Comprehensive comparison of copy number variations detection using Illumina Omni 2.5M and Affymetrix CytoScan® arrays

Posters: Genome Structure, Variation and Function: abstract no. 552TStructural variation has been recognized as a genetic risk factor contributing to human diseases, and in particular, congenital disorders. Smaller scale copy number variations (CNVs) have also been linked to a number of neurodevelopmental phenotypes, including intellectual disability as well as autism spectrum disorders. The precise detection of CNVs is therefore necessary for ...postprin

Patient complexity and genotype-phenotype correlations in biliary atresia: a cross-sectional analysis

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Cost effective assay choice for rare disease study designs

High throughput assays tend to be expensive per subject. Often studies are limited not so much by the number of subjects available as by assay costs, making assay choice a critical issue. We have developed a framework for assay choice that maximises the number of true disease causing mechanisms ‘seen’, given limited resources. Although straightforward, some of the ramifications of our methodology run counter to received wisdom on study design. We illustrate our methodology with examples, and have built a website allowing calculation of quantities of interest to those designing rare disease studies.published_or_final_versio

Vertically aligned smooth ZnO nanorod films for planar device applications

The growth of smooth and continuous zinc oxide (ZnO) films, consisting of densely packed vertical ZnO nanorods with (002) crystal orientation on silicon substrates has been achieved in this work by a chemical solution method. These ZnO thin films have much stronger photoluminescence emission than those from discrete ZnO nanorods under identical conditions. Large area surface acoustic wave devices were fabricated on these films using conventional photolithography, and exhibited two well-defined resonant modes of the Sezawa wave and its harmonic mode

Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis

Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two

Holographic Brownian Motion in Magnetic Environments

Using the gauge/gravity correspondence, we study the dynamics of a heavy quark in two strongly-coupled systems at finite temperature: Super-Yang-Mills in the presence of a magnetic field and non-commutative Super-Yang-Mills. In the former, our results agree qualitatively with the expected behavior from weakly-coupled theories. In the latter, we propose a Langevin equation that accounts for the effects of non-commutativity and we find new interesting features. The equation resembles the structure of Brownian motion in the presence of a magnetic field and implies that the fluctuations along non-commutative directions are correlated. Moreover, our results show that the viscosity is smaller than the commutative case and that the diffusion properties of the quark are unaffected by non-commutativity. Finally, we compute the random force autocorrelator and verify that the fluctuation-dissipation theorem holds in the presence of non-commutativity.Comment: 34 pages. v2: typos corrected. v3: title and abstract slightly modified in order to better reflect the contents of the paper; footnote 3 and one reference were also added; version accepted for publication in JHE

Bilateral ischemic optic neuropathy after transurethral prostatic resection: a case report

BACKGROUND: Nonarteritic ischemic optic neuropathy affects the anterior portion of the optic nerve and is characterized by sudden, painless visual loss. The affected eye has a relative afferent pupillary defect. The typical funduscopic appearance includes optic disc edema, with associated nerve fiber layer hemorrhage. Risk factors include advanced age, systemic hypertension, nocturnal hypotension, diabetes mellitus, and a small cup-to-disc ratio. Bilateral presentation is rare. Postoperative optic neuropathy has been associated with nonocular surgery; risk factors include a combination of prolonged surgical times, acute systemic hypotension, anemia due to blood loss, or prone positioning. We report for the first time a patient with bilateral, simultaneous anterior ischemic optic neuropathy after elective transurethral prostatic resection. CASE PRESENTATION: A 66-year old man underwent surgery for benign prostatic hyperplasia. The preoperative blood pressure was 140/85 mmHg, hemoglobin 15.9 g/dL, and hematocrit 48.6%. Two hours postoperatively, the blood pressure, hemoglobin, and hematocrit dropped dramatically. One day later, transient horizontal diplopia developed. Funduscopy showed a congenitally small cup-to-disc ratio without papillary edema. Other ocular findings were unremarkable. By 4 days postoperatively, sudden and painless amaurosis bilaterally developed when the patient awoke with nausea and vomiting. Visual acuity was no light perception bilaterally. The optic discs were swollen with small hemorrhages. Scans of the head and orbits and electrolyte levels were normal. There were no responses on visual evoked potentials bilaterally. The blood pressure was 90/50 mm Hg, the hemoglobin 7.0 g/dL, and the hematocrit 22.9%, necessitating infusion of three units of packed red blood cells. The blood pressure, hematocrit, and hemoglobin increased to normal levels. Three months later the visual acuity remained no light perception. The pupils were unreactive and there was marked optic disc atrophy bilaterally. CONCLUSION: Bilateral and simultaneous acute ischemic optic neuropathy may be a rare but devastating surgical complication. The combination of anemia and hypotension may increase the risk of anterior ischemic optic neuropathy postoperatively after transurethral prostatic resection

Mobocertinib (TAK-788) in EGFR Exon 20 Insertion+ Metastatic NSCLC: Patient-Reported Outcomes from EXCLAIM Extension Cohort.

Mobocertinib, an oral, first-in-class epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor selective for EGFR exon 20 insertions (ex20ins), achieved durable responses in adults with previously treated EGFR ex20ins+ metastatic non-small cell lung cancer (mNSCLC) in the EXCLAIM extension cohort of a phase 1/2 study (N = 96; NCT02716116). We assessed patient-reported outcomes (PROs) with mobocertinib 160 mg once daily (28-day cycles) in EXCLAIM (N = 90) with the European Organisation for Research and Treatment of Cancer Core Quality-of-Life Questionnaire (EORTC QLQ-C30) v3.0, lung cancer module (QLQ-LC13), EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) questionnaire, and selected PRO Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaire. Median treatment duration was 6.8 (range, 0.0-18.8) months (median follow-up: 13.0 [0.7-18.8] months; data cutoff: 1 November 2020). Clinically meaningful improvements in lung cancer symptoms measured by EORTC QLQ-LC13 were observed for dyspnea (54.4% of patients), cough (46.7%), and chest pain (38.9%), evident at cycle 2 and throughout treatment (least-squares mean [LSM] changes from baseline: dyspnea, -3.2 [p = 0.019]; cough, -9.3 [p < 0.001]; chest pain, -8.2 [p < 0.001]). EORTC QLQ-C30 results indicated no statistically significant changes in global health status/quality of life (LSM change from baseline: -1.8 [p = 0.235]). On symptom scores, significant worsening from baseline was observed for diarrhea (LSM change from baseline: +34.1; p < 0.001) and appetite loss (+6.6; p = 0.004), while improvements were observed for dyspnea (LSM change from baseline: -5.1 [p = 0.002]), insomnia (-6.5 [p = 0.001]), and constipation (-5.7 [p < 0.001]). EQ-5D-5L health status was maintained. Common PRO-CTCAE symptoms were diarrhea, dry skin, rash, and decreased appetite (mostly low grade); in the first 24 weeks of treatment, 64.4% of patients had worsening diarrhea frequency and 67.8% had worsening dry skin severity. Overall, PROs with mobocertinib showed clinically meaningful improvement in lung cancer-related symptoms, with health-related quality of life maintained despite changes in some adverse event symptom scales

Lattice potentials and fermions in holographic non Fermi-liquids: hybridizing local quantum criticality

We study lattice effects in strongly coupled systems of fermions at a finite density described by a holographic dual consisting of fermions in Anti-de-Sitter space in the presence of a Reissner-Nordstrom black hole. The lattice effect is encoded by a periodic modulation of the chemical potential with a wavelength of order of the intrinsic length scales of the system. This corresponds with a highly complicated "band structure" problem in AdS, which we only manage to solve in the weak potential limit. The "domain wall" fermions in AdS encoding for the Fermi surfaces in the boundary field theory diffract as usually against the periodic lattice, giving rise to band gaps. However, the deep infrared of the field theory as encoded by the near horizon AdS2 geometry in the bulk reacts in a surprising way to the weak potential. The hybridization of the fermions bulk dualizes into a linear combination of CFT1 "local quantum critical" propagators in the bulk, characterized by momentum dependent exponents displaced by lattice Umklapp vectors. This has the consequence that the metals showing quasi-Fermi surfaces cannot be localized in band insulators. In the AdS2 metal regime, where the conformal dimension of the fermionic operator is large and no Fermi surfaces are present at low T/\mu, the lattice gives rise to a characteristic dependence of the energy scaling as a function of momentum. We predict crossovers from a high energy standard momentum AdS2 scaling to a low energy regime where exponents found associated with momenta "backscattered" to a lower Brillioun zone in the extended zone scheme. We comment on how these findings can be used as a unique fingerprint for the detection of AdS2 like "pseudogap metals" in the laboratory.Comment: 42 pages, 5 figures; v2, minor correction, to appear in JHE