Precision Determination of the Neutron Spin Structure Function g1n

We report on a precision measurement of the neutron spin structure function $g^n_1$ using deep inelastic scattering of polarized electrons by polarized ^3He. For the kinematic range 0.014<x<0.7 and 1 (GeV/c)^2< Q^2< 17 (GeV/c)^2, we obtain $\int^{0.7}_{0.014} g^n_1(x)dx = -0.036 \pm 0.004 (stat) \pm 0.005 (syst)$ at an average $Q^2=5 (GeV/c)^2$. We find relatively large negative values for $g^n_1$ at low $x$. The results call into question the usual Regge theory method for extrapolating to x=0 to find the full neutron integral $\int^1_0 g^n_1(x)dx$, needed for testing quark-parton model and QCD sum rules.Comment: 5 pages, 3 figures To be published in Phys. Rev. Let

Policy evaluation programme vehicle safety standards: improving car crashworthiness

This project aims to offer a comprehensive identification, evaluation and understanding of the extent to which the Department for Transport (DfT) has met policy aims for road casualty reduction through its contribution to regulations, in particular the development of the front and side impact Economic Commission for Europe Directives (ECE R94 and ECE R95) and the European New Car Assessment Programme (EuroNCAP)

Vaccine responses in newborns.

Immunisation of the newborn represents a key global strategy in overcoming morbidity and mortality due to infection in early life. Potential limitations, however, include poor immunogenicity, safety concerns and the development of tolerogenicity or hypo-responsiveness to either the same antigen and/or concomitant antigens administered at birth or in the subsequent months. Furthermore, the neonatal immunological milieu is polarised towards Th2-type immunity with dampening of Th1-type responses and impaired humoral immunity, resulting in qualitatively and quantitatively poorer antibody responses compared to older infants. Innate immunity also shows functional deficiency in antigen-presenting cells: the expression and signalling of Toll-like receptors undergo maturational changes associated with distinct functional responses. Nevertheless, the effectiveness of BCG, hepatitis B and oral polio vaccines, the only immunisations currently in use in the neonatal period, is proof of concept that vaccines can be successfully administered to the newborn via different routes of delivery to induce a range of protective mechanisms for three different diseases. In this review paper, we discuss the rationale for and challenges to neonatal immunisation, summarising progress made in the field, including lessons learnt from newborn vaccines in the pipeline. Furthermore, we explore important maternal, infant and environmental co-factors that may impede the success of current and future neonatal immunisation strategies. A variety of approaches have been proposed to overcome the inherent regulatory constraints of the newborn innate and adaptive immune system, including alternative routes of delivery, novel vaccine configurations, improved innate receptor agonists and optimised antigen-adjuvant combinations. Crucially, a dual strategy may be employed whereby immunisation at birth is used to prime the immune system in order to improve immunogenicity to subsequent homologous or heterologous boosters in later infancy. Similarly, potent non-specific immunomodulatory effects may be elicited when challenged with unrelated antigens, with the potential to reduce the overall risk of infection and allergic disease in early life

Blood transfusion during radical chemo-radiotherapy does not reduce tumour hypoxia in squamous cell cancer of the head and neck.

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) undergoing radical chemo-radiation (CRT) frequently receive transfusion with packed red cells (PRCT) during radiotherapy on the basis that PRCT increases tumour oxygenation and overcomes hypoxia-induced radio-resistance. This is likely to be a significant oversimplification given the fact that tumour hypoxia is the result of several intrinsic and extrinsic factors, including many that are not directly related to serum haemoglobin (Hb). Therefore, we have studied the effect of PRCT on tumour oxygenation in a prospective cohort of patients who developed low Hb during radical CRT for HNSCC. METHODS: This was a prospective study of 20 patients with HNSCC receiving radical CRT undergoing PRCT for Hb<11.5 g dl-1. Patients underwent pretransfusion and posttransfusion intrinsic susceptibility-weighted (SWI) MRI and dynamic contrast-enhanced (DCE) MRI. Blood samples were obtained at the time of MRI scanning and two further time points for measuring Hb and a panel of serum cytokine markers of tumour hypoxia. 3D T2* and Ktrans maps were calculated from the MRI data for primary tumours and cervical lymph node metastases. RESULTS: PRCT produced no change (11 patients) or reduced (1 patient) T2* (tumour oxygenation) in 12 of the 16 (75%) evaluable primary tumours. Three of the four patients with improved tumour oxygenation progressed or had partial response following treatment completion. There were variable changes in Ktrans (tumour perfusion or vessel permeability) following PRCT that were of small magnitude for most tumours. Pre- and Post-PRCT levels of measured cytokines were not significantly different. CONCLUSIONS: This study suggests that PRCT during radical CRT for HNSCC does not improve tumour oxygenation. Therefore, oncologists should consider changing practice according to NICE and American Association of Blood Banks guidelines on PRCT for anaemia

Cystic Fibrosis in Korean Children: A Case Report Identified by a Quantitative Pilocarpine Iontophoresis Sweat Test and Genetic Analysis

Cystic fibrosis (CF) is inherited as an autosomal recessive trait, and the mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene contributes to the CF syndrome. Although CF is common in Caucasians, it is known to be rare in Asians. Recently, we experienced two cases of CF in Korean children. The patients were girls with chronic productive cough since early infancy. Chest computed tomography showed the diffuse bronchiectasis in both lungs, and their diagnosis was confirmed by the repeated analysis of a quantitative pilocarpine iontophoresis test (QPIT). The sweat chloride concentrations of the first patient were 108.1 mM/L and 96.7 mM/L. The genetic analysis revealed that she was the compound heterozygote of Q1291X and IVS8 T5-M470V. In the second case, the sweat chloride concentrations were 95.0 mM/L and 77.5 mM/L. Although we performed a comprehensive search for the coding regions and exon-intron splicing junctions of CFTR gene, no obvious disease-related mutations were detected in the second case. To our knowledge, this is the first report of CF in Korean children identified by a QPIT and genetic analysis. The possibility of CF should be suspected in those patients with chronic respiratory symptoms even in Korea

Changes in multimodality functional imaging parameters early during chemoradiation predict treatment response in patients with locally advanced head and neck cancer.

Objective To assess the optimal timing and predictive value of early intra-treatment changes in multimodality functional and molecular imaging (FMI) parameters as biomarkers for clinical remission in patients receiving chemoradiation for head and neck squamous cell carcinoma (HNSCC).Methods Thirty-five patients with stage III-IVb (AJCC 7th edition) HNSCC prospectively underwent 18F-FDG-PET/CT, and diffusion-weighted (DW), dynamic contrast-enhanced (DCE) and susceptibility-weighted MRI at baseline, week 1 and week 2 of chemoradiation. Patients with evidence of persistent or recurrent disease during follow-up were classed as non-responders. Changes in FMI parameters at week 1 and week 2 were compared between responders and non-responders with the Mann-Whitney U test. The significance threshold was set at a p value of 40%; p = 0.007) and maximum standardized uptake value (SUVmax; p = 0.034) after week 1 than non-responders but these differences were absent by week 2. In contrast, it was not until week 2 that MRI-derived parameters were able to discriminate between the two groups: larger fractional increases in primary tumor apparent diffusion coefficient (ADC; p trans; p = 0.012) and interstitial space volume fraction (Ve; p = 0.047) were observed in responders versus non-responders. ADC was the most powerful predictor (∆ >17%, AUC 0.937).Conclusion Early intra-treatment changes in FDG-PET, DW and DCE MRI-derived parameters are predictive of ultimate response to chemoradiation in HNSCC. However, the optimal timing for assessment with FDG-PET parameters (week 1) differed from MRI parameters (week 2). This highlighted the importance of scanning time points for the design of FMI risk-stratified interventional studies

MRI-based Assessment of 3D Intrafractional Motion of Head and Neck Cancer for Radiation Therapy.

Purpose To determine the 3-dimensional (3D) intrafractional motion of head and neck squamous cell carcinoma (HNSCC).Methods and materials Dynamic contrast-enhanced magnetic resonance images from 56 patients with HNSCC in the treatment position were analyzed. Dynamic contrast-enhanced magnetic resonance imaging consisted of 3D images acquired every 2.9 seconds for 4 minutes 50 seconds. Intrafractional tumor motion was studied in the 3 minutes 43 seconds of images obtained after initial contrast enhancement. To assess tumor motion, rigid registration (translations only) was performed using a region of interest (ROI) mask around the tumor. The results were compared with bulk body motion from registration to all voxels. Motion was split into systematic motion and random motion. Correlations between the tumor site and random motion were tested. The within-subject coefficient of variation was determined from 8 patients with repeated baseline measures. Random motion was also assessed at the end of the first week (38 patients) and second week (25 patients) of radiation therapy to investigate trends of motion.Results Tumors showed irregular occasional rapid motion (eg, swallowing or coughing), periodic intermediate motion (respiration), and slower systematic drifts throughout treatment. For 95% of the patients, displacements due to systematic and random motion were <1.4 mm and <2.1 mm, respectively, 95% of the time. The motion without an ROI mask was significantly (P<.0001, Wilcoxon signed rank test) less than the motion with an ROI mask, indicating that tumors can move independently from the bony anatomy. Tumor motion was significantly (P=.005, Mann-Whitney U test) larger in the hypopharynx and larynx than in the oropharynx. The within-subject coefficient of variation for random motion was 0.33. The average random tumor motion did not increase notably during the first 2 weeks of treatment.Conclusions The 3D intrafractional tumor motion of HNSCC is small, with systematic motion <1.4 mm and random motion <2.1 mm 95% of the time

Noninvasive Imaging of Cycling Hypoxia in Head and Neck Cancer Using Intrinsic Susceptibility MRI.

Purpose: To evaluate intrinsic susceptibility (IS) MRI for the identification of cycling hypoxia, and the assessment of its extent and spatial distribution, in head and neck squamous cell carcinoma (HNSCC) xenografts and patients.Experimental Design: Quantitation of the transverse relaxation rate, R2*, which is sensitive to paramagnetic deoxyhemoglobin, using serial IS-MRI acquisitions, was used to monitor temporal oscillations in levels of paramagnetic deoxyhemoglobin in human CALR xenografts and patients with HNSCC at 3T. Autocovariance and power spectrum analysis of variations in R2* was performed for each imaged voxel, to assess statistical significance and frequencies of cycling changes in tumor blood oxygenation. Pathologic correlates with tumor perfusion (Hoechst 33342), hypoxia (pimonidazole), and vascular density (CD31) were sought in the xenografts, and dynamic contrast-enhanced (DCE) MRI was used to assess patient tumor vascularization. The prevalence of fluctuations within patient tumors, DCE parameters, and treatment outcome were reported.Results: Spontaneous R2* fluctuations with a median periodicity of 15 minutes were detected in both xenografts and patient tumors. Spatially, these fluctuations were predominantly associated with regions of heterogeneous perfusion and hypoxia in the CALR xenografts. In patients, R2* fluctuations spatially correlated with regions of lymph nodes with low Ktrans values, typically in the vicinity of necrotic cores.Conclusions: IS-MRI can be used to monitor variations in levels of paramagnetic deoxyhemoglobin, associated with cycling hypoxia. The presence of such fluctuations may be linked with impaired tumor vasculature, the presence of which may impact treatment outcome. Clin Cancer Res; 23(15); 4233-41. ©2017 AACR

Ice loss from the East Antarctic Ice Sheet during late Pleistocene interglacials

Understanding ice sheet behaviour in the geological past is essential for evaluating the role of the cryosphere in the climate system and for projecting rates and magnitudes of sea level rise in future warming scenarios1,2,3,4. Although both geological data5,6,7 and ice sheet models3,8 indicate that marine-based sectors of the East Antarctic Ice Sheet were unstable during Pliocene warm intervals, the ice sheet dynamics during late Pleistocene interglacial intervals are highly uncertain3,9,10. Here we provide evidence from marine sedimentological and geochemical records for ice margin retreat or thinning in the vicinity of the Wilkes Subglacial Basin of East Antarctica during warm late Pleistocene interglacial intervals. The most extreme changes in sediment provenance, recording changes in the locus of glacial erosion, occurred during marine isotope stages 5, 9, and 11, when Antarctic air temperatures11 were at least two degrees Celsius warmer than pre-industrial temperatures for 2,500 years or more. Hence, our study indicates a close link between extended Antarctic warmth and ice loss from the Wilkes Subglacial Basin, providing ice-proximal data to support a contribution to sea level from a reduced East Antarctic Ice Sheet during warm interglacial intervals. While the behaviour of other regions of the East Antarctic Ice Sheet remains to be assessed, it appears that modest future warming may be sufficient to cause ice loss from the Wilkes Subglacial Basin