Mapping eQTLs in the Norfolk Island genetic isolate identifies candidate genes for CVD risk traits

Cardiovascular disease (CVD) affects millions of people worldwide and is influenced by numerous factors, including lifestyle and genetics. Expression quantitative trait loci (eQTLs) influence gene expression and are good candidates for CVD risk. Founder-effect pedigrees can provide additional power to map genes associated with disease risk. Therefore, we identified eQTLs in the genetic isolate of Norfolk Island (NI) and tested for associations between these and CVD risk factors. We measured genome-wide transcript levels of blood lymphocytes in 330 individuals and used pedigree-based heritability analysis to identify heritable transcripts. eQTLs were identified by genome-wide association testing of these transcripts. Testing for association between CVD risk factors (i.e., blood lipids, blood pressure, and body fat indices) and eQTLs revealed 1,712 heritable transcripts (p < 0.05) with heritability values ranging from 0.18 to 0.84. From these, we identified 200 cis-acting and 70 trans-acting eQTLs (p < 1.84 × 10(-7)) An eQTL-centric analysis of CVD risk traits revealed multiple associations, including 12 previously associated with CVD-related traits. Trait versus eQTL regression modeling identified four CVD risk candidates (NAAA, PAPSS1, NME1, and PRDX1), all of which have known biological roles in disease. In addition, we implicated several genes previously associated with CVD risk traits, including MTHFR and FN3KRP. We have successfully identified a panel of eQTLs in the NI pedigree and used this to implicate several genes in CVD risk. Future studies are required for further assessing the functional importance of these eQTLs and whether the findings here also relate to outbred populations.

Common secure index for conjunctive keyword-based retrieval over encrypted data

We consider the following problem: users in a dynamic group store their encrypted documents on an untrusted server, and wish to retrieve documents containing some keywords without any loss of data confidentiality. In this paper, we investigate common secure indices which can make multi-users in a dynamic group to obtain securely the encrypted documents shared among the group members without re-encrypting them. We give a formal definition of common secure index for conjunctive keyword-based retrieval over encrypted data (CSI-CKR), define the security requirement for CSI-CKR, and construct a CSI-CKR based on dynamic accumulators, Paillier’s cryptosystem and blind signatures. The security of proposed scheme is proved under strong RSA and co-DDH assumptions.

Field validation of controlled Monte Carlo data generation for statistical damage identification employing Mahalanobis squared distance

This article presents the field applications and validations for the controlled Monte Carlo data generation scheme. This scheme was previously derived to assist the Mahalanobis squared distance–based damage identification method to cope with data-shortage problems which often cause inadequate data multinormality and unreliable identification outcome. To do so, real-vibration datasets from two actual civil engineering structures with such data (and identification) problems are selected as the test objects which are then shown to be in need of enhancement to consolidate their conditions. By utilizing the robust probability measures of the data condition indices in controlled Monte Carlo data generation and statistical sensitivity analysis of the Mahalanobis squared distance computational system, well-conditioned synthetic data generated by an optimal controlled Monte Carlo data generation configurations can be unbiasedly evaluated against those generated by other set-ups and against the original data. The analysis results reconfirm that controlled Monte Carlo data generation is able to overcome the shortage of observations, improve the data multinormality and enhance the reliability of the Mahalanobis squared distance–based damage identification method particularly with respect to false-positive errors. The results also highlight the dynamic structure of controlled Monte Carlo data generation that makes this scheme well adaptive to any type of input data with any (original) distributional condition.

Renormalization group interpretation of the Born and Rytov approximations

In this paper the method of renormalization group (RG) [Phys. Rev. E 54, 376 (1996)] is related to the well-known approximations of Rytov and Born used in wave propagation in deterministic and random media. Certain problems in linear and nonlinear media are examined from the viewpoint of RG and compared with the literature on Born and Rytov approximations. It is found that the Rytov approximation forms a special case of the asymptotic expansion generated by the RG, and as such it gives a superior approximation to the exact solution compared with its Born counterpart. Analogous conclusions are reached for nonlinear equations with an intensity-dependent index of refraction where the RG recovers the exact solution. © 2008 Optical Society of America.

Improvement of a dynamic accumulator at ICICS 07 and its application in multi-user keyword-based retrieval on encrypted data

A dynamic accumulator is an algorithm, which merges a large set of elements into a constant-size value such that for an element accumulated, there is a witness confirming that the element was included into the value, with a property that accumulated elements can be dynamically added and deleted into/from the original set. Recently Wang et al. presented a dynamic accumulator for batch updates at ICICS 2007. However, their construction suffers from two serious problems. We analyze them and propose a way to repair their scheme. We use the accumulator to construct a new scheme for common secure indices with conjunctive keyword-based retrieval.

Visualization of long-duration acoustic recordings of the environment

Acoustic recordings of the environment are an important aid to ecologists monitoring biodiversity and environmental health. However, rapid advances in recording technology, storage and computing make it possible to accumulate thousands of hours of recordings, of which, ecologists can only listen to a small fraction. The big-data challenge addressed in this paper is to visualize the content of long-duration audio recordings on multiple scales, from hours, days, months to years. The visualization should facilitate navigation and yield ecologically meaningful information. Our approach is to extract (at one minute resolution) acoustic indices which reflect content of ecological interest. An acoustic index is a statistic that summarizes some aspect of the distribution of acoustic energy in a recording. We combine indices to produce false-color images that reveal acoustic content and facilitate navigation through recordings that are months or even years in duration.

Correlations and volatility spillovers across commodity and stock markets: Linking energies, food, and gold

This paper employs a VAR-GARCH model to investigate the return links and volatility transmission between the S&P 500 and commodity price indices for energy, food, gold and beverages over the turbulent period from 2000 to 2011. Understanding the price behavior of commodity prices and the volatility transmission mechanism between these markets and the stock exchanges are crucial for each participant, including governments, traders, portfolio managers, consumers, and producers. For return and volatility spillover, the results show significant transmission among the S&P 500 and commodity markets. The past shocks and volatility of the S&P 500 strongly influenced the oil and gold markets. This study finds that the highest conditional correlations are between the S&P 500 and gold index and the S&P 500 and WTI index. We also analyze the optimal weights and hedge ratios for commodities/S&P 500 portfolio holdings using the estimates for each index. Overall, our findings illustrate several important implications for portfolio hedgers for making optimal portfolio allocations, engaging in risk management and forecasting future volatility in equity and commodity markets. © 2013 Elsevier B.V.

Stock prices of clean energy firms, oil and carbon markets : a vector autoregressive analysis

Recent discussions of energy security and climate change have attracted significant attention to clean energy. We hypothesize that rising prices of conventional energy and/or placement of a price on carbon emissions would encourage investments in clean energy firms. The data from three clean energy indices show that oil prices and technology stock prices separately affect the stock prices of clean energy firms. However, the data fail to demonstrate a significant relationship between carbon prices and the stock prices of the firms.

Estrogen deficiency-associated bone loss in the maxilla: A methodology to quantify the changes in the maxillary intra-radicular alveolar bone in an ovariectomized rat osteoporosis model

The effects of estrogen deficiency on bone characteristics are site-dependent, with the most commonly studied sites being appendicular long bones (proximal femur and tibia) and axial bones (vertebra). The effect on the maxillary and mandibular bones is still inconsistent and requires further investigation. This study was designed to evaluate bone quality in the posterior maxilla of ovariectomized rats in order to validate this site as an appropriate model to study the effect of osteoporotic changes. Methods: Forty-eight 3-month-old female Sprague-Dawley rats were randomly divided into two groups: an ovariectomized group (OVX, n=24) and Sham-operated group (SHAM, n=24). Six rats were randomly sacrificed from both groups at time points 8, 12, 16 and 20 weeks. The samples from tibia and maxilla were collected for Micro CT and histological analysis. For the maxilla, the volume of interest (VOI) area focused on the furcation areas of the first and second molar. Trabecular bone volume fraction (BV/TV, %), trabecular thickness (Tb.Th.), trabecular number (Tb.N.), trabecular separation (Tb.Sp.), and connectivity density (Conn.Dens) were analysed after Micro CT scanning. Results: At 8 weeks the indices BV/TV, Tb.Sp, Tb.N and Conn.Dens showed significant differences (P<0.05) between the OVX and SHAM groups in the tibia. Compared with the tibia, the maxilla developed osteoporosis at a later stage, with significant changes in maxillary bone density only occurring after 12 weeks. Compared with the SHAM group, both the first and second molars of the OVX group showed significantly decreased BV/TV values from 12 weeks, and these changes were sustained through 16 and 20 weeks. For Tb.Sp, there were significant increases in bone values for the OVX group compared with the SHAM group at 12, 16 and 20 weeks. Histological changes were highly consistent with Micro CT results. Conclusion: This study established a method to quantify the changes of intra-radicular alveolar bone in the posterior maxilla in an accepted rat osteoporosis model. The degree of the osteoporotic changes to trabecular bone architecture is site-dependent and at least 3 months are required for the osteoporotic effects to be apparent in the posterior maxilla following rat OVX.

Stop-signal response inhibition in schizophrenia : Behavioural, event-related potential and functional neuroimaging data

Inhibitory control deficits are well documented in schizophrenia, supported by impairment in an established measure of response inhibition, the stop-signal reaction time (SSRT). We investigated the neural basis of this impairment by comparing schizophrenia patients and controls matched for age, sex and education on behavioural, functional magnetic resonance imaging (fMRI) and event-related potential (ERP) indices of stop-signal task performance. Compared to controls, patients exhibited slower SSRT and reduced right inferior frontal gyrus (rIFG) activation, but rIFG activation correlated with SSRT in both groups. Go stimulus and stop-signal ERP components (N1/P3) were smaller in patients, but the peak latencies of stop-signal N1 and P3 were also delayed in patients, indicating impairment early in stop-signal processing. Additionally, response-locked lateralised readiness potentials indicated response preparation was prolonged in patients. An inability to engage rIFG may predicate slowed inhibition in patients, however multiple spatiotemporal irregularities in the networks underpinning stop-signal task performance may contribute to this deficit.

Weight-related differences in glucose metabolism and free fatty acid production in two South African population groups

OBJECTIVE The effects of free fatty acids (FFA), leptin, tumour necrosis factor (TNF) alpha and body fat distribution on in vivo oxidation of a glucose load were studied in two South African ethnic groups. DESIGN AND MEASUREMENTS Anthropometric and various metabolic indices were measured at fasting and during a 7h oral glucose tolerance test (OGTT). Body composition was measured using bioelectrical impedance analysis and subcutaneous and visceral fat mass was assessed using a five- and two-level CT-scan respectively. Glucose oxidation was evaluated by measuring the ratio of (13)CO(2) to (12)CO(2) in breath following ingestion of 1-(13)C-labelled glucose. SUBJECTS Ten lean black women (LBW), ten obese black women (OBW), nine lean white women (LWW) and nine obese white women (OWW) were investigated after an overnight fast. RESULTS Visceral fat levels were significantly higher (P < 0.01) in obese white than black women, despite similar body mass indexes (BMIs). There were no ethnic differences in glucose oxidation however; in the lean subjects of both ethnic groups the area under the curve (AUC) was higher than in obese subjects (P < 0.05 for both) and was found to correlate negatively with weight (r = -0.69, P < 0.01) after correcting for age. Basal TNF alpha concentrations were similar in all groups. Percentage suppression of FFAs at 30 min of the OCTT was 24 +/- 12% in OWW and - 38 +/- 23% (P < 0.05) in OBW, ie the 30 min FFA level was higher than the fasting level in the latter group. AUC for FFAs during the late postprandial period (120 - 420 min) was significantly higher in OWW than OBW (P < 0.01) and LWW (P < 0.01) and correlated positively with visceral fat mass independent of age (r = 0.78, P < 0.05) in the OWW only. Leptin levels were higher (P < 0.01) both at fasting and during the course of the OCTT in obese women from both ethnic groups compared to the lean women. CONCLUSIONS Glucose oxidation is reduced in obese subjects of both ethnic groups; inter- and intra-ethnic differences were observed in visceral fat mass and FFA production and it is possible that such differences may play a role in the differing prevalences of obesity-related disorders that have been reported in these two populations.

Choice impulsivity: Definitions, measurement issues, and clinical implications

Background Impulsivity critically relates to many psychiatric disorders. Given the multifaceted construct that impulsivity represents, defining core aspects of impulsivity is vital for the assessment and understanding of clinical conditions. Choice impulsivity (CI), involving the preferential selection of smaller sooner rewards over larger later rewards, represents one important type of impulsivity. Method The International Society for Research on Impulsivity (InSRI) convened to discuss the definition and assessment of CI and provide recommendations regarding measurement across species. Results Commonly used preclinical and clinical CI behavioral tasks are described, and considerations for each task are provided to guide CI task selection. Differences in assessment of CI (self-report, behavioral) and calculating CI indices (e.g., area-under-the-curve, indifference point, steepness of discounting curve) are discussed along with properties of specific behavioral tasks used in preclinical and clinical settings. Conclusions The InSRI group recommends inclusion of measures of CI in human studies examining impulsivity. Animal studies examining impulsivity should also include assessments of CI and these measures should be harmonized in accordance with human studies of the disorders being modeled in the preclinical investigations. The choice of specific CI measures to be included should be based on the goals of the study and existing preclinical and clinical literature using established CI measures.

Age related differences in the validity of the OMNI perceived exertion scale during lifestyle activities

PURPOSE The OMNI Perceived Exertion Scale was developed for children to report perceived effort while performing physical activity; however no studies have formally examined age-related differences in validity. This study evaluated the validity of the OMNI-RPE in four age groups performing a range of lifestyle activities. METHODS 206 participants were stratified into four age groups: 6-8 years (n = 42), 9-10 years (n = 46), 11-12 years (n = 47), and 13-15 years (n = 71). Heart rate and VO2 were measured during 11 activity trials ranging in intensity from sedentary to vigorous. After each trial, participants reported effort from the OMNI walk/run scale. Concurrent validity was assessed by calculating within-subject correlations between OMNI ratings and the two physiological indices. RESULTS The average correlation between OMNI ratings and VO2 was 0.67, 0.77, 0.85 and 0.87 for the 6-8, 9-10, 11-12 and 13-15 y age groups, respectively. CONCLUSION The OMNI RPE scale demonstrated fair to good evidence of validity across a range of lifestyle activities among 6-15 year old children. The validity of the scale appears to be developmentally related with RPE reports closely reflecting physiological responses among children older than 8 years.

The potential for new understandings of normal and abnormal cognition by integration of neuroimaging and behavioral data : Not an exercise in carrying coals to Newcastle

Discovering the means to prevent and cure schizophrenia is a vision that motivates many scientists. But in order to achieve this goal, we need to understand its neurobiological basis. The emergent metadiscipline of cognitive neuroscience fields an impressive array of tools that can be marshaled towards achieving this goal, including powerful new methods of imaging the brain (both structural and functional) as well as assessments of perceptual and cognitive capacities based on psychophysical procedures, experimental tasks and models developed by cognitive science. We believe that the integration of data from this array of tools offers the greatest possibilities and potential for advancing understanding of the neural basis of not only normal cognition but also the cognitive impairments that are fundamental to schizophrenia. Since sufficient expertise in the application of these tools and methods rarely reside in a single individual, or even a single laboratory, collaboration is a key element in this endeavor. Here, we review some of the products of our integrative efforts in collaboration with our colleagues on the East Coast of Australia and Pacific Rim. This research focuses on the neural basis of executive function deficits and impairments in early auditory processing in patients using various combinations of performance indices (from perceptual and cognitive paradigms), ERPs, fMRI and sMRI. In each case, integration of two or more sources of information provides more information than any one source alone by revealing new insights into structure-function relationships. Furthermore, the addition of other imaging methodologies (such as DTI) and approaches (such as computational models of cognition) offers new horizons in human brain imaging research and in understanding human behavior.

Age-related changes in perception of movement in driving scenes

Purpose Age-related changes in motion sensitivity have been found to relate to reductions in various indices of driving performance and safety. The aim of this study was to investigate the basis of this relationship in terms of determining which aspects of motion perception are most relevant to driving. Methods Participants included 61 regular drivers (age range 22–87 years). Visual performance was measured binocularly. Measures included visual acuity, contrast sensitivity and motion sensitivity assessed using four different approaches: (1) threshold minimum drift rate for a drifting Gabor patch, (2) Dmin from a random dot display, (3) threshold coherence from a random dot display, and (4) threshold drift rate for a second-order (contrast modulated) sinusoidal grating. Participants then completed the Hazard Perception Test (HPT) in which they were required to identify moving hazards in videos of real driving scenes, and also a Direction of Heading task (DOH) in which they identified deviations from normal lane keeping in brief videos of driving filmed from the interior of a vehicle. Results In bivariate correlation analyses, all motion sensitivity measures significantly declined with age. Motion coherence thresholds, and minimum drift rate threshold for the first-order stimulus (Gabor patch) both significantly predicted HPT performance even after controlling for age, visual acuity and contrast sensitivity. Bootstrap mediation analysis showed that individual differences in DOH accuracy partly explained these relationships, where those individuals with poorer motion sensitivity on the coherence and Gabor tests showed decreased ability to perceive deviations in motion in the driving videos, which related in turn to their ability to detect the moving hazards. Conclusions The ability to detect subtle movements in the driving environment (as determined by the DOH task) may be an important contributor to effective hazard perception, and is associated with age, and an individuals' performance on tests of motion sensitivity. The locus of the processing deficits appears to lie in first-order, rather than second-order motion pathways.