Winner-take-all selection in a neural system with delayed feedback

We consider the effects of temporal delay in a neural feedback system with excitation and inhibition. The topology of our model system reflects the anatomy of the avian isthmic circuitry, a feedback structure found in all classes of vertebrates. We show that the system is capable of performing a `winner-take-all' selection rule for certain combinations of excitatory and inhibitory feedback. In particular, we show that when the time delays are sufficiently large a system with local inhibition and global excitation can function as a `winner-take-all' network and exhibit oscillatory dynamics. We demonstrate how the origin of the oscillations can be attributed to the finite delays through a linear stability analysis.Comment: 8 pages, 6 figure

SARS-CoV-2 anti-spike IgG antibody responses after second dose of ChAdOx1 or BNT162b2 and correlates of protection in the UK general population

Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination. However, antibody trajectories and the associated duration of protection after a second vaccine dose remain unclear. In this study, we investigated anti-spike IgG antibody responses and correlates of protection after second doses of ChAdOx1 or BNT162b2 vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United Kingdom general population. In 222,493 individuals, we found significant boosting of anti-spike IgG by the second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Older individuals and males had lower peak levels with BNT162b2 but not ChAdOx1, whereas declines were similar across ages and sexes with ChAdOX1 or BNT162b2. Prior infection significantly increased antibody peak level and half-life with both vaccines. Anti-spike IgG levels were associated with protection from infection after vaccination and, to an even greater degree, after prior infection. At least 67% protection against infection was estimated to last for 2–3 months after two ChAdOx1 doses, for 5–8 months after two BNT162b2 doses in those without prior infection and for 1–2 years for those unvaccinated after natural infection. A third booster dose might be needed, prioritized to ChAdOx1 recipients and those more clinically vulnerable

Development of a reliable and construct valid measure of nutritional literacy in adults

BACKGROUND: Research into the relation of literacy to health status has not included measures of nutritional literacy. This may be a critical area in the study of chronic conditions such as hypertension and diabetes, which can both relate to obesity and nutrition. This paper details the development and psychometric characteristics of the Nutritional Literacy Scale (NLS), offered as a measure of adults' ability to comprehend nutritional information. METHODS: In order to assess the internal consistency and construct validity of the NLS, demographic data, readability statistics, NLS scores and scores on the Reading Comprehension Section of the Short Test of Functional Health Literacy in Adults (S-TOFHLA) were collected in a cross-sectional study of 341 patients from two primary care practices. RESULTS: The NLS score showed acceptable internal consistency of 0.84 by Cronbach's alpha coefficient. The Pearson correlation between the NLS and the S-TOFHLA was 0.61, supporting evidence for construct validity. CONCLUSION: Given the importance of proper weight and nutrition in the health of the public, as well as the absence of research on literacy skills as related to nutritional concepts, the NLS has the potential to add to the national research agenda in these areas

Consanguineous marriages and endemic malaria: can inbreeding increase population fitness?

<p>Abstract</p> <p>Background</p> <p>The practice of consanguineous marriages is widespread in countries with endemic malaria. In these regions, consanguinity increases the prevalence of α⁺-thalassemia, which is protective against malaria. However, it also causes an excessive mortality amongst the offspring due to an increase in homozygosis of recessive lethal alleles. The aim of this study was to explore the overall effects of inbreeding on the fitness of a population infested with malaria.</p> <p>Methods</p> <p>In a stochastic computer model of population growth, the sizes of inbred and outbred populations were compared. The model has been previously validated producing results for inbred populations that have agreed with analytical predictions. Survival likelihoods for different α⁺-thalassemia genotypes were obtained from the odds of severe forms of disease from a field study. Survivals were further estimated for different values of mortality from malaria.</p> <p>Results</p> <p>Inbreeding increases the frequency of α⁺-thalassemia allele and the loss of life due to homozygosis of recessive lethal alleles; both are proportional to the coefficient of inbreeding and the frequency of alleles in population. Inbreeding-mediated decrease in mortality from malaria (produced via enhanced α⁺-thalassemia frequency) mitigates inbreeding-related increases in fatality (produced via increased homozygosity of recessive lethals). When the death rate due to malaria is high, the net effect of inbreeding is a reduction in the overall mortality of the population.</p> <p>Conclusion</p> <p>Consanguineous marriages may increase the overall fitness of populations with endemic malaria.</p

Real-time imaging of hepatitis C virus infection using a fluorescent cell-based reporter system

Author Manuscript 2010 August 1Hepatitis C virus (HCV), which infects 2–3% of the world population, is a causative agent of chronic hepatitis and the leading indication for liver transplantation1. The ability to propagate HCV in cell culture (HCVcc) is a relatively recent breakthrough and a key tool in the quest for specific antiviral therapeutics. Monitoring HCV infection in culture generally involves bulk population assays, use of genetically modified viruses and/or terminal processing of potentially precious samples. Here we develop a cell-based fluorescent reporter system that allows sensitive distinction of individual HCV-infected cells in live or fixed samples. We demonstrate use of this technology for several previously intractable applications, including live-cell imaging of viral propagation and host response, as well as visualizing infection of primary hepatocyte cultures. Integration of this reporter with modern image-based analysis methods could open new doors for HCV research.New York (State). Dept. of Health (Empire State Stem Cell Fund Contract C023046)United States. Public Health Service (Grant R01 DK56966)National Institutes of Health (U.S.) (Roadmap for Medical Research Grant 1 R01 DK085713-01)Howard Hughes Medical Institute (Investigator

Overcoming language barriers with foreign-language speaking patients: a survey to investigate intra-hospital variation in attitudes and practices

Background Use of available interpreter services by hospital clincial staff is often suboptimal, despite evidence that trained interpreters contribute to quality of care and patient safety. Examination of intra-hospital variations in attitudes and practices regarding interpreter use can contribute to identifying factors that facilitate good practice. The purpose of this study was to describe attitudes, practices and preferences regarding communication with limited French proficiency (LFP) patients, examine how these vary across professions and departments within the hospital, and identify factors associated with good practices. Methods A self-administered questionnaire was mailed to random samples of 700 doctors, 700 nurses and 93 social workers at the Geneva University Hospitals, Switzerland. Results Seventy percent of respondents encounter LFP patients at least once a month, but this varied by department. 66% of respondents said they preferred working with ad hoc interpreters (patient's family and bilingual staff), mainly because these were easier to access. During the 6 months preceding the study, ad hoc interpreters were used at least once by 71% of respondents, and professional interpreters were used at least once by 51%. Overall, only nine percent of respondents had received any training in how and why to work with a trained interpreter. Only 23.2% of respondents said the clinical service in which they currently worked encouraged them to use professional interpreters. Respondents working in services where use of professional interpreters was encouraged were more likely to be of the opinion that the hospital should systematically provide a professional interpreter to LFP patients (40.3%) as compared with those working in a department that discouraged use of professional interpreters (15.5%) and they used professional interpreters more often during the previous 6 months. Conclusion Attitudes and practices regarding communication with LFP patients vary across professions and hospital departments. In order to foster an institution-wide culture conducive to ensuring adequate communication with LFP patients will require both the development of a hospital-wide policy and service-level activities aimed at reinforcing this policy and putting it into practice

A Therapeutic Antibody against West Nile Virus Neutralizes Infection by Blocking Fusion within Endosomes

Defining the precise cellular mechanisms of neutralization by potently inhibitory antibodies is important for understanding how the immune system successfully limits viral infections. We recently described a potently inhibitory monoclonal antibody (MAb E16) against the envelope (E) protein of West Nile virus (WNV) that neutralizes infection even after virus has spread to the central nervous system. Herein, we define its mechanism of inhibition. E16 blocks infection primarily at a post-attachment step as antibody-opsonized WNV enters permissive cells but cannot escape from endocytic compartments. These cellular experiments suggest that E16 blocks the acid-catalyzed fusion step that is required for nucleocapsid entry into the cytoplasm. Indeed, E16 directly inhibits fusion of WNV with liposomes. Additionally, low-pH exposure of E16–WNV complexes in the absence of target membranes did not fully inactivate infectious virus, further suggesting that E16 prevents a structural transition required for fusion. Thus, a strongly neutralizing anti–WNV MAb with therapeutic potential is potently inhibitory because it blocks viral fusion and thereby promotes clearance by delivering virus to the lysosome for destruction

Protective Antiviral Immunity Conferred by a Nonintegrative Lentiviral Vector-Based Vaccine

Lentiviral vectors are under intense scrutiny as unique candidate viral vector vaccines against tumor and aggressive pathogens because of their ability to initiate potent and durable specific immune responses. Strategies that alleviate safety concerns will facilitate the clinical developments involving lentiviral vectors. In this respect, the development of integration deficient lentiviral vectors circumvents the safety concerns relative to insertional mutagenesis and might pave the way for clinical applications in which gene transfer is targeted to non-dividing cells. We thus evaluated the potential use of nonintegrative lentiviral vectors as vaccination tools since the main targeted cell in vaccination procedures is the non-dividing dendritic cell (DC). In this study, we demonstrated that a single administration of nonintegrative vectors encoding a secreted form of the envelope of a virulent strain of West Nile Virus (WNV) induces a robust B cell response. Remarkably, nonintegrative lentiviral vectors fully protected mice from a challenge with a lethal dose of WNV and a single immunization was sufficient to induce early and long-lasting protective immunity. Thus, nonintegrative lentiviral vectors might represent a safe and efficacious vaccination platform for the development of prophylactic vaccines against infectious agents