Reinvestigating the relationships between the Badenoch Group, Dalradian Supergroup and the Grampian Shear Zone

In situ monazite and titanite U-Pb LA-ICP-MS geochronology and combined petrological and microstructural analysis has revealed both Neoproterozoic and Ordovician deformation within the Grampian Shear Zone (GSZ), central Scotland. The Grampian Shear Zone has been posited to separate the Dalradian Supergroup from the Badenoch Group, representing either, a structural break, an orogenic unconformity or a shear zone that predominantly affects the top of the Glen Banchor Subgroup. New monazite U-Pb data gave Neoproterozoic ages which provide a youngest age of deformation/monazite growth within the GSZ at 824 ± 2.73Ma, with subsequent Neoproterozoic resetting of the monazite at 751.81 ± 3.56Ma and a further resetting during the Early Ordovician/Late Cambrian at 485.85 ± 2.63Ma, from within sample RG1716. Monazite U-Pb data from sample RG1718 Ruthven Semipelite of the Corrieyairack Sub-Group (Grampian Group, of the Dalradian Supergroup) produced two distinct populations of monazite, one population of monazite growth associated with the Grampian Orogeny at 475.03 ± 1.11Ma, the other population from a detrital domain within the monazite produced lower intercept age of 475.51 ± 2.84Ma and an upper intercept age of 3004.7 ± 58Ma, revealing that the Ruthven Semipelite shows a distinct lack of Neoproterozoic deformation. The titanite U-Pb data collected produced an age of 467.45 ± 1.84Ma from Sample RG1703 a sheared garnet amphibolite from within the GSZ and 469 ± 0.3Ma from sample RG1710 a Badenoch Group lithology. The titanites dated within the Garnet amphibolite are from a titanite population within the garnet cores and must date or predate the onset of garnet growth. These garnets subsequently developed large strain shadows indicating a reactivation of the GSZ after the garnet growth. Sample RG1710s titanite population contains rare rutile cores, biotite quartz intergrowth textures and, cordierite pseudomorphs indicating a higher grade mineralogy predating the titanites. This mineralogy may be related to eclogite deformation within the Badenoch Group which predates migmitization of the Dava Sub-Group

Hazardous cosleeping environments and risk factors amenable to change: case-control study of SIDS in south west England

Objectives: To investigate the factors associated with sudden infant death syndrome (SIDS) from birth to age 2 years, whether recent advice has been followed, whether any new risk factors have emerged, and the specific circumstances in which SIDS occurs while cosleeping (infant sharing the same bed or sofa with an adult or child). Design: Four year population based case-control study. Parents were interviewed shortly after the death or after the reference sleep (within 24 hours) of the two control groups. Setting: South west region of England (population 4.9 million, 184 800 births). Participants: 80 SIDS infants and two control groups weighted for age and time of reference sleep: 87 randomly selected controls and 82 controls at high risk of SIDS (young, socially deprived, multiparous mothers who smoked). Results: The median age at death (66 days) was more than three weeks less than in a study in the same region a decade earlier. Of the SIDS infants, 54% died while cosleeping compared with 20% among both control groups. Much of this excess may be explained by a significant multivariable interaction between cosleeping and recent parental use of alcohol or drugs (31% v 3% random controls) and the increased proportion of SIDS infants who had coslept on a sofa (17% v 1%). One fifth of SIDS infants used a pillow for the last sleep (21% v 3%) and one quarter were swaddled (24% v 6%). More mothers of SIDS infants than random control infants smoked during pregnancy (60% v 14%), whereas one quarter of the SIDS infants were preterm (26% v 5%) or were in fair or poor health for the last sleep (28% v 6%). All of these differences were significant in the multivariable analysis regardless of which control group was used for comparison. The significance of covering the infant’s head, postnatal exposure to tobacco smoke, dummy use, and sleeping in the side position has diminished although a significant proportion of SIDS infants were still found prone (29% v 10%). Conclusions: Many of the SIDS infants had coslept in a hazardous environment. The major influences on risk, regardless of markers for socioeconomic deprivation, are amenable to change and specific advice needs to be given, particularly on use of alcohol or drugs before cosleeping and cosleeping on a sofa

Responding to unexpected infant deaths : experience in one English region

New national procedures for responding to the unexpected death of a child in England require a joint agency approach to investigate each death and support the bereaved family. As part of a wider population-based study of sudden unexpected deaths in infancy (SUDI) we evaluated the implementation of this approach. Methods: A process evaluation using a population-based study of all unexpected deaths from birth to 2 years in the South West of England between January 2003 and December 2006. Local police and health professionals followed a standardised approach to the investigation of each death, supported by the research team set up to facilitate this joint approach as well as collect data for a wider research project. Results: We were notified of 155/157 SUDI, with a median time to notification of 2 hours. Initial multi-agency discussions took place in 93.5% of cases. A joint home visit by police officers with health professionals was carried out in 117 cases, 75% within 24 hours of the death. Time to notification and interview reduced during the 4 years of the study. Autopsies were conducted on all cases, the median time to autopsy being 3 days. At the conclusion of the investigation, a local multi-agency case discussion was held in 88% of cases. The median time for the whole process (including family support) was 5 months. Conclusions: This study has demonstrated that with appropriate protocols and support, the joint agency approach to the investigation of unexpected infant deaths can be successfully implemented

Genetic and Pharmacological Factors That Influence Reproductive Aging in Nematodes

Age-related degenerative changes in the reproductive system are an important aspect of aging, because reproductive success is the major determinant of evolutionary fitness. Caenorhabditis elegans is a prominent organism for studies of somatic aging, since many factors that extend adult lifespan have been identified. However, mechanisms that control reproductive aging in nematodes or other animals are not well characterized. To use C. elegans to measure reproductive aging, we analyzed mated hermaphrodites that do not become sperm depleted and monitored the duration and level of progeny production. Mated hermaphrodites display a decline of progeny production that culminates in reproductive cessation before the end of the lifespan, demonstrating that hermaphrodites undergo reproductive aging. To identify factors that influence reproductive aging, we analyzed genetic, environmental, and pharmacological factors that extend lifespan. Dietary restriction and reduced insulin/insulin-like growth factor signaling delayed reproductive aging, indicating that nutritional status and a signaling pathway that responds to environmental stress influence reproductive aging. Cold temperature delayed reproductive aging. The anticonvulsant medicine ethosuximide, which affects neural activity, delayed reproductive aging, indicating that neural activity can influence reproductive aging. Some of these factors decrease early progeny production, but there is no consistent relationship between early progeny production and reproductive aging in strains with an extended lifespan. To directly examine the effects of early progeny production on reproductive aging, we used sperm availability to modulate the level of early reproduction. Early progeny production neither accelerated nor delayed reproductive aging, indicating that reproductive aging is not controlled by use-dependent mechanisms. The implications of these findings for evolutionary theories of aging are discussed

The Anticonvulsant Ethosuximide Disrupts Sensory Function to Extend C. elegans Lifespan

Ethosuximide is a medication used to treat seizure disorders in humans, and we previously demonstrated that ethosuximide can delay age-related changes and extend the lifespan of the nematode Caenorhabditis elegans. The mechanism of action of ethosuximide in lifespan extension is unknown, and elucidating how ethosuximide functions is important for defining endogenous processes that influence lifespan and for exploring the potential of ethosuximide as a therapeutic for age-related diseases. To identify genes that mediate the activity of ethosuximide, we conducted a genetic screen and identified mutations in two genes, che-3 and osm-3, that cause resistance to ethosuximide-mediated toxicity. Mutations in che-3 and osm-3 cause defects in overlapping sets of chemosensory neurons, resulting in defective chemosensation and an extended lifespan. These findings suggest that ethosuximide extends lifespan by inhibiting the function of specific chemosensory neurons. This model is supported by the observation that ethosuximide-treated animals displayed numerous phenotypic similarities with mutants that have chemosensory defects, indicating that ethosuximide inhibits chemosensory function. Furthermore, ethosuximide extends lifespan by inhibiting chemosensation, since the long-lived osm-3 mutants were resistant to the lifespan extension caused by ethosuximide. These studies demonstrate a novel mechanism of action for a lifespan-extending drug and indicate that sensory perception has a critical role in controlling lifespan. Sensory perception also influences the lifespan of Drosophila, suggesting that sensory perception has an evolutionarily conserved role in lifespan control. These studies highlight the potential of ethosuximide and related drugs that modulate sensory perception to extend lifespan in diverse animals

Development of a questionnaire to evaluate patients’ awareness of cardiovascular disease risk in England’s National Health Service Health Check preventive cardiovascular programme

Background The National Health Service (NHS) Health Check is a CVD risk assessment and management programme in England aiming to increase CVD risk awareness among people at increased risk of CVD. There is no tool to assess the effectiveness of the programme in communicating CVD risk to patients. Aims The aim of this paper was to develop a questionnaire examining patients’ CVD risk awareness for use in health service research evaluations of the NHS Health Check programme. Methods We developed an 85 item questionnaire to determine patients’ views of their risk of CVD. The questionnaire was based on a review of the relevant literature. After review by an expert panel and focus group discussion, 22 items were dropped and 2 new items were added. The resulting 65 item questionnaire with satisfactory content validity (content validity indices >=0.80) and face validity was tested on 110 NHS Health Check attendees in primary care in a cross sectional study between May 21 and July 28, 2014. Results Following analyses of data, we reduced the questionnaire from 65 to 26 items. The 26 item questionnaire constitutes 4 scales: Knowledge of CVD Risk and Prevention, Perceived Risk of Heart Attack/Stroke, Perceived Benefits and Intention to Change Behaviour and Healthy Eating Intentions. Perceived Risk (Cronbach’s α = 0.85) and Perceived Benefits and Intention to Change Behaviour (Cronbach’s α = 0.82) have satisfactory reliability (Cronbach’s α >=0.70). Healthy Eating Intentions (Cronbach’s α = 0.56) is below minimum threshold for reliability but acceptable for a three item scale. Conclusions The resulting questionnaire, with satisfactory reliability and validity, may be used in assessing patients’ awareness of CVD risk among NHS Health Check attendees

Rapid discrimination between methicillin-sensitive and methicillin-resistant Staphylococcus aureus by intact cell mass spectrometry

Rapid, accurate discrimination between methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains is essential for appropriate therapeutic management and timely intervention for infection control. A rapid method involving intact cell mass spectrometry (ICMS) is presented that shows promise for identification, discrimination of MSSA from MRSA and typing. In ICMS, cells from a bacterial colony are emulsified in a chemical matrix, added to a sample slide, dried and analysed by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS). This technique examines the chemistry of the intact bacterial cell surface, yielding spectra consisting of a series of peaks from 500 to 10 000, which represent the mass:charge (m:z) ratios. Each peak corresponds to a molecular fragment released from the cell surface during laser desorption. Specimens can be prepared in a few seconds from plate cultures and a spectrum can be obtained within 2 min. ICMS spectra for 20 staphylococcal isolates showed characteristic peaks, some of which were conserved at species level, some at strain level and some were characteristic of the methicillin susceptibility status of the strain. ICMS may have potential for MRSA identification and typing, and may improve infection control measures