Deep Neural Networks for Human's Fall-risk Prediction using Force-Plate Time Series Signal.

Early and accurate identification of the balance deficits could reduce falls, in particular for older adults, a prone population. Our work investigates deep neural networks' capacity to identify human balance patterns towards predicting fall-risk. Human balance ability can be characterized based on commonly-used balance metrics, such as those derived from the force-plate time series. We hypothesized that low, moderate, and high risk of falling can be characterized based on balance metrics, derived from the force-plate time series, in conjunction with deep learning algorithms. Further, we predicted that our proposed One-One-One Deep Neural Networks algorithm provides a considerable increase in performance compared to other algorithms. Here, an open source force-plate dataset, which quantified human balance from a wide demographic of human participants (163 females and males aged 18-86) for varied standing conditions (eyes-open firm surface, eyes-closed firm surface, eyes-open foam surface, eyes-closed foam surface) was used. Classification was based on one of the several indicators of fall-risk tied to the fear of falling: the clinically-used Falls Efficacy Scale (FES) assessment. For human fall-risk prediction, the deep learning architecture implemented comprised of: Recurrent Neural Network (RNN), Long-Short Time Memory (LSTM), One Dimensional Convolutional Neural Network (1D-CNN), and a proposed One-One-One Deep Neural Network. Results showed that our One-One-One Deep Neural Networks algorithm outperformed the other aforementioned algorithms and state-of-the-art models on the same dataset. With an accuracy, precision, and sensitivity of 99.9%, 100%, 100%, respectively at the 12th epoch, we found that our proposed One-One-One Deep Neural Network model is the most efficient neural network in predicting human's fall-risk (based on the FES measure) using the force-plate time series signal. This is a novel methodology for an accurate prediction of human risk of fall.

Effects of health status on pressure-induced changes in phocid immune function and implications for dive ability.

The ability of marine mammals to cope with environmental challenges is a key determining factor in strandings and successful release of rehabilitated animals. Dive behavior is related to foraging and thus survival. While dive adaptations have been well studied, it is unknown how the immune system responds to diving and whether health status impacts immune function during diving. This study investigated the functional response of ex situ immune cells from stranded phocids to in vitro increased pressure, over the course of rehabilitation. Blood samples were drawn from stranded harbor seals (Phoca vitulina), gray seals (Halichoerus grypus) and harp seals (Phoca groenlandica) at the time of admit to the Mystic Aquarium, Mystic, CT and again after rehabilitation (pre-release). Phagocytosis, lymphocyte proliferation and immune cell activation were measured in vitro, with and without exposure to 2000 psi (simulated dive depth of 1360 m). Plasma epinephrine and norepinephrine, and serum cortisol were measured in vivo. All hormone values decreased between admit and release conditions. Under admit or release conditions, pressure exposures resulted in significant changes in granulocyte and monocyte phagocytosis, granulocyte expression of CD11b and lymphocyte expression of the IL2 receptor (IL2R). Overall, pressure exposures resulted in decreased phagocytosis for admit conditions, but increased phagocytosis in release samples. Expression of leukocyte activation markers, CD11b and IL2R, increased and the response did not differ between admit and release samples. Specific hematological and serum chemistry values also changed significantly between admit and release and were significantly correlated with pressure-induced changes in immune function. Results suggest (1) dive duration affects the response of immune cells, (2) different white blood cell types respond differently to pressure and (3) response varies with animal health. This is the first study describing the relationship between diving, immune function and health status in phocids.

Human Health Risk from Consumption of Marine Fish Contaminated with DDT and Its Metabolites in Maputo Bay, Mozambique.

Many countries with incidence of malaria, including those surrounding Maputo Bay, use dichloro-diphenyl-trichloroethane (DDT) to reduce mosquitoes. This study is the first to estimate the human health risk associated with consumption of marine fish from Maputo Bay contaminated with DDTs. The median for ∑DDTs was 3.8 ng/g ww (maximum 280.9 ng/g ww). The overall hazard ratio for samples was 1.5 at the 75th percentile concentration and 28.2 at the 95th percentile. These calculations show increased potential cancer risks due to contamination by DDTs, data which will help policy makers perform a risk-benefit analysis of DDT use in malaria control programs in the region.

Concentrations and human health risk assessment of DDT and its metabolites in free-range and commercial chicken products from KwaZulu-Natal, South Africa.

Organochlorine pesticides such as dichlorodiphenyltrichloroethane (DDT) have been used in agriculture and for disease control purposes over many decades. Reports suggest that DDT exposure may result in a number of adverse effects in humans. In the KwaZulu-Natal Province of South Africa, DDT is sprayed annually in homes (indoor residual spraying) to control the mosquito vector of malaria. In the northern part of the Province, samples of free-range chicken meat (n = 48) and eggs (n = 13), and commercially produced chicken meat (n = 6) and eggs (n = 11), were collected and analysed. Of the free-range chicken meat samples, 94% (45/48) contained DDTs (ΣDDTs median 6.1 ng/g wet weight [ww], maximum 79.1 ng/g ww). Chicken egg contents were also contaminated (ΣDDTs in free-range eggs median 9544 ng/g ww, maximum 96.666 ng/g ww; and in commercial eggs median 1.3 ng/g ww, maximum 4.6 ng/g ww). The predominant DDT congener detected was p,p'-DDE in both free-range meat (>63%) and eggs (>66%), followed by p,p'-DDT and then p,p'-DDD. Based on estimated daily intake values, calculated human risk ratio (carcinogenic) values were >1 for DDTs detected in both free-range chicken products. Consumption of free-range eggs poses a particularly high health risk.

Determinants of longitudinal health-related quality-of-life change in children with asthma from low-income families: a report from the PROMIS® Pediatric Asthma Study.

BACKGROUND: How the longitudinal asthma control status and other socio-demographic factors influence the changes of health-related quality of life (HRQOL) among asthmatic children, especially from low-income families, has not been fully investigated. OBJECTIVES: This study aimed to describe the trajectories of asthma-specific HRQOL over 15 months and examine the effect of asthma control status on HRQOL by taking socio-demographic factors into consideration. METHODS: A total of 229 dyads of asthmatic children and their parents enroled in public insurance programs were recruited for assessing asthma control status and HRQOL over four time points of assessment. Asthma control status was measured using the Asthma Control and Communication Instrument, and asthma-specific HRQOL was assessed using the Patient-Reported Outcomes Measurement Information System's Pediatric Asthma Impact Scale. Latent growth models (LGMs) were applied to examine the trajectory of HRQOL and the factors contributing to the changes of HRQOL. RESULTS: Unconditional LGM revealed that HRQOL was improved over time. Conditional LGM suggested that accounting for asthma control and participants' socio-demographic factors, the variation in the initial level of HRQOL was significant, yet the rate of change was not. Conditional LGM also revealed that poorly controlled asthma status was associated with poor HRQOL at each time point (P's < 0.05). Lower parental education was associated with lower baseline HRQOL (P < 0.05). Hispanic children had a larger increase in HRQOL over time (P < 0.01) than non-Hispanic White children. CONCLUSIONS: Vulnerable socio-demographic characteristics and poorly controlled asthma status affect HRQOL in children. This finding encourages interventions to improve asthma control status and HRQOL in minority children.

Antimicrobial management of septic arthritis of the hand and wrist.

PURPOSE: The optimal antimicrobial treatment for patients with hand or wrist septic arthritis is unknown. We report the treatment outcomes in patients with these infections. METHODS: The medical records of 40 consecutive adult patients with hand or wrist septic arthritis treated at our institution from 2000 to 2008 were retrospectively reviewed. The primary outcome measure was treatment failure (histopathologic or microbiologic evidence of relapsed infection from the same joint or a contiguous anatomic area). RESULTS: Involved joints were the wrist (n = 10, 25 %), metacarpal-phalangeal (n = 11, 27.5 %), proximal interphalangeal (n = 8, 20 %), distal interphalangeal (n = 10, 25 %), and thumb interphalangeal (n = 1, 2.5 %). Methicillin-sensitive (n = 15, 45 %) and -resistant (n = 7, 17.5 %) Staphylococcus aureus were the most common pathogens. Surgical therapies included open arthrotomy with debridement (n = 33, 82.5 %), arthroscopic debridement (n = 2, 5 %), and aspiration alone (n = 5, 12.5 %). Most patients (23/40, 58 %) received less than 1 week of parenteral antimicrobial therapy. Only two patients developed definite antimicrobial treatment failure, one of whom had an atypical mycobacterium infection. Patients with subacute to chronic infections were at high risk for finger amputation. CONCLUSIONS: When combined with surgical debridement, relatively short courses of parenteral antimicrobial treatment (<1 week) supplemented with oral therapy for an additional 2-3 weeks is usually sufficient antimicrobial therapy for hand or wrist septic arthritis.

Temporal changes in blood variables during final maturation and senescence in male sockeye salmon Oncorhynchus nerka: reduced osmoregulatory ability can predict mortality.

This study is the first to characterize temporal changes in blood chemistry of individuals from one population of male sockeye salmon Oncorhynchus nerka during the final 6 weeks of sexual maturation and senescence in the freshwater stage of their spawning migration. Fish that died before the start of their historic mean spawning period (c. 5 November) were characterized by a 20-40% decrease in plasma osmolality, chloride and sodium, probably representing a complete loss of osmoregulatory ability. As fish became moribund, they were further characterized by elevated levels of plasma cortisol, lactate and potassium. Regressions between time to death and plasma chloride (8 October: P < 0·001; 15 October: P < 0·001) indicate that plasma chloride was a strong predictor of longevity in O. nerka. That major plasma ion levels started to decline 2-10 days (mean of 6 days) before fish became moribund, and before other stress, metabolic or reproductive hormone variables started to change, suggests that a dysfunctional osmoregulatory system may initiate rapid senescence and influence other physiological changes (i.e. elevated stress and collapsed reproductive hormones) which occur as O. nerka die on spawning grounds.

The heritability of general cognitive ability increases linearly from childhood to young adulthood.

Although common sense suggests that environmental influences increasingly account for individual differences in behavior as experiences accumulate during the course of life, this hypothesis has not previously been tested, in part because of the large sample sizes needed for an adequately powered analysis. Here we show for general cognitive ability that, to the contrary, genetic influence increases with age. The heritability of general cognitive ability increases significantly and linearly from 41% in childhood (9 years) to 55% in adolescence (12 years) and to 66% in young adulthood (17 years) in a sample of 11 000 pairs of twins from four countries, a larger sample than all previous studies combined. In addition to its far-reaching implications for neuroscience and molecular genetics, this finding suggests new ways of thinking about the interface between nature and nurture during the school years. Why, despite life's 'slings and arrows of outrageous fortune', do genetically driven differences increasingly account for differences in general cognitive ability? We suggest that the answer lies with genotype-environment correlation: as children grow up, they increasingly select, modify and even create their own experiences in part based on their genetic propensities.

Geoacoustic inversion of short range source data using a plane wave reflection coefficient approach.

Acoustic time series data were collected in a shallow, hard bottom lake environment located in central Texas using both short range (2 m) implosive data, obtained with the source and a single hydrophone located near mid-depth in the waveguide, along with longer range implosive and explosive data from a near surface source to a bottom mounted hydrophone. Matched field inversions using simulated annealing were performed with a ray trace plus complex plane wave reflection coefficient forward propagation model that was validated in previous work. Isolating bottom interacting paths to perform the inversions is shown to be essential to reduce parameter uncertainties in the hard bottom environment and enables a systematic approach to the inversions which establishes the number of layers needed to represent the lake environment. Measured transmission loss data from a towed source were compared through a RMS error analysis to modeled transmission loss, constructed with the parameters from inversions of data from several source types, to further establish the validity of the inversion approach for this environment. Geoacoustic parameters obtained by inversions of short range, low frequency impulsive data are used to predict transmission loss at longer ranges and higher frequencies. The range dependence of the global minimum is discussed.

Attention resources and visible speech encoding in older and younger adults.

Two experiments investigated adult age differences in the distribution of attention across a speaker's face during auditory-visual language processing. Dots were superimposed on the faces of speakers for 17-ms presentations, and participants reported the spatial locations of the dots. In Experiment 1, older adults showed relatively better detection performance at the mouth area than the eye area compared to younger adults. In Experiment 2, in the absence of audible language, both age groups did not differentially focus on the mouth area. The results are interpreted in light of Massaro's (1998, Perceiving talking faces: From speech perception to a behavioral principle. Cambridge, MA: MIT Press) theoretical framework for understanding auditory-visual speech perception. It is claimed that older adults' greater reliance on visible speech is due to a reallocation of resources away from the eyes and toward the mouth area of the face.

Broadband sound propagation in shallow water and geoacoustic inversion.

Part of an experiment to test a measurement package in a shallow water region in the Gulf of Mexico was designed to gather broadband acoustic data suitable for inversion to estimate seabed geoacoustic parameters. Continuous wave tow acoustic signals at multiple frequencies and broadband impulsive source signals were recorded on a horizontal line array in a high-noise environment. Simulated annealing with a normal mode forward propagation model is utilized to invert for a geoacoustic representation of the seabed. Several inversions are made from different data samples of two light bulb implosions, the measured sound speed profiles at the HLA and at the positions of the light bulb deployments, and for two different cost functions. The different cost functions, measured sound speed profiles, and measured time series result in different inverted geoacoustic profiles from which transmission loss is generated for comparison with measurements. On the basis of physical consistency and from the comparison of the transmission loss and time series, a best estimate geoacoustic profile is selected and compared to those obtained from previously reported inversions. Uncertainties in the sound speed profile are shown to affect the uncertainties of the estimated seabed parameters.

Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-alpha.

The binding of tumor necrosis factor alpha (TNF-alpha) to the type-1 TNF receptor (TNFRc1) plays an important role in inflammation. Despite the clinical success of biologics (antibodies, soluble receptors) for treating TNF-based autoimmune conditions, no potent small molecule antagonists have been developed. Our screening of chemical libraries revealed that N-alkyl 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones were antagonists of this protein-protein interaction. After chemical optimization, we discovered IW927, which potently disrupted the binding of TNF-alpha to TNFRc1 (IC(50) = 50 nM) and also blocked TNF-stimulated phosphorylation of Ikappa-B in Ramos cells (IC(50) = 600 nM). This compound did not bind detectably to the related cytokine receptors TNFRc2 or CD40, and did not display any cytotoxicity at concentrations as high as 100 microM. Detailed evaluation of this and related molecules revealed that compounds in this class are "photochemically enhanced" inhibitors, in that they bind reversibly to the TNFRc1 with weak affinity (ca. 40-100 microM) and then covalently modify the receptor via a photochemical reaction. We obtained a crystal structure of IV703 (a close analog of IW927) bound to the TNFRc1. This structure clearly revealed that one of the aromatic rings of the inhibitor was covalently linked to the receptor through the main-chain nitrogen of Ala-62, a residue that has already been implicated in the binding of TNF-alpha to the TNFRc1. When combined with the fact that our inhibitors are reversible binders in light-excluded conditions, the results of the crystallography provide the basis for the rational design of nonphotoreactive inhibitors of the TNF-alpha-TNFRc1 interaction.

Context-dependent memory under stressful conditions: the case of skydiving.

Two experiments examined the effect of differing levels of emotional arousal on learning and memory for words in matching and mismatching contexts. In Experiment 1, experienced skydivers learned words either in the air or on the ground and recalled them in the same context or in the other context. Experiment 2 replicated the stimuli and design of the first experiment except that participants were shown a skydiving video in lieu of skydiving. Recall was poor in air-learning conditions with actual skydiving, but when lists were learned on land, recall was higher in the matching context than in the mismatching context. In the skydiving video experiment, recall was higher in matching learn-recall contexts regardless of the situation in which learning occurred. We propose that under extremely emotionally arousing circumstances, environmental and/or mood cues are unlikely to become encoded or linked to newly acquired information and thus cannot serve as cues to retrieval. Results can be applied to understanding variations in context-dependent memory in occupations (e.g., police, military special operations, and Special Weapons and Tactics teams) in which the worker experiences considerable emotional stress while learning or recalling new information.

A genome-wide scan of 1842 DNA markers for allelic associations with general cognitive ability: a five-stage design using DNA pooling and extreme selected groups.

All measures of cognitive processes correlate moderately at the phenotypic level and correlate substantially at the genetic level. General cognitive ability (g) refers to what diverse cognitive processes have in common. Our goal is to identify quantitative trait loci (QTLs) associated with high g compared with average g. In order to detect QTLs of small effect size, we used extreme selected samples and a five-stage design with nominal alpha levels that permit false positive results in early stages but remove false positives in later stages. As a first step toward a systematic genome scan for allelic association, we used DNA pooling to screen 1842 simple sequence repeat (SSR) markers approximately evenly spaced at 2 cM throughout the genome in a five-stage design: (1) case-control DNA pooling (101 cases with mean IQ of 136 and 101 controls with mean IQ of 100), (2) case-control DNA pooling (96 cases with IQ > 160 and 100 controls with mean IQ of 102), (3) individual genotyping of Stage 1 sample, (4) individual genotyping of Stage 2 sample, (5) transmission disequilibrium test (TDT; 196 parent-child trios for offspring with IQ > 160). The over all Type I error rate is 0.000125, which robustly protects against false positive results. The numbers of markers surviving each stage using a conservative allele-specific directional test were 108, 6, 4, 2, and 0, respectively, for the five stages. A genomic control test using DNA pooling suggested that the failure to replicate the positive case-control results in the TDT analysis was not due to ethnic stratification. Several markers that were close to significance at all stages are being investigated further. Relying on indirect association based on linkage disequilibrium between markers and QTLs means that 100,000 markers may be needed to exclude QTL associations. Because power drops off precipitously for indirect association approaches when a marker is not close to the QTL, we are not planning to genotype additional SSR markers. Instead we are using the same design to screen markers such as cSNPs and SNPs in regulatory regions that are likely to include functional polymorphisms in which the marker can be presumed to be the QTL.

Infants attend to second-order relational properties of faces.

Two experiments investigated whether 7-month-old infants attend to the spatial distance measurements relating internal features of the human face. A visual preference paradigm was used, in which two versions of the same female face (one either lengthened or shortened, and one nonmodified) were presented simultaneously. In Experiment 1, infants looked longer at the nonmodified faces, which were determined to match the average distance relationships found in a sample of faces drawn from the same population. Longer looking times for modified faces were found in Experiment 2, in which the nonmodified faces were unusually long and the modified faces conformed to average distance measurements. It is proposed that infants' attention to the spatial relations of internal face features is an optimal tool for lifelong face recognition.

The salience of temporal cues in the developing structure of event knowledge.

Two experiments used a novel method called Pathfinder to examine whether the salience of temporal cues embedded in event structure increases developmentally and whether people link event actions by simple adjacency relationships or embed them in an organized whole. A sequential format for eliciting knowledge was compared with a less structured format for dinner and bedtime events. Adults and their 8- and 10-year-old children demonstrated well-developed script organizations regardless of format, and organization improved across this age range. In Experiment 1, temporal cues were not a salient basis of comparison for 6-year-olds, but in Experiment 2 they could use temporal cues when instructed to do so. The results suggest that temporal salience increases between 6 and 10 years and that temporal knowledge of event actions is highly organized in this age range. Furthermore, children's event knowledge functions partly in the interaction between their developing event knowledge and the support provided by sequential constraints in the environment.

Presenilin-1 and -2 are molecular targets for gamma-secretase inhibitors.

Presenilins are integral membrane protein involved in the production of amyloid beta-protein. Mutations of the presenilin-1 and -2 gene are associated with familial Alzheimer's disease and are thought to alter gamma-secretase cleavage of the beta-amyloid precursor protein, leading to increased production of longer and more amyloidogenic forms of A beta, the 4-kDa beta-peptide. Here, we show that radiolabeled gamma-secretase inhibitors bind to mammalian cell membranes, and a benzophenone analog specifically photocross-links three major membrane polypeptides. A positive correlation is observed among these compounds for inhibition of cellular A beta formation, inhibition of membrane binding and cross-linking. Immunological techniques establish N- and C-terminal fragments of presenilin-1 as specifically cross-linked polypeptides. Furthermore, binding of gamma-secretase inhibitors to embryonic membranes derived from presenilin-1 knockout embryos is reduced in a gene dose-dependent manner. In addition, C-terminal fragments of presenilin-2 are specifically cross-linked. Taken together, these results indicate that potent and selective gamma-secretase inhibitors block A beta formation by binding to presenilin-1 and -2.

A counterselection for the tryptophan pathway in yeast: 5-fluoroanthranilic acid resistance.

The ability to counterselect, as well as to select for, a genetic marker has numerous applications in microbial genetics. Described here is the use of 5-fluoroanthranilic acid for the counterselection of TRP1, a commonly used genetic marker in the yeast Saccharomyces cerevisiae. Counterselection using 5-fluoroanthranilic acid involves antimetabolism by the enzymes of the tryptophan biosynthetic pathway, such that trp1, trp3, trp4 or trp5 strains, which lack enzymes required for the conversion of anthranilic acid to tryptophan, are resistant to 5-fluoroanthranilic acid. Commonly used genetic procedures, such as selection for loss of a chromosomally integrated plasmid, and a replica-plating method to rapidly assess genetic linkage in self-replicating shuttle vectors, can now be carried out using the TRP1 marker gene. In addition, novel tryptophan auxotrophs can be selected using 5-fluoroanthranilic acid.

Recent applications of polymer-supported reagents and scavengers in combinatorial, parallel, or multistep synthesis.

There has been a wealth of recent reports concerning support-bound reagents and scavengers in the solution-phase synthesis of compound libraries and natural products. Important advances in 1999 include the continued development and use of novel reagents for heterocycle synthesis, the increased use of catch-and-release purification, and the development of increasingly sophisticated techniques to allow sequestering of many types of impurities from desired compounds. These techniques have all been combined to enable the complicated multistep synthesis of natural products and of libraries of novel drug-like molecules, without conventional purification.

Neurotic butterflies in my stomach: the role of anxiety, anxiety sensitivity and depression in functional gastrointestinal disorders.

This study examined the prevalence of functional gastrointestinal (FGI) disorders, and the association between FGI disorders and measures of affective distress, among a sample of 127 university students. Subjects completed a questionnaire battery including Research Diagnostic Questions for Functional Gastrointestinal Disorders, the Beck Anxiety Inventory, the Anxiety Sensitivity Index, the Beck Depression Inventory, and a medical utilization questionnaire. FGI disorders were diagnosed in 51.2% of the sample. Functional dyspepsia (22.8%), dyschezia (20.5%), functional heartburn (19.7%), functional chest pain (18.1%), and globus (12.6%) were the most frequently diagnosed disorders. Participants experiencing globus, functional dyspepsia, or functional heartburn showed significant differences in terms of anxiety, anxiety sensitivity, depression, and/or physician visits, when compared with participants without these disorders. Our results suggest that FGI disorders are strikingly prevalent among young adults, and specific FGI disorders are associated with affective distress. Implications of the observed association between psychological factors and FGI disorders are discussed.