Ubiquitous Crossmodal Stochastic Resonance in Humans: Auditory Noise Facilitates Tactile, Visual and Proprioceptive Sensations

BACKGROUND: Stochastic resonance is a nonlinear phenomenon whereby the addition of noise can improve the detection of weak stimuli. An optimal amount of added noise results in the maximum enhancement, whereas further increases in noise intensity only degrade detection or information content. The phenomenon does not occur in linear systems, where the addition of noise to either the system or the stimulus only degrades the signal quality. Stochastic Resonance (SR) has been extensively studied in different physical systems. It has been extended to human sensory systems where it can be classified as unimodal, central, behavioral and recently crossmodal. However what has not been explored is the extension of this crossmodal SR in humans. For instance, if under the same auditory noise conditions the crossmodal SR persists among different sensory systems. METHODOLOGY/PRINCIPAL FINDINGS: Using physiological and psychophysical techniques we demonstrate that the same auditory noise can enhance the sensitivity of tactile, visual and propioceptive system responses to weak signals. Specifically, we show that the effective auditory noise significantly increased tactile sensations of the finger, decreased luminance and contrast visual thresholds and significantly changed EMG recordings of the leg muscles during posture maintenance. CONCLUSIONS/SIGNIFICANCE: We conclude that crossmodal SR is a ubiquitous phenomenon in humans that can be interpreted within an energy and frequency model of multisensory neurons spontaneous activity. Initially the energy and frequency content of the multisensory neurons' activity (supplied by the weak signals) is not enough to be detected but when the auditory noise enters the brain, it generates a general activation among multisensory neurons of different regions, modifying their original activity. The result is an integrated activation that promotes sensitivity transitions and the signals are then perceived. A physiologically plausible model for crossmodal stochastic resonance is presented

Bicycle Use for Transport in an Australian and a Belgian City: Associations with Built-Environment Attributes

The walkability attributes of neighborhood environments (residential density, land use mixture, and connectedness of streets) have been found to be associated with higher rates of walking. However, relatively less is known about the associations of walkability attributes with bicycle use for transport. We examined the relationships between adults' bicycle use for transport and measures of neighborhood walkability in two settings: an Australian city (Adelaide) with low rates of bicycle use and a Belgian city (Ghent) with high rates of bicycle use. A total of 2,159 and 382 participants were recruited in Adelaide and Ghent, respectively. A walkability index was derived from objectively measured data in Adelaide, while a similar index was derived from perceived measures in Ghent. Logistic regression models were employed to examine associations of bicycle use with different levels of walkability. There were higher rates of bicycle ownership for Ghent compared to Adelaide participants (96% versus 61%), and there was a higher prevalence of bicycle use for transport for Ghent compared to Adelaide participants (50% vs. 14%). Despite the large differences in bicycle ownership and use, living in a high-walkable neighborhood was associated with significantly higher odds of bicycle use for transport in both cities, after adjusting for relevant confounding factors. Built-environment innovations that are increasingly being advocated by health authorities and transport planners, primarily to promote higher rates of walking for transport, should also impact positively on bicycle use

Planning and Designing Walkable Cities: A Smart Approach

Walking may be considered one of the most sustainable and democratic ways of travelling within a city, thus providing benefits not only to pedestrians but also to the urban environment. Besides, walking is also one of the means of transport most likely subjected to factors outside an individual\u2019s control, like social or physical abilities to walk and the presence of comfortable and safe street infrastructures and services. Therefore, improving urban conditions provided to pedestrians has positive impacts on walkability. At the same time technological solutions and innovations have the power to encourage and support people to walk by overcoming immaterial barriers due to a lack of information or boring travel and they give to decision makers the possibility to gain data to understand how and where people travel. Merging these two dimensions into a unique approach can drastically improve accessibility, attractiveness, safety, comfort and security of urban spaces. In this context, this paper aims to draw a more multifaceted context for walkability, where new technologies assume a key role for introducing new approaches to pedestrian paths planning and design and thus for enhancing this mode of transport. Indeed, by combining more traditional spatial-based and perceptual analysis of the urban environment with technological applications and social media exploitation there will be room to better support the decision on and to enhance satisfaction of walking as well as to easier plan and design more walkable cities

Training pediatric health care providers in prevention of dental decay: results from a randomized controlled trial

Background: Physicians report willingness to provide preventive dental care, but optimal methods for their training and support in such procedures are not known. This study aimed to evaluate the effect of three forms of continuing medical education (CME) on provision of preventive dental services to Medicaid-enrolled children by medical personnel in primary care physician offices. Methods: Practice-based, randomized controlled trial. Setting: 1,400 pediatric and family physician practices in North Carolina providing care to an estimated 240,000 Medicaid-eligible children aged 0–3 years. Interventions: Group A practices (n = 39) received didactic training and course materials in oral health screening, referral, counseling and application of fluoride varnish. Group B practices (n = 41) received the same as Group A and were offered weekly conference calls providing advice and support. Group C practices (n = 41) received the same as Group B and were offered in-office visit providing hands-on advice and support. In all groups, physicians were reimbursed $38–$43 per preventive dental visit. Outcome measures were computed from reimbursement claims submitted to NC Division of Medical Assistance. Primary outcome measure: rate of preventive dental services provision per 100 well-child visits. Secondary outcome measure: % of practices providing 20 or more preventive dental visits. Results: 121 practices were randomized, and 107 provided data for analysis. Only one half of Group B and C practices took part in conference calls or in-office visits. Using intention-to-treat analysis, rates of preventive dental visits did not differ significantly among CME groups: GroupA = 9.4, GroupB = 12.9 and GroupC = 8.5 (P = 0.32). Twenty or more preventive dental visits were provided by 38–49% of practices in the three study groups (P = 0.64). Conclusion: A relatively high proportion of medical practices appear capable of adopting these preventive dental services within a one year period regardless of the methods used to train primary health care providers.Gary D Slade, R Gary Rozier, Leslie P Zeldin, and Peter A Margoli

Primary histologic diagnosis using automated whole slide imaging: a validation study

BACKGROUND: Only prototypes 5 years ago, high-speed, automated whole slide imaging (WSI) systems (also called digital slide systems, virtual microscopes or wide field imagers) are becoming increasingly capable and robust. Modern devices can capture a slide in 5 minutes at spatial sampling periods of less than 0.5 micron/pixel. The capacity to rapidly digitize large numbers of slides should eventually have a profound, positive impact on pathology. It is important, however, that pathologists validate these systems during development, not only to identify their limitations but to guide their evolution. METHODS: Three pathologists fully signed out 25 cases representing 31 parts. The laboratory information system was used to simulate real-world sign-out conditions including entering a full diagnostic field and comment (when appropriate) and ordering special stains and recuts. For each case, discrepancies between diagnoses were documented by committee and a "consensus" report was formed and then compared with the microscope-based, sign-out report from the clinical archive. RESULTS: In 17 of 25 cases there were no discrepancies between the individual study pathologist reports. In 8 of the remaining cases, there were 12 discrepancies, including 3 in which image quality could be at least partially implicated. When the WSI consensus diagnoses were compared with the original sign-out diagnoses, no significant discrepancies were found. Full text of the pathologist reports, the WSI consensus diagnoses, and the original sign-out diagnoses are available as an attachment to this publication. CONCLUSION: The results indicated that the image information contained in current whole slide images is sufficient for pathologists to make reliable diagnostic decisions and compose complex diagnostic reports. This is a very positive result; however, this does not mean that WSI is as good as a microscope. Virtually every slide had focal areas in which image quality (focus and dynamic range) was less than perfect. In some cases, there was evidence of over-compression and regions made "soft" by less than perfect focus. We expect systems will continue to get better, image quality and speed will continue to improve, but that further validation studies will be needed to guide development of this promising technology

Effects of Sample Size on Estimates of Population Growth Rates Calculated with Matrix Models

BACKGROUND: Matrix models are widely used to study the dynamics and demography of populations. An important but overlooked issue is how the number of individuals sampled influences estimates of the population growth rate (lambda) calculated with matrix models. Even unbiased estimates of vital rates do not ensure unbiased estimates of lambda-Jensen's Inequality implies that even when the estimates of the vital rates are accurate, small sample sizes lead to biased estimates of lambda due to increased sampling variance. We investigated if sampling variability and the distribution of sampling effort among size classes lead to biases in estimates of lambda. METHODOLOGY/PRINCIPAL FINDINGS: Using data from a long-term field study of plant demography, we simulated the effects of sampling variance by drawing vital rates and calculating lambda for increasingly larger populations drawn from a total population of 3842 plants. We then compared these estimates of lambda with those based on the entire population and calculated the resulting bias. Finally, we conducted a review of the literature to determine the sample sizes typically used when parameterizing matrix models used to study plant demography. CONCLUSIONS/SIGNIFICANCE: We found significant bias at small sample sizes when survival was low (survival = 0.5), and that sampling with a more-realistic inverse J-shaped population structure exacerbated this bias. However our simulations also demonstrate that these biases rapidly become negligible with increasing sample sizes or as survival increases. For many of the sample sizes used in demographic studies, matrix models are probably robust to the biases resulting from sampling variance of vital rates. However, this conclusion may depend on the structure of populations or the distribution of sampling effort in ways that are unexplored. We suggest more intensive sampling of populations when individual survival is low and greater sampling of stages with high elasticities

Perceived crime and traffic safety is related to physical activity among adults in Nigeria

Background: Neighborhood safety is inconsistently related to physical activity, but is seldom studied in developing countries. This study examined associations between perceived neighborhood safety and physical activity among Nigerian adults. Methods: In a cross-sectional study, accelerometer-based physical activity (MVPA), reported walking, perceived crime and traffic safety were measured in 219 Nigerian adults. Logistic regression analysis was conducted, and the odds ratio for meeting health guidelines for MVPA and walking was calculated in relation to four safety variables, after adjustment for potential confounders. Results: Sufficient MVPA was related to more perception of safety from traffic to walk (OR = 2.28, CI = 1.13-6.25) and more safety from crime at night (OR = 1.68, CI = 1.07-3.64), but with less perception of safety from crime during the day to walk (OR = 0.34, CI = 0.06- 0.91). More crime safety during the day and night were associated with more walking. Conclusions: Perceived safety from crime and traffic were associated with physical activity among Nigerian adults. These findings provide preliminary evidence on the need to provide safe traffic and crime environments that will make it easier and more likely for African adults to be physically active

Reproductive factors and breast cancer risk according to joint estrogen and progesterone receptor status: a meta-analysis of epidemiological studies

INTRODUCTION: Although reproductive factors have been known for decades to be associated with breast cancer risk, it is unclear to what extent these associations differ by estrogen and progesterone receptor (ER/PR) status. This report presents the first meta-analysis of results from epidemiological studies that have investigated parity, age at first birth, breastfeeding, and age at menarche in relation to ER(+)PR(+ )and ER(-)PR(- )cancer risk. MATERIALS AND METHODS: We calculated summary relative risks (RRs) and corresponding 95% confidence intervals (CIs) using a fixed effects model. RESULTS: Each birth reduced the risk of ER(+)PR(+ )cancer by 11% (RR per birth = 0.89, 95% CI = 0.84–0.94), and women who were in the highest age at first birth category had, on average, 27% higher risk of ER(+)PR(+ )cancer compared with women who were in the youngest age at first birth category (RR = 1.27, 95% CI = 1.07–1.50). Neither parity nor age at first birth was associated with the risk of ER(-)PR(- )cancer (RR per birth = 0.99, 95% CI = 0.94–1.05; RR of oldest versus youngest age at first birth category = 1.01, 95% CI = 0.85–1.20). Breastfeeding and late age at menarche decreased the risk of both receptor subtypes of breast cancer. The protective effect of late age at menarche was statistically significantly greater for ER(+)PR(+ )than ER(-)PR(- )cancer (RR = 0.72 for ER(+)PR(+ )cancer; RR = 0.84 for ER(-)PR(- )cancer, p for homogeneity = 0.006). CONCLUSION: Our findings suggest that breastfeeding (and age at menarche) may act through different hormonal mechanisms than do parity and age at first birth

L1TD1 Is a Marker for Undifferentiated Human Embryonic Stem Cells

Human embryonic stem cells (hESC) are stem cells capable of differentiating into cells representative of the three primary embryonic germ layers. There has been considerable interest in understanding the mechanisms regulating stem cell pluripotency, which will ultimately lead to development of more efficient methods to derive and culture hESC. In particular, Oct4, Sox2 and Nanog are transcription factors known to be important in maintenance of hESC. However, many of the downstream targets of these transcription factors are not well characterized. Furthermore, it remains unknown whether additional novel stem cell factors are involved in the establishment and maintenance of the stem cell state.Here we show that a novel gene, L1TD1 (also known as FLJ10884 or ECAT11), is abundantly expressed in undifferentiated hESC. Differentiation of hESC via embryoid body (EB) formation or BMP4 treatment results in the rapid down-regulation of L1TD1 expression. Furthermore, populations of undifferentiated and differentiated hESC were sorted using the stem cell markers SSEA4 and TRA160. Our results show that L1TD1 is enriched in the SSEA4-positive or TRA160-positive population of hESC. Using chromatin immunoprecipitation we found enriched association of Nanog to the predicted promoter region of L1TD1. Furthermore, siRNA-mediated knockdown of Nanog in hESC also resulted in downregulation of L1TD1 expression. Finally, using luciferase reporter assay we demonstrated that Nanog can activate the L1TD1 upstream promoter region. Altogether, these results provide evidence that L1TD1 is a downstream target of Nanog.Taken together, our results suggest that L1TD1 is a downstream target of Nanog and represents a useful marker for identifying undifferentiated hESC