815 resultados para OF-ONSET
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Driving on an approach to a signalized intersection while distracted is particularly dangerous, as potential vehicular conflicts and resulting angle collisions tend to be severe. Given the prevalence and importance of this particular scenario, the decisions and actions of distracted drivers during the onset of yellow lights are the focus of this study. Driving simulator data were obtained from a sample of 58 drivers under baseline and handheld mobile phone conditions at the University of Iowa - National Advanced Driving Simulator. Explanatory variables included age, gender, cell phone use, distance to stop-line, and speed. Although there is extensive research on drivers’ responses to yellow traffic signals, the examination has been conducted from a traditional regression-based approach, which does not necessary provide the underlying relations and patterns among the sampled data. In this paper, we exploit the benefits of both classical statistical inference and data mining techniques to identify the a priori relationships among main effects, non-linearities, and interaction effects. Results suggest that novice (16-17 years) and young drivers’ (18-25 years) have heightened yellow light running risk while distracted by a cell phone conversation. Driver experience captured by age has a multiplicative effect with distraction, making the combined effect of being inexperienced and distracted particularly risky. Overall, distracted drivers across most tested groups tend to reduce the propensity of yellow light running as the distance to stop line increases, exhibiting risk compensation on a critical driving situation.
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Purpose: Photoreceptor interactions reduce the temporal bandwidth of the visual system under mesopic illumination. The dynamics of these interactions are not clear. This study investigated cone-cone and rod-cone interactions when the rod (R) and three cone (L, M, S) photoreceptor classes contribute to vision via shared post-receptoral pathways. Methods: A four-primary photostimulator independently controlled photoreceptor activity in human observers. To determine the temporal dynamics of receptoral (L, S, R) and post-receptoral (LMS, LMSR, +L-M) pathways (5 Td, 7° eccentricity) in Experiment 1, ON-pathway sensitivity was assayed with an incremental probe (25ms) presented relative to onset of an incremental sawtooth conditioning pulse (1000ms). To define the post-receptoral pathways mediating the rod stimulus, Experiment 2 matched the color appearance of increased rod activation (30% contrast, 25-1000ms; constant cone excitation) with cone stimuli (variable L+M, L/L+M, S/L+M; constant rod excitation). Results: Cone-cone interactions with luminance stimuli (LMS, LMSR, L-cone) reduced Weber contrast sensitivity by 13% and the time course of adaptation was 23.7±1ms (μ±SE). With chromatic stimuli (+L-M, S), cone pathway sensitivity was also reduced and recovery was slower (+L-M 8%, 2.9±0.1ms; S 38%, 1.5±0.3ms). Threshold patterns at ON-conditioning pulse onset were monophasic for luminance and biphasic for chromatic stimuli. Rod-rod interactions increased sensitivity(19%) with a recovery time of 0.7±0.2ms. Compared to cone-cone interactions, rod-cone interactions with luminance stimuli reduced sensitivity to a lesser degree (5%) with faster recovery (42.9±0.7ms). Rod-cone interactions were absent with chromatic stimuli. Experiment 2 showed that rod activation generated luminance (L+M) signals at all durations, and chromatic signals (L/L+M, S/L+M) for durations >75ms. Conclusions: Temporal dynamics of cone-cone interactions are consistent with contrast sensitivity loss in the MC pathway for luminance stimuli and chromatically opponent responses in the PC and KC pathway with chromatic stimuli. Rod-cone interactions limit contrast sensitivity loss during dynamic illumination changes and increase the speed of mesopic light adaptation. The change in relative weighting of the temporal rod signal within the major post-receptoral pathways modifies the sensitivity and dynamics of photoreceptor interactions.
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Background: When experiencing sleep problems for the first time, consumers may often approach community pharmacists for advice as they are easily accessible health care professionals in the community. In Australian community pharmacies there are no specific tools available for use by pharmacists to assist with the assessment and handling of consumers with sleep enquiries. Objective: To assess the feasibility of improving the detection of sleep disorders within the community through the pilot of a newly developed Community Pharmacy Sleep Assessment Tool (COP-SAT). Method: The COP-SAT was designed to incorporate elements from a number of existing, standardized, and validated clinical screening measures. The COP-SAT was trialed in four Australian community pharmacies over a 4-week period. Key findings: A total of 241 community pharmacy consumers were assessed using the COP-SAT. A total of 74 (30.7%) were assessed as being at risk of insomnia, 26 (10.7%) were at risk of daytime sleepiness, 19 (7.9%) were at risk of obstructive sleep apnea, and 121 (50.2%) were regular snorers. A total of 116 (48.1%) participants indicated that they consume caffeine before bedtime, of which 55 (47%) had associated symptoms of sleep onset insomnia. Moreover, 85 (35%) consumed alcohol before bedtime, of which 50 (58%) experienced fragmented sleep, 50 (58%) were regular snorers, and nine (10.6%) had apnea symptoms. The COP-SAT was feasible in the community pharmacy setting. The prevalence of sleep disorders in the sampled population was high, but generally consistent with previous studies on the general population. Conclusion: A large proportion of participants reported sleep disorder symptoms, and a link was found between the consumption of alcohol and caffeine substances at bedtime and associated symptoms. While larger studies are needed to assess the clinical properties of the tool, the results of this feasibility study have demonstrated that the COP-SAT may be a practical tool for the identification of patients at risk of developing sleep disorders in the community.
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Cenozoic extension in western Mexico has been divided into two episodes separated by the change from convergence to oblique divergence at the plate boundary. The Gulf Extensional Province is thought to have started once subduction ended at ~12.5 Ma whereas early extension is classified as Basin and Range. Mid-Miocene volcanism of the Comondú group has been considered as a subduction-related arc, whereas post ~12.5 Ma volcanism would be extension-related. Our new integration of the continental onshore and offshore geology of the south-east Gulf region, backed by tens of Ar-Ar and U-Pb ages and geochemical studies, document an early-mid Miocene rifting and extension-related bimodal to andesitic magmatism prior to subduction termination. Between ~21 and 11 Ma a system of NNW-SSE high-angle extensional faults rifted the western side of the Sierra Madre Occidental (SMO) ignimbrite plateau. In Nayarit, rhyolitic domes and some basalts were emplaced along this extensional belt at 18-17 Ma. These rocks show strong antecrystic inheritance but an absence of Mesozoic and older xenocrysts, suggesting a genesis in the mid-upper crust triggered by extension-induced basaltic influx. In Sinaloa, large grabens were floored by huge dome complexes at ~21-17 Ma and filled by continental sediments with interlayered basalts dated at 15 Ma. Mid-Miocene volcanism, including the largely volcaniclastic Comondú strata in Baja California, was thus emplaced in rift basins and appears associated to decompression melting rather than subduction. Along the coast, flat-lying basaltic lava flows dated at 11-10 Ma are exposed just above the present sea level. Here crustal thickness is 25-20 Km, almost half that in the core of the SMO, implying significant lithosphere stretching before ~11 Ma. This mafic pulse, with relatively high Ti but still clear Nb-Ta negative spikes, may be related to the detachment of the lower part of the subducted slab, allowing asthenosphere to flow into parts of the mantle previously fluxed by subduction fluids. Very uniform OIB-like lavas appear in late Pliocene and Pleistocene, only 18 m.y. after the onset of rifting and ~9 m.y. after the end of subduction. Our study shows that rifting began much earlier than Late Miocene and progressively overwhelmed subduction in generating magmatism.
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The Gulf of California (GoC) has been an important focus site for understanding the spatial and temporal evolution of rifts, with recent studies concluding: 1) rapid crustal rupturing within 10 Myrs; 2) surprisingly abrupt variations in rifting style and magmatism with apparently wide magma-poor and narrow, magmatic rift segments; and 3) that high sedimentation rates may promote switching from wide to narrow rift modes or thermally blanket the crust to enhance rift magmatism. Critical to these conclusions is the onset of rifting at~12 Ma following the cessation of subduction. New field-based volcanostratigraphic and geochronologic studies along the southeastern GoC margin reveal Early Miocene (~25-18 Ma) bimodal volcanism in wide rifting mode (~400 km width), followed by a mid-Miocene (~18-12 Ma) phase of dominantly intermediate composition magmatism in and around the nascent GoC with lavas/domes often emplaced into actively subsiding basins, but contemporaneous with bimodal volcanism regionally. Flat-lying intraplate basaltic lava fields emplaced ~12-10 Ma along the GoC east coast abut tilted blocks of ~20 Ma ignimbrites onshore, and also occur offshore. The reduction in crustal thickness from ~55 to 20 km along the eastern GoC edge must have been largely achieved by 12 Ma. Extension has demonstrably began earlier than previously thought, downplaying rapid rifting and any thermal effects from <6 Ma sedimentation. New age data from onshore indicate significant structurally controlled corridors of magmatism during 18-12 Ma extension in apparently magma-poor rift segments, and this magmatism temporally coincides with the switch from wide to narrow rifting.
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Executive Summary Child sexual abuse (CSA) in Christian Institutions continues to be of serious concern in public, criminal justice and institutional discourse. This study was conducted in conjunction with Project Kidsafe Foundation and sought the perspectives of Australian survivors of CSA by Personnel in Christian Institutions (PICIs). In total, 81 individual survivors responded to an online survey which asked them a range of questions about their current and childhood life circumstance; the nature, extent and location of abuse; grooming strategies utilised by perpetrators; their experiences of disclosure; and outcomes of official reporting to both criminal justice agencies and also official processes Christian institutions. Survey participants were given the option to further participate in a qualitative interview with the principal researcher. These interviews are not considered within this report. In summary, survey data examined here indicate that: • Instances of abuse included a range of offences from touching outside of clothing to serious penetrative offences. • The onset of abuse occurred at a young age: between 6 and 10 years for most female participants, and 11 and 13 years for male participants. • In the majority of cases the abuse ceased because of actions by survivors, not by adults within families or the Christian institution. • Participants waited significant time before disclosing their abuse, with many waiting 20 years or more. • Where survivors disclosed to family members or PICIs, they were often met with disbelief and unhelpful responses aimed at minimising the harm. • Where an official report was made, it was most often made to police. In these cases 53% resulted in an official investigations. • The primary reasons for reporting were to protect others from the perpetrator and make the Christian institution accountable to an external agency. • Where reports to Christian institutions were made, most survivors were dissatisfied with outcomes, and a smaller majority was extremely dissatisfied. This report reflects the long-held understanding that responding to CSA is a complex and difficult task. If effective and meaningful responses are not made, however, trauma to the survivor is most often compounded and recovery delayed. This report demonstrates the need for further independent analysis and oversight of responses made to CSA by both criminal justice, religious and social institutions. Meaningful change will only be accessible, however, if family, community and institutional environments are safe places for survivors to disclose their experiences of abuse and begin to seek ways of healing. There is much to be learnt from survivors that have already made this journey.
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Introduction The onset of Personally Controlled Electronic Health Records in Australia demand healthcare decision making processes to comprise, understand and accept electronic health records (EHR). Nurses play a key, central role in the healthcare decision making process and their perceptions and attitudes of EHRs are significant [1], which develop during their academic life. However, studies aimed at nursing students’ attitudes of EHRs are very limited [2-4]. A proper understanding of these attitudes and how they evolve with academic progress is important. This paper presents results from a survey conducted at a leading University in Queensland, Australia as a first step to filling this gap.
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We report on an accurate numerical scheme for the evolution of an inviscid bubble in radial Hele-Shaw flow, where the nonlinear boundary effects of surface tension and kinetic undercooling are included on the bubble-fluid interface. As well as demonstrating the onset of the Saffman-Taylor instability for growing bubbles, the numerical method is used to show the effect of the boundary conditions on the separation (pinch-off) of a contracting bubble into multiple bubbles, and the existence of multiple possible asymptotic bubble shapes in the extinction limit. The numerical scheme also allows for the accurate computation of bubbles which pinch off very close to the theoretical extinction time, raising the possibility of computing solutions for the evolution of bubbles with non-generic extinction behaviour.
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Alterations in cognitive function are characteristic of the aging process in humans and other animals. However, the nature of these age related changes in cognition is complex and is likely to be influenced by interactions between genetic predispositions and environmental factors resulting in dynamic fluctuations within and between individuals. These inter and intra-individual fluctuations are evident in both so-called normal cognitive aging and at the onset of cognitive pathology. Mild Cognitive Impairment (MCI), thought to be a prodromal phase of dementia, represents perhaps the final opportunity to mitigate cognitive declines that may lead to terminal conditions such as dementia. The prognosis for people with MCI is mixed with the evidence suggesting that many will remain stable within 10-years of diagnosis, many will improve, and many will transition to dementia. If the characteristics of people who do not progress to dementia from MCI can be identified and replicated in others it may be possible to reduce or delay dementia onset, thus reducing a growing personal and public health burden. Furthermore, if MCI onset can be prevented or delayed, the burden of cognitive decline in aging populations worldwide may be reduced. A cognitive domain that is sensitive to the effects of advancing age, and declines in which have been shown to presage the onset of dementia in MCI patients, is executive function. Moreover, environmental factors such as diet and physical activity have been shown to affect performance on tests of executive function. For example, improvements in executive function have been demonstrated as a result of increased aerobic and anaerobic physical activity and, although the evidence is not as strong, findings from dietary interventions suggest certain nutrients may preserve or improve executive functions in old age. These encouraging findings have been demonstrated in older adults with MCI and their non-impaired peers. However, there are some gaps in the literature that need to be addressed. For example, little is known about the effect on cognition of an interaction between diet and physical activity. Both are important contributors to health and wellbeing, and a growing body of evidence attests to their importance in mental and cognitive health in aging individuals. Yet physical activity and diet are rarely considered together in the context of cognitive function. There is also little known about potential underlying biological mechanisms that might explain the physical activity/diet/cognition relationship. The first aim of this program of research was to examine the individual and interactive role of physical activity and diet, specifically long chain polyunsaturated fatty acid consumption(LCn3) as predictors of MCI status. The second aim is to examine executive function in MCI in the context of the individual and interactive effects of physical activity and LCn3.. A third aim was to explore the role of immune and endocrine system biomarkers as possible mediators in the relationship between LCn3, physical activity and cognition. Study 1a was a cross-sectional analysis of MCI status as a function of erythrocyte proportions of an interaction between physical activity and LCn3. The marine based LCn3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both received support in the literature as having cognitive benefits, although comparisons of the relative benefits of EPA or DHA, particularly in relation to the aetiology of MCI, are rare. Furthermore, a limited amount of research has examined the cognitive benefits of physical activity in terms of MCI onset. No studies have examined the potential interactive benefits of physical activity and either EPA or DHA. Eighty-four male and female adults aged 65 to 87 years, 50 with MCI and 34 without, participated in Study 1a. A logistic binary regression was conducted with MCI status as a dependent variable, and the individual and interactive relationships between physical activity and either EPA or DHA as predictors. Physical activity was measured using a questionnaire and specific physical activity categories were weighted according to the metabolic equivalents (METs) of each activity to create a physical activity intensity index (PAI). A significant relationship was identified between MCI outcome and the interaction between the PAI and EPA; participants with a higher PAI and higher erythrocyte proportions of EPA were more likely to be classified as non-MCI than their less active peers with less EPA. Study 1b was a randomised control trial using the participants from Study 1a who were identified with MCI. Given the importance of executive function as a determinant of progression to more severe forms of cognitive impairment and dementia, Study 1b aimed to examine the individual and interactive effect of physical activity and supplementation with either EPA or DHA on executive function in a sample of older adults with MCI. Fifty male and female participants were randomly allocated to supplementation groups to receive 6-months of supplementation with EPA, or DHA, or linoleic acid (LA), a long chain polyunsaturated omega-6 fatty acid not known for its cognitive enhancing properties. Physical activity was measured using the PAI from Study 1a at baseline and follow-up. Executive function was measured using five tests thought to measure different executive function domains. Erythrocyte proportions of EPA and DHA were higher at follow-up; however, PAI was not significantly different. There was also a significant improvement in three of the five executive function tests at follow-up. However, regression analyses revealed that none of the variance in executive function at follow-up was predicted by EPA, DHA, PAI, the EPA by PAI interaction, or the DHA by PAI interaction. The absence of an effect may be due to a small sample resulting in limited power to find an effect, the lack of change in physical activity over time in terms of volume and/or intensity, or a combination of both reduced power and no change in physical activity. Study 2a was a cross-sectional study using cognitively unimpaired older adults to examine the individual and interactive effects of LCn3 and PAI on executive function. Several possible explanations for the absence of an effect were identified. From this consideration of alternative explanations it was hypothesised that post-onset interventions with LCn3 either alone or in interation with self-reported physical activity may not be beneficial in MCI. Thus executive function responses to the individual and interactive effects of physical activity and LCn3 were examined in a sample of older male and female adults without cognitive impairment (n = 50). A further aim of study 2a was to operationalise executive function using principal components analysis (PCA) of several executive function tests. This approach was used firstly as a data reduction technique to overcome the task impurity problem, and secondly to examine the executive function structure of the sample for evidence of de-differentiation. Two executive function components were identified as a result of the PCA (EF 1 and EF 2). However, EPA, DHA, the PAI, or the EPA by PAI or DHA by PAI interactions did not account for any variance in the executive function components in subsequent hierarchical multiple regressions. Study 2b was an exploratory correlational study designed to explore the possibility that immune and endocrine system biomarkers may act as mediators of the relationship between LCn3, PAI, the interaction between LCn3 and PAI, and executive functions. Insulin-like growth factor-1 (IGF-1), an endocrine system growth hormone, and interleukin-6 (IL-6) an immune system cytokine involved in the acute inflammatory response, have both been shown to affect cognition including executive functions. Moreover, IGF-1 and IL-6 have been shown to be antithetical in so far as chronically increased IL-6 has been associated with reduced IGF-1 levels, a relationship that has been linked to age related morbidity. Further, physical activity and LCn3 have been shown to modulate levels of both IGF-1 and IL-6. Thus, it is possible that the cognitive enhancing effects of LCn3, physical activity or their interaction are mediated by changes in the balance between IL-6 and IGF-1. Partial and non-parametric correlations were conducted in a subsample of participants from Study 2a (n = 13) to explore these relationships. Correlations of interest did not reach significance; however, the coefficients were quite large for several relationships suggesting studies with larger samples may be warranted. In summary, the current program of research found some evidence supporting an interaction between EPA, not DHA, and higher energy expenditure via physical activity in differentiating between older adults with and without MCI. However, a RCT examining executive function in older adults with MCI found no support for increasing EPA or DHA while maintaining current levels of energy expenditure. Furthermore, a cross-sectional study examining executive function in older adults without MCI found no support for better executive function performance as a function of increased EPA or DHA consumption, greater energy expenditure via physical activity or an interaction between physical activity and either EPA or DHA. Finally, an examination of endocrine and immune system biomarkers revealed promising relationships in terms of executive function in non-MCI older adults particularly with respect to LCn3 and physical activity. Taken together, these findings demonstrate a potential benefit of increasing physical activity and LCn3 consumption, particularly EPA, in mitigating the risk of developing MCI. In contrast, no support was found for a benefit to executive function as a result of increased physical activity, LCn3 consumption or an interaction between physical activity and LCn3, in participants with and without MCI. These results are discussed with reference to previous findings in the literature including possible limitations and opportunities for future research.
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Poor health and injury represent major obstacles to the future economic security of Australia. The national economic cost of work-related injury is estimated at $57.5 billion p/a. Since exposure to high physical demands is a major risk factor for musculoskeletal injury, monitoring and managing such physical activity levels in workers is a potentially important injury prevention strategy. Current injury monitoring practices are inadequate for the provision of clinically valuable information about the tissue specific responses to physical exertion. Injury of various soft tissue structures can manifest over time through accumulation of micro-trauma. Such micro-trauma has a propensity to increase the risk of acute injuries to soft-tissue structures such as muscle or tendon. As such, the capacity to monitor biomarkers that result from the disruption of these tissues offers a means of assisting the pre-emptive management of subclinical injury prior to acute failure or for evaluation of recovery processes. Here we have adopted an in-vivo exercise induced muscle damage model allowing the application of laboratory controlled conditions to assist in uncovering biochemical indicators associated with soft-tissue trauma and recovery. Importantly, urine was utilised as the diagnostic medium since it is non-invasive to collect, more acceptable to workers and less costly to employers. Moreover, it is our hypothesis that exercise induced tissue degradation products enter the circulation and are subsequently filtered by the kidney and pass through to the urine. To test this hypothesis a range of metabolomic and proteomic discovery-phase techniques were used, along with targeted approaches. Several small molecules relating to tissue damage were identified along with a series of skeletal muscle-specific protein fragments resulting from exercise induced soft-tissue damage. Each of the potential biomolecular markers appeared to be temporally present within urine. Moreover, the regulation of abundance seemed to be associated with functional recovery following the injury. This discovery may have important clinical applications for monitoring of a variety of inflammatory myopathies as well as novel applications in monitoring of the musculoskeletal health status of workers, professional athletes and/or military personnel to reduce the onset of potentially debilitating musculoskeletal injuries within these professions.
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Intensive Care Paramedics (ICPs) attend to only the most clinically challenging of emergency medical cases, often working in a chaotic and frenetic atmosphere. They are regularly exposed to human tragedy and with that, the potential to experience traumatic events is not uncommon. There is very little known about the well-being of ICPs; how they cope with the demands of their role, or about their mental health in general. Nineteen experienced ICPs (4 female, 15 male) participated in a semi-structured interview. Themes were extracted from the data using an Interpretive Phenomenological Analysis approach. All participants discussed a work-related event they attended that traumatized them, usually experienced in the earlier parts of their career. Some spoke of an immediate overwhelming of their capacity to cope and others of a gradual onset of traumatic stress when reflecting on the event at a later time. More than half of the participants described events that involved children as the most difficult. Data revealed four superordinate themes: Social Support, Cognitive Coping, Proactive Coping, and Long Term Effects. Each superordinate theme comprised a number of constituent themes which are presented in this paper and exemplified with participant quotes. Although ongoing distress was described by some participants, all of the ICPs interviewed discussed positive aspects of their job; things that made the role worthwhile and fulfilling. This research highlights the important factors involved in coping with, and growing from, the extraordinary events that ICPs face. Results have implications for employing organizations and staff support services as well as for paramedics more broadly as they learn to cope with events inherent in their career. Findings indicate that positive adaptation and personal growth as a result of exposure to extremely high levels of potentially traumatic experiences is not only possible, but highly probable.
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Although Basin and Range–style extension affected large areas of western Mexico after the Late Eocene, most consider that extension in the Gulf of California region began as subduction waned and ended ca. 14–12.5 Ma. A general consensus also exists in considering Early and Middle Miocene volcanism of the Sierra Madre Occidental and Comondú Group as subduction related, whereas volcanism after ca. 12.5 Ma is extension related. Here we present a new regional geologic study of the eastern Gulf of California margin in the states of Nayarit and Sinaloa, Mexico, backed by 43 new Ar-Ar and U-Pb mineral ages, and geochemical data that document an earlier widespread phase of extension. This extension across the southern and central Gulf Extensional Province began between Late Oligocene and Early Miocene time, but was focused in the region of the future Gulf of California in the Middle Miocene. Late Oligocene to Early Miocene rocks across northern Nayarit and southern Sinaloa were affected by major approximately north-south– to north-northwest– striking normal faults prior to ca. 21 Ma. Between ca. 21 and 11 Ma, a system of north-northwest–south-southeast high angle extensional faults continued extending the southwestern side of the Sierra Madre Occidental. Rhyolitic domes, shallow intrusive bodies, and lesser basalts were emplaced along this extensional belt at 20–17 Ma. Rhyolitic rocks, in particular the domes and lavas, often show strong antecrystic inheritance but only a few Mesozoic or older xenocrysts, suggesting silicic magma generation in the mid-upper crust triggered by an extension induced basaltic infl ux. In northern Sinaloa, large grabens were occupied by huge volcanic dome complexes ca. 21–17 Ma and filled by continental sediments with interlayered basalts dated as 15–14 Ma, a stratigraphy and timing very similar to those found in central Sonora (northeastern Gulf of California margin). Early to Middle Miocene volcanism occurred thus in rift basins, and was likely associated with decompression melting of upper mantle (inducing crustal partial melting) rather than with fluxing by fluids from the young and slow subducting microplates. Along the eastern side of the Gulf of California coast, from Farallón de San Ignacio island offshore Los Mochis, Sinaloa, to San Blas, Nayarit, a strike distance of >700 km, flat lying basaltic lavas dated as ca. 11.5–10 Ma are exposed just above the present sea level. Here crustal thickness is almost half that in the unextended core of the adjacent Sierra Madre Occidental, implying signifi cant lithosphere stretching before ca. 11 Ma. This mafic pulse, with subdued Nb-Ta negative spikes, may be related to the detachment of the lower part of the subducted slab, allowing an upward asthenospheric flow into an upper mantle previously modified by fluid fluxes related to past subduction. Widespread eruption of very uniform oceanic island basalt–like lavas occurred by the late Pliocene and Pleistocene, only 20 m.y. after the onset of rifting and ~9 m.y. after the end of subduction, implying that preexisting subduction-modified mantle had now become isolated from melt source regions. Our study shows that rifting across the southern-central Gulf Extensional Province began much earlier than the Late Miocene and provided a fundamental control on the style and composition of volcanism from at least 30 Ma. We envision a sustained period of lithospheric stretching and magmatism during which the pace and breadth of extension changed ca. 20–18 Ma to be narrower, and again after ca. 12.5 Ma, when the kinematics of rifting became more oblique.
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Migraine is the most common neurological disorder worldwide affecting about 12% of the worldwide population. This disorder has been classed into two main types of migraine—with and without aura. While a number of factors can influence the onset of migraine, a major factor is that of genetics. The GABAA gene encodes for the GABAA receptor. Along with other receptors, the GABAA receptor is involved in the mediation of neuronal activities. In this study, a GABRG2 gene (GABAA receptor gamma-2-subunit) SNP (rs211037) was genotyped on a migraine case–control population of 546 (273 affected and an equal number of healthy) individuals. Using specifically designed primers, a high resolution melt (HRM) assay was carried out in the genotyping process. After genotyping, results were compared in the case and control populations. Analysis of results showed no significant differences in the allele frequencies between case and control populations. Similarly no differences were detected for subtypes or for a specific gender of migraine (p > 0.05). Although this gene has been previously found to be involved in febrile seizures and there is some co-morbidity between epilepsy and migraine, we decided to investigate this marker for involvement in migraine. The results did not support a role for the tested GABRG2 variant in migraine.
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The T-box family transcription factor gene TBX20 acts in a conserved regulatory network, guiding heart formation and patterning in diverse species. Mouse Tbx20 is expressed in cardiac progenitor cells, differentiating cardiomyocytes, and developing valvular tissue, and its deletion or RNA interference-mediated knockdown is catastrophic for heart development. TBX20 interacts physically, functionally, and genetically with other cardiac transcription factors, including NKX2-5, GATA4, and TBX5, mutations of which cause congenital heart disease (CHD). Here, we report nonsense (Q195X) and missense (I152M) germline mutations within the T-box DNA-binding domain of human TBX20 that were associated with a family history of CHD and a complex spectrum of developmental anomalies, including defects in septation, chamber growth, and valvulogenesis. Biophysical characterization of wild-type and mutant proteins indicated how the missense mutation disrupts the structure and function of the TBX20 T-box. Dilated cardiomyopathy was a feature of the TBX20 mutant phenotype in humans and mice, suggesting that mutations in developmental transcription factors can provide a sensitized template for adult-onset heart disease. Our findings are the first to link TBX20 mutations to human pathology. They provide insights into how mutation of different genes in an interactive regulatory circuit lead to diverse clinical phenotypes, with implications for diagnosis, genetic screening, and patient follow-up.
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Migraine, with and without aura (MA and MO), is a prevalent and complex neurovascular disorder that is likely to be influenced by multiple genes some of which may be capable of causing vascular changes leading to disease onset. This study was conducted to determine whether the ACE I/D gene variant is involved in migraine risk and whether this variant might act in combination with the previously implicated MTHFR C677T genetic variant in 270 migraine cases and 270 matched controls. Statistical analysis of the ACE I/D variant indicated no significant difference in allele or genotype frequencies (P > 0.05). However, grouping of genotypes showed a modest, yet significant, over-representation of the DD/ID genotype in the migraine group (88%) compared to controls (81%) (OR of 1.64, 95% CI: 1.00–2.69, P = 0.048). Multivariate analysis, including genotype data for the MTHFR C677T, provided evidence that the MTHFR (TT) and ACE (ID/DD) genotypes act in combination to increase migraine susceptibility (OR = 2.18, 95% CI: 1.15–4.16, P = 0.018). This effect was greatest for the MA subtype where the genotype combination corresponded to an OR of 2.89 (95% CI:1.47–5.72, P = 0.002). In Caucasians, the ACE D allele confers a weak independent risk to migraine susceptibility and also appears to act in combination with the C677T variant in the MTHFR gene to confer a stronger influence on the disease.