STDP Allows Fast Rate-Modulated Coding with Poisson-Like Spike Trains

Spike timing-dependent plasticity (STDP) has been shown to enable single neurons to detect repeatedly presented spatiotemporal spike patterns. This holds even when such patterns are embedded in equally dense random spiking activity, that is, in the absence of external reference times such as a stimulus onset. Here we demonstrate, both analytically and numerically, that STDP can also learn repeating rate-modulated patterns, which have received more experimental evidence, for example, through post-stimulus time histograms (PSTHs). Each input spike train is generated from a rate function using a stochastic sampling mechanism, chosen to be an inhomogeneous Poisson process here. Learning is feasible provided significant covarying rate modulations occur within the typical timescale of STDP (∼10–20 ms) for sufficiently many inputs (∼100 among 1000 in our simulations), a condition that is met by many experimental PSTHs. Repeated pattern presentations induce spike-time correlations that are captured by STDP. Despite imprecise input spike times and even variable spike counts, a single trained neuron robustly detects the pattern just a few milliseconds after its presentation. Therefore, temporal imprecision and Poisson-like firing variability are not an obstacle to fast temporal coding. STDP provides an appealing mechanism to learn such rate patterns, which, beyond sensory processing, may also be involved in many cognitive tasks

Seeing the woods for the trees: the problem of information inefficiency and information overload on operator performance

One of the recurring questions in designing dynamic control environments is whether providing more information leads to better operational decisions. The idea of having every piece of information is increasingly tempting (and in safety critical domains often mandatory) but has become a potential obstacle for designers and operators. The present research study examined this challenge of appropriate information design and usability within a railway control setting. A laboratory study was conducted to investigate the presentation of different levels of information (taken from data processing framework, Dadashi et al., 2014) and the association with, and potential prediction of, the performance of a human operator when completing a cognitively demanding problem solving scenario within railways. Results indicated that presenting users only with information corresponding to their cognitive task, and in the absence of other, non task-relevant information, improves the performance of their problem solving/alarm handling. Knowing the key features of interest to various agents (machine or human) and using the data processing framework to guide the optimal level of information required by each of these agents could potentially lead to safer and more usable designs

The relationship between trust in mass media and the healthcare system and individual health: evidence from the AsiaBarometer Survey

<p>Abstract</p> <p>Background</p> <p>Vertical and horizontal trust, as dimensions of social capital, may be important determinants of health. As mass media campaigns have been used extensively to promote healthy lifestyles and convey health-related information, high levels of individual trust in the media may facilitate the success of such campaigns and, hence, have a positive influence on health. However, few studies have investigated the relationship between trust levels in mass media, an aspect of vertical trust, and health.</p> <p>Methods</p> <p>Based on cross-sectional data of the general population from the AsiaBarometer Survey (2003–2006), we analyzed the relationship between self-rated health and trust in mass media, using a multilevel logistic model, adjusted for age, gender, marital status, income, education, occupation, horizontal trust, and trust in the healthcare system.</p> <p>Results</p> <p>In a total of 39082 participants (mean age 38; 49% male), 26808 (69%) were classified as in good health. By the levels of trust in mass media, there were 6399 (16%) who reported that they trust a lot, 16327 (42%) reporting trust to a degree, 9838 (25%) who do not really trust, 3307 (9%) who do not trust at all, and 191 (0.5%) who have not thought about it. In the multilevel model, trust in mass media was associated with good health (do not trust at all as the base group): the odds ratios (OR) of 1.16 (95% confidence interval (CI) = 1.05–1.27) for do not really trust; OR of 1.35 (95% CI = 1.23–1.49) for trust to a degree, and 1.57 (95% CI = 1.36–1.81) for trust a lot. Horizontal trust and trust in the healthcare system were also associated with health.</p> <p>Conclusion</p> <p>Vertical trust in mass media is associated with better health in Asian people. Since mass media is likely an important arena for public health, media trust should be enhanced to make people healthier.</p

Institutional trust and alcohol consumption in Sweden: The Swedish National Public Health Survey 2006

<p>Abstract</p> <p>Background</p> <p>Trust as a measure of social capital has been documented to be associated with health. Mediating factors for this association are not well investigated. Harmful alcohol consumption is believed to be one of the mediating factors. We hypothesized that low social capital defined as low institutional trust is associated with harmful alcohol consumption.</p> <p>Methods</p> <p>Data from the 2006 Swedish National Survey of Public Health were used for analyses. The total study population comprised a randomly selected representative sample of 26.305 men and 30.584 women aged 16–84 years. Harmful alcohol consumption was measured using a short version the Alcohol Use Disorders Identification Test (AUDIT), developed and recommended by the World Health Organisation. Low institutional trust was defined based on trust in ten main welfare institutions in Sweden.</p> <p>Results</p> <p>Independent of age, country of birth and socioeconomic circumstances, low institutional trust was associated with increased likelihood of harmful alcohol consumption (OR (men) = 1.52, 95% CI 1.34–1.70) and (OR (women) = 1.50, 95% CI 1.35–1.66). This association was marginally altered after adjustment for interpersonal trust.</p> <p>Conclusion</p> <p>Findings of the present study show that lack of trust in institutions is associated with increased likelihood of harmful alcohol consumption. We hope that findings in the present study will inspire similar studies in other contexts and contribute to more knowledge on the association between institutional trust and lifestyle patterns. This evidence may contribute to policies and strategies related to alcohol consumption.</p

Guidance for Evidence-Informed Policies about Health Systems: Linking Guidance Development to Policy Development

In the second paper in a three-part series on health systems guidance, John Lavis and colleagues explore the challenge of linking guidance development and policy development at global and national levels

Has decentralisation affected child immunisation status in Indonesia?

Background: The past two decades have seen many countries, including a number in Southeast Asia, decentralising their health system with the expectation that this reform will improve their citizens’ health. However, the consequences of this reform remain largely unknown. Objective: This study analyses the effects of fiscal decentralisation on child immunisation status in Indonesia. Design: We used multilevel logistic regression analysis to estimate these effects, and multilevel multiple imputation to manage missing data. The 2011 publication of Indonesia's national socio-economic survey (Susenas) is the source of household data, while the Podes village census survey from the same year provides village-level data. We supplement these with local government fiscal data from the Ministry of Finance. Results: The findings show that decentralising the fiscal allocation of responsibilities to local governments has a lack of association with child immunisation status and the results are robust. The results also suggest that increasing the number of village health centres (posyandu) per 1,000 population improves probability of children to receive full immunisation significantly, while increasing that of hospitals and health centres (puskesmas) has no significant effect. Conclusion: These findings suggest that merely decentralising the health system does not guarantee improvement in a country's immunisation coverage. Any successful decentralisation demands good capacity and capability of local governments

Identification of Plasmodium vivax Proteins with Potential Role in Invasion Using Sequence Redundancy Reduction and Profile Hidden Markov Models

BACKGROUND: This study describes a bioinformatics approach designed to identify Plasmodium vivax proteins potentially involved in reticulocyte invasion. Specifically, different protein training sets were built and tuned based on different biological parameters, such as experimental evidence of secretion and/or involvement in invasion-related processes. A profile-based sequence method supported by hidden Markov models (HMMs) was then used to build classifiers to search for biologically-related proteins. The transcriptional profile of the P. vivax intra-erythrocyte developmental cycle was then screened using these classifiers. RESULTS: A bioinformatics methodology for identifying potentially secreted P. vivax proteins was designed using sequence redundancy reduction and probabilistic profiles. This methodology led to identifying a set of 45 proteins that are potentially secreted during the P. vivax intra-erythrocyte development cycle and could be involved in cell invasion. Thirteen of the 45 proteins have already been described as vaccine candidates; there is experimental evidence of protein expression for 7 of the 32 remaining ones, while no previous studies of expression, function or immunology have been carried out for the additional 25. CONCLUSIONS: The results support the idea that probabilistic techniques like profile HMMs improve similarity searches. Also, different adjustments such as sequence redundancy reduction using Pisces or Cd-Hit allowed data clustering based on rational reproducible measurements. This kind of approach for selecting proteins with specific functions is highly important for supporting large-scale analyses that could aid in the identification of genes encoding potential new target antigens for vaccine development and drug design. The present study has led to targeting 32 proteins for further testing regarding their ability to induce protective immune responses against P. vivax malaria

Molecular Dynamics Simulations Suggest that Electrostatic Funnel Directs Binding of Tamiflu to Influenza N1 Neuraminidases

Oseltamivir (Tamiflu) is currently the frontline antiviral drug employed to fight the flu virus in infected individuals by inhibiting neuraminidase, a flu protein responsible for the release of newly synthesized virions. However, oseltamivir resistance has become a critical problem due to rapid mutation of the flu virus. Unfortunately, how mutations actually confer drug resistance is not well understood. In this study, we employ molecular dynamics (MD) and steered molecular dynamics (SMD) simulations, as well as graphics processing unit (GPU)-accelerated electrostatic mapping, to uncover the mechanism behind point mutation induced oseltamivir-resistance in both H5N1 “avian” and H1N1pdm “swine” flu N1-subtype neuraminidases. The simulations reveal an electrostatic binding funnel that plays a key role in directing oseltamivir into and out of its binding site on N1 neuraminidase. The binding pathway for oseltamivir suggests how mutations disrupt drug binding and how new drugs may circumvent the resistance mechanisms

Factors associated with paradoxical immune response to antiretroviral therapy in HIV infected patients: a case control study

<p>Abstract</p> <p>Background</p> <p>A paradoxical immunologic response (PIR) to Highly Active Antiretroviral Therapy (HAART), defined as viral suppression without CD4 cell-count improvement, has been reported in the literature as 8 to 42%, around 15% in most instances. The present study aims to determine, in a cohort of HIV infected patients in Brazil, what factors were independently associated with such a discordant response to HAART.</p> <p>Methods</p> <p>A case-control study (1:4) matched by gender was conducted among 934 HIV infected patients on HAART in Brazil. Cases: patients with PIR, defined as CD4 < 350 cells/mm³(hazard ratio for AIDS or death of at least 8.5) and undetectable HIV viral load on HAART for at least one year. Controls: similar to cases, but with CD4 counts ≥ 350 cells/mm³. Eligibility criteria were applied. Data were collected from medical records using a standardized form. Variables were introduced in a hierarchical logistic regression model if a p-value < 0.1 was determined in a bivariate analysis.</p> <p>Results</p> <p>Among 934 patients, 39 cases and 160 controls were consecutively selected. Factors associated with PIR in the logistic regression model were: total time in use of HAART (OR 0.981; CI 95%: 0.96-0.99), nadir CD4-count (OR 0.985; CI 95%: 0.97-0.99), and time of undetectable HIV viral load (OR 0.969; CI 95%: 0.94-0.99).</p> <p>Conclusions</p> <p>PIR seems to be related to a delay in the management of immunodeficient patients, as shown by its negative association with nadir CD4-count. Strategies should be implemented to avoid such a delay and improve the adherence to HAART as a way to implement concordant responses.</p