First-trimester or second-trimester screening, or both, for Down's syndrome

BACKGROUND: It is uncertain how best to screen pregnant women for the presence of fetal Down's syndrome: to perform first-trimester screening, to perform second-trimester screening, or to use strategies incorporating measurements in both trimesters.METHODS: Women with singleton pregnancies underwent first-trimester combined screening (measurement of nuchal translucency, pregnancy-associated plasma protein A [PAPP-A], and the free beta subunit of human chorionic gonadotropin at 10 weeks 3 days through 13 weeks 6 days of gestation) and second-trimester quadruple screening (measurement of alpha-fetoprotein, total human chorionic gonadotropin, unconjugated estriol, and inhibin A at 15 through 18 weeks of gestation). We compared the results of stepwise sequential screening (risk results provided after each test), fully integrated screening (single risk result provided), and serum integrated screening (identical to fully integrated screening, but without nuchal translucency).RESULTS: First-trimester screening was performed in 38,167 patients; 117 had a fetus with Down's syndrome. At a 5 percent false positive rate, the rates of detection of Down's syndrome were as follows: with first-trimester combined screening, 87 percent, 85 percent, and 82 percent for measurements performed at 11, 12, and 13 weeks, respectively; with second-trimester quadruple screening, 81 percent; with stepwise sequential screening, 95 percent; with serum integrated screening, 88 percent; and with fully integrated screening with first-trimester measurements performed at 11 weeks, 96 percent. Paired comparisons found significant differences between the tests, except for the comparison between serum integrated screening and combined screening.CONCLUSIONS: First-trimester combined screening at 11 weeks of gestation is better than second-trimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening. Both stepwise sequential screening and fully integrated screening have high rates of detection of Down's syndrome, with low false positive rates

Predictors of Resilience Among Infants at Risk for Rapid Weight Gain

Objective: The study objective was to investigate factors associated with resilience to rapid weight gain (RWG) among predominantly bottle-fed infants. Methods: Data came from 1,353 mothers who participated in the Infant Feeding Practices Study 2. Mothers completed a prenatal questionnaire and monthly surveys of infant feeding and growth between birth and 12 months. Infants were classified as resilient if they were predominantly bottle fed but did not exhibit RWG between birth and the latter half of infancy (≥ +0.67 change in weight-for-age z score). Results: Thirty-five percent of the sample (n = 467) was predominantly bottle fed but did not exhibit RWG (“Resilient”), 17% (n = 228) was predominantly bottle fed and exhibited RWG (“Not Resilient”), and 49% (n = 658) was not predominantly bottle fed (“Low Risk”). Significant predictors of resilience to RWG were greater gestational age (P = 0.042) and weight (P \u3c 0.001) at birth, lower frequency of adding cereal to the bottle (P = 0.022), lower frequency of infant-led bottle-emptying (P = 0.047), and greater frequency of maternal encouragement of bottle-emptying (P = 0.002). Conclusions: Associations between bottle-feeding and RWG may be moderated by infant characteristics and maternal feeding practices. The present study highlighted several characteristics of predominantly bottle-fed infants who were resilient to RWG, but further research is needed to identify a broader array of key targets for future intervention efforts

Supersymmetric constraints from Bs -> mu+mu- and B -> K* mu+mu- observables

We study the implications of the recent LHCb limit and results on Bs -> mu+mu- and B -> K* mu+mu- observables in the constrained SUSY scenarios. After discussing the Standard Model predictions and carefully estimating the theoretical errors, we show the constraining power of these observables in CMSSM and NUHM. The latest limit on BR(Bs -> mu+mu-), being very close to the SM prediction, constrains strongly the large tan(beta) regime and we show that the various angular observables from B -> K* mu+mu- decay can provide complementary information in particular for moderate tan(beta) values.Comment: 30 pages, 14 figure

Model-independent constraints on new physics in b --> s transitions

We provide a comprehensive model-independent analysis of rare decays involving the b --> s transition to put constraints on dimension-six Delta(F)=1 effective operators. The constraints are derived from all the available up-to-date experimental data from the B-factories, CDF and LHCb. The implications and future prospects for observables in b --> s l+l- and b --> s nu nu transitions in view of improved measurements are also investigated. The present work updates and generalises previous studies providing, at the same time, a useful tool to test the flavour structure of any theory beyond the SM.Comment: 1+39 pages, 12 figures, 3 tables. v2: minor modifications, typos corrected, references added, version to be published in JHE

Exploring New Physics in the C7-C7' plane

The Wilson coefficient C7 governing the radiative electromagnetic decays of B meson has been calculated to a very high accuracy in the Standard Model, but experimental bounds on either the magnitude or the sign of C7 are often model-dependent. In the present paper, we attempt at constraining both the magnitude and sign of C7 using a systematic approach. We consider already measured observables like the branching ratios of B \rightarrow Xs mu+ mu- and B \rightarrow Xs gamma, the isospin and CP asymmetries in B \rightarrow K* gamma, as well as AFB and FL in B \rightarrow K*l+l-. We also discuss the transverse observable AT2 which, once measured, may help to disentangle some of the scenarios considered. We explore the constraints on C7, C9, C10 as well as their chirality-flipped counterparts. Within our framework, we find that we need to extend the constraints up to 1.6 sigma to allow for the "flipped-sign solution" of C7. The SM solution for C7 exhibits a very mild tension if New Physics is allowed in dipole operators only. We provide semi-numerical expressions for all these observables as functions of the relevant Wilson coefficients at the low scale.Comment: 54 pages, 16 figures, 15 tables. Normalization factor introduced for the integrated AFB and FL in Sec.2.5 (Eq.2.35-2.38). Conclusions unchanged. Not updated in JHE

B-> D* zero-recoil formfactor and the heavy quark expansion in QCD: a systematic study

We present a QCD analysis of heavy quark mesons focussing on the B -> D* formfactor at zero recoil, F_D*(1). An advanced treatment of the perturbative corrections in the Wilsonian approach is presented. We estimate the higher-order power corrections to the OPE sum rule and describe a refined analysis of the nonresonant continuum contribution. In the framework of a model-independent approach, we show that the inelastic contribution in the phenomenological part of the OPE is related to the mQ-dependence of the hyperfine splitting and conclude that the former is large, lowering the prediction for F_D*(1) down to about 0.86. This likewise implies an enhanced yield of radial and D-wave charm excitations in semileptonic B decays and alleviates the problem with the inclusive yield of the wide excited states. We also apply the approach to the expectation values of dimension 7 and 8 local operators and to a few other issues in the heavy quark expansion.Comment: 70 pages, 13 figure

New physics reach of the decay mode Bˉ→Kˉ∗0ℓ+ℓ−\bar{B} \to \bar{K}^{*0}\ell^+\ell^-

We present a complete method to construct QCD-protected observables based on the exclusive 4-body $B$-meson decay $\bar{B} \to \bar{K}^{*0}\ell^+\ell^-$ in the low dilepton mass region. The core of the method is the requirement that the constructed quantities should fulfil the symmetries of the angular distribution. We have identified all symmetries of the angular distribution in the limit of massless leptons and explore: a new non-trivial relation between the coefficients of the angular distribution, the possibility to fully solve the system for the $K^{*}$ amplitudes, and the construction of non-trivial observables. We also present a phenomenological analysis of the new physics sensitivity of angular observables in the decay based on QCD factorisation. We further analyse the CP-conserving observables, $A_{T}^{(2)}$, $A_{T}^{(3)}$ and $A_{T}^{(4)}$. They are practically free of theoretical uncertainties due to the soft form factors for the full range of dilepton masses rather than just at a single point as for $A_{FB}$. They also have a higher sensitivity to specific new physics scenarios compared to observables such as $A_{FB}$. Moreover, we critically examine the new physics reach of CP-violating observables via a complete error analysis due to scale dependences, form factors and $\Lambda/m_b$ corrections. We have developed an ensemble method to evaluate the error on observables from $\Lambda/m_b$ corrections. Finally, we explore the experimental prospects of CP-violating observables and find that they are rather limited. Indeed, the CP-conserving (averaged) observables $A_{T}^{(i)}$ (with $i=2,3,4$) will offer a better sensitivity to large CP phases and may be more suitable for experimental analysis.Comment: 38 pages, 17 figures, updated version to fix a few typo

What do general practitioners know about ADHD? Attitudes and knowledge among first-contact gatekeepers: systematic narrative review

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood disorder with international prevalence estimates of 5 % in childhood, yet significant evidence exists that far fewer children receive ADHD services. In many countries, ADHD is assessed and diagnosed in specialist mental health or neuro-developmental paediatric clinics, to which referral by General (Family) Practitioners (GPs) is required. In such ‘gatekeeper’ settings, where GPs act as a filter to diagnosis and treatment, GPs may either not recognise potential ADHD cases, or may be reluctant to refer. This study systematically reviews the literature regarding GPs’ views of ADHD in such settings. Methods: A search of nine major databases was conducted, with wide search parameters; 3776 records were initially retrieved. Studies were included if they were from settings where GPs are typically gatekeepers to ADHD services; if they addressed GPs’ ADHD attitudes and knowledge; if methods were clearly described; and if results for GPs were reported separately from those of other health professionals. Results: Few studies specifically addressed GP attitudes to ADHD. Only 11 papers (10 studies), spanning 2000–2010, met inclusion criteria, predominantly from the UK, Europe and Australia. As studies varied methodologically, findings are reported as a thematic narrative, under the following themes: Recognition rate; ADHD controversy (medicalisation, stigma, labelling); Causes of ADHD; GPs and ADHD diagnosis; GPs and ADHD treatment; GP ADHD training and sources of information; and Age, sex differences in knowledge and attitudes. Conclusions: Across times and settings, GPs practising in first-contact gatekeeper settings had mixed and often unhelpful attitudes regarding the validity of ADHD as a construct, the role of medication and how parenting contributed to presentation. A paucity of training was identified, alongside a reluctance of GPs to become involved in shared care practice. If access to services is to be improved for possible ADHD cases, there needs to be a focused and collaborative approach to training

Intragenic DNA methylation: implications of this epigenetic mechanism for cancer research

Epigenetics is the study of all mechanisms that regulate gene transcription and genome stability that are maintained throughout the cell division, but do not include the DNA sequence itself. The best-studied epigenetic mechanism to date is DNA methylation, where methyl groups are added to the cytosine base within cytosine–guanine dinucleotides (CpG sites). CpGs are frequently clustered in high density (CpG islands (CGIs)) at the promoter of over half of all genes. Current knowledge of transcriptional regulation by DNA methylation centres on its role at the promoter where unmethylated CGIs are present at most actively transcribed genes, whereas hypermethylation of the promoter results in gene repression. Over the last 5 years, research has gradually incorporated a broader understanding that methylation patterns across the gene (so-called intragenic or gene body methylation) may have a role in transcriptional regulation and efficiency. Numerous genome-wide DNA methylation profiling studies now support this notion, although whether DNA methylation patterns are a cause or consequence of other regulatory mechanisms is not yet clear. This review will examine the evidence for the function of intragenic methylation in gene transcription, and discuss the significance of this in carcinogenesis and for the future use of therapies targeted against DNA methylation