A method for acquiring random range uncertainty probability distributions in proton therapy.

In treatment planning we depend upon accurate knowledge of geometric and range uncertainties. If the uncertainty model is inaccurate then the plan will produce under-dosing of the target and/or overdosing of OAR. We aim to provide a method for which centre and site-specific population range uncertainty due to inter-fraction motion can be quantified to improve the uncertainty model in proton treatment planning. Daily volumetric MVCT data from previously treated radiotherapy patients has been used to investigate inter-fraction changes to water equivalent path-length (WEPL). Daily image-guidance scans were carried out for each patient and corrected for changes in CTV position (using rigid transformations). An effective depth algorithm was used to determine residual range changes, after corrections had been applied, throughout the treatment by comparing WEPL within the CTV at each fraction for several beam angles. As a proof of principle this method was used to quantify uncertainties for inter-fraction range changes for a sample of head and neck patients of [Formula: see text] mm, [Formula: see text] mm and overall [Formula: see text] mm. For prostate [Formula: see text] mm, [Formula: see text] mm and overall [Formula: see text] mm. The choice of beam angle for head and neck did not affect the inter-fraction range error significantly; however this was not the same for prostate. Greater range changes were seen using a lateral beam compared to an anterior beam for prostate due to relative motion of the prostate and femoral heads. A method has been developed to quantify population range changes due to inter-fraction motion that can be adapted for the clinic. The results of this work highlight the importance of robust planning and analysis in proton therapy. Such information could be used in robust optimisation algorithms or treatment plan robustness analysis. Such knowledge will aid in establishing beam start conditions at planning and for establishing adaptive planning protocols.This work was funded by a Medical Research Council Studentship to the University of Cambridge (G1000384). Dr S. Holloway is currently supported by a Cancer Research UK Centres Network Accelerator Award Grant (A21993) to the ART-NET consortium

A ‘quiet revolution’? The impact of Training Schools on initial teacher training partnerships

This paper discusses the impact on initial teacher training of a new policy initiative in England: the introduction of Training Schools. First, the Training School project is set in context by exploring the evolution of a partnership approach to initial teacher training in England. Ways in which Training Schools represent a break with established practice are considered together with their implications for the dominant mode of partnership led by higher education institutions (HEIs). The capacity of Training Schools to achieve their own policy objectives is examined, especially their efficacy as a strategy for managing innovation and the dissemination of innovation. The paper ends by focusing on a particular Training School project which has adopted an unusual approach to its work and enquires whether this alternative approach could offer a more profitable way forward. During the course of the paper, five different models of partnership are considered: collaborative, complementary, HEI-led, school-led and partnership within a partnership

Recombination dynamics of a human Y-chromosomal palindrome:rapid GC-biased gene conversion, multi-kilobase conversion tracts, and rare inversions

The male-specific region of the human Y chromosome (MSY) includes eight large inverted repeats (palindromes) in which arm-to-arm similarity exceeds 99.9%, due to gene conversion activity. Here, we studied one of these palindromes, P6, in order to illuminate the dynamics of the gene conversion process. We genotyped ten paralogous sequence variants (PSVs) within the arms of P6 in 378 Y chromosomes whose evolutionary relationships within the SNP-defined Y phylogeny are known. This allowed the identification of 146 historical gene conversion events involving individual PSVs, occurring at a rate of 2.9-8.4×10(-4) events per generation. A consideration of the nature of nucleotide change and the ancestral state of each PSV showed that the conversion process was significantly biased towards the fixation of G or C nucleotides (GC-biased), and also towards the ancestral state. Determination of haplotypes by long-PCR allowed likely co-conversion of PSVs to be identified, and suggested that conversion tract lengths are large, with a mean of 2068 bp, and a maximum in excess of 9 kb. Despite the frequent formation of recombination intermediates implied by the rapid observed gene conversion activity, resolution via crossover is rare: only three inversions within P6 were detected in the sample. An analysis of chimpanzee and gorilla P6 orthologs showed that the ancestral state bias has existed in all three species, and comparison of human and chimpanzee sequences with the gorilla outgroup confirmed that GC bias of the conversion process has apparently been active in both the human and chimpanzee lineages

Measurement of the decay of laser-driven linear plasma wakefields.

We present measurements of the temporal decay rate of one-dimensional (1D), linear Langmuir waves excited by an ultrashort laser pulse. Langmuir waves with relative amplitudes of approximately 6% were driven by 1.7J, 50fs laser pulses in hydrogen and deuterium plasmas of density n_{e0}=8.4×10^{17}cm^{-3}. The wakefield lifetimes were measured to be τ_{wf}^{H_{2}}=(9±2) ps and τ_{wf}^{D_{2}}=(16±8) ps, respectively, for hydrogen and deuterium. The experimental results were found to be in good agreement with 2D particle-in-cell simulations. In addition to being of fundamental interest, these results are particularly relevant to the development of laser wakefield accelerators and wakefield acceleration schemes using multiple pulses, such as multipulse laser wakefield accelerators

Promiscuous Expression of α-Tubulin II in Maturing Male and Female Plasmodium falciparum Gametocytes

BACKGROUND: Antimalarial interventions designed to impact on the transmissible sexual stages of Plasmodium falciparum are evaluated by measurement of peripheral gametocyte carriage in vivo and infectivity to mosquitoes. Drug or vaccine-elicited effects may differentially affect the relative abundance of mature male and female sexual forms, and this can be measured by estimation of sex ratios before and after intervention in vivo and in vitro. Measuring the impact of anti-gametocyte drugs on sexual commitment of immature gametocyte stages in vitro is not currently possible as male and female parasites cannot be distinguished by morphology alone prior to stage IV. METHODOLOGY/PRINCIPAL FINDINGS: We have modified an existing immunofluorescence-based approach for distinguishing male and female gametocytes during development in vitro, by using highly synchronised magnetically-enriched gametocyte preparations at different stages of maturity. Antibodies recognising α-tubulin II (males) and Pfg377 (females) were used to attempt to discriminate the sexes. Transcription of these two proteins was not coordinated during in vitro development, with pfg377 transcripts accumulating only late in development, immediately prior to immunofluorescent signals from the PfG377 protein appearing in stage IV gametocytes. Contrary to previous descriptions of this protein as male-specific in P. falciparum, α-tubulin II recognised both male and female gametocytes at stages I to IV, but evidence of differential expression levels of this protein in late stage male and female gametocytes was found. Using antibodies recognising PfG377 as the primary marker and α-tubulin II as a secondary marker, robust estimates of sex ratio in in vitro cultures were obtained for gametocytes at stage IV or later, and validated by light microscopic counts. However, sex ratio estimation was not possible for early stage gametocytes due to the promiscuity of α-tubulin II protein expression, and the relatively late accumulation of PfG377 during the development process. CONCLUSIONS/SIGNIFICANCE: This approach is a feasible method for the evaluation of drug impacts on late-stage gametocyte sex ratio in in vitro studies. Additional sex-specific antigens need to be evaluated for sex ratio estimation in early stage gametocyte preparations

Low-density hydrodynamic optical-field-ionized plasma channels generated with an axicon lens

We demonstrate optical guiding of high-intensity laser pulses in long, low density hydrodynamic optical-field-ionized (HOFI) plasma channels. An axicon lens is used to generate HOFI plasma channels with on-axis electron densities as low as $n_e(0) = 1.5\times 10^{17}\, \mathrm{cm}^{-3}$ and matched spot sizes in the range $20 \mu \mathrm{m} \lesssim W_M \lesssim 40 \mu \mathrm{m}$. Control of these channel parameters via adjustment of the initial cell pressure and the delay after the arrival of the channel-forming pulse is demonstrated. For laser pulses with a peak axial intensity of $4 \times 10^{17}\, \mathrm{W\,cm}^{-2}$, highly reproducible, high-quality guiding over more than 14 Rayleigh ranges is achieved at a pulse repetition rate of 5 Hz, limited by the available channel-forming laser and vacuum pumping system. Plasma channels of this type would seem to be well suited to multi-GeV laser wakefield accelerators operating in the quasi-linear regime

Women Have Higher Protein Content of β-Oxidation Enzymes in Skeletal Muscle than Men

It is well recognized that compared with men, women have better ultra-endurance capacity, oxidize more fat during endurance exercise, and are more resistant to fat oxidation defects i.e. diet-induced insulin resistance. Several groups have shown that the mRNA and protein transcribed and translated from genes related to transport of fatty acids into the muscle are greater in women than men; however, the mechanism(s) for the observed sex differences in fat oxidation remains to be determined. Muscle biopsies from the vastus lateralis were obtained from moderately active men (N = 12) and women (N = 11) at rest to examine mRNA and protein content of genes involved in lipid oxidation. Our results show that women have significantly higher protein content for tri-functional protein alpha (TFPα), very long chain acyl-CoA dehydrogenase (VLCAD), and medium chain acyl-CoA dehydrogenase (MCAD) (P<0.05). There was no significant sex difference in the expression of short-chain hydroxyacyl-CoA dehydrogenase (SCHAD), or peroxisome proliferator activated receptor alpha (PPARα), or PPARγ, genes potentially involved in the transcriptional regulation of lipid metabolism. In conclusion, women have more protein content of the major enzymes involved in long and medium chain fatty acid oxidation which could account for the observed differences in fat oxidation during exercise

Assessing the perceived impact of post Minamata amalgam phase down on oral health inequalities: a mixed-methods investigation

Background: Data from countries that have implemented a complete phase out of dental amalgam following the Minamata agreement suggest increased costs and time related to the placement of alternatives with consumers absorbing the additional costs. This aim of this study was to investigate the impact of a complete phase out of dental amalgam on oral health inequalities in particular for countries dependent on state run oral health services. Methods: A mixed methods component design quantitative and qualitative study in the United Kingdom. The quantitative study involved acquisition and analysis of datasets from NHS Scotland to compare trends in placement of dental amalgam and a survey of GDPs in Yorkshire, UK. The qualitative study involved analysis of the free text of the survey and a supplementary secondary analysis of semi-structured interviews and focus groups with GDPs (private and NHS), dental school teaching leads and NHS dental commissioners to understand the impact of amalgam phase down on oral health inequalities. Results: Time-trends for amalgam placement showed that there was a significant (p < 0.05) reduction in amalgam use compared with composites and glass ionomers. However dental amalgam still represented a large proportion (42%) of the restorations (circa 1.8 million) placed in the 2016–2017 financial year. Survey respondents suggest that direct impacts of a phase down were related to increased costs and time to place alternative restorations and reduced quality of care. This in turn would lead to increased tooth extractions, reduced access to care and privatisation of dental services with the greatest impact on deprived populations. Conclusion: Amalgam is still a widely placed material in state run oral health services. The complete phase down of dental amalgam poses a threat to such services and threatens to widen oral health inequalities. Our data suggest that a complete phase out is not currently feasible unless appropriate measures are in place to ensure cheaper, long-lasting and easy to use alternatives are available and can be readily adopted by primary care oral health providers

Addressing Women's Non-Maternal Healthcare Financing in Developing Countries: What Can We Learn from the Experiences of Rural Indian Women?

Background and Objectives: This paper focuses on the inadequate attention on women’s non-maternal healthcare in lowand middle-income countries. The study assessed the purchase of and financial access to non-maternal healthcare. It also scoped for mainstreaming household financial resources in this regard to suggest for alternatives. Methods: A household survey through multi-stage stratified sampling in the state of Orissa interviewed rural women above 15 years who were neither pregnant nor had any pregnancy-related outcome six weeks preceding the survey. The questions explored on the processes, determinants and outcomes of health seeking for non-maternal ailments. The outcome measures were healthcare access, cost of care and financial access. The independent variables for bivariate and multivariate analyses were contextual factors, health seeking and financing pattern. Results: The survey obtained a response rate of 98.64 % and among 800 women, 43.8 % had no schooling and 51 % were above 60 years. Each woman reported at least one episode of non-maternal ailment; financial constraints prevented 68% from receiving timely and complete care. Distress coping measures (e.g. borrowings) dominated the financing source (67.9%) followed by community–based measures (32.1%). Only 6 % had financial risk-protection; financial risk of not obtaining care doubled for women aged over 60 years (OR 2.00, 95 % CI 0.84–4.80), seeking outpatient consultation (OR 2.01, 95 % CI 0.89–4.81), facing unfavourable household response (OR 2.04, 95 % CI 1.09–3.83), and lacking other financia