Importance of second-order piezoelectric effects in zincblende semiconductors

We show that the piezoelectric effect that describes the emergence of an electric field in response to a crystal deformation in III-V semiconductors such as GaAs and InAs has strong contributions from second-order effects that have been neglected so far. We calculate the second-order piezoelectric tensors using density functional theory and obtain the piezoelectric field for [111]-oriented In$_x$Ga$_{1-x}$As quantum wells of realistic dimensions and concentration $x$. We find that the linear and the quadratic piezoelectric coefficients have the opposite effect on the field, and for large strains the quadratic terms even dominate. Thus, the piezoelectric field turns out to be a rare example of a physical quantity for which the first- and second-order contributions are of comparable magnitude.Comment: 4 pages, 3 figures, Submitted to Phys. Rev. Let

Covariate-adjusted analysis of the Phase 3 REFLECT study of lenvatinib versus sorafenib in the treatment of unresectable hepatocellular carcinoma.

BACKGROUND: In the Phase 3 REFLECT trial in patients with unresectable hepatocellular carcinoma (uHCC), the multitargeted tyrosine kinase inhibitor, lenvatinib, was noninferior to sorafenib in the primary outcome of overall survival. Post-hoc review revealed imbalances in prognostic variables between treatment arms. Here, we re-analyse overall survival data from REFLECT to adjust for the imbalance in covariates. METHODS: Univariable and multivariable adjustments were undertaken for a candidate set of covariate values that a physician panel indicated could be prognostically associated with overall survival in uHCC. The values included baseline variables observed pre- and post-randomisation. Univariable analyses were based on a stratified Cox model. The multivariable analysis used a "forwards stepwise" Cox model. RESULTS: Univariable analysis identified alpha-fetoprotein (AFP) as the most influential variable. The chosen multivariable Cox model analysis resulted in an estimated adjusted hazard ratio for lenvatinib of 0.814 (95% CI: 0.699-0.948) when only baseline variables were included. Adjusting for post-randomisation treatment variables further increased the estimated superiority of lenvatinib. CONCLUSIONS: Covariate adjustment of REFLECT suggests that the original noninferiority trial likely underestimated the true effect of lenvatinib on overall survival due to an imbalance in baseline prognostic covariates and the greater use of post-treatment therapies in the sorafenib arm. TRIAL REGISTRATION: Trial number: NCT01761266 (Submitted January 2, 2013)

Erratum to: Oncoplastic Breast-Conserving Surgery for Tumors Larger than 2 Centimeters: Is it Oncologically Safe? A Matched-Cohort Analysis

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Fine Mapping of the 1p36 Deletion Syndrome Identifies Mutation of PRDM16 as a Cause of Cardiomyopathy

Deletion 1p36 syndrome is recognized as the most common terminal deletion syndrome. Here, we describe the loss of a gene within the deletion that is responsible for the cardiomyopathy associated with monosomy 1p36, and we confirm its role in nonsyndromic left ventricular noncompaction cardiomyopathy (LVNC) and dilated cardiomyopathy (DCM). With our own data and publically available data from array comparative genomic hybridization (aCGH), we identified a minimal deletion for the cardiomyopathy associated with 1p36del syndrome that included only the terminal 14 exons of the transcription factor PRDM16 (PR domain containing 16), a gene that had previously been shown to direct brown fat determination and differentiation. Resequencing of PRDM16 in a cohort of 75 nonsyndromic individuals with LVNC detected three mutations, including one truncation mutant, one frameshift null mutation, and a single missense mutant. In addition, in a series of cardiac biopsies from 131 individuals with DCM, we found 5 individuals with 4 previously unreported nonsynonymous variants in the coding region of PRDM16. None of the PRDM16 mutations identified were observed in more than 6,400 controls. PRDM16 has not previously been associated with cardiac disease but is localized in the nuclei of cardiomyocytes throughout murine and human development and in the adult heart. Modeling of PRDM16 haploinsufficiency and a human truncation mutant in zebrafish resulted in both contractile dysfunction and partial uncoupling of cardiomyocytes and also revealed evidence of impaired cardiomyocyte proliferative capacity. In conclusion, mutation of PRDM16 causes the cardiomyopathy in 1p36 deletion syndrome as well as a proportion of nonsyndromic LVNC and DCM

Differential Allelic Expression in the Human Genome: A Robust Approach To Identify Genetic and Epigenetic Cis-Acting Mechanisms Regulating Gene Expression

The recent development of whole genome association studies has lead to the robust identification of several loci involved in different common human diseases. Interestingly, some of the strongest signals of association observed in these studies arise from non-coding regions located in very large introns or far away from any annotated genes, raising the possibility that these regions are involved in the etiology of the disease through some unidentified regulatory mechanisms. These findings highlight the importance of better understanding the mechanisms leading to inter-individual differences in gene expression in humans. Most of the existing approaches developed to identify common regulatory polymorphisms are based on linkage/association mapping of gene expression to genotypes. However, these methods have some limitations, notably their cost and the requirement of extensive genotyping information from all the individuals studied which limits their applications to a specific cohort or tissue. Here we describe a robust and high-throughput method to directly measure differences in allelic expression for a large number of genes using the Illumina Allele-Specific Expression BeadArray platform and quantitative sequencing of RT-PCR products. We show that this approach allows reliable identification of differences in the relative expression of the two alleles larger than 1.5-fold (i.e., deviations of the allelic ratio larger than 60∶40) and offers several advantages over the mapping of total gene expression, particularly for studying humans or outbred populations. Our analysis of more than 80 individuals for 2,968 SNPs located in 1,380 genes confirms that differential allelic expression is a widespread phenomenon affecting the expression of 20% of human genes and shows that our method successfully captures expression differences resulting from both genetic and epigenetic cis-acting mechanisms

A cruel pedagogia do vírus: as lições da pandemia à humanidade

A cruel pedagogia do vírus, pequena obra do sociólogo português Boaventura de Sousa Santos, publicada em abril de 2020 pela editora brasileira Boitempo, faz parte de uma coletânea denominada “Pandemia Capital” que visa aprofundar as problemáticas sociais que subjazem à pandemia do coronavírus. O livreto desnuda uma série de questões relacionadas ao Covid-19 e seus desdobramentos sociais, culturais e políticos em âmbito mundial, tendo como pano de fundo os aspectos políticos e econômicos correntes. Como o próprio título sugere, o adjetivo cruel demonstra que a pedagogia do coronavírus tem descortinado e nos ensinado, de maneira um tanto quanto dura, uma série de lições que, ou aprendemos para nos tornarmos seres menos danosos à vida na Terra, ou sucumbiremos mediante nossas más escolhas

A prediction model to refine the timing of an early second-look laparoscopic exploration in patients with colon cancer at high risk of early peritoneal metastasis recurrence.

In patients at high risk of peritoneal metastasis (PM) recurrence following surgical treatment of colon cancer (CC), second-look laparoscopic exploration (SLLE) is mandatory; however, the best timing is unknown. We created a tool to refine the timing of early SLLE in patients at high risk of PM recurrence.info:eu-repo/semantics/publishe