Relative biological effectiveness (RBE) and out-of-field cell survival responses to passive scattering and pencil beam scanning proton beam deliveries

The relative biological effectiveness (RBE) of passive scattered (PS) and pencil beam scanned (PBS) proton beam delivery techniques for uniform beam configurations was determined by clonogenic survival. The radiobiological impact of modulated beam configurations on cell survival occurring in- or out-of-field for both delivery techniques was determined with intercellular communication intact or physically inhibited. Cell survival responses were compared to those observed using a 6 MV photon beam produced with a linear accelerator. DU-145 cells showed no significant difference in survival response to proton beams delivered by PS and PBS or 6 MV photons taking into account a RBE of 1.1 for protons at the centre of the spread out Bragg peak. Significant out-of-field effects similar to those observed for 6 MV photons were observed for both PS and PBS proton deliveries with cell survival decreasing to 50-60% survival for scattered doses of 0.05 and 0.03 Gy for passive scattered and pencil beam scanned beams respectively. The observed out-of-field responses were shown to be dependent on intercellular communication between the in-and out-of-field cell populations. These data demonstrate, for the first time, a similar RBE between passive and actively scanned proton beams and confirm that out-of-field effects may be important determinants of cell survival following exposure to modulated photon and proton fields

Genetic variants influencing human aging from late-onset Alzheimer's disease (LOAD) genome-wide association studies (GWAS)

Genetics plays a crucial role in human aging with up to 30% of those living to the mid-80s being determined by genetic variation. Survival to older ages likely entails an even greater genetic contribution. There is increasing evidence that genes implicated in age-related diseases, such as cancer and neuronal disease, play a role in affecting human life span. We have selected the 10 most promising late-onset Alzheimer's disease (LOAD) susceptibility genes identified through several recent large genome-wide association studies (GWAS). These 10 LOAD genes (APOE, CLU, PICALM, CR1, BIN1, ABCA7, MS4A6A, CD33, CD2AP, and EPHA1) have been tested for association with human aging in our dataset (1385 samples with documented age at death [AAD], age range: 58-108 years; mean age at death: 80.2) using the most significant single nucleotide polymorphisms (SNPs) found in the previous studies. Apart from the APOE locus (rs2075650) which showed compelling evidence of association with risk on human life span (p = 5.27 × 10(-4)), none of the other LOAD gene loci demonstrated significant evidence of association. In addition to examining the known LOAD genes, we carried out analyses using age at death as a quantitative trait. No genome-wide significant SNPs were discovered. Increasing sample size and statistical power will be imperative to detect genuine aging-associated variants in the future. In this report, we also discuss issues relating to the analysis of genome-wide association studies data from different centers and the bioinformatic approach required to distinguish spurious genome-wide significant signals from real SNP associations.

In-vitro investigation of out-of-field cell survival following the delivery of conformal, intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans

The aim of this work is to determine the out-of-field survival of cells irradiated with either the primary field or scattered radiation in the presence and absence of intercellular communication following delivery of conformal, IMRT and VMAT treatment plans. Single beam, conformal, IMRT and VMAT plans were created to deliver 3 Gy to half the area of a T80 flask containing either DU-145 or AGO-1522 cells allowing intercellular communication between the in-and out-of-field cell populations. The same plans were delivered to a similar custom made phantom used to hold two T25 culture flasks, one flask in-field and one out-of-field to allow comparison of cell survival responses when intercellular communication is physically inhibited. Plans were created for the delivery of 8 Gy to the more radio-resistant DU-145 cells only in the presence and absence of intercellular communication. Cell survival was determined by clonogenic assay. In both cell lines, the out-of-field survival was not statistically different between delivery techniques for either cell line or dose. There was however, a statistically significant difference between survival out-of-field when intercellular communication was intact (single T80 culture flask) or inhibited (multiple T25 culture flasks) to in-field for all plans. No statistically significant difference was observed in-field with or without cellular communication to out-of-field for all plans. These data demonstrate out-of-field effects as important determinants of cell survival following exposure to modulated irradiation fields when cellular communication between differentially irradiated cell populations is present. This data is further evidence that refinement of existing radiobiological models to include indirect cell killing effects is required.

Transcriptional regulation of a brown adipocyte-specific gene, UCP1, by KLF11 and KLF15

Several growth factors and transcription factors have been reported to play important roles in brown adipocyte differentiation and modulation of thermogenic gene expression, especially the expression of UCP1. In this study, we focused on KLF11 and KLF15, which were expressed highly in brown adipose tissue. Our data demonstrated that KLF11 and KLF15 interacted directly with the UCP1 promoter using GC-box and GT-boxes, respectively. Co-transfection of KLF11 and KLF15 in the mesenchymal stem cell line muBM3.1 during brown adipocyte differentiation enhanced the expression level of UCP1. KLF11, but not KLF15, was essential for UCP1 expression during brown adipocyte differentiation of muBM3.1.

Speciation and localization of arsenic in white and brown rice grains

Synchrotron-based X-ray fluorescence (S-XRF) was utilized to locate arsenic (As) in polished (white) and unpolished (brown) rice grains from the United States, China, and Bangladesh. In white rice As was generally dispersed throughout the grain, the bulk of which constitutes the endosperm. In brown rice As was found to be preferentially localized at the surface, in the region corresponding to the pericarp and aleurone layer. Copper, iron, manganese, and zinc localization followed that of arsenic in brown rice, while the location for cadmium and nickel was distinctly different, showing relatively even distribution throughout the endosperm. The localization of As in the outer grain of brown rice was confirmed by laser ablation ICP-MS. Arsenic speciation of all grains using spatially resolved X-ray absorption near edge structure (micro-XANES) and bulk extraction followed by anion exchange HPLC-ICP-MS revealed the presence of mainly inorganic As and dimethylarsinic acid (DMA). However, the two techniques indicated different proportions of inorganic:organic As species. A wider survey of whole grain speciation of white (n=39) and brown (n=45) rice samples from numerous sources (field collected, supermarket survey, and pot trials) showed that brown rice had a higher proportion of inorganic arsenic present than white rice. Furthermore, the percentage of DMA present in the grain increased along with total grain arsenic.

Moving in and out of poverty - The impact of welfare regimes on poverty dynamics in the EU

Although many of the debates around social exclusion and cumulative disadvantage relate to processes that occur across time, there has been relatively little research into poverty dynamics except in a few notable countries such as Britain, the USA and Germany. This neglect is almost entirely because of the absence of comparative longitudinal data on income for other countries, but it is regrettable given the central importance of this area. By studying poverty dynamics we not only get a better insight into the processes leading to patterns of disadvantage and inequality, but we can also understand better the influence of different welfare state regimes on the social risks experienced by different types of individuals and households. The extent to which different national contexts protect their citizens from poverty persistence, or vary in the factors leading to poverty persistence, tells us a great deal about the workings of their socioeconomic systems and welfare regimes.

In this article we use the recent availability of five waves of the European Community Household Panel Survey to outline the nature of poverty persistence and poverty dynamics across a large number of countries. In doing so we ask three important questions. First, is poverty a more common experience when viewed longitudinally rather than cross-sectionally, and how is this affected by the income poverty line used? Second, can we identify a tendency toward poverty persistence, and does this vary in its extent across countries? Third and lastly, what types of events are more likely to lead to entry into and exit from poverty, and does the importance of these events differ between countries? The article shows that the experience of poverty is far wider than is appreciated from cross-sectional data, and also tends to be more concentrated on a particular population than would be expected from cross-sectional rates. Moreover, the pattern of poverty persistence is congruent with welfare regime theory. The importance of country institutions and welfare regimes is also underlined by the finding that social welfare and market incomes play different roles in poverty transitions across countries, and that Southern European, or residualist, welfare regimes focus poverty risks on the experience of the household's primary earner to a far greater extent than Northern European welfare states do.

Pull-out behaviour of axially loaded Basalt Fibre Reinforced Polymer (BFRP) rods bonded perpendicular to the grain of glulam elements

The behaviour of Basalt Fibre Reinforced Polymer (BFRP) loaded perpendicular to glulam timber elements was investigated. It was found that pull-out load increased approximately linearly with the bonded length up to maximum which occurred at a bonded length of 250 mm (~15 times the hole diameter) and did not increase beyond this bonded length. Failure mode of the samples was mostly shear fracture which was located at the cylindrical zone at the timber/adhesive interface. Increased bonded lengths resulted in corresponding decrease in interfacial bond stress. At 250 mm bonded length, the pull-out capacity of the proposed design model was about 2% lower than that of the tests. The results also showed that the bond stress of the theoretical model (at the ascending and descending branches) of the stress–slip curve was approximately 5–10% of that of the experiment.

Stress, coping and burn-out in nursing students

Aim: To explore the relationship between sources of stress and psychological burn-out and to consider the moderating and mediating role played sources of stress and different coping resources on burn-out.

Background: Most research exploring sources of stress and coping in nursing students construes stress as psychological distress. Little research has considered those sources of stress likely to enhance well-being and, by implication, learning.

Method: A questionnaire was administered to 171 final year nursing students. Questions were asked which measured sources of stress when rated as likely to contribute to distress (a hassle) and rated as likely to help one achieve (an uplift). Support, control, self-efficacy and coping style were also measured, along with their potential moderating and mediating effect on burn-out.

Findings: The sources of stress likely to lead to distress were more often predictors of wellbeing than sources of stress likely to lead to positive, eustress states. However, placement experience was an important source of stress likely to lead to eustress. Self-efficacy, dispositional control and support were other important predictors. Avoidance coping was the strongest predictor of burn-out and, even if used only occasionally, it can have an adverse effect on burn-out. Initiatives to promote support and self-efficacy are likely to have the more immediate benefits in enhancing student well-being.

Conclusion: Nurse educators need to consider how course experiences contribute not just to potential distress but to eustress. How educators interact with their students and how they give feedback offers important opportunities to promote self-efficacy and provide valuable support. Peer support is a critical coping resource and can be bolstered through induction and through learning and teaching initiatives.