Timing and trajectory in rhythm production

The Wing-Kristofferson movement timing model (A. M. Wing & A. B. Kristofferson, 1973a, 1973b) distinguishes central timer and motor implementation processes. Previous studies have shown that increases in interresponse interval (IRI) variability with mean IRI are due to central timer processes, not motor implementation. The authors examine whether this is true with IRI duration changes in binary rhythm production. Ten participants provided IRI and movement data in bimanual synchronous tapping under equal (isochronous) and alternating (rhythm) interval conditions. Movement trajectory changes were observed with IRI duration (300, 500, or 833 ms) and for 500-ms IRIs produced in rhythm contexts (300/500 ms, 500/833 ms). However, application of the Wing-Kristofferson model showed that duration and context effects on IRI variability were attributable largely to timer processes with relatively little effect on motor processes.

Para-inflammation-mediated retinal recruitment of bone marrow-derived myeloid cells following whole-body irradiation is CCL2 dependent

Previous studies have shown that following whole-body irradiation bone marrow (BM)-derived cells can migrate into the central nervous system, including the retina, to give rise to microglia-like cells. The detailed mechanism, however, remains elusive. We show in this study that a single-dose whole-body ?-ray irradiation (8 Gy) induced subclinical damage (i.e., DNA damage) in the neuronal retina, which is accompanied by a low-grade chronic inflammation, para-inflammation, characterized by upregulated expression of chemokines (CCL2, CXCL12, and CX3CL1) and complement components (C4 and CFH), and microglial activation. The upregulation of chemokines CCL2 and CXCL12 and complement C4 lasted for more than 160 days, whereas the expression of CX3CL1 and CFH was upregulated for 2 weeks. Both resident microglia and BM-derived phagocytes displayed mild activation in the neuronal retina following irradiation. When BM cells from CX3CR1gfp/+ mice or CX3CR1gfp/gfp mice were transplanted to wild-type C57BL/6 mice, more than 90% of resident CD11b+ cells were replaced by donor-derived GFP+ cells after 6 months. However, when transplanting CX3CR1gfp/+ BM cells into CCL2-deficient mice, only 20% of retinal CD11b+ cells were replaced by donor-derived cells at 6 month. Our results suggest that the neuronal retina suffers from a chronic stress following whole-body irradiation, and a para-inflammatory response is initiated, presumably to rectify the insults and maintain homeostasis. The recruitment of BM-derived myeloid cells is a part of the para-inflammatory response and is CCL2 but not CX3CL1 dependent. © 2012 Wiley Periodicals, Inc.

Drug repositioning for Alzheimer's disease

Existing drugs for Alzheimer's disease provide symptomatic benefit for up to 12 months, but there are no approved disease-modifying therapies. Given the recent failures of various novel disease-modifying therapies in clinical trials, a complementary strategy based on repositioning drugs that are approved for other indications could be attractive. Indeed, a substantial body of preclinical work indicates that several classes of such drugs have potentially beneficial effects on Alzheimer's-like brain pathology, and for some drugs the evidence is also supported by epidemiological data or preliminary clinical trials. Here, we present a formal consensus evaluation of these opportunities, based on a systematic review of published literature. We highlight several compounds for which sufficient evidence is available to encourage further investigation to clarify an optimal dose and consider progression to clinical trials in patients with Alzheimer's disease.

Parameter study on laser welding of nitinol wire by Taguchi method

A L27 Taguchi experiment was done to investigate the effect of laser power, welding time, laser mode (CW and two pulsed modes), focus position, and their possible interactions on the weld-bead aspect ratio of laser-welded NiTi wires by using a 100W fibre laser. The optimized parameter setting to produce the full penetrated weldment with minimum welding defects is successfully determined in the Taguchi experiment. The laser mode is found to be the most important parameter that directly controls the weld-bead aspect ratio. The focus position is the secondly important parameter for the laser welding of NiTi wires. Strong interaction between the power and focus position is found in the Taguchi experiment. The optimized weldment produced by the Taguchi experiment is mainly of columnar dendritic structure in the weld zone (WZ) with the size of 1-3µm, while the HAZ exhibits equiaxed grain structure with the size of 5-10µm. The Vickers micro-hardness test indicted that the WZ and HAZ in the weldment are softened to certain extends after fibre laser welding.

Weathering rinds as mirror images of palaeosols: Examples from the Western Alps with correlation to Antarctica and Mars

Weathering rinds have been used for decades as relative age indicators to differentiate glacial deposits in long Quaternary sequences, but only recently has it been shown that rinds contain long and extensive palaeoenvironmental records that often extend far beyond mere repositories of chemical weathering on both Earth and Mars. When compared with associated palaeosols in deposits of the same age, rinds often carry a zonal weathering record that can be correlated with palaeosol horizon characteristics, with respect to both abiotic and biotic parameters. As demonstrated with examples from the French and Italian Alps, rinds in coarse clastic sediment contain weathering zones that correlate closely with horizon development in associated palaeosols of presumed Late Glacial age. In addition to weathering histories in both rinds and palaeosols, considerable evidence exists to indicate that the black mat impact (12.8 ka) reached the European Alps, a connection with the Younger Dryas readvance supported by both mineral and chemical composition. Preliminary metagenomic microbial analysis using density gradient gel electrophoresis suggests that the eubacterial microbial population found in at least one Ah palaeosol horizon associated with a rind impact site is different from that in other Late Glacial and Younger Dryas surface palaeosol horizons. © 2013 The Geological Society of London.

Drivers of inequality in disability-free expectancy at birth and age 85 across space and time in Great Britain

Background: Although mortality and health inequalities at birth have increased both geographically and in socioeconomic terms, little is known about inequalities at age 85, the fastest growing sector of the population in Great Britain (GB).

Aim: To determine whether trends and drivers of inequalities in life expectancy (LE) and disability-free life expectancy (DFLE) at age 85 between 1991 and 2001 are the same as those at birth.

Methods: DFLE at birth and age 85 for 1991 and 2001 by gender were calculated for each local authority in GB using the Sullivan method. Regression modelling was used to identify area characteristics (rurality, deprivation, social class composition, ethnicity, unemployment, retirement migration) that could explain inequalities in LE and DFLE.

Results: Similar to values at birth, LE and DFLE at age 85 both increased between 1991 and 2001 (though DFLE increased less than LE) and gaps across local areas widened (and more for DFLE than LE). The significantly greater increases in LE and DFLE at birth for less-deprived compared with more-deprived areas were still partly present at age 85. Considering all factors, inequalities in DFLE at birth were largely driven by social class composition and unemployment rate, but these associations appear to be less influential at age 85.

Conclusions: Inequalities between areas in LE and DFLE at birth and age 85 have increased over time though factors explaining inequalities at birth (mainly social class and unemployment rates) appear less important for inequalities at age 85.

Statin Use and Survival from Lung Cancer: A Population-Based Cohort Study

Background: Preclinical evidence from lung cancer cell lines and animal models suggest that statins could have anticancer properties. We investigated whether statin users had reduced risk of cancer-specific mortality in a population based cohort of lung cancer patients.
Methods: Newly diagnosed lung cancer patients, from 1998 to 2009, were identified from English cancer registry data and linked to the UK Clinical Practice Research Datalink, providing prescription records, and to Office of National Statistics mortality data up to 2012. Cox regression models were used to calculate hazard ratios (HR) for cancer-specific mortality and 95% confidence intervals (CIs) by statin use before and after diagnosis and to adjust these HRs for potential confounders.
Results: In 3,638 lung cancer patients, there was some evidence that statin use after diagnosis was associated with reduced lung cancer-specific mortality (adjusted HR=0.89, 95% CI 0.78, 1.02; P=0.09). Associations were more marked after 12 prescriptions (adjusted HR=0.81, 95% CI 0.67, 0.98; P=0.03) and when lipophilic statins were investigated (adjusted HR=0.81, 95% CI 0.70, 0.94; P=0.01) but were attenuated in some sensitivity analyses. Furthermore, in 11,051 lung cancer patients, statin use before diagnosis was associated with reduced lung cancer-specific mortality (adjusted HR=0.88, 95% CI, 0.83, 0.93; P<0.001).
Conclusions: There was some evidence that lung cancer patients who used statins, and particularly simvastatin, had reduced rates of cancer-specific mortality.
 Impact: These findings should first be confirmed in observational studies, but provide some support for conducting randomized controlled trials of simvastatin as adjuvant cancer therapy in lung cancer patients.

Constrained Multi-Objective Aerofoil Design Using a Multi-Level Optimisation Strategy

A novel approach for the multi-objective design optimisation of aerofoil profiles is presented. The proposed method aims to exploit the relative strengths of global and local optimisation algorithms, whilst using surrogate models to limit the number of computationally expensive CFD simulations required. The local search stage utilises a re-parameterisation scheme that increases the flexibility of the geometry description by iteratively increasing the number of design variables, enabling superior designs to be generated with minimal user intervention. Capability of the algorithm is demonstrated via the conceptual design of aerofoil sections for use on a lightweight laminar flow business jet. The design case is formulated to account for take-off performance while reducing sensitivity to leading edge contamination. The algorithm successfully manipulates boundary layer transition location to provide a potential set of aerofoils that represent the trade-offs between drag at cruise and climb conditions in the presence of a challenging constraint set. Variations in the underlying flow physics between Pareto-optimal aerofoils are examined to aid understanding of the mechanisms that drive the trade-offs in objective functions.

HOLOGRAPHIC IMAGES OF IODINE ATOMS ON A SILVER SURFACE FROM ELECTRON-EMISSION PATTERNS

BARTON 1 has suggested that photoelectron interference patterns may be used directly as holograms to obtain atomic-resolution images of surface structures. Bulk structures have been obtained previously by this means from experimental patterns of high-energy Kikuchi(quasi-elastically scattered) and Auger electrons 2,3. Here we test the feasibility of this technique for determination of surface structures using Auger intensity patterns obtained 4,5 from iodine chemisorbed on a pseudomorphic silver monolayer on Pt{111}. By direct numerical holographic inversion, we obtain three-dimensional images which show that iodine adatoms are located in hollows of 3-fold symmetry on the surface. The images yield the site symmetry with good atomic resolution in the surface plane, but suffer from poor resolution along the Ag-I axis. We anticipate that data with better angular resolution obtained at low temperatures would improve the spatial resolution of such images.

Energy levels and radiative rates for transitions in Ti VII

We report calculations of energy levels, radiative rates, oscillator strengths and line strengths for transitions among the lowest 231 levels of Ti VII. The general-purpose relativistic atomic structure package and flexible atomic code are adopted for the calculations. Radiative rates, oscillator strengths and line strengths are provided for all electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2) and magnetic quadrupole (M2) transitions among the 231 levels, although calculations have been performed for a much larger number of levels (159 162). In addition, lifetimes for all 231 levels are listed. Comparisons are made with existing results and the accuracy of the data is assessed. In particular, the most recent calculations reported by Singh et al (2012 Can. J. Phys. 90 833) are found to be unreliable, with discrepancies for energy levels of up to 1 Ryd and for radiative rates of up to five orders of magnitude for several transitions, particularly the weaker ones. Based on several comparisons among a variety of calculations with two independent codes, as well as with the earlier results, our listed energy levels are estimated to be accurate to better than 1% (within 0.1 Ryd), whereas results for radiative rates and other related parameters should be accurate to better than 20%.

Prevalence, Nature, Severity and Risk Factors for Prescribing Errors in Hospital Inpatients: Prospective Study in 20 UK Hospitals

Introduction: It has been suggested that doctors in their first year of post-graduate training make a disproportionate number of prescribing errors.

Obkective: This study aimed to compare the prevalence of prescribing errors made by first-year post-graduate doctors with that of errors by senior doctors and non-medical prescribers and to investigate the predictors of potentially serious prescribing errors.

Methods: Pharmacists in 20 hospitals over 7 prospectively selected days collected data on the number of medication orders checked, the grade of prescriber and details of any prescribing errors. Logistic regression models (adjusted for clustering by hospital) identified factors predicting the likelihood of prescribing erroneously and the severity of prescribing errors.

Results: Pharmacists reviewed 26,019 patients and 124,260 medication orders; 11,235 prescribing errors were detected in 10,986 orders. The mean error rate was 8.8 % (95 % confidence interval [CI] 8.6-9.1) errors per 100 medication orders. Rates of errors for all doctors in training were significantly higher than rates for medical consultants. Doctors who were 1 year (odds ratio [OR] 2.13; 95 % CI 1.80-2.52) or 2 years in training (OR 2.23; 95 % CI 1.89-2.65) were more than twice as likely to prescribe erroneously. Prescribing errors were 70 % (OR 1.70; 95 % CI 1.61-1.80) more likely to occur at the time of hospital admission than when medication orders were issued during the hospital stay. No significant differences in severity of error were observed between grades of prescriber. Potentially serious errors were more likely to be associated with prescriptions for parenteral administration, especially for cardiovascular or endocrine disorders.

Conclusions: The problem of prescribing errors in hospitals is substantial and not solely a problem of the most junior medical prescribers, particularly for those errors most likely to cause significant patient harm. Interventions are needed to target these high-risk errors by all grades of staff and hence improve patient safety.

Trophic Level Asynchrony in Rates of Phenological Change For Marine, Freshwater and Terrestrial Environments

Recent changes in the seasonal timing (phenology) of familiar biological events have been one of the most conspicuous signs of climate change. However, the lack of a standardised approach to analysing change has hampered assessment of consistency in such changes among different taxa and trophic levels and across freshwater, terrestrial and marine environments. We present a standardised assessment of 25 532 rates of phenological change for 726 UK terrestrial, freshwater and marine taxa. The majority of spring and summer events have advanced, and more rapidly than previously documented. Such consistency is indicative of shared large-scale drivers. Furthermore, average rates of change have accelerated in a way that is consistent with observed warming trends. Less coherent patterns in some groups of organisms point to the agency of more local scale processes and multiple drivers. For the first time we show a broad scale signal of differential phenological change among trophic levels; across environments advances in timing were slowest for secondary consumers, thus heightening the potential risk of temporal mismatch in key trophic interactions. If current patterns and rates of phenological change are indicative of future trends, future climate warming may exacerbate trophic mismatching, further disrupting the functioning, persistence and resilience of many ecosystems and having a major impact on ecosystem services