Antiproton induced DNA damage: proton like in flight, carbon-ion like near rest

Biological validation of new radiotherapy modalities is essential to understand their therapeutic potential. Antiprotons have been proposed for cancer therapy due to enhanced dose deposition provided by antiproton-nucleon annihilation. We assessed cellular DNA damage and relative biological effectiveness (RBE) of a clinically relevant antiproton beam. Despite a modest LET (,19 keV/mm), antiproton spread out Bragg peak (SOBP) irradiation caused significant residual c-H2AX foci compared to X-ray, proton and antiproton plateau irradiation. RBE of ,1.48 in the SOBP and ,1 in the plateau were measured and used for a qualitative effective dose curve comparison with proton and carbon-ions. Foci in the antiproton SOBP were larger and more structured compared to X-rays, protons and carbon-ions. This is likely due to overlapping particle tracks near the annihilation vertex, creating spatially correlated DNA lesions. No biological effects were observed at 28–42 mm away from the primary beam suggesting minimal risk from long-range secondary particles.

Higher education in flight:a new direction for international assignments research

This paper draws attention to the significant internationalisation of the higher education sector and role of international assignments in supporting and driving this. The paper then proceeds to identify the similarities and unique features of the sector in the context of international assignments which we argue, primarily revolve around alternative forms, namely international frequent flyers and short-term assignments. Finally, a model is proposed that may facilitate higher education institutes in more effective international assignment utilisation. © 2012 Copyright Taylor and Francis Group, LLC.

The hierarchy of directional interactions in visual motion processing

It is well known that context influences our perception of visual motion direction. For example, spatial and temporal context manipulations can be used to induce two well-known motion illusions: direction repulsion and the direction after-effect (DAE). Both result in inaccurate perception of direction when a moving pattern is either superimposed on (direction repulsion), or presented following adaptation to (DAE), another pattern moving in a different direction. Remarkable similarities in tuning characteristics suggest that common processes underlie the two illusions. What is not clear, however, is whether the processes driving the two illusions are expressions of the same or different neural substrates. Here we report two experiments demonstrating that direction repulsion and the DAE are, in fact, expressions of different neural substrates. Our strategy was to use each of the illusions to create a distorted perceptual representation upon which the mechanisms generating the other illusion could potentially operate. We found that the processes mediating direction repulsion did indeed access the distorted perceptual representation induced by the DAE. Conversely, the DAE was unaffected by direction repulsion. Thus parallels in perceptual phenomenology do not necessarily imply common neural substrates. Our results also demonstrate that the neural processes driving the DAE occur at an earlier stage of motion processing than those underlying direction repulsion.

Impact of persistent substance misuse on 1-year outcome in first-episode psychosis

Background: Substance misuse is a common comorbid problem in people presenting with first-episode psychosis and is associated with a poor short-term outcome.

Aims: The aim of this study is to examine differences in baseline characteristics and 1-year outcome between individuals with first-episode psychosis who have never misused substances, those who stop misusing substances after initial presentation and those who persistently misuse substances over the 1-year assessment period.

Method: Patients were recruited to the Northern Ireland First Episode Psychosis Study (n=272). Clinical assessments were performed at baseline and at 1 year (n=194) and data were collected from the case notes.

Results: Individuals with persistent substance misuse had more severe depression, more positive symptoms, poorer functional outcome and greater rates of relapse at 1 year than those who stopped and those who had never misused substances. There were no differences in outcome between people who had never misused substances and those who stopped misusing after presentation.

Conclusions: These results support assertive intervention targeted at comorbid substance misuse in individuals with first-episode psychosis.

Auditory observation of stepping actions can cue both spatial and temporal components of gait in Parkinson's disease patients

Objectives: A common behavioural symptom of Parkinson’s disease (PD) is reduced step length (SL). Whilst sensory cueing strategies can be effective in increasing SL and reducing gait variability, current cueing strategies conveying spatial or temporal information are generally confined to the use of either visual or auditory cue modalities, respectively. We describe a novel cueing strategy using ecologically-valid ‘action-related’ sounds (footsteps on gravel) that convey both spatial and temporal parameters of a specific action within a single cue.
Methods: The current study used a real-time imitation task to examine whether PD affects the ability to re-enact changes in spatial characteristics of stepping actions, based solely on auditory information. In a second experimental session, these procedures were repeated using synthesized sounds derived from recordings of the kinetic interactions between the foot and walking surface. A third experimental session examined whether adaptations observed when participants walked to action-sounds were preserved when participants imagined either real recorded or synthesized sounds.
Results: Whilst healthy control participants were able to re-enact significant changes in SL in all cue conditions, these adaptations, in conjunction with reduced variability of SL were only observed in the PD group when walking to, or imagining the recorded sounds.
Conclusions: The findings show that while recordings of stepping sounds convey action information to allow PD patients to re-enact and imagine spatial characteristics of gait, synthesis of sounds purely from gait kinetics is insufficient to evoke similar changes in behaviour, perhaps indicating that PD patients have a higher threshold to cue sensorimotor resonant responses.

A Note on Race, Ethnicity and Nativity Differences in Remarriage in the United States

The objectives of this study are to produce up-to-date estimates of race/ethnic/nativity differentials for remarriage and repartnership among women in the United States and to see if these differences are due to across-group differences in demographic characteristics. First, we produce lifetable estimates of remarriage and repartnering for white, black, U.S. born Latina and foreign born Latina women. Next, we estimate race/ethnic/nativity differentials for remarriage and repartnership using event-history analysis with and without controls for demographic characteristics. The results suggest a continued overall decline in remarriage rates, while many women repartner by cohabitating. Whites are more likely than blacks or Latinas to remarry and they are also more likely to repartner. Race/ethnic/nativity differentials remain even after accounting for variations in demographic characteristics. This suggests that race/ethnic/nativity differentials in remarriage and repartnering rates, rather than ameliorating disadvantages associated with divorce, reinforce these differentials.

High resolution monitoring of surface morphological change of building limestones in response to simulated salt weathering

A salt weathering simulation using a mix of sodium chloride (5%) and magnesium sulphate (5%) in a salt corrosion cabinet and five granular limestones is described. Progressive surface loss from vertical exposed faces was mapped using a high resolution (sub-millimetre) object scanner (Konica Minolta Vi9i). Patterns of loss are related to surface porosity/permeability measurements obtained using a hand-held gas permeameter. Introduction of this spatial dimension into damage assessment is seen as essential for understanding the initial conditions that allow surface loss to be triggered, and changes in surface characteristics as weathering proceeds which dictate subsequent decay in space and time. Preliminary observations suggest that scanning at this high resolution is particularly valuable in quantifying very subtle trends and distortions that are pre-cursors to material loss, including surface swelling and pore filling.

Initiating advance care planning on end-of-life issues in dementia: Ambiguity among UK and Dutch physicians

Background
In dementia, advance care planning (ACP) of end-of-life issues may start as early as possible in view of the patient’s decreasing ability to participate in decision making. We aimed to assess whether practicing physicians in the Netherlands and the United Kingdom who provide most of the end-of-life care, differ in finding that ACP in dementia should start at diagnosis.

Methods
In a cross-sectional study, we surveyed 188 Dutch elderly care physicians who are on the staff of nursing homes and 133 general practitioners from Northern Ireland. We compared difference by country in the outcome (perception of ACP timing), rated on a 1–5 agreement scale. Regression analyses examined whether a country difference can be explained by contrasts in demographics, presence, exposure and role perceptions.

Results
There was wide variability in agreement with the initiation of ACP at dementia diagnosis, in particular in the UK but also in the Netherlands (60.8% agreed, 25.3% disagreed and 14.0% neither agreed, nor disagreed). Large differences in physician characteristics (Dutch physicians being more present, exposed and adopting a stronger role perception) hardly explained the modest country difference. The perception that the physician should take the initiative was independently associated with agreeing with ACP at diagnosis.

Conclusions
There is considerable ambiguity about initiating ACP in dementia at diagnosis among physicians practicing in two different European health care systems and caring for different patient populations. ACP strategies should accommodate not only variations in readiness to engage in ACP early among patient and families, but also among physicians.

Gelsolin-mediated activation of PI3K/Akt pathway is crucial for hepatocyte growth factor-induced cell scattering in gastric carcinoma

In gastric cancer (GC), the main subtypes (diffuse and intestinal types) differ in pathological characteristics, with diffuse GC exhibiting early disseminative and invasive behaviour. A distinctive feature of diffuse GC is loss of intercellular adhesion. Although widely attributed to mutations in the CDH1 gene encoding E-cadherin, a significant percentage of diffuse GC do not harbor CDH1 mutations. We found that the expression of the actin-modulating cytoskeletal protein, gelsolin, is significantly higher in diffuse-type compared to intestinal-type GCs, using immunohistochemical and microarray analysis. Furthermore, in GCs with wild-type CDH1, gelsolin expression correlated inversely with CDH1 gene expression. Downregulating gelsolin using siRNA in GC cells enhanced intercellular adhesion and E-cadherin expression, and reduced invasive capacity. Interestingly, hepatocyte growth factor (HGF) induced increased gelsolin expression, and gelsolin was essential for HGF-medicated cell scattering and E-cadherin transcriptional repression through Snail, Twist and Zeb2. The HGF-dependent effect on E-cadherin was found to be mediated by interactions between gelsolin and PI3K-Akt signaling. This study reveals for the first time a function of gelsolin in the HGF/cMet oncogenic pathway, which leads to E-cadherin repression and cell scattering in gastric cancer. Our study highlights gelsolin as an important pro-disseminative factor contributing to the aggressive phenotype of diffuse GC.

Passive Control of Plume Interference on Slender Axisymmetric Bodies

The physics of the plume-induced shock and separation, particularly at high plume to exit pressure ratios with and without shock-turbulent boundary-layer control methods, were studied using computational techniques. Mass-averaged Navier-Stokes equations with a two-equation turbulence model were solved by using a fully implicit finite volume scheme and time.marching algorithm. The control methodologies for shock interactions included a porous tail and a porous extension attached at the nozzle exit or trailing edge. The porous tail produced a weaker shock and fixed the shock position on the control surface. The effect of the porous extension on shock interactions was mainly to restrain the plume from strongly underexpanding during a change in flight conditions. These techniques could give an additional dimension to the design and control of supersonic missiles.

Geophysical imaging of stimulated microbial biomineralization

Understanding how microorganisms influence the physical and chemical properties of the subsurface is hindered by our inability to observe microbial dynamics in real time and with high spatial resolution. Here, we investigate the use of noninvasive geophysical methods to monitor biomineralization at the laboratory scale during stimulated sulfate reduction under dynamic flow conditions. Alterations in sediment characteristics resulting from microbe-mediated sulfide mineral precipitation were concomitant with changes in complex resistivity and acoustic wave propagation signatures. The sequestration of zinc and iron in insoluble sulfides led to alterations in the ability of the pore fluid to conduct electrical charge and of the saturated sediments to dissipate acoustic energy. These changes resulted directly from the nucleation, growth, and development of nanoparticulate precipitates along grain surfaces and within the pore space. Scanning and transmission electron microscopy (SEM and TEM) confirmed the sulfides to be associated with cell surfaces, with precipitates ranging from aggregates of individual 3-5 nm nanocrystals to larger assemblages of up to 10-20 m in diameter. Anomalies in the geophysical data reflected the distribution of mineral precipitates and biomass over space and time, with temporal variations in the signals corresponding to changes in the aggregation state of the nanocrystalline sulfides. These results suggest the potential for using geophysical techniques to image certain subsurface biogeochemical processes, such as those accompanying the bioremediation of metal-contaminated aquifers.

SEM-EDX of morphology of electroless nickel coatings with tin and tungsten

Electroless plating of binary Ni-P, ternary Ni-Sn-P and Ni-W-P, and quaternary Ni-W-Sn-P alloy coatings was carried out in alkalicitrate baths. After the plating, several kinds of test were carried out to determine the improvement in the characteristics and properties due to the additional elements as well as to study the change in behaviour when heat treatment was applied to these coatings. The coatings were subjected to X-ray diffraction analysis where it was found that all the coatings were amorphous. Interesting surface morphology features were examined using scanning electron microscopy. Addition of a third element improved the hardness.

Interfacial shear strength and tensile properties of injection-molded, short- and long-glass fiber-reinforced polyamide 6,6 composites

Injection-molded short- and long-glass fiber/polyamide 6,6 composites were subjected to tensile tests. To measure the effectiveness of the fibers in reinforcing the composites, a computational approach was employed to compute the fiber– matrix ISS, orientation factor, reinforcement efficiency, tensile-, and fiber length-related properties. Although the LFCs showed great improvement in fiber characteristics compared to the SFCs, enhancement in tensile properties was small, which is believed to be due to the larger fiber diameter. Kelly–Tyson model provides good approximation for the computation of ISS and tensile-related properties.

The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis

STUDY QUESTION Is there an association between high levels of sperm DNA damage and miscarriage?SUMMARY ANSWERMiscarriage rates are positively correlated with sperm DNA damage levels.WHAT IS KNOWN ALREADYMost ejaculates contain a subpopulation of sperm with DNA damage, also referred to as DNA fragmentation, in the form of double or single-strand breaks which have been induced in the DNA prior to or following ejaculation. This DNA damage may be particularly elevated in some subfertile men, hence several studies have examined the link between sperm DNA damage levels and conception and miscarriage rates.STUDY DESIGN, SIZE, DURATIONA systematic review and meta-analysis of studies which examined the effect of sperm DNA damage on miscarriage rates was performed. Searches were conducted on MEDLINE, EMBASE and the Cochrane Library without any language restrictions from database inception to January 2012.PARTICIPANTS/MATERIALS, SETTING, METHODSWe used the terms 'DNA damage' or 'DNA fragmentation' combined with 'miscarriage', 'abortion' or 'pregnancy' to generate a set of relevant citations. Data extraction was performed by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of relative risks of miscarriage was performed with a random effects model. Subgroup analyses were performed by the type of DNA damage test, whether the sperm examined were prepared or from raw semen and for pregnancies resulting from IVF or ICSI treatment.MAIN RESULTS AND THE ROLE OF CHANCEWe identified 16 cohort studies (2969 couples), 14 of which were prospective. Eight studies used acridine orange-based assays, six the TUNEL assay and two the COMET assay. Meta-analysis showed a significant increase in miscarriage in patients with high DNA damage compared with those with low DNA damage [risk ratio (RR) = 2.16 (1.54, 3.03), P <0.00001)]. A subgroup analysis showed that the miscarriage association is strongest for the TUNEL assay (RR = 3.94 (2.45, 6.32), P <0.00001).LIMITATIONS, REASONS FOR CAUTIONThere is some variation in study characteristics, including the use of different assays and different thresholds for DNA damage and the definition of pregnancy loss.WIDER IMPLICATIONS OF THE FINDINGSThe use of methods which select sperm without DNA damage for use in assisted conception treatment may reduce the risk of miscarriage. This finding indicates that assays detecting DNA damage could be considered in those suffering from recurrent pregnancy loss. Further research is necessary to study the mechanisms of DNA damage and the potential therapeutic effects of antioxidant therapy.STUDY FUNDING/COMPETING INTEREST(S)None.