Investigation of the CACNA1A gene as a candidate for typical migraine susceptibility

Typical migraine is a complex neurological disorder comprised of two main subtypes: migraine with (MA) and without aura (MO). The disease etiology is still unclear, but family studies provide strong evidence that defective genes play an important role. Familial hemiplegic migraine (FHM) is a very rare and severe subtype of MA. It has been proposed that FHM and MA may have a similar genetic etiology. Therefore, genetic studies on FHM provide a useful model for investigating the more prevalent types of typical migraine. FHM in some families has been shown to be caused by mutations in a brain-specific P/Q-type calcium channel alpha1 subunit gene (CACNA1A) on chromosome 19p13. There has also been a report of a CACNA1A mutation being associated with MA in a patient from a family with predominant FHM. We have previously demonstrated suggestive linkage of typical migraine in a large Australian family to the FHM region on chromosome 19p13. These findings suggest that CACNA1A may also be implicated in the etiology of typical migraine in this pedigree. To investigate this possibility, we sequenced two patients carrying the critical susceptibility haplotype surrounding CACNA1A. No disease-causing mutations or polymorphisms were revealed in any of the 47 exons screened. To determine whether the CACNA1A gene was implicated in typical migraine susceptibility in the general Caucasian population, we also analyzed 82 independent pedigrees and a large case control group. We did not detect any linkage or association in these groups and conclude that if CACNA1A plays a role in typical migraine, it does not confer a major effect on the disease.

Evidence for allelic association of the dopamine β-hydroxylase gene (DBH) with susceptibility to typical migraine

Migraine is a debilitating neurological disorder characterized by recurrent attacks of severe headache. The disorder is highly prevalent, affecting approximately 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the type and number of genes involved is not yet clear. However, the calcium channel gene, CACNA1A, on chromosome 19 contains mutations responsible for familial hemiplegic migraine, a rare and severe subtype of migraine. There is also evidence to suggest that serotonin- and dopamine-related genes may be involved in the pathogenesis of migraine. This study employed a linkage and association approach to investigate neurotransmitter-related migraine candidate genes. Polymorphisms within the dopamine beta-hydroxylase (DBH) gene, serotonin transporter gene (SERT), and dopamine receptor gene (DRD2) were tested in 177 unrelated Caucasian migraineurs and 182 control individuals. In addition, an independent sample of 82 families affected with migraine was examined. Unrelated case-control association analysis of a DBH intragenic dinucleotide polymorphism indicated altered allelic distribution between migraine and control groups (L2=16.53, P=0.019). Furthermore, the transmission/disequilibrium test, which was implemented on the family data, also indicated distortion of allele transmission for the same DBH marker (L2=4.44, P=0.035). Together, these results provide evidence for allelic association of the DBH gene with typical migraine susceptibility (Fisher's combined P value=0.006) and indicate that further research into the role of the DBH gene in the etiology of migraine is warranted.

Physical activity promotion as a school priority : what do parents think?

The demands and responsibilities placed on schools in contemporary education systems are vast. However, with growing obesity levels and physical inactivity, the prevention of chronic disease has focused on youth populations, with schools playing the focal educative asset in this strategy. Parents play a decisive role in their child’s educational setting, and as fee and tax payers, are ultimately a consumer. Parents (82 males and 208 females) of secondary school children were recruited from three private (n=151) and two government schools (n=150) in Brisbane, Australia. The mean (standard deviation) age was 44.57 (6.21) years. Participants responded to a series of questions about physical activity at their child’s school, in addition to completing the International Physical Activity Questionnaire. Data were analysed using descriptive statistics, frequency distributions and logistic regressions. Parents were deemed sufficiently physically active if they participated in at least 150 minutes of moderate-to-vigorous physical activity per week. Overall, 83 (59.7%) parents from private and 60 (50.8%) parents from government schools were deemed sufficiently physically active. Concerning whether physical activity promotion should be a priority at their child’s school, 111 (73.5%) parents from private schools either agreed or strongly agreed, as opposed to 97 (64.7%) parents from government schools. Logistic regressions indicated that the concept of physical activity promotion being prioritised at schools was dependent on whether the child attended a private school (OR =1.34, z = 2.30, p = 0.02), and whether the participant was sufficiently active (OR =.71, z = -2.48, p = 0.01). Physical activity promotion within schools may provide substantial future benefits on a population scale. The demands on schools may need to be addressed to meet the needs of students and the desires of their parents.

Setting water quality objectives for the health of freshwater fish

An important responsibility of the Environment Protection Authority, Victoria, is to set objectives for levels of environmental contaminants. To support the development of environmental objectives for water quality, a need has been identified to understand the dual impacts of concentration and duration of a contaminant on biota in freshwater streams. For suspended solids contamination, information reported by Newcombe and Jensen [ North American Journal of Fisheries Management , 16(4):693--727, 1996] study of freshwater fish and the daily suspended solids data from the United States Geological Survey stream monitoring network is utilised. The study group was requested to examine both the utility of the Newcombe and Jensen and the USA data, as well as the formulation of a procedure for use by the Environment Protection Authority Victoria that takes concentration and duration of harmful episodes into account when assessing water quality. The extent to which the impact of a toxic event on fish health could be modelled deterministically was also considered. It was found that concentration and exposure duration were the main compounding factors on the severity of effects of suspended solids on freshwater fish. A protocol for assessing the cumulative effect on fish health and a simple deterministic model, based on the biology of gill harm and recovery, was proposed. References D. W. T. Au, C. A. Pollino, R. S. S Wu, P. K. S. Shin, S. T. F. Lau, and J. Y. M. Tang. Chronic effects of suspended solids on gill structure, osmoregulation, growth, and triiodothyronine in juvenile green grouper epinephelus coioides . Marine Ecology Press Series , 266:255--264, 2004. J.C. Bezdek, S.K. Chuah, and D. Leep. Generalized k-nearest neighbor rules. Fuzzy Sets and Systems , 18:237--26, 1986. E. T. Champagne, K. L. Bett-Garber, A. M. McClung, and C. Bergman. {Sensory characteristics of diverse rice cultivars as influenced by genetic and environmental factors}. Cereal Chem. , {81}:{237--243}, {2004}. S. G. Cheung and P. K. S. Shin. Size effects of suspended particles on gill damage in green-lipped mussel perna viridis. Marine Pollution Bulletin , 51(8--12):801--810, 2005. D. H. Evans. The fish gill: site of action and model for toxic effects of environmental pollutants. Environmental Health Perspectives , 71:44--58, 1987. G. C. Grigg. The failure of oxygen transport in a fish at low levels of ambient oxygen. Comp. Biochem. Physiol. , 29:1253--1257, 1969. G. Holmes, A. Donkin, and I.H. Witten. {Weka: A machine learning workbench}. In Proceedings of the Second Australia and New Zealand Conference on Intelligent Information Systems , volume {24}, pages {357--361}, {Brisbane, Australia}, {1994}. {IEEE Computer Society}. D. D. Macdonald and C. P. Newcombe. Utility of the stress index for predicting suspended sediment effects: response to comments. North American Journal of Fisheries Management , 13:873--876, 1993. C. P. Newcombe. Suspended sediment in aquatic ecosystems: ill effects as a function of concentration and duration of exposure. Technical report, British Columbia Ministry of Environment, Lands and Parks, Habitat Protection branch, Victoria, 1994. C. P. Newcombe and J. O. T. Jensen. Channel suspended sediment and fisheries: A synthesis for quantitative assessment of risk and impact. North American Journal of Fisheries Management , 16(4):693--727, 1996. C. P. Newcombe and D. D. Macdonald. Effects of suspended sediments on aquatic ecosystems. North American Journal of Fisheries Management , 11(1):72--82, 1991. K. Schmidt-Nielsen. Scaling. Why is animal size so important? Cambridge University Press, NY, 1984. J. S. Schwartz, A. Simon, and L. Klimetz. Use of fish functional traits to associate in-stream suspended sediment transport metrics with biological impairment. Environmental Monitoring and Assessment , 179(1--4):347--369, 2011. E. Al Shaw and J. S. Richardson. Direct and indirect effects of sediment pulse duration on stream invertebrate assemb ages and rainbow trout ( Oncorhynchus mykiss ) growth and survival. Canadian Journal of Fish and Aquatic Science , 58:2213--2221, 2001. P. Tiwari and H. Hasegawa. {Demand for housing in Tokyo: A discrete choice analysis}. Regional Studies , {38}:{27--42}, {2004}. Y. Tramblay, A. Saint-Hilaire, T. B. M. J. Ouarda, F. Moatar, and B Hecht. Estimation of local extreme suspended sediment concentrations in california rivers. Science of the Total Environment , 408:4221--

The analysis of large scale data taken from the world groundnut (Arachis hypogaea L.) germplasm collection. II. Two-way data with mixed data types

As a sequel to a paper that dealt with the analysis of two-way quantitative data in large germplasm collections, this paper presents analytical methods appropriate for two-way data matrices consisting of mixed data types, namely, ordered multicategory and quantitative data types. While various pattern analysis techniques have been identified as suitable for analysis of the mixed data types which occur in germplasm collections, the clustering and ordination methods used often can not deal explicitly with the computational consequences of large data sets (i.e. greater than 5000 accessions) with incomplete information. However, it is shown that the ordination technique of principal component analysis and the mixture maximum likelihood method of clustering can be employed to achieve such analyses. Germplasm evaluation data for 11436 accessions of groundnut (Arachis hypogaea L.) from the International Research Institute of the Semi-Arid Tropics, Andhra Pradesh, India were examined. Data for nine quantitative descriptors measured in the post-rainy season and five ordered multicategory descriptors were used. Pattern analysis results generally indicated that the accessions could be distinguished into four regions along the continuum of growth habit (or plant erectness). Interpretation of accession membership in these regions was found to be consistent with taxonomic information, such as subspecies. Each growth habit region contained accessions from three of the most common groundnut botanical varieties. This implies that within each of the habit types there is the full range of expression for the other descriptors used in the analysis. Using these types of insights, the patterns of variability in germplasm collections can provide scientists with valuable information for their plant improvement programs.

Capital cost model for Robert evaporators

ROBERT EVAPORATORS in Australian sugar factories are traditionally constructed with 44.45 mm outside diameter stainless steel tubes of ~2 m length for all stages of evaporation. There are a few vessels with longer tubes (up to 2.8 m) and smaller and larger diameters (38.1 and 50.8 mm). Queensland University of Technology is undertaking a study to investigate the heat transfer performance of tubes of different lengths and diameters for the whole range of process conditions typically encountered in the evaporator set. Incorporation of these results into practical evaporator designs requires an understanding of the cost implications for constructing evaporator vessels with calandrias having tubes of different dimensions. Cost savings are expected for tubes of smaller diameter and longer length in terms of material, labour and installation costs in the factory. However these savings must be considered in terms of the heat transfer area requirements for the evaporation duty, which will likely be a function of the tube dimensions. In this paper a capital cost model is described which provides a relative cost of constructing and installing Robert evaporators of the same heating surface area but with different tube dimensions. Evaporators of 2000, 3000, 4000 and 5000 m2 are investigated. This model will be used in conjunction with the heat transfer efficiency data (when available) to determine the optimum tube dimensions for a new evaporator at a specified evaporation duty. Consideration is also given to other factors such as juice residence time (and implications for sucrose degradation and control) and droplet de-entrainment in evaporators of different tube dimensions.

Dynamic capabilities and performance : an empirical study of audiovisual producers in Europe

This study tests Teece’s conceptualization of dynamic capabilities in the context of small and medium sized firms competing in creative industries, i.e. the European audio-visual production industry. This industry is characterized by immature and evolving markets where firms’ dynamic capabilities are expected to lead to superior innovative performance. Using survey data from audio-visual producers in ten European countries we find that both sensing and seizing capabilities have a positive effect on firms' innovative performance. The effect however, is curvilinear and positive effects appear only when capabilities overcome a threshold level.

Energy use assessment of educational buildings: Toward a campus-wide sustainable energy policy

The purpose of this article is to assess the viability of blanket sustainability policies, such as Building Rating Systems in achieving energy efficiency in university campus buildings. We analyzed the energy consumption trends of 10 LEED-certified buildings and 14 non-LEED certified buildings at a major university in the US. Energy Use Intensity (EUI) of the LEED buildings was significantly higher (EUILEED= 331.20 kBtu/sf/yr) than non-LEED buildings (EUInon-LEED=222.70 kBtu/sf/yr); however, the median EUI values were comparable (EUILEED= 172.64 and EUInon-LEED= 178.16). Because the distributions of EUI values were non-symmetrical in this dataset, both measures can be used for energy comparisons—this was also evident when EUI computations exclude outliers, EUILEED=171.82 and EUInon-LEED=195.41. Additional analyses were conducted to further explore the impact of LEED certification on university campus buildings energy performance. No statistically significant differences were observed between certified and non-certified buildings through a range of robust comparison criteria. These findings were then leveraged to devise strategies to achieve sustainable energy policies for university campus buildings and to identify potential issues with portfolio level building energy performance comparisons.

Relation between variants in the neurotrophin receptor gene, NTRK3, and white matter integrity in healthy young adults

The NTRK3 gene (also known as TRKC) encodes a high affinity receptor for the neurotrophin 3'-nucleotidase (NT3), which is implicated in oligodendrocyte and myelin development. We previously found that white matter integrity in young adults is related to common variants in genes encoding neurotrophins and their receptors. This underscores the importance of neurotrophins for white matter development. NTRK3 variants are putative risk factors for schizophrenia, bipolar disorder, and obsessive-compulsive disorder hoarding, suggesting that some NTRK3 variants may affect the brain.To test this, we scanned 392 healthy adult twins and their siblings (mean age, 23.6. ±. 2.2. years; range: 20-29. years) with 105-gradient 4-Tesla diffusion tensor imaging (DTI). We identified 18 single nucleotide polymorphisms (SNPs) in the NTRK3 gene that have been associated with neuropsychiatric disorders. We used a multi-SNP model, adjusting for family relatedness, age, and sex, to relate these variants to voxelwise fractional anisotropy (FA) - a DTI measure of white matter integrity.FA was optimally predicted (based on the highest false discovery rate critical p), by five SNPs (rs1017412, rs2114252, rs16941261, rs3784406, and rs7176429; overall FDR critical p=. 0.028). Gene effects were widespread and included the corpus callosum genu and inferior longitudinal fasciculus - regions implicated in several neuropsychiatric disorders and previously associated with other neurotrophin-related genetic variants in an overlapping sample of subjects. NTRK3 genetic variants, and neurotrophins more generally, may influence white matter integrity in brain regions implicated in neuropsychiatric disorders.

fMRI evidence of word frequency and strength effects during episodic memory encoding

Word frequency (WF) and strength effects are two important phenomena associated with episodic memory. The former refers to the superior hit-rate (HR) for low (LF) compared to high frequency (HF) words in recognition memory, while the latter describes the incremental effect(s) upon HRs associated with repeating an item at study. Using the "subsequent memory" method with event-related fMRI, we tested the attention-at-encoding (AE) [M. Glanzer, J.K. Adams, The mirror effect in recognition memory: data and theory, J. Exp. Psychol.: Learn Mem. Cogn. 16 (1990) 5-16] explanation of the WF effect. In addition to investigating encoding strength, we addressed if study involves accessing prior representations of repeated items via the same mechanism as that at test [J.L. McClelland, M. Chappell, Familiarity breeds differentiation: a subjective-likelihood approach to the effects of experience in recognition memory, Psychol. Rev. 105 (1998) 724-760], entailing recollection [K.J. Malmberg, J.E. Holden, R.M. Shiffrin, Modeling the effects of repetitions, similarity, and normative word frequency on judgments of frequency and recognition memory, J. Exp. Psychol.: Learn Mem. Cogn. 30 (2004) 319-331] and whether less processing effort is entailed for encoding each repetition [M. Cary, L.M. Reder, A dual-process account of the list-length and strength-based mirror effects in recognition, J. Mem. Lang. 49 (2003) 231-248]. The increased BOLD responses observed in the left inferior prefrontal cortex (LIPC) for the WF effect provide support for an AE account. Less effort does appear to be required for encoding each repetition of an item, as reduced BOLD responses were observed in the LIPC and left lateral temporal cortex; both regions demonstrated increased responses in the conventional subsequent memory analysis. At test, a left lateral parietal BOLD response was observed for studied versus unstudied items, while only medial parietal activity was observed for repeated items at study, indicating that accessing prior representations at encoding does not necessarily occur via the same mechanism as that at test, and is unlikely to involve a conscious recall-like process such as recollection. This information may prove useful for constraining cognitive theories of episodic memory.

The association between ambient temperature and children's lung function in Baotou, China

The objective of this study is to examine the association between ambient temperature and children’s lung function in Baotou, China. We recruited 315 children (8–12 years) from Baotou, China in the spring of 2004, 2005, and 2006. They performed three successive forced expiratory measurements three times daily (morning, noon, and evening) for about 5 weeks. The highest peak expiratory flow (PEF) was recorded for each session. Daily data on ambient temperature, relative humidity, and air pollution were monitored during the same period. Mixed models with a distributed lag structure were used to examine the effects of temperature on lung function while adjusting for individual characteristics and environmental factors. Low temperatures were significantly associated with decreases in PEF. The effects lasted for lag 0–2 days. For all participants, the cumulative effect estimates (lag 0–2 days) were −1.44 (−1.93, −0.94) L/min, −1.39 (−1.92, −0.86) L/min, −1.40 (−1.97, −0.82) L/min, and −1.28 (−1.69, −0.88) L/min for morning, noon, evening, and daily mean PEF, respectively, associated with 1 °C decrease in daily mean temperature. Generally, the effects of temperature were slightly stronger in boys than in girls for noon, evening, and daily mean PEF, while the effects were stronger in girls for morning PEF. PM2.5 had joint effects with temperature on children’s PEF. Higher PM2.5 increased the impacts of low temperature. Low ambient temperatures are associated with lower lung function in children in Baotou, China. Preventive health policies will be required for protecting children from the cold weather.

The role of environmental factors in the spatial distribution of Japanese encephalitis in mainland China

Japanese encephalitis (JE) is the most common cause of viral encephalitis and an important public health concern in the Asia-Pacific region, particularly in China where 50% of global cases are notified. To explore the association between environmental factors and human JE cases and identify the high risk areas for JE transmission in China, we used annual notified data on JE cases at the center of administrative township and environmental variables with a pixel resolution of 1 km×1 km from 2005 to 2011 to construct models using ecological niche modeling (ENM) approaches based on maximum entropy. These models were then validated by overlaying reported human JE case localities from 2006 to 2012 onto each prediction map. ENMs had good discriminatory ability with the area under the curve (AUC) of the receiver operating curve (ROC) of 0.82-0.91, and low extrinsic omission rate of 5.44-7.42%. Resulting maps showed JE being presented extensively throughout southwestern and central China, with local spatial variations in probability influenced by minimum temperatures, human population density, mean temperatures, and elevation, with contribution of 17.94%-38.37%, 15.47%-21.82%, 3.86%-21.22%, and 12.05%-16.02%, respectively. Approximately 60% of JE cases occurred in predicted high risk areas, which covered less than 6% of areas in mainland China. Our findings will help inform optimal geographical allocation of the limited resources available for JE prevention and control in China, find hidden high-risk areas, and increase the effectiveness of public health interventions against JE transmission.

Melanopsin ganglion cell function in early age-related macular degeneration

Purpose Melanopsin-expressing retinal ganglion cells (mRGCs) have non-image forming functions including mediation of the pupil light reflex (PLR). There is limited knowledge about mRGC function in retinal disease. Initial retinal changes in age-related macular degeneration (AMD) occur in the paracentral region where mRGCs have their highest density, making them vulnerable during disease onset. In this cross-sectional clinical study, we measured the PLR to determine if mRGC function is altered in early stages of macular degeneration. Methods Pupil responses were measured in 8 early AMD patients (AREDS 2001 classification; mean age 72.6 ± 7.2 years, 5M, and 3F) and 12 healthy control participants (mean age 66.6 ± 6.1 years, 8M and 4F) using a custom-built Maxwellian-view pupillometer. Stimuli were 0.5 Hz sinewaves (10 s duration, 35.6° diameter) of short wavelength light (464nm, blue; retinal irradiance = 14.5 log quanta.cm-2.s-1) to produce high melanopsin excitation and of long wavelength light (638nm, red; retinal irradiance = 14.9 log quanta.cm-2.s-1), to bias activation to outer retina and provide a control. Baseline pupil diameter was determined during a 10 s pre-stimulus period. The post illumination pupil response (PIPR) was recorded for 40 s. The 6 s PIPR and maximum pupil constriction were expressed as percentage baseline (M ± SD). Results The blue PIPR was significantly less sustained (p<0.01) in the early AMD group (75.49 ± 7.88%) than the control group (58.28 ± 9.05%). The red PIPR was not significantly different (p>0.05) between the early AMD (84.79 ± 4.03%) and control groups (82.01 ± 5.86%). Maximum constriction amplitude in the early AMD group for blue (43.67 ± 6.35%) and red (48.64 ± 6.49%) stimuli were not significantly different to the control group for blue (39.94 ± 3.66%) and red (44.98 ± 3.15%) stimuli (p>0.05). Conclusions These results are suggestive of inner retinal mRGC deficits in early AMD. This non-invasive, objective measure of pupil responses may provide a new method for quantifying mRGC function and monitoring AMD progression.