Hippocampal lesions disrupt an associative mismatch process

Novel assays were used to assess inter alia whether the hippocampus is involved in detecting novelty per se or in an associative mismatch process. During training, rats received two audiovisual sequences (tone–left constant light and click– left flashing light). In both sham-operated control rats and those with excitotoxic hippocampal lesions, novel visual targets provoked an orienting response that habituated during training. Moreover, like sham-operated rats, rats with hippocampal lesions acquired associations between the elements of two audiovisual sequences. However, subsequent test trials in which the auditory stimuli preceding the visual targets were switched (click–left constant light and tone–left flashing light) provoked renewed orienting to the visual targets in sham-operated rats but not in hippocampal rats. These results support the view that hippocampal damage results in a failure to detect (or act on) mismatches that are generated when an auditory stimulus associatively evokes the memory of one visual stimulus and a different (familiar) visual stimulus is present in the environment

Shock wave apparatus for studying minerals at high pressure and impact phenomena on planetary surfaces

Shock wave and experimental impact phenomena research on geological and planetary materials is being carried out using two propellant (18 and 40 mm) guns (up to 2.5 km/sec) and a two‐stage light gas gun (up to 7 km/sec). Equation of state measurements on samples initially at room temperature and at low and high temperatures are being conducted using the 40 mm propellant apparatus in conjunction with Helmholtz coils, and radiative detectors and, in the case of the light gas gun, with streak cameras. The 18 mm propellant gun is used for recovery experiments on minerals, impact on cryogenic targets, and radiative post‐shock temperature measurements

The Lancet Oral Health Series – implications for oral and dental research

No abstract available

Stratigraphy and age of the Eocene Igtertivâ Formation basalts, alkaline pebbles and sediments of the Kap Dalton Group in the graben at Kap Dalton, East Greenland

A NE–SW-trending graben at Kap Dalton on the Blosseville Kyst contains an at least 600 m thick succession of Eocene basalt lavas and sediments. The succession has been investigated by new field work, geochemical analysis and radiometric dating by the ⁴⁰Ar-³⁹Ar incremental heating method. The results show that the volcanic succession comprises about 220 m of the uppermost plateau basalt formation, the Skrænterne Formation. This is separated from the overlying lava flows of the Igtertivâ Formation by 7 m of sediments that represent a period of around six million years. The two formations can be distinguished by different trace element ratios. The Igtertivâ Formation comprises an at least 300 m thick main succession of flows dated to 49.09 ± 0.48 Ma, overlain by sediments of the Bopladsdalen Formation. A basal conglomerate in the sediments contains pebbles of alkaline igneous rocks of which three were dated at 49.17 ± 0.35 Ma, 47.60 ± 0.25 Ma, and 46.98 ± 0.24 Ma. The sediments are thus younger than 47 Ma. Above 30 m of sediments occur two Igtertivâ Formation lava flows dated to 43.77 ± 1.08 Ma. The overlying sediments of the Bopladsdalen and Krabbedalen Formations are therefore not older than about 44 Ma and palynological evidence shows that they are also not much younger than this. Use of the Geological Time Scale 2012 has resulted in good agreement between radiometric and palynological ages. The Igtertivâ Formation lava flows were fed from a regional coast-parallel dyke swarm indicating a new rifting episode at 49–44 Ma. This coincides with a major mid-Eocene plate reorganisation event in the North Atlantic and the start of northward-propagation of the Reykjanes Ridge through the continent. The Igtertivâ rift may have been directly instrumental for the initiation of this process.Keywords: Kap Dalton, Igtertivâ Formation, radiometric ages, alkaline pebbles, East Greenland, ridge propagation, plateau basalts, Bopladsdalen Formatio

Variations in achievement of evidence-based, high-impact quality indicators in general practice: an observational study

Background: There are widely recognised variations in the delivery and outcomes of healthcare but an incomplete understanding of their causes. There is a growing interest in using routinely collected ‘big data’ in the evaluation of healthcare. We developed a set of evidence-based ‘high impact’ quality indicators (QIs) for primary care and examined variations in achievement of these indicators using routinely collected data in the United Kingdom (UK). Methods: Cross-sectional analysis of routinely collected, electronic primary care data from a sample of general practices in West Yorkshire, UK (n = 89). The QIs covered aspects of care (including processes and intermediate clinical outcomes) in relation to diabetes, hypertension, atrial fibrillation, myocardial infarction, chronic kidney disease (CKD) and ‘risky’ prescribing combinations. Regression models explored the impact of practice and patient characteristics. Clustering within practice was accounted for by including a random intercept for practice. Results: Median practice achievement of the QIs ranged from 43.2% (diabetes control) to 72.2% (blood pressure control in CKD). Considerable between-practice variation existed for all indicators: the difference between the highest and lowest performing practices was 26.3 percentage points for risky prescribing and 100 percentage points for anticoagulation in atrial fibrillation. Odds ratios associated with the random effects for practices emphasised this; there was a greater than ten-fold difference in the likelihood of achieving the hypertension indicator between the lowest and highest performing practices. Patient characteristics, in particular age, gender and comorbidity, were consistently but modestly associated with indicator achievement. Statistically significant practice characteristics were identified less frequently in adjusted models. Conclusions: Despite various policy and improvement initiatives, there are enduring inappropriate variations in the delivery of evidence-based care. Much of this variation is not explained by routinely collected patient or practice variables, and is likely to be attributable to differences in clinical and organisational behaviour

Modelling chemistry in the nocturnal boundary layer above tropical rainforest and a generalised effective nocturnal ozone deposition velocity for sub-ppbv NOx conditions

Measurements of atmospheric composition have been made over a remote rainforest landscape. A box model has previously been demonstrated to model the observed daytime chemistry well. However the box model is unable to explain the nocturnal measurements of relatively high [NO] and [O3], but relatively low observed [NO2]. It is shown that a one-dimensional (1-D) column model with simple O3 -NOx chemistry and a simple representation of vertical transport is able to explain the observed nocturnal concentrations and predict the likely vertical profiles of these species in the nocturnal boundary layer (NBL). Concentrations of tracers carried over from the end of the night can affect the atmospheric chemistry of the following day. To ascertain the anomaly introduced by using the box model to represent the NBL, vertically-averaged NBL concentrations at the end of the night are compared between the 1-D model and the box model. It is found that, under low to medium [NOx] conditions (NOx <1 ppbv), a simple parametrisation can be used to modify the box model deposition velocity of ozone, in order to achieve good agreement between the box and 1-D models for these end-of-night concentrations of NOx and O3. This parametrisation would could also be used in global climate-chemistry models with limited vertical resolution near the surface. Box-model results for the following day differ significantly if this effective nocturnal deposition velocity for ozone is implemented; for instance, there is a 9% increase in the following day’s peak ozone concentration. However under medium to high [NOx] conditions (NOx > 1 ppbv), the effect on the chemistry due to the vertical distribution of the species means no box model can adequately represent chemistry in the NBL without modifying reaction rate constants

Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity.

Bloom's syndrome is a rare autosomal recessive disorder characterized by genomic instability and predisposition to cancer. BLM, the gene defective in Bloom's syndrome, encodes a 159-kDa protein possessing DNA-stimulated ATPase and ATP-dependent DNA helicase activities. We have examined mechanistic aspects of the catalytic functions of purified recombinant BLM protein. Through analyzing the effects of different lengths of DNA cofactor on ATPase activity, we provide evidence to suggest that BLM translocates along single-stranded DNA in a processive manner. The helicase reaction catalyzed by BLM protein was examined as a function of duplex DNA length. We show that BLM catalyzes unwinding of short DNA duplexes (/=259-bp). The presence of the human single-stranded DNA-binding protein (human replication protein A (hRPA)) stimulates the BLM unwinding reaction on the 259-bp partial duplex DNA substrate. Heterologous single-stranded DNA-binding proteins fail to stimulate similarly the helicase activity of BLM protein. This is the first demonstration of a functional interaction between BLM and another protein. Consistent with a functional interaction between hRPA and the BLM helicase, we demonstrate a direct physical interaction between the two proteins mediated by the 70-kDa subunit of RPA. The interactions between BLM and hRPA suggest that the two proteins function together in vivo to unwind DNA duplexes during replication, recombination, or repair

The distribution of burden of dental caries in schoolchildren: a critique of the high-risk caries prevention strategy for populations

BACKGROUND: The 'high-risk approach' is a commonly adopted strategy recommended for the prevention of dental caries in populations. The scientific basis for the strategy has been questioned. The objective of this study is to assess the contribution that children identified at 'high-risk' made towards the total of new caries lesions over a 4-year period, by analysing the distribution of new lesions per 100 children. METHODS: Data are from the National Preventive Dentistry Demonstration Programme (NPDDP) in the United States. The analyses identified the distribution of new carious lesions over a 4-year period in four groups of 7 year-old children who received differing preventive regimes. RESULTS: The majority of new lesions occurred in those children classified at lowest caries risk at baseline. Irrespective of the preventive regime adopted and the initial caries levels, children classified as 'highest risk' contributed less than 6% of the total number of new lesions developing over 4 years. CONCLUSION: These findings challenge the basis for the adoption of a high-risk strategy

Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS

Funder: Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation); doi: https://doi.org/10.13039/100000865Funder: Christopher and Dana Reeve Foundation (Christopher & Dana Reeve Foundation); doi: https://doi.org/10.13039/100001305Funder: International Foundation for Research in Paraplegia (Internationale Stiftung für Forschung in Paraplegie); doi: https://doi.org/10.13039/501100001708Funder: Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.); doi: https://doi.org/10.13039/100000009Funder: Christopher and Dana Reeve Foundation (Christopher & Dana Reeve Foundation)Abstract: Adult mammalian central nervous system axons have intrinsically poor regenerative capacity, so axonal injury has permanent consequences. One approach to enhancing regeneration is to increase the axonal supply of growth molecules and organelles. We achieved this by expressing the adaptor molecule Protrudin which is normally found at low levels in non-regenerative neurons. Elevated Protrudin expression enabled robust central nervous system regeneration both in vitro in primary cortical neurons and in vivo in the injured adult optic nerve. Protrudin overexpression facilitated the accumulation of endoplasmic reticulum, integrins and Rab11 endosomes in the distal axon, whilst removing Protrudin’s endoplasmic reticulum localization, kinesin-binding or phosphoinositide-binding properties abrogated the regenerative effects. These results demonstrate that Protrudin promotes regeneration by functioning as a scaffold to link axonal organelles, motors and membranes, establishing important roles for these cellular components in mediating regeneration in the adult central nervous system