Very small deletions within the NESP55 gene in pseudohypoparathyroidism type 1b

Pseudohypoparathyroidism (PHP) is caused by reduced expression of genes within the GNAS cluster, resulting in parathormone resistance. The cluster contains multiple imprinted transcripts, including the stimulatory G protein α subunit (Gs-α) and NESP55 transcript preferentially expressed from the maternal allele, and the paternally expressed XLas, A/B and antisense transcripts. PHP1b can be caused by loss of imprinting affecting GNAS A/B alone (associated with STX16 deletion), or the entire GNAS cluster (associated with deletions of NESP55 in a minority of cases). We performed targeted genomic next-generation sequencing (NGS) of the GNAS cluster to seek variants and indels underlying PHP1b. Seven patients were sequenced by hybridisation-based capture and fourteen more by long-range PCR and transposon-mediated insertion and sequencing. A bioinformatic pipeline was developed for variant and indel detection. In one family with two affected siblings, and in a second family with a single affected individual, we detected maternally inherited deletions of 40 and 33 bp, respectively, within the deletion previously reported in rare families with PHP1b. All three affected individuals presented with atypically severe PHP1b; interestingly, the unaffected mother in one family had the detected deletion on her maternally inherited allele. Targeted NGS can reveal sequence changes undetectable by current diagnostic methods. Identification of genetic mutations underlying epigenetic changes can facilitate accurate diagnosis and counselling, and potentially highlight genetic elements critical for normal imprint settin

Conditional generation of sub-Poissonian light from two-mode squeezed vacuum via balanced homodyne detection on idler mode

A simple scheme for conditional generation of nonclassical light with sub-Poissonian photon-number statistics is proposed. The method utilizes entanglement of signal and idler modes in two-mode squeezed vacuum state generated in optical parametric amplifier. A quadrature component of the idler mode is measured in balanced homodyne detector and only those experimental runs where the absolute value of the measured quadrature is higher than certain threshold are accepted. If the threshold is large enough then the conditional output state of signal mode exhibits reduction of photon-number fluctuations below the coherent-state level.Comment: 7 pages, 6 figures, REVTe

Dichromatic polynomials and Potts models summed over rooted maps

We consider the sum of dichromatic polynomials over non-separable rooted planar maps, an interesting special case of which is the enumeration of such maps. We present some known results and derive new ones. The general problem is equivalent to the $q$-state Potts model randomized over such maps. Like the regular ferromagnetic lattice models, it has a first-order transition when $q$ is greater than a critical value $q_c$, but $q_c$ is much larger - about 72 instead of 4.Comment: 29 pages, three figures changes in App D, introduction and acknowledgement

A controlled crossover trial of fendluramine in autism

Introduction: Against a background of variable results achieved by the treatment of childhood autism with dopaminergic agonists or antagonists, and opiate antagonists and mild behavioural improvements achieved following treatment with fenfluramine (Geller et al., 1982; Ritvo et al., 1984 among others) a 12 month double-blind crossover trial of fenfluramine was undertaken. [the d-isomer releases serotonin, the l-isomer modestly blocks dopamine receptors.] Methods: Six female and 14 male children and adolescents with autism were enrolled (median 9y; range 5-17 years of age) in a trial run over a 1 month baseline, 5 months of treatment, 2 months placebo, and 5 months of treatment. Parent diaries were kept. Various tests and rating scales for development, verbal and noverbal abilities along with measures of blood serotonin, urinary catecholamines and auditory event-related potentials (ERPs) were measured at 6-month intervals. Results: a) With fenfluramine treatment children lost weight, blood serotonin decreased by 60% and urinary catecholamine levels fell (25-45%, but dopamine utilization (HVA/DA) increased 2-4-fold. b) Under fenfluramine some autistic subjects improved on measures of cognitive and language function. Two mute subjects began to speak, but for the group overall the improvements did not prove significant. [British Ability Scale, Reynell developmental language and Vineland social maturity scale improvements were significant.] c) Treatment improved early stages of information processing, but impaired later stages as measured in the ERP (i.e. early negative going excitatory vs. later positive going inhibitory response, respectively in 7 patients). The early negativity changes (especially over the right hemisphere) correlated inversely with HVA/DA actvivity. d) Side effects reported included lethargy and irritability.. Conclusions: While individuals showed marked reductions of stereotypies, hyperactivity, and improvements on develepmental and cognitive measures, the absence of clear group-wide effects suggests that fenfluramine would have but a limited place in the management of some patients with autism

Collinear helium under periodic driving: stabilization of the asymmetric stretch orbit

The collinear eZe configuration of helium, with the electrons on opposite sides of the nucleus, is studied in the presence of an external electromagnetic (laser or microwave) field. We show that the classically unstable "asymmetric stretch" orbit, on which doubly excited intrashell states of helium with maximum interelectronic angle are anchored, can be stabilized by means of a resonant driving where the frequency of the electromagnetic field equals the frequency of Kepler-like oscillations along the orbit. A static magnetic field, oriented parallel to the oscillating electric field of the driving, can be used to enforce the stability of the configuration with respect to deviations from collinearity. Quantum Floquet calculations within a collinear model of the driven two-electron atom reveal the existence of nondispersive wave packets localized on the stabilized asymmetric stretch orbit, for double excitations corresponding to principal quantum numbers of the order of N > 10.Comment: 13 pages, 12 figure

Response, relaxation and transport in unconventional superconductors

We investigate the collision-limited electronic Raman response and the attenuation of ultrasound in spin-singlet d-wave superconductors at low temperatures. The dominating elastic collisions are treated within a t-matrix approximation, which combines the description of weak (Born) and strong (unitary) impurity scattering. In the long wavelength limit a two-fluid description of both response and transport emerges. Collisions are here seen to exclusively dominate the relaxational dynamics of the (Bogoliubov) quasiparticle system and the analysis allows for a clear connection of response and transport phenomena. When applied to quasi-2-d superconductors like the cuprates, it turns out that the transport parameter associated with the Raman scattering intensity for B1g and B2g photon polarization is closely related to the corresponding components of the shear viscosity tensor, which dominates the attenuation of ultrasound. At low temperatures we present analytic solutions of the transport equations, resulting in a non-power-law behavior of the transport parameters on temperature.Comment: 22 pages, 3 figure

Cost and cost‐effectiveness of a simplified treatment model with direct‐acting antivirals for chronic hepatitis C in Cambodia

Background & Aims In 2016, Médecins Sans Frontières established the first general population Hepatitis C virus (HCV) screening and treatment site in Cambodia, offering free direct‐acting antiviral (DAA) treatment. This study analysed the cost‐effectiveness of this intervention. Methods Costs, quality adjusted life years (QALYs) and cost‐effectiveness of the intervention were projected with a Markov model over a lifetime horizon, discounted at 3%/year. Patient‐level resource‐use and outcome data, treatment costs, costs of HCV‐related healthcare and EQ‐5D‐5L health states were collected from an observational cohort study evaluating the effectiveness of DAA treatment under full and simplified models of care compared to no treatment; other model parameters were derived from literature. Incremental cost‐effectiveness ratios (cost/QALY gained) were compared to an opportunity cost‐based willingness‐to‐pay threshold for Cambodia ($248/QALY). Results The total cost of testing and treatment per patient for the full model of care was$925(IQR $668‐1631), reducing to$376(IQR $344‐422) for the simplified model of care. EQ‐5D‐5L values varied by fibrosis stage: decompensated cirrhosis had the lowest value, values increased during and following treatment. The simplified model of care was cost saving compared to no treatment, while the full model of care, although cost‐effective compared to no treatment ($187/QALY), cost an additional $14 485/QALY compared to the simplified model, above the willingness‐to‐pay threshold for Cambodia. This result is robust to variation in parameters. Conclusions The simplified model of care was cost saving compared to no treatment, emphasizing the importance of simplifying pathways of care for improving access to HCV treatment in low‐resource settings

Octet-Baryon Form Factors in the Diquark Model

We present an alternative parameterization of the quark-diquark model of baryons which particularly takes care of the most recent proton electric form-factor data from the E136 experiment at SLAC. In addition to electromagnetic form factors of the nucleon, for which good agreement with data is achieved, we discuss the weak axial vector form factor of the nucleon as well as electromagnetic form factors of $\Lambda$ and $\Sigma$ hyperons. Technical advance in calculating the pertinent analytic expressions within perturbative quantum chromodynamics is gained by formulating the wave function of the quark-diquark system in a covariant way. Finally, we also comment on the influence of Sudakov corrections within the scope of the diquark model.Comment: 16 pages, WU-B 93-07, latex, uuencoded postscript files of 7 figures appended at the end of the latex fil