Tracking and predicting hand, foot, and mouth disease (HFMD) epidemics in China by Baidu queries.

Hand, foot, and mouth disease (HFMD) is highly prevalent in China, and more efficient methods of epidemic detection and early warning need to be developed to augment traditional surveillance systems. In this paper, a method that uses Baidu search queries to track and predict HFMD epidemics is presented, and the outbreaks of HFMD in China during the 60-month period from January 2011 to December 2015 are predicted. The Pearson correlation coefficient (R) of the predictive model and the mean absolute percentage errors between observed HFMD case counts and the predicted number show that our predictive model gives excellent fit to the data. This implies that Baidu search queries can be used in China to track and reliably predict HFMD epidemics, and can serve as a supplement to official systems for HFMD epidemic surveillance.

Risk of malignant progression in Barrett's esophagus indefinite for dysplasia.

Barrett's esophagus is a well-recognized risk factor for esophageal adenocarcinoma. The natural history of Barrett's esophagus classified as 'indefinite for dysplasia' (IND) is poorly characterized. The aim of this study is to characterize the natural history of IND by determining the rate of neoplastic progression and identifying risk factors for progression. Patients from the University of Pennsylvania Health System pathology database and Barrett's esophagus registry with a diagnosis of IND between 2000 and 2014 were identified. Exclusion criteria included: (1) prior diagnosis of low-grade dysplasia (LGD), high-grade dysplasia (HGD), or esophageal adenocarcinoma (EAC); (2) presence of LGD, HGD, or EAC at the time of diagnosis of IND; and (3) lack of follow-up endoscopy after diagnosis. Patients with neoplastic progression were classified as having either prevalent disease (LGD, HGD, or EAC on surveillance biopsy within 12 months of IND diagnosis) or incident disease (LGD, HGD, or EAC on surveillance biopsy >12 months after IND diagnosis). One hundred six patients were eligible for analysis. Of 87 patients with follow-up endoscopy and biopsies within 1 year of IND diagnosis, 7 (8%) had prevalent disease (2 LGD, 4 HGD, 1 EAC). The prevalence of LGD was 2.3%, HGD was 4.6%, and EAC was 1.1%. Importantly, four of the seven prevalent (2 LGD, 2 HGD) cases were found to have dysplasia within 6 months of IND diagnosis. No demographic or endoscopic characteristics studied were associated with prevalent disease. Of the 106 IND patients, there were 66 patients without prevalent dysplasia with >1-year follow-up. Three (4.5%) progressed (1 to LGD after 12 months, 2 to HGD after 16.5 and 28 months), yielding an incidence rate for any dysplasia of 1.4 cases/100 person-years and HGD/EAC of 0.9/100 person-years. Risk factors for incident disease were smoking (p = 0.02) and Barrett's esophagus segment length (p = 0.03). IND is associated with considerable risk of prevalent dysplasia, especially within the first 6 months after diagnosis. However, the incidence of HGD/EAC is low and similar to previous studies of IND. These data suggest that IND patients should have repeat endoscopy within 6 months with careful surveillance protocols. Longer BE length and smoking history may help predict which patients are more likely to develop dysplasia, and therefore identify patients who may warrant even closer monitoring.

Family structure and quality of life of elders in rural China: the role of the new rural social pension.

Using data from a survey in Ankang district of Shaanxi province of China in 2011, this article examines the protective effect of the New Rural Social Pension (NRSP) on quality of life of rural elders, as well the moderating effect on association between family structure and quality of life. An instrumental variable approach is used. NRSP is shown to significantly improve the quality of life of rural elders, and a robustness check shows that this effect is consistent across different sets of subgroups. Compared with the elders who have at least one son, the quality of life of those who are childless or have only one child is significantly lower. The NRSP is more likely to significantly improve the quality of life of one-child elders. In addition, the associations between the NRSP and the different facets of quality of life of the elders are significant except for the facet of sensory abilities.

Phylogenetic resolution power of microsatellites and various single-nucleotide polymorphism types assessed in 10 divergent chicken populations.

There has been some debate over the question of which types of DNA variation are most appropriate to accurately reconstruct evolutionary events. We compared the capacity of microsatellites (STRs) and various types of single-nucleotide polymorphism (SNP) loci in the chicken genome. The SNP types differ in their location: in exons, introns and promoters. Genetic distances between all possible pairs of 10 populations were calculated for each marker type. STR loci, which are much more polymorphic than are SNPs, are considered to have occurred at recent time compared with old evolutionary events of SNPs. Using structure software, STR loci assigned individuals to their population much more correctly than did any other marker types, whereas SNPs at promoter regions gave the poorest ascription. Furthermore, 29 STR markers were even better than all 152 SNPs together. Ancient evolutionary events that produced genetic differences between the most distant populations such as Red Jungle Fowl and domestic chicken were detected better by exons and introns than by STR loci and promoters. The significant interactions found between marker types and populations suggest that marker types had different phylogenetic histories, possibly related to a different timescale.

Where are persons with intellectual disabilities in medical research? A survey of published clinical trials.

BACKGROUND: Persons with intellectual disabilities (ID) are exposed to the same medical interventions as everyone else. Given the unique health profiles of many persons with ID, it cannot be assumed that they will react to medical treatments the same as persons without ID. It is not clear if medical clinical trials routinely include persons with ID. The purpose of this research survey was to examine the inclusion of persons with ID in medical research trials, and to determine whether accommodations and/or study modifications could have been made to promote greater inclusion in medical research. METHOD: Three hundred randomised control and clinical trials published between 2007 and 2011 in the six highest impact medical journals were randomly selected. Each study was reviewed for inclusion of persons with ID, and possible accommodations that could have been put in place without compromising research integrity. Corresponding authors received a follow-up survey to determine whether persons with ID were included, but were not mentioned in the article. RESULTS: Only 6 (2%) of 300 randomly chosen studies clearly included persons with ID. Over 90% of studies were designed in ways that would automatically exclude persons with ID from participating. The author survey revealed three additional studies including persons with ID. Most persons with ID could have participated in at least 70% of the studies with simple accommodations and/or minor procedural modifications. DISCUSSION: The findings highlight the exclusion of persons with ID in medical research. Efforts are needed to increase inclusion through research policy initiatives and education.

The neurobiology of interoception and affect.

Scholars have argued for centuries that affective states involve interoception, or representations of the state of the body. Yet, we lack a mechanistic understanding of how signals from the body are transduced, transmitted, compressed, and integrated by the brains of humans to produce affective states. We suggest that to understand how the body contributes to affect, we first need to understand information flow through the nervous system's interoceptive pathways. We outline such a model and discuss how unique anatomical and physiological aspects of interoceptive pathways may give rise to the qualities of affective experiences in general and valence and arousal in particular. We conclude by considering implications and future directions for research on interoception, affect, emotions, and human mental experiences.

The role of cultural transmission in human demographic change: an age-structured model.

Human populations vary demographically with population sizes ranging from small groups of hunter-gatherers with less than fifty individuals to vast cities containing many millions. Here we investigate how the cultural transmission of traits affecting survival, fertility, or both can influence the birth rate, age structure, and asymptotic growth rate of a population. We show that the strong spread of such a trait can lead to a demographic transition, similar to that experienced in Europe in the late 19th and early 20th centuries, without using ecological or economic optimizing models. We also show that the spread of a cultural trait that increases fertility, but not survival, can cause demographic change similar to the 'Neolithic demographic transition': a period of increased population growth that is thought to have accompanied the transition from hunter-gatherer to agricultural lifestyles. We investigate the roles of vertical, oblique, and horizontal learning of such a trait in this transition and find that compared to vertical learning alone, horizontal and oblique learning can accelerate the trait's spread, lead to faster population growth, and increase its equilibrium frequency.

The coevolution of long-term pair bonds and cooperation.

The evolution of social traits may not only depend on but also change the social structure of the population. In particular, the evolution of pairwise cooperation, such as biparental care, depends on the pair-matching distribution of the population, and the latter often emerges as a collective outcome of individual pair-bonding traits, which are also under selection. Here, we develop an analytical model and individual-based simulations to study the coevolution of long-term pair bonds and cooperation in parental care, where partners play a Snowdrift game in each breeding season. We illustrate that long-term pair bonds may coevolve with cooperation when bonding cost is below a threshold. As long-term pair bonds lead to assortative interactions through pair-matching dynamics, they may promote the prevalence of cooperation. In addition to the pay-off matrix of a single game, the evolutionarily stable equilibrium also depends on bonding cost and accidental divorce rate, and it is determined by a form of balancing selection because the benefit from pair-bond maintenance diminishes as the frequency of cooperators increases. Our findings highlight the importance of ecological factors affecting social bonding cost and stability in understanding the coevolution of social behaviour and social structures, which may lead to the diversity of biological social systems.

Growth of textured thin Au coatings on iron oxide nanoparticles with near infrared absorbance.

A homologous series of Au coated iron oxide nanoparticles with hydrodynamic diameters smaller than 60 nm was synthesized with very low Au-to-iron mass ratios, as low as 0.15. The hydrodynamic diameter was determined by dynamic light scattering and the composition by atomic absorption spectroscopy and energy dispersive x-ray spectroscopy. Unusually low Au precursor supersaturation levels were utilized to nucleate and grow Au coatings on iron oxide relative to the formation of pure Au nanoparticles. This approach produced unusually thin coatings by lowering autocatalytic growth of Au on Au, as shown by transmission electron microscopy. Nearly all of the nanoparticles were attracted by a magnet, indicating a minimal number of pure Au particles. The coatings were sufficiently thin to shift the surface plasmon resonance to the near infrared with large extinction coefficients, despite the small particle hydrodynamic diameters observed from dynamic light scattering to be less than 60 nm.

Y chromosome sequence variation and the history of human populations.

Binary polymorphisms associated with the non-recombining region of the human Y chromosome (NRY) preserve the paternal genetic legacy of our species that has persisted to the present, permitting inference of human evolution, population affinity and demographic history. We used denaturing high-performance liquid chromatography (DHPLC; ref. 2) to identify 160 of the 166 bi-allelic and 1 tri-allelic site that formed a parsimonious genealogy of 116 haplotypes, several of which display distinct population affinities based on the analysis of 1062 globally representative individuals. A minority of contemporary East Africans and Khoisan represent the descendants of the most ancestral patrilineages of anatomically modern humans that left Africa between 35,000 and 89,000 years ago.

Evaluation of plant and fungal extracts for their potential antigingivitis and anticaries activity.

The link between diet and health has lead to the promotion of functional foods which can enhance health. In this study, the oral health benefits of a number of food homogenates and high molecular mass and low molecular mass fractions were investigated. A comprehensive range of assays were performed to assess the action of these foods on the development of gingivitis and caries using bacterial species associated with these diseases. Both antigingivitis and anticaries effects were investigated by assays examining the prevention of biofilm formation and coaggregation, disruption of preexisting biofilms, and the foods' antibacterial effects. Assays investigating interactions with gingival epithelial cells and cytokine production were carried out to assess the foods' anti- gingivitis properties. Anti-caries properties such as interactions with hydroxyapatite, disruption of signal transduction, and the inhibition of acid production were investigated. The mushroom and chicory homogenates and low molecular mass fractions show promise as anti-caries and anti-gingivitis agents, and further testing and clinical trials will need to be performed to evaluate their true effectiveness in humans.

Forced bachelors, migration and HIV transmission risk in the context of China's gender imbalance: a meta-analysis.

China has experienced continual increase in the sex ratio at birth (SRB) since the 1980s, which has led to a serious gender imbalance. To identify whether the future forced bachelors, especially those who migrate to cities, will increase the risk of HIV spread, a systematic review was carried out of studies published since 2000 that include the sexual risks of male migrants of China. Five studies comparing risk differences between migrants and non-migrants showed male migrants had greater risk of having multiple sexual partners and engaging in commercial sex. Ten studies concerning the relationship between sexual risks and socio-demographic characteristics showed that unmarried male migrants were more likely to engage in commercial sex and be infected with STDs than married migrants, while male migrants with higher income were more likely to have multiple sexual partners and be infected with STDs. In an analysis stratified by sample characteristics, the association between marriage and sexual risk was greater among samples with lower mean age, higher average income and education. In addition, the risk selection on education and income disappeared in the samples of migrants of whom more than half were unmarried.

Cranberry proanthocyanidins act in synergy with licochalcone A to reduce Porphyromonas gingivalis growth and virulence properties, and to suppress cytokine secretion by macrophages.

AIMS: Periodontitis is an inflammatory disease of polymicrobial origin that affects the tooth-supporting tissues. With the spread of antibiotic resistance among pathogenic bacteria, alternative strategies are required to better control infectious diseases such as periodontitis. The aim of our study was to investigate whether two natural compounds, A-type cranberry proanthocyanidins (AC-PACs) and licochalcone A, act in synergy against Porphyromonas gingivalis and the host inflammatory response of a macrophage model. METHODS AND RESULTS: Using a checkerboard microtitre test, AC-PACs and licochalcone A were found to act in synergy to inhibit P. gingivalis growth and biofilm formation. Fluorescein isothiocyanate-labelled P. gingivalis adhesion to oral epithelial cells was also inhibited by a combination of the two natural compounds in a synergistic manner. Fluorometric assays showed that although AC-PACs and licochalcone A reduced both MMP-9 and P. gingivalis collagenase activities, no synergy was obtained with a combination of the compounds. Lastly, AC-PACs and licochalcone A also acted in synergy to reduce the lipopolysaccharide (LPS)-induced secretion of the pro-inflammatory mediators IL-1ß, TNF-α, IL-6 and IL-8 in a macrophage model. CONCLUSIONS: A-type cranberry proanthocyanidins and licochalcone A, natural compounds from cranberry and licorice, respectively, act in synergy on both P. gingivalis and the host immune response, the two principal etiological factors of periodontitis. SIGNIFICANCE AND IMPACT OF THE STUDY: The combined use of AC-PACs and licochalcone A may be a potential novel therapeutic strategy for the treatment and prevention of periodontal disease.

Health self-advocacy training for persons with intellectual disabilities.

BACKGROUND: People with intellectual disabilities (ID) have unequal access to health care. While systemic efforts are addressing health inequalities, there remains a need to demonstrate that persons with ID can increase their health self-advocacy skills. METHOD: A randomised control design with up to 6-month follow-up was used to evaluate the 3Rs (Rights, Respect and Responsibility) health self-advocacy training program for persons with ID (n = 31). Training involved teaching participants to recognise and redress health rights violations in the context of respect and responsibility. Training materials included PowerPoint slides and interactive video scenarios illustrating health rights, respect and responsibility problem and non-problems. Two-hour training sessions were conducted twice a week in a group format where participants played a game and answered questions. RESULTS: The health rights training group made significantly more correct responses on post training and follow-up tests than the control group. Training effects generalised to untrained scenarios and in situ health interviews. CONCLUSIONS: The results of this study suggest that persons with ID can learn complex skills related to health self-advocacy. More research is needed to improve in situ generalisation.

Colorectal two-week wait service and quantitative FIT: it's not just about colon cancer.

INTRODUCTION: The aim of this study was to assess faecal immunochemical test (FIT) negativity in terms of its effect on cancer risk in the local symptomatic two-week wait (2WW) population. FIT was introduced to the colorectal 2WW pathway at the start of the pandemic. This study analyses the FIT-negative (<10µg Hb/g) cohort and calculates the relative risk and odds ratio associated with a negative FIT test. METHODS: FIT tests were sent to symptomatic 2WW patients without rectal bleeding, iron-deficient anaemia or palpable mass. Where FIT was <10µg Hb/g investigations were moved to a radiology protocol. RESULTS: The test return rate was 91% with a FIT-negative (<10µg Hb/g) rate of 82%. The FIT-negative group in the symptomatic referral pathway in Cornwall have a low (1.4%) risk of colon cancer but a significant risk (6.6%) when all cancer types are considered. The impact of a negative quantitative FIT changes the odds ratio of a patient having a luminal cancer by 0.26. The odds ratio for 'all cancer' risk was affected by 0.83. CONCLUSION: A negative FIT test within the local NG12 symptomatic patient group signifies a low risk of colon cancer and identifies patients who can be initially investigated with cross-sectional imaging. However, when all cancer types are considered, cancer prevalence in this group remains above 6%. In relative risk terms a negative FIT represents a small change in overall risk and this patient group still qualify for investigation through 2WW pathways.

Regression of established murine carcinoma metastases following vaccination with tumour-associated antigen peptides.

The cure of micrometastases following surgery is the major goal of cancer immunotherapy. We have recently isolated tumour-associated antigen (TAA) peptides, MUT 1 and MUT 2, derived from a mutated connexin 37 gap-junction protein, from the malignant 3LL-D122 murine lung carcinoma. We now report that synthetic MUT 1 or MUT 2 induces effective antitumour cytoxic T lymphocytes. Peptide vaccines protect mice from spontaneous metastases of 3LL-D122 tumours. Moreover, peptide vaccines reduce metastatic loads in mice carrying pre-established micrometastases. Tumour-specific immunity was primarily mediated by CD8+ T cells. This is the first evidence that peptide therapy may be effective in treatment of residual tumours and provides a rationale for the development of peptide vaccines as a modality for cancer therapy.

From cholera to burns: a role for oral rehydration therapy.

According to the practice guidelines of the American Bum Association on burn shock resuscitation, intravenous (i.v.) fluid therapy is the standard of care for the replacement of fluid and electrolyte losses in burn injury of > or = 20% of the total body surface area. However, in mass burn casualties, i.v. fluid resuscitation may be delayed or unavailable. Oral rehydration therapy (ORT), which has been shown to be highly effective in the treatment of dehydration in epidemics of cholera, could be an alternate way to replace fluid losses in burns. A prospective case series of three patients was carried out as an initial step to establish whether oral Ceralyte 90 could replace fluid losses requiring i.v. fluid therapy in thermal injury. The requirement of the continuing i.v. fluid therapy was reduced by an average of 58% in the first 24 hours after the injury (range 37-78%). ORT may be a feasible alternative to i.v. fluid therapy in the resuscitation of burns. It could also potentially save many lives in mass casualty situations or in resource-poor settings where i.v. fluid therapy is not immediately available. Further studies are needed to assess the efficacy of this treatment and to determine whether the present formulations of ORT for cholera need modification.

Studies on the competence of single cells to produce antibodies of two specificities.

Two series of experiments were performed, utilizing a modification of the hemolysin plaque technique which registers 19S antibody, in an attempt to determine the frequency of cells capable of simultaneously producing antibody to two non-cross-reacting antigens. Mice were immunized i.v. with rabbit and camel RBC and their spleens assayed for cells producing antibody against both antigens. 16,904 cells producing antibody of one or the other specificity, from 26 mice, were counted. Not one cell was detected which produced antibody of two specificities. Rabbits were immunized intradermally with HSA to which polyalanyl and p-azobenzenearsonate groups were chemically attached. The individual haptens, polyalanyl, and p-azobenzenearsonate groups were coupled to separate aliquots of SRBC, and the lymph nodes of immunized rabbits were assayed for cells releasing antibody against both haptens. In a study of 11 rabbits, after counting 27,845 cells producing antibody, we detected no "double" plaques.

In vitro generation of memory lymphocytes reactive to transplantation antigens.

The in vitro generation of memory cells reactive to transplantation antigens is described. Blast cells, obtained from rat lymphocytes sensitized on xenogeneic or allogeneic fibroblast monolayers, reverted to secondary small lymphocytes after transfer from the foreign sensitizing to syngeneic monolayers. These secondary small lymphocytes had a limited in vitro life span of 4-6 wk. They manifested properties of memory cells: upon re-exposure to fibroblasts of the sensitizing phenotype, the secondary lymphocytes adhered to the fibroblast monolayer and transformed into blast cells with cytotoxic activity. The response of secondary lymphocytes was rapid, compared to that of normal lymphocytes, and directed specifically against the primary sensitizing antigens.

Autosensitization in vitro.

Autosensitization of rat or mouse lymphoid cells against syngeneic fibroblast antigens was induced in cell culture. Rat lymphoid cells autosensitized by this method were able to produce immunospecific lysis of syngeneic target fibroblasts in vitro or GvH reactions in newborn rats. Autosensitized mouse spleen cells mediated similar GvH reactions when injected into newborn mice. The nature of the system used to induce immunity in vitro appears to argue against the possibility that lymphocytes capable of reacting against self-antigens could arise by mutation in cell culture. Hence, it is likely that cells potentially reactive against self-antigens preexisted in the lymphoid cell donors. The ability of autosensitized cells to mediate immune reactions in vivo suggests that the immunogenic self-antigens present on sensitizing fibroblasts also were accessible in the intact animals. Loss of natural self-tolerance in vitro, therefore, can be explained most simply by the existence of lymphocytes which are reversibly tolerant to self. Hence, ontogenic elimination of potentially self-reactive cells may not be the only basis for natural tolerance. Regulatory mechanisms, such as antigen excess, may have to function in vivo to prevent differentiation of self-tolerant lymphocytes. These regulatory mechanisms appear to be annulled in the cell-culture system. The present system thus may offer a new approach to studies of tolerance and regulation of cellular immunity.