detect any changes in cyanobacteria. SEM analysis revealed major shifts in diatom assemblage composition as CO2 levels increased. The responses of benthic microalgae to rising anthropogenic CO2 emissions are likely to have significant ecological ramifications for coastal systems. © 2011 Springer-Verlag

Of monkeys and men:Impatience in perceptual decision-making

For decades sequential sampling models have successfully accounted for human and monkey decision-making, relying on the standard assumption that decision makers maintain a pre-set decision standard throughout the decision process. Based on the theoretical argument of reward rate maximization, some authors have recently suggested that decision makers become increasingly impatient as time passes and therefore lower their decision standard. Indeed, a number of studies show that computational models with an impatience component provide a good fit to human and monkey decision behavior. However, many of these studies lack quantitative model comparisons and systematic manipulations of rewards. Moreover, the often-cited evidence from single-cell recordings is not unequivocal and complimentary data from human subjects is largely missing. We conclude that, despite some enthusiastic calls for the abandonment of the standard model, the idea of an impatience component has yet to be fully established; we suggest a number of recently developed tools that will help bring the debate to a conclusive settlement

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Interaction of smoking and occupational noise exposure on hearing loss: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Noise is the most common hazardous agent at workplaces. Noise induced hearing loss (NIHL) has been known since the industrial revolution. Although NIHL is permanent, irreversible and frequent, it is preventable. The economic costs of NIHL have been estimated to be about billions of dollars. Besides, cigarette smoking is a common habit worldwide, and according to some recent studies smoking and noise may act in common causal pathways for hearing loss.</p> <p>Methods</p> <p>A cross-sectional study was designed to study the effect of smoking on NIHL in 206 male smoker workers and 206 male non-smoker workers in a large food-producing factory, in which workers were exposed to noise levels exceeding 85dBA. To determine noise exposure level, we used sound level measurements reported by industrial hygienists.</p> <p>A qualified audiologist assessed hearing acuity by using standardized audiometric procedures assuring at least 14 h of noise avoidance.</p> <p>Results</p> <p>We observed that the percentage of workers with hearing threshold differences of greater than or equal to 30 dB between 4000 Hz and 1000 Hz in both ears were 49.5% and 11.2% in smoker and non smoker groups, respectively (Odds ratio = 7.8, 95% CI = 4.7 – 13), and the percentage of workers with a hearing threshold of greater than 25dB at 4000 Hz in the better ear were 63.6% and 18.4% in smoker and non smoker groups, respectively. This difference was statistically significant after adjustment for age and exposure duration.</p> <p>Conclusion</p> <p>It can be concluded that smoking can accelerate noise induced hearing loss, but more research is needed to understand the underlying mechanisms. Accurate follow up of smoker workers who are exposed to noise levels exceeding 85 dBA is suggested. Smokers should periodically attend educational courses on "smoking cessation", especially in noisy workplaces.</p

Control of Cerebellar Long-Term Potentiation by P-Rex-Family Guanine-Nucleotide Exchange Factors and Phosphoinositide 3-Kinase

Long-term potentiation (LTP) at the parallel fibre-Purkinje cell synapse in the cerebellum is a recently described and poorly characterized form of synaptic plasticity. The induction mechanism for LTP at this synapse is considered reciprocal to "classical" LTP at hippocampal CA1 pyramidal neurons: kinases promote increased trafficking of AMPA receptors into the postsynaptic density in the hippocampus, whereas phosphatases decrease internalization of AMPA receptors in the cerebellum. In the hippocampus, LTP occurs in overlapping phases, with the transition from early to late phases requiring the consolidation of initial induction processes by structural re-arrangements at the synapse. Many signalling pathways have been implicated in this process, including PI3 kinases and Rho GTPases.We hypothesized that analogous phases are present in cerebellar LTP, and took as the starting point for investigation our recent discovery that P-Rex--a Rac guanine nucleotide exchange factor which is activated by PtdIns(3,4,5)P(3)--is highly expressed in mouse cerebellar Purkinje neurons and plays a role in motor coordination. We found that LTP evoked at parallel fibre synapses by 1 Hz stimulation or by NO donors was not sustained beyond 30 min when P-Rex was eliminated or Rac inhibited, suggesting that cerebellar LTP exhibits a late phase analogous to hippocampal LTP. In contrast, inhibition of PI3 kinase activity eliminated LTP at the induction stage.Our data suggest that a PI3K/P-Rex/Rac pathway is required for late phase LTP in the mouse cerebellum, and that other PI3K targets, which remain to be discovered, control LTP induction

Inhibition of alpha-synuclein fibrillization by dopamine is mediated by interactions with five C-terminal residues and with E83 in the NAC region

The interplay between dopamine and alpha-synuclein (AS) plays a central role in Parkinson's disease (PD). PD results primarily from a severe and selective devastation of dopaminergic neurons in substantia nigra pars compacta. The neuropathological hallmark of the disease is the presence of intraneuronal proteinaceous inclusions known as Lewy bodies within the surviving neurons, enriched in filamentous AS. In vitro, dopamine inhibits AS fibril formation, but the molecular determinants of this inhibition remain obscure. Here we use molecular dynamic (MD) simulations to investigate the binding of dopamine and several of its derivatives onto conformers representative of an NMR ensemble of AS structures in aqueous solution. Within the limitations inherent to MD simulations of unstructured proteins, our calculations suggest that the ligands bind to the (125)YEMPS(129) region, consistent with experimental findings. The ligands are further stabilized by long-range electrostatic interactions with glutamate 83 (E83) in the NAC region. These results suggest that by forming these interactions with AS, dopamine may affect AS aggregation and fibrillization properties. To test this hypothesis, we investigated in vitro the effects of dopamine on the aggregation of mutants designed to alter or abolish these interactions. We found that point mutations in the (125)YEMPS(129) region do not affect AS aggregation, which is consistent with the fact that dopamine interacts non-specifically with this region. In contrast, and consistent with our modeling studies, the replacement of glutamate by alanine at position 83 (E83A) abolishes the ability of dopamine to inhibit AS fibrillization