Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial

Background Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. Methods Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36–43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. Findings The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference −0·01, 95% CI −0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. Interpretation Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia

Minimal gauge-Higgs unification with a flavour symmetry

We show that a flavour symmetry a la Froggatt-Nielsen can be naturally incorporated in models with gauge-Higgs unification, by exploiting the heavy fermions that are anyhow needed to realize realistic Yukawa couplings. The case of the minimal five-dimensional model, in which the SU(2)_L x U(1)_Y electroweak group is enlarged to an SU(3)_W group, and then broken to U(1)_em by the combination of an orbifold projection and a Scherk-Schwarz twist, is studied in detail. We show that the minimal way of incorporating a U(1)_F flavour symmetry is to enlarge it to an SU(2)_F group, which is then completely broken by the same orbifold projection and Scherk-Schwarz twist. The general features of this construction, where ordinary fermions live on the branes defined by the orbifold fixed-points and messenger fermions live in the bulk, are compared to those of ordinary four-dimensional flavour models, and some explicit examples are constructed.Comment: LaTex, 37 pages, 2 figures; some clarifying comments and a few references adde

On the Cosmology of Massive Vector Fields with SO(3) Global Symmetry

A relevant reference ([14]) has been added.Comment: 19 pages, plain tex, DF/IST-3/92 and DFFCUL 03-5/199

Cohort profile: Examining Neighbourhood Activities in Built Living Environments in London: the ENABLE London-Olympic Park cohort.

PURPOSE: The Examining Neighbourhood Activities in Built Living Environments in London (ENABLE London) project is a natural experiment which aims to establish whether physical activity and other health behaviours show sustained changes among individuals and families relocating to East Village (formerly the London 2012 Olympics Athletes' Village), when compared with a control population living outside East Village throughout. PARTICIPANTS: Between January 2013 and December 2015, 1497 individuals from 1006 households were recruited and assessed (at baseline) (including 392 households seeking social housing, 421 seeking intermediate and 193 seeking market rent homes). The 2-year follow-up rate is 62% of households to date, of which 57% have moved to East Village. FINDINGS TO DATE: Assessments of physical activity (measured objectively using accelerometers) combined with Global Positioning System technology and Geographic Information System mapping of the local area are being used to characterise physical activity patterns and location among study participants and assess the attributes of the environments to which they are exposed. Assessments of body composition, based on weight, height and bioelectrical impedance, have been made and detailed participant questionnaires provide information on socioeconomic position, general health/health status, well-being, anxiety, depression, attitudes to leisure time activities and other personal, social and environmental influences on physical activity, including the use of recreational space and facilities in their residential neighbourhood. FUTURE PLANS: The main analyses will examine the changes in physical activity, health and well-being observed in the East Village group compared with controls and the influence of specific elements of the built environment on observed changes. The ENABLE London project exploits a unique opportunity to evaluate a 'natural experiment', provided by the building and rapid occupation of East Village. Findings from the study will be generalisable to other urban residential housing developments, and will help inform future evidence-based urban planning

Coset Space Dimensional Reduction and Wilson Flux Breaking of Ten-Dimensional N=1, E(8) Gauge Theory

We consider a N=1 supersymmetric E(8) gauge theory, defined in ten dimensions and we determine all four-dimensional gauge theories resulting from the generalized dimensional reduction a la Forgacs-Manton over coset spaces, followed by a subsequent application of the Wilson flux spontaneous symmetry breaking mechanism. Our investigation is constrained only by the requirements that (i) the dimensional reduction leads to the potentially phenomenologically interesting, anomaly free, four-dimensional E(6), SO(10) and SU(5) GUTs and (ii) the Wilson flux mechanism makes use only of the freely acting discrete symmetries of all possible six-dimensional coset spaces.Comment: 45 pages, 2 figures, 10 tables, uses xy.sty, longtable.sty, ltxtable.sty, (a shorter version will be published in Eur. Phys. J. C

Ambient particulate pollution and the world-wide prevalence of asthma, rhinoconjunctivitis and eczema in children: Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC)

Objectives: To investigate the effect of ambient particulate matter on variation in childhood prevalence of asthma, rhinoconjunctivitis and eczema. Methods: Prevalences of asthma, rhinoconjunctivitis and eczema obtained in Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC) were matched with city-level estimates of residential PM10 obtained from a World Bank model. Associations were investigated using binomial regression adjusting for GNP per capita and for clustering within country. For countries with more than one centre, a two stage meta-analysis was carried out. The results were compared with a meta-analysis of published multi-centre studies. Results: Annual concentrations of PM₁₀ at city level were obtained for 105 ISAAC centres in 51 countries. After controlling for GNP per capita, there was a weak negative association between PM₁₀ and various outcomes. For severe wheeze in 13-14-year-olds, the OR for a 10 μg/m³ increase in PM₁₀ was 0.92 (95 CI 0.84 to 1.00). In 24 countries with more than one centre, most summary estimates for within-country associations were weakly positive. For severe wheeze in 13-14-year-olds, the summary OR for a 10 μg/m³ increase in PM₁₀ was 1.01 (0.92 to 1.10). This result was close to a summary OR of 0.99 (0.91 to 1.06) obtained from published multi-centre studies. Conclusions: Modelled estimates of particulate matter at city level are imprecise and incomplete estimates of personal exposure to ambient air pollutants. Nevertheless, our results together with those of previous multi-centre studies, suggest that urban background PM₁₀ has little or no association with the prevalence of childhood asthma, rhinoconjunctivitis or eczema either within or between countries

`Natural Masslessness Conservation' for neutrinos in two Higgs-doublet models

We present a model which supplements the Standard Electroweak Model with three right-handed neutrinos and one extra scalar doublet which does not develop a vacuum expectation value. With the aid of a discrete symmetry the neutrinos are kept strictly massless. This model has several interesting features. It has unsuppressed lepton flavour violating processes, in particular $\mu \rightarrow e \gamma$, hinting at the possibility that these may soon be within experimental reach. The $Z$ and $W$ interactions become non-diagonal at one loop level. In particular, a non-trivial leptonic mixing matrix is seen to arise from the clash between the charged gauge boson and the charged scalar interactions.Comment: (Latex file, 12 pages. Two figures available upon request). CMU-preprin

Yang-Mills instantons and dyons on homogeneous G_2-manifolds

We consider Lie G-valued Yang-Mills fields on the space R x G/H, where G/H is a compact nearly K"ahler six-dimensional homogeneous space, and the manifold R x G/H carries a G_2-structure. After imposing a general G-invariance condition, Yang-Mills theory with torsion on R x G/H is reduced to Newtonian mechanics of a particle moving in R^6, R^4 or R^2 under the influence of an inverted double-well-type potential for the cases G/H = SU(3)/U(1)xU(1), Sp(2)/Sp(1)xU(1) or G_2/SU(3), respectively. We analyze all critical points and present analytical and numerical kink- and bounce-type solutions, which yield G-invariant instanton configurations on those cosets. Periodic solutions on S^1 x G/H and dyons on iR x G/H are also given.Comment: 1+26 pages, 14 figures, 6 miniplot

Fermion Masses, Mixing Angles and Supersymmetric SO(10) Unification

We reanalyse the problem of fermion masses in supersymmetric SO(10) grand unified models. In the minimal model, both low energy Higgs doublets belong to the same {\bf{10}} representation of SO(10) implying the unification not only of the gauge but also of the third generation Yukawa couplings. These models predict large values of $\tan\beta \sim 50$. In this paper we study the effects of departing from the minimal conditions in order to see if we can find models with a reduced value of $\tan\beta$. In order to maintain predictability, however, we try to do this with the addition of only one new parameter. We still assume that the fermion masses arise from interactions of the spinor representations with a single ${\bf 10}$ representation, but this ${\bf 10}$ now only contains a part of the two light Higgs doublets. This enables us to introduce one new parameter $\omega=\lambda_b/\lambda_t$. For values of $\omega \ll 1$ we can in principle reduce the value of $\tan\beta$. In fact, $\omega$ is an overall factor which multiplies the down quark and charged lepton Yukawa matrices. Thus the theory is still highly constrained. We show that the first generation quark masses and the CP-violation parameter $\epsilon_K$ yield strong constraints on the phenomenologically allowed models. In the end, we find that large values of $\tan\beta$ are still preferred.Comment: 15 pages, latex, 6 uuencoded figure

Standard Model Higgs from Higher Dimensional Gauge Fields

We consider the possibility that the standard model Higgs fields may originate from extra components of higher dimensional gauge fields. Theories of this type considered before have had problems accommodating the standard model fermion content and Yukawa couplings different from the gauge coupling. Considering orbifolds based on abelian discrete groups we are lead to a 6 dimensional G_2 gauge theory compactified on T^2/Z_4. This theory can naturally produce the SM Higgs fields with the right quantum numbers while predicting the value of the weak mixing angle sin^2 theta_W = 0.25 at the tree-level, close to the experimentally observed one. The quartic scalar coupling for the Higgs is generated by the higher dimensional gauge interaction and predicts the existence of a light Higgs. We point out that one can write a quadratically divergent counter term for Higgs mass localized to the orbifold fixed point. However, we calculate these operators and show that higher dimensional gauge interactions do not generate them at least at one loop. Fermions are introduced at orbifold fixed points, making it easy to accommodate the standard model fermion content. Yukawa interactions are generated by Wilson lines. They may be generated by the exchange of massive bulk fermions, and the fermion mass hierarchy can be obtained. Around a TeV, the first KK modes would appear as well as additional fermion modes localized at the fixed point needed to cancel the quadratic divergences from the Yukawa interactions. The cutoff scale of the theory could be a few times 10 TeV.Comment: 29 pages, 1 figure, LaTeX. v2: Section on the absence of tadpole at all order removed. Typos corrected. Refs. added. Final version appeared in PR