Response variability in balanced cortical networks

We study the spike statistics of neurons in a network with dynamically balanced excitation and inhibition. Our model, intended to represent a generic cortical column, comprises randomly connected excitatory and inhibitory leaky integrate-and-fire neurons, driven by excitatory input from an external population. The high connectivity permits a mean-field description in which synaptic currents can be treated as Gaussian noise, the mean and autocorrelation function of which are calculated self-consistently from the firing statistics of single model neurons. Within this description, we find that the irregularity of spike trains is controlled mainly by the strength of the synapses relative to the difference between the firing threshold and the post-firing reset level of the membrane potential. For moderately strong synapses we find spike statistics very similar to those observed in primary visual cortex.Comment: 22 pages, 7 figures, submitted to Neural Computatio

Refusal to enrol in Ghana's National Health Insurance Scheme: is affordability the problem?

BACKGROUND: Access to health insurance is expected to have positive effect in improving access to healthcare and offer financial risk protection to households. Ghana began the implementation of a National Health Insurance Scheme (NHIS) in 2004 as a way to ensure equitable access to basic healthcare for all residents. After a decade of its implementation, national coverage is just about 34% of the national population. Affordability of the NHIS contribution is often cited by households as a major barrier to enrolment in the NHIS without any rigorous analysis of this claim. In light of the global interest in achieving universal health insurance coverage, this study seeks to examine the extent to which affordability of the NHIS contribution is a barrier to full insurance for households and a burden on their resources. METHODS: The study uses data from a cross-sectional household survey involving 2,430 households from three districts in Ghana conducted between January-April, 2011. Affordability of the NHIS contribution is analysed using the household budget-based approach based on the normative definition of affordability. The burden of the NHIS contributions to households is assessed by relating the expected annual NHIS contribution to household non-food expenditure and total consumption expenditure. Households which cannot afford full insurance were identified. RESULTS: Results show that 66% of uninsured households and 70% of partially insured households could afford full insurance for their members. Enroling all household members in the NHIS would account for 5.9% of household non-food expenditure or 2.0% of total expenditure but higher for households in the first (11.4%) and second (7.0%) socio-economic quintiles. All the households (29%) identified as unable to afford full insurance were in the two lower socio-economic quintiles and had large household sizes. Non-financial factors relating to attributes of the insurer and health system problems also affect enrolment in the NHIS. CONCLUSION: Affordability of full insurance would be a burden on households with low socio-economic status and large household size. Innovative measures are needed to encourage abled households to enrol. Policy should aim at abolishing the registration fee for children, pricing insurance according to socio-economic status of households and addressing the inimical non-financial factors to increase NHIS coverage

Inclusion of the value of herd immunity in economic evaluations of vaccines. A systematic review of methods used.

OBJECTIVE: The objectives of this review were to identify vaccine economic evaluations that include herd immunity and describe the methodological approaches used. METHODS: We used Kim and Goldie's search strategy from a systematic review (1976-2007) of modelling approaches used in vaccine economic evaluations and additionally searched PubMed/MEDLINE and Embase for 2007-2015. Studies were classified according to modelling approach used. Methods for estimating herd immunity effects were described, in particular for the static models. RESULTS: We identified 625 economic evaluations of vaccines against human-transmissible diseases from 1976 to 2015. Of these, 172 (28%) included herd immunity. While 4% of studies included herd immunity in 2001, 53% of those published in 2015 did this. Pneumococcal, human papilloma and rotavirus vaccines represented the majority of studies (63%) considering herd immunity. Ninety-five of the 172 studies utilised a static model, 59 applied a dynamic model, eight a hybrid model and ten did not clearly state which method was used. Relatively crude methods and assumptions were used in the majority of the static model studies. CONCLUSION: The proportion of economic evaluations using a dynamic model has increased in recent years. However, 55% of the included studies used a static model for estimating herd immunity. Values from a static model can only be considered reliable if high quality surveillance data are incorporated into the analysis. Without this, the results are questionable and they should only be included in sensitivity analysis

Dynamic look at DNA unwinding by a replicative helicase

A prerequisite for DNA replication is the unwinding of duplex DNA catalyzed by a replicative hexameric helicase. Despite a growing body of research, key elements of helicase mechanism remain under substantial debate. In particular, the number of DNA strands encircled by the helicase ring during unwinding and the ring orientation at the replication fork completely contrast in contemporary mechanistic models. Here we use single-molecule and ensemble assays to address these questions for the papillomavirus E1 helicase. We find that E1 unwinds DNA with a strand-exclusion mechanism, with the N-terminal side of the helicase ring facing the replication fork. We show that E1 generates strikingly heterogeneous unwinding patterns stemming from varying degrees of repetitive movements, which is modulated by the DNA-binding domain. Together, our studies reveal previously unrecognized dynamic facets of replicative helicase unwinding mechanisms

Anti-parasitic activity of pelleted sainfoin (Onobrychis viciifolia) against Ostertagia ostertagi and Cooperia oncophora in calves

BACKGROUND: Increasing anthelmintic-resistance in nematodes of ruminants emphasises the need for sustainable parasite control. Condensed tannin-containing legume forages such as sainfoin (Onobrychis viciifolia) have shown promising anthelmintic properties in small ruminants but this has never been explored in cattle. Therefore, our aim was to examine the efficacy of sainfoin against cattle nematodes in vivo. METHODS: Fifteen Jersey male calves (2–4 month-old) were allocated into two groups and fed isoproteic and isoenergetic diets mainly composed of sainfoin pellets (Group SF; n = 9, three pens) or concentrate and grass-clover hay (Group CO; n = 6, two pens). After 16 days of adaptation, all animals were experimentally infected with 10,000 and 66,000 third-stage larvae of Ostertagia ostertagi and Cooperia oncophora, respectively. Egg excretion, blood parameters and bodyweights were recorded throughout the study. Worms were harvested by sieving for quantification and scanning electron microscopy (SEM) 42 days post-infection (dpi) when the calves were necropsied. RESULTS: The number of O. ostertagi adults in the abomasum was reduced by 50 % in Group SF compared with Group CO (P < 0.05). This was further reflected in higher albumin (P < 0.1) and lower pepsinogen levels (P < 0.05) in Group SF at 21 dpi, and structural damage of the worm cuticle could be visualised by SEM. Yet, the nematode egg excretion in Group SF was not significantly different from that of the controls (P > 0.05). Likewise, no statistical difference in total worm burdens of C. oncophora was found between the groups. Weight gains were lower for Group SF (P < 0.05), which may reflect lower digestibility and phosphorus levels in the SF diet, despite similar feed intake at pen-level. CONCLUSIONS: Overall, the effect of sainfoin on abomasal nematodes corroborates results from studies with small ruminants and encourages further investigations of the use of this crop for control of cattle nematodes

Household experience and costs of seeking measles vaccination in rural Guinea-Bissau.

OBJECTIVES: Children younger than 12 months of age are eligible for childhood vaccines through the public health system in Guinea-Bissau. To limit open vial wastage, a restrictive vial opening policy has been implemented; 10-dose measles vaccine vials are only opened if six or more children aged 9-11 months are present at the vaccination post. Consequently, mothers who bring their child for measles vaccination can be told to return another day. We aimed to describe the household experience and estimate household costs of seeking measles vaccination in rural Guinea-Bissau. METHODS: Within a national sample of village clusters under demographic surveillance, we interviewed mothers of children aged 9-21 months about their experience with seeking measles vaccination. From information about time and money spent, we calculated household costs of seeking measles vaccination. RESULTS: We interviewed mothers of 1308 children of whom 1043 (80%) had sought measles vaccination at least once. Measles vaccination coverage was 70% (910/1308). Coverage decreased with increasing distance to the health centre. On average, mothers who had taken their child for vaccination took their child 1.4 times. Mean costs of achieving 70% coverage were 2.04 USD (SD 3.86) per child taken for vaccination. Half of the mothers spent more than 2 h seeking vaccination and 11% spent money on transportation. CONCLUSIONS: We found several indications of missed opportunities for measles vaccination resulting in suboptimal coverage. The household costs comprised 3.3% of the average monthly income and should be taken into account when assessing the costs of delivering vaccinations