The case for early use of rapid whole-genome sequencing in management of critically ill infants: late diagnosis of Coffin-Siris syndrome in an infant with left congenital diaphragmatic hernia, congenital heart disease, and recurrent infections.

Congenital diaphragmatic hernia (CDH) results from incomplete formation of the diaphragm leading to herniation of abdominal organs into the thoracic cavity. CDH is associated with pulmonary hypoplasia, congenital heart disease, and pulmonary hypertension. Genetically, it is associated with aneuploidies, chromosomal copy-number variants, and single gene mutations. CDH is the most expensive noncardiac congenital defect. Management frequently requires implementation of extracorporeal membrane oxygenation (ECMO), which increases management expenditures 2.4-3.5-fold. The cost of management of CDH has been estimated to exceed $250 million per year. Despite in-hospital survival of 80%-90%, current management is imperfect, as a great proportion of surviving children have long-term functional deficits. We report the case of a premature infant prenatally diagnosed with CDH and congenital heart disease, who had a protracted and complicated course in the intensive care unit with multiple surgical interventions, including postcardiac surgery ECMO, gastrostomy tube placement with Nissen fundoplication, tracheostomy for respiratory failure, recurrent infections, and developmental delay. Rapid whole-genome sequencing (rWGS) identified a de novo, likely pathogenic, c.3096_ 3100delCAAAG (p.Lys1033Argfs*32) variant in ARID1B, providing a diagnosis of Coffin-Siris syndrome. Her parents elected palliative care and she died later that day

Elastic and magnetic effects on the infrared phonon spectra of MnF2

We measured the temperature dependent infrared reflectivity spectra of MnF2 between 4 K and room temperature. We show that the phonon spectrum undergoes a strong renormalization at TN. The ab-initio calculation we performed on this compound accurately predict the magnitude and the direction of the phonon parameters changes across the antiferromagnetic transition, showing that they are mainly induced by the magnetic order. In this material, we found that the dielectric constant is mostly from phonon origin. The large change in the lattice parameters with temperature seen by X-ray diffraction as well as the A2u phonon softening below TN indicate that magnetic order induced distortions in MnF2 are compatible with the ferroelectric instabilities observed in TiO2, FeF2 and other rutile-type fluorides. This study also shows the anomalous temperature evolution of the lower energy Eu mode in the paramagnetic phase, which can be compared to that of the B1g one seen by Raman spectroscopy in many isostructural materials. This was interpreted as being a precursor of a phase transition from rutile to CaCl2 structure which was observed under pressure in ZnF2.Comment: 8 pages, 8 figures, updated version accepted in PR

Comparação dos imuno-ensaios de fluorescência polarizada (TDx) e enzimático competitivo (EMIT 2000 ) na dosagem da concentração de ciclosporina A no sangue total

Evaluation of Cyclosporin A (CyA) blood concentration is imperative in solid organ transplantation in order to achieve maximal immunosuppression with the least side effects. We compared the results of whole blood concentrations of CyA in 50 blood samples simultaneously evaluated by the fluorescent polarization immune assay (TDx) and the enzymatic competitive immune assay (EMIT 2000). There was a strong correlation between both kits for any range of CyA blood concentration (R=0.99, pA avaliação da concentração sanguínea de ciclosporina A (CyA) é necessária em transplantes de órgãos sólidos para obter-se máxima imunosupressão e mínimos efeitos colaterais. Nós comparamos os resultados da concentração de CyA em 50 amostras sanguíneas analisadas pelos métodos dos imuno-ensaios de fluorescência polarizada (TDx) e enzimático competitivo (EMIT 2000). Houve uma forte correlação entre ambos métodos para qualquer faixa de concentração de CyA (R=0.99,

Gupta-Bleuler quantization for minimally coupled scalar fields in de Sitter space

We present in this paper a fully covariant quantization of the minimally-coupled massless field on de Sitter space. We thus obtain a formalism free of any infrared (e.g logarithmic) divergence. Our method is based on a rigorous group theoretical approach combined with a suitable adaptation (Krein spaces) of the Wightman-G\"{a}rding axiomatic for massless fields (Gupta-Bleuler scheme). We make explicit the correspondence between unitary irreducible representations of the de Sitter group and the field theory on de Sitter space-time. The minimally-coupled massless field is associated with a representation which is the lowest term of the discrete series of unitary representations of the de Sitter group. In spite of the presence of negative norm modes in the theory, no negative energy can be measured: expressions as \le n_{k_1}n_{k_2}...|T_{00}|n_{k_1}n_{k_2}...\re are always positive.Comment: 20 pages, appear in class. quantum gra

Spin-Wave-Assisted Thermal Reversal of Epitaxial Perpendicular Magnetic Nanodots

The magnetic susceptibility of self-organized two-dimensional Co nanodots on Au(111) has been measured as a function of their size in the 2-7~nm diameter range. We show that the activation energy for the thermal reversal displays a power law behavior with the dot volume. Atomic scale simulations based on the Heisenberg hamiltonian show that this behavior is due to a deviation from the macrospin model for dot size as small as 3~nm in diameter. This discrepancy is attributed to finite temperature effects through the thermal excitation of spin-wave modes inside the particlesComment: 4 pages, 4 figure

Reconstructing the Optical Parameters of a Layered Medium with Optical Coherence Elastography

In this work we consider the inverse problem of reconstructing the optical properties of a layered medium from an elastography measurement where optical coherence tomography is used as the imaging method. We hereby model the sample as a linear dielectric medium so that the imaging parameter is given by its electric susceptibility, which is a frequency- and depth-dependent parameter. Additionally to the layered structure (assumed to be valid at least in the small illuminated region), we allow for small scatterers which we consider to be randomly distributed, a situation which seems more realistic compared to purely homogeneous layers. We then show that a unique reconstruction of the susceptibility of the medium (after averaging over the small scatterers) can be achieved from optical coherence tomography measurements for different compression states of the medium.Comment: 19 pages, 1 figur

Preventing type 2 diabetes mellitus in Qatar by reducing obesity, smoking, and physical inactivity: mathematical modeling analyses.

BACKGROUND: The aim of this study was to estimate the impact of reducing the prevalence of obesity, smoking, and physical inactivity, and introducing physical activity as an explicit intervention, on the burden of type 2 diabetes mellitus (T2DM), using Qatar as an example. METHODS: A population-level mathematical model was adapted and expanded. The model was stratified by sex, age group, risk factor status, T2DM status, and intervention status, and parameterized by nationally representative data. Modeled interventions were introduced in 2016, reached targeted level by 2031, and then maintained up to 2050. Diverse intervention scenarios were assessed and compared with a counter-factual no intervention baseline scenario. RESULTS: T2DM prevalence increased from 16.7% in 2016 to 24.0% in 2050 in the baseline scenario. By 2050, through halting the rise or reducing obesity prevalence by 10-50%, T2DM prevalence was reduced by 7.8-33.7%, incidence by 8.4-38.9%, and related deaths by 2.1-13.2%. For smoking, through halting the rise or reducing smoking prevalence by 10-50%, T2DM prevalence was reduced by 0.5-2.8%, incidence by 0.5-3.2%, and related deaths by 0.1-0.7%. For physical inactivity, through halting the rise or reducing physical inactivity prevalence by 10-50%, T2DM prevalence was reduced by 0.5-6.9%, incidence by 0.5-7.9%, and related deaths by 0.2-2.8%. Introduction of physical activity with varying intensity at 25% coverage reduced T2DM prevalence by 3.3-9.2%, incidence by 4.2-11.5%, and related deaths by 1.9-5.2%. CONCLUSIONS: Major reductions in T2DM incidence could be accomplished by reducing obesity, while modest reductions could be accomplished by reducing smoking and physical inactivity, or by introducing physical activity as an intervention

Surgical treatment of rectal prolapse: experience and late results with 51 patients

The "best" surgical technique for the management of complete rectal prolapse remains unknown. Due to its low incidence, it is very difficult to achieve a representative number of cases, and there are no large prospective randomized trials to attest to the superiority of one operation over another. PURPOSE: Analyze the results of surgical treatment of complete rectal prolapse during 1980 and 2002. METHOD: Retrospective study. RESULTS: Fifty-one patients underwent surgical treatment during this period. The mean age was 56.7 years, with 39 females. Besides the prolapse itself, 33 patients complained of mucous discharge, 31 of fecal incontinence, 14 of constipation, 17 of rectal bleeding, and 3 of urinary incontinence. Abdominal operations were performed in 36 (71%) cases. Presacral rectopexy was the most common abdominal procedure (29 cases) followed by presacral rectopexy associated with sigmoidectomy (5 cases). The most common perineal procedure was perineal rectosigmoidectomy associated with levatorplasty (12 cases). Intraoperative bleeding from the presacral space developed in 2 cases, and a rectovaginal fistula occurred in another patient after a perineal rectosigmoidectomy. There were 2 recurrences after a mean follow-up of 49 months, which were treated by reoperation. CONCLUSION: Abdominal and perineal procedures can be used to manage complete rectal prolapse with safety and good long-term results. Age, associated medical conditions, and symptoms of fecal incontinence or constipation are the main features that one should bear in mind in order to choose the best surgical approach.A técnica cirúrgica mais apropriada para a correção da procidência retal permanece motivo de controvérsia. Por se tratar de afecção pouco freqüente, há dificuldade de avaliação de número adequado de pacientes em estudos randomizados e existe pouca evidência para comprovar a superioridade de alguma das técnicas. OBJETIVO: Analisar os resultados de eficácia e segurança do tratamento cirúrgico da procidência retal em pacientes operados entre 1980 e 2002. MÉTODO: Estudo retrospectivo. RESULTADOS: Cinqüenta e um pacientes foram operados. A idade média foi de 56,7 anos e 39 eram mulheres. Além do prolapso, 33 pacientes queixavam-se de eliminação de muco, 31 tinham incontinência anal, 14 apresentavam constipação, 17 com sangramento retal e 3 incontinência urinária. Operações abdominais foram realizadas em 36 (71%) casos, sendo a retopexia sem prótese a operação mais realizada (29 casos) seguida pela retossigmoidectomia com retopexia (5 casos). A operação perineal mais realizada foi a retossigmoidectomia com plastia dos elevadores (12 casos). O sangramento sacral foi a única complicação intra-operatória e ocorreu em dois casos. Como complicação pós-operatória, houve um caso de fístula retovaginal após operação de retossigmoidectomia perineal. Após seguimento médio de 49 meses, observamos recidiva da procidência em 2 casos. CONCLUSÕES: Operações abdominais e perineais podem ser utilizadas com segurança e eficácia no tratamento cirúrgico da procidência do reto. A idade, a presença de afecções associadas, comorbidades e os sintomas de constipação e incontinência são as principais variáveis envolvidas na escolha da operação. As operações de retopexia abdominal e retossigmoidectomia perineal estão associadas a bons resultados