Investigation of negative cross-resistance as a resistance-management tool for insecticide-treated nets.

Resistance management for insecticide-treated nets (ITNs) remains a challenge. Options are limited, because a safe and highly active insecticide with a persistence of several months is required. These criteria have only been met by pyrethroids, although organophosphates (OPs) and carbamates have been considered as alternatives for impregnation of eave curtains. It has been observed that some pyrethroid-resistant mosquito strains show increased OP susceptibility over pyrethroid-susceptible strains (i.e., negative cross-resistance). The current study investigated whether this phenomenon applies to a range of mosquito species and strains, because a mixture or rotation strategy for resistance management could then be envisaged. Adult female mosquitoes from laboratory strains of Anopheles stephensi Liston, Anopheles gambiae Giles, and Culex quinquefasciatus Say were tested in World Health Organization susceptibility test kits. For An. stephensi, the highly pyrethroid-resistant DUB 234 strain showed the same level of resistance to malathion as the pyrethroid-susceptible DUB S. The malathion-resistant ST MAL strain was as susceptible to pyrethroids as the insecticide-susceptible BEECH. For An. gambiae, the malathion tolerance of the previously pyrethroid-resistant RSP strain was significantly higher than that of the insecticide-susceptible KWA. For Cx. quinquefasciatus, selection of the QUINQ strain with permethrin abolished preexisting resistance to the OP malathion as pyrethroid resistance increased, rendering the strain more susceptible to malathion than PEL SS. Some indication of negative cross-resistance to malathion was found for the permethrin-resistant MUHEZA strain. The occurrence of negative cross-resistance seems dependent on the history of insecticide selection and is not generally applicable. Resistance management for ITNs will need to use mechanisms other than negative cross-resistance to be effective

Minor differences in haplotype frequency estimates can produce very large differences in heterogeneity test statistics

<p>Abstract</p> <p>Background</p> <p>Tests for association between a haplotype and disease are commonly performed using a likelihood ratio test for heterogeneity between case and control haplotype frequencies. Using data from a study of association between heroin dependence and the DRD2 gene, we obtained estimated haplotype frequencies and the associated likelihood ratio statistic using two different computer programs, MLOCUS and GENECOUNTING. We also carried out permutation testing to assess the empirical significance of the results obtained.</p> <p>Results</p> <p>Both programs yielded similar, though not identical, estimates for the haplotype frequencies. MLOCUS produced a p value of 1.8*10^-15and GENECOUNTING produced a p value of 5.4*10^-4. Permutation testing produced a p value 2.8*10^-4.</p> <p>Conclusion</p> <p>The fact that very large differences occur between the likelihood ratio statistics from the two programs may reflect the fact that the haplotype frequencies for the combined group are not constrained to be equal to the weighted averages of the frequencies for the cases and controls, as they would be if they were directly observed rather than being estimated. Minor differences in haplotype frequency estimates can result in very large differences in the likelihood ratio statistic and associated <it>p </it>value.</p

Comparison of artificial neural network analysis with other multimarker methods for detecting genetic association

<p>Abstract</p> <p>Background</p> <p>Debate remains as to the optimal method for utilising genotype data obtained from multiple markers in case-control association studies. I and colleagues have previously described a method of association analysis using artificial neural networks (ANNs), whose performance compared favourably to single-marker methods. Here, the perfomance of ANN analysis is compared with other multi-marker methods, comprising different haplotype-based analyses and locus-based analyses.</p> <p>Results</p> <p>Of several methods studied and applied to simulated SNP datasets, heterogeneity testing of estimated haplotype frequencies using asymptotic <it>p </it>values rather than permutation testing had the lowest power of the methods studied and ANN analysis had the highest power. The difference in power to detect association between these two methods was statistically significant (<it>p </it>= 0.001) but other comparisons between methods were not significant. The raw <it>t </it>statistic obtained from ANN analysis correlated highly with the empirical statistical significance obtained from permutation testing of the ANN results and with the <it>p </it>value obtained from the heterogeneity test.</p> <p>Conclusion</p> <p>Although ANN analysis was more powerful than the standard haplotype-based test it is unlikely to be taken up widely. The permutation testing necessary to obtain a valid <it>p </it>value makes it slow to perform and it is not underpinned by a theoretical model relating marker genotypes to disease phenotype. Nevertheless, the superior performance of this method does imply that the widely-used haplotype-based methods for detecting association with multiple markers are not optimal and efforts could be made to improve upon them. The fact that the <it>t </it>statistic obtained from ANN analysis is highly correlated with the statistical significance does suggest a possibility to use ANN analysis in situations where large numbers of markers have been genotyped, since the <it>t</it> value could be used as a proxy for the <it>p </it>value in preliminary analyses.</p

Paleolimnological Assessment of Six Lakes on the Kissimmee Chain, with Implications for Restoration of the Kissimmee-Okeechobee-Everglades system, Florida, USA

Whitmore TJ, Riedinger-Whitmore MA, Reed ZE, Curtis JH, Yang H, Evans DE, Cropper NR, Alvarado KS, Lauterman FM, Scott A, Leonard CR, Franklin DL. 2020. Paleolimnological assessment of six lakes on the Kissimmee Chain, with implications for restoration of the Kissimmee–Okeechobee–Everglades system, Florida, USA. Lake Reserv Manage. 36:218–242. The Kissimmee Basin in south central Florida contains a large, freshwater network that includes the Kissimmee River and nearly 2 dozen lakes that are headwaters of the Florida Everglades. Management of these lakes is an important part of Everglades restoration. We report a paleolimnological investigation of 6 lakes in the Upper Kissimmee Basin. Engineering activities connected the lakes and permanently altered hydrology in the 19th and 20th centuries. The lakes were naturally meso-eutrophic, but changes in lake levels and nutrient loading contributed to different degrees of eutrophication. Cyanobacteria were present historically at low levels in Lakes East Tohopekaliga, Cypress, and Tohopekaliga, but increased during the 20th century. Lake Jackson lacked cyanobacteria until recently, but Lakes Kissimmee and Marian have had high levels of cyanobacteria since predisturbance times. Profound changes in the lakes occurred after engineering activities eliminated natural large fluctuations in water levels that periodically dried large portions of the basins. Salt-tolerant biological indicators previously alternated with freshwater organisms. Large water-level fluctuations moderated aquatic-plant standing crops and reduced organic matter accumulation. Lakes Kissimmee and Marian showed greatest evidence of former associated wetlands, but lacked large variations in water levels. We recommend disconnecting these lakes from each other and from the Kissimmee River to reestablish large, natural fluctuations in water levels that were part of healthy ecosystem function. Former wetlands should be restored to slow the downstream cascade of nutrients to Lake Okeechobee and the Everglades. This study demonstrates that paleolimnology is useful for assessing hydrological changes that potentially affect lake restoration efforts

Look duration at the face as a developmental endophenotype: elucidating pathways to autism and ADHD.

Identifying developmental endophenotypes on the pathway between genetics and behavior is critical to uncovering the mechanisms underlying neurodevelopmental conditions. In this proof-of-principle study, we explored whether early disruptions in visual attention are a unique or shared candidate endophenotype of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). We calculated the duration of the longest look (i.e., peak look) to faces in an array-based eye-tracking task for 335 14-month-old infants with and without first-degree relatives with ASD and/or ADHD. We leveraged parent-report and genotype data available for a proportion of these infants to evaluate the relation of looking behavior to familial (n = 285) and genetic liability (using polygenic scores, n = 185) as well as ASD and ADHD-relevant temperament traits at 2 years of age (shyness and inhibitory control, respectively, n = 272) and ASD and ADHD clinical traits at 6 years of age (n = 94).Results showed that longer peak looks at the face were associated with elevated polygenic scores for ADHD (β = 0.078, p = .023), but not ASD (β = 0.002, p = .944), and with elevated ADHD traits in mid-childhood (F(1,88) = 6.401, p = .013, $\eta _p^2$=0.068; ASD: F (1,88) = 3.218, p = .076), but not in toddlerhood (ps > 0.2). This pattern of results did not emerge when considering mean peak look duration across face and nonface stimuli. Thus, alterations in attention to faces during spontaneous visual exploration may be more consistent with a developmental endophenotype of ADHD than ASD. Our work shows that dissecting paths to neurodevelopmental conditions requires longitudinal data incorporating polygenic contribution, early neurocognitive function, and clinical phenotypic variation

Z' signals in polarised top-antitop final states

We study the sensitivity of top-antitop samples produced at all energy stages of the Large Hadron Collider (LHC) to the nature of an underlying Z' boson, in presence of full tree level standard model (SM) background effects and relative interferences. We concentrate on differential mass spectra as well as both spatial and spin asymmetries thereby demonstrating that exploiting combinations of these observables will enable one to distinguish between sequential Z's and those pertaining to Left-Right symmetric models as well as E6 inspired ones, assuming realistic final state reconstruction efficiencies and error estimates.Comment: 21 pages, 6 colour figures, 10 table

Children and older adults exhibit distinct sub-optimal cost-benefit functions when preparing to move their eyes and hands

"© 2015 Gonzalez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited"Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented 'cued' and 'non-cued' conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18 -25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation)

Effects among healthy subjects of the duration of regularly practicing a guided imagery program

BACKGROUND: We examined a large number of healthy adults in the general community who had individually participated in a guided imagery (GI) program daily and for various durations, to examine the psychophysiological effects of a GI program within a healthy group. METHODS: We studied 176 subjects who had participated in sessions that were part of a guided imagery program, and who had practiced GI at home for 20 minutes once daily in a quiet place after mastering GI in the group sessions. The average duration of GI practiced at home was 6.88 ± 14.06 months (n = 138, range: 0 to 72). The Multiple Mood Scale (MMS), Betts (1909) Shortened Questionnaire on Mental Imagery (QMI), and a visual analog scale (VAS) of imagery vividness, salivary cortisol (C(S)) levels, general stress and general health were used in the sessions. RESULTS: We examined the relationship between the duration of daily GI practiced at home and MMS, QMI, C(S), general health, and general stress at baseline. The subjects who had practiced GI at home longer had lower negative mood scores at baseline and lower severity of stress, and higher positive mood at baseline (both at a session and at home), general health, and QMI scores at baseline. The MMS change during a session and the duration of daily GI practiced at home were not correlated. Repeated-measures analysis of covariance showed that the duration of daily GI practiced as the covariate was not associated with changes in the three C(S )levels. CONCLUSION: Although regularly practicing a GI program daily for 20 min did not affect the C(S )level or mood during a GI session for several hours, it kept a good condition of the general mental, physical well-being and their overall stress of the practitioners as they had practiced it for long duration. We postulate that subjects who have the high ability of imaging vividness showed the better mood, health status and less stress than those subjects who have the low ability of it did. The ability of image vividness of the long-term regular practitioners of GI was higher than its short-term or inexperienced practitioners, which allowed practitioners to produce more comfortable imagery. Consequently, the longer the duration that they had practiced GI program once a day regularly, the lower scores of their stress were and the higher scores of their health were. We suggest that the regular daily practice of a GI program might be connected to less stress and better health

Neural networks for genetic epidemiology: past, present, and future

During the past two decades, the field of human genetics has experienced an information explosion. The completion of the human genome project and the development of high throughput SNP technologies have created a wealth of data; however, the analysis and interpretation of these data have created a research bottleneck. While technology facilitates the measurement of hundreds or thousands of genes, statistical and computational methodologies are lacking for the analysis of these data. New statistical methods and variable selection strategies must be explored for identifying disease susceptibility genes for common, complex diseases. Neural networks (NN) are a class of pattern recognition methods that have been successfully implemented for data mining and prediction in a variety of fields. The application of NN for statistical genetics studies is an active area of research. Neural networks have been applied in both linkage and association analysis for the identification of disease susceptibility genes

Big hearts, small hands:A focus group study exploring parental food portion behaviours

© The Author(s). 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: The development of healthy food portion sizes among families is deemed critical to childhood weight management; yet little is known about the interacting factors influencing parents' portion control behaviours. This study aimed to use two synergistic theoretical models of behaviour: the COM-B model (Capability, Opportunity, Motivation - Behaviour) and Theoretical Domains Framework (TDF) to identify a broad spectrum of theoretically derived influences on parents' portion control behaviours including examination of affective and habitual influences often excluded from prevailing theories of behaviour change. Methods: Six focus groups exploring family weight management comprised of one with caseworkers (n = 4), four with parents of overweight children (n = 14) and one with parents of healthy weight children (n = 8). A thematic analysis was performed across the dataset where the TDF/COM-B were used as coding frameworks. Results: To achieve the target behaviour, the behavioural analysis revealed the need for eliciting change in all three COM-B domains and nine associated TDF domains. Findings suggest parents' internal processes such as their emotional responses, habits and beliefs, along with social influences from partners and grandparents, and environmental influences relating to items such as household objects, interact to influence portion size behaviours within the home environment. Conclusion: This is the first study underpinned by COM-B/TDF frameworks applied to childhood weight management and provides new targets for intervention development and the opportunity for future research to explore the mediating and moderating effects of these variables on one another.Peer reviewedFinal Published versio