Metrics with Prescribed Ricci Curvature near the Boundary of a Manifold

Suppose $M$ is a manifold with boundary. Choose a point $o\in\partial M$. We investigate the prescribed Ricci curvature equation \Ric(G)=T in a neighborhood of $o$ under natural boundary conditions. The unknown $G$ here is a Riemannian metric. The letter $T$ in the right-hand side denotes a (0,2)-tensor. Our main theorems address the questions of the existence and the uniqueness of solutions. We explain, among other things, how these theorems may be used to study rotationally symmetric metrics near the boundary of a solid torus $\mathcal T$. The paper concludes with a brief discussion of the Einstein equation on $\mathcal T$.Comment: 13 page

Liquid biopsy for disease monitoring in non-small cell lung cancer: The link between biology and the clinic

Introduction: Cell-free DNA (cfDNA) analysis offers a non-invasive method to identify sensitising and resistance mutations in advanced Non-Small Cell Lung Cancer (NSCLC) patients. Next-generation sequencing (NGS) of circulating free DNA (cfDNA) is a valuable tool for mutations detection and disease' s clonal monitoring. Material and methods: An amplicon-based targeted gene NGS panel was used to analyse 101 plasma samples of advanced non-small cell lung cancer (NSCLC) patients with known oncogenic mutations, mostly EGFR mutations, serially collected at different clinically relevant time points of the disease. Results: The variant allelic frequency (VAF) monitoring in consecutive plasma samples demonstrated different molecular response and progression patterns. The decrease in or the clearance of the mutant alleles was associated with response and the increase in or the emergence of novel alterations with progression. At the best response, the median VAF was 0% (0.0% to 3.62%), lower than that at baseline, with a median of 0.53% (0.0% to 9.9%) (p = 0.004). At progression, the VAF was significantly higher (median 4.67; range: 0.0–36.9%) than that observed at the best response (p = 0.001) and baseline (p = 0.006). These variations anticipated radiographic changes in most cases, with a median time of 0.86 months. Overall, the VAF evolution of different oncogenic mutations predicts clinical outcomes. Conclusion: The targeted NGS of circulating tumour DNA (ctDNA) has clinical utility to monitor treatment response in patients with advanced lung adenocarcinoma.This work was supported by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020; and by FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the projects “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274), and “Transferencia horizontal de resistencia à terapia: mudança de paradigma na monitorização de pacientes com cancro” (PTDC/DTPPIC/2500/2014); and by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), in the framework of the project NORTE-01-0145-FEDER-000029

Targeted gene next-generation sequencing panel in patients with advanced lung adenocarcinoma: Paving the way for clinical implementation

Identification of targetable molecular changes is essential for selecting appropriate treatment in patients with advanced lung adenocarcinoma. Methods: In this study, a Sanger sequencing plus Fluorescence In Situ Hybridization (FISH) sequential approach was compared with a Next-Generation Sequencing (NGS)-based approach for the detection of actionable genomic mutations in an experimental cohort (EC) of 117 patients with advanced lung adenocarcinoma. Its applicability was assessed in small biopsies and cytology specimens previously tested for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutational status, comparing the molecular changes identified and the impact on clinical outcomes. Subsequently, an NGS-based approach was applied and tested in an implementation cohort (IC) in clinical practice. Using Sanger and FISH, patients were classified as EGFR-mutated (n = 22, 18.8%), ALK-mutated (n = 9, 7.7%), and unclassifiable (UC) (n = 86, 73.5%). Retesting the EC with NGS led to the identification of at least one gene variant in 56 (47.9%) patients, totaling 68 variants among all samples. Still, in the EC, combining NGS plus FISH for ALK, patients were classified as 23 (19.7%) EGFR; 20 (17.1%) KRAS; five (4.3%) B-Raf proto-oncogene (BRAF); one (0.9%) Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2); one (0.9%) STK11; one (0.9%) TP53, and nine (7.7%) ALK mutated. Only 57 (48.7%) remained genomically UC, reducing the UC rate by 24.8%. Fourteen (12.0%) patients presented synchronous alterations. Concordance between NGS and Sanger for EGFR status was very high (¿ = 0.972; 99.1%). In the IC, a combined DNA and RNA NGS panel was used in 123 patients. Genomic variants were found in 79 (64.2%). In addition, eight (6.3%) EML4-ALK, four (3.1%), KIF5B-RET, four (3.1%) CD74-ROS1, one (0.8%) TPM3-NTRK translocations and three (2.4%) exon 14 skipping MET Proto-Oncogene (MET) mutations were detected, and 36% were treatable alterations. Conclusions: This study supports the use of NGS as the first-line test for genomic profiling of patients with advanced lung adenocarcinoma.We acknowledge the work of the members of our department, especially doctors from the thoracic oncology unit, oncology and pulmonology nurses and, patients and their relatives. N. Martins would like to thank the Portuguese Foundation for Science and Technology (FCT-Portugal) for the Strategic project ref. UID/BIM/04293/2013 and "NORTE2020—Northern Regional Operational Program" (NORTE-01-0145-FEDER-000012)

Hospital Resource Utilization and Treatment Cost of Skeletal-Related Events in Patients with Metastatic Breast or Prostate Cancer: Estimation for the Portuguese National Health System

BACKGROUND: Skeletal-related events (SREs) occur frequently in patients with bone metastases as a result of breast (BC) and prostate (PC) cancers. They increase both morbidity and mortality and lead to extensive health-care resource utilization. METHODS: Health care resource utilization by BC/PC patients with at least one SRE during the preceding 12 months was assessed through retrospective chart review. SRE-treatment costs were estimated using the Portuguese Ministry of Health cost database and analyzed using generalized linear models. RESULTS: This study included 152 patients from nine hospitals. The mean (SD) annual SRE-treatment cost per patient was €5963 (€3646) and €5711 (€4347), for BC (n=121) and PC (n=31) patients, respectively. Mean cost per single episode ranged between €1485 (radiotherapy) and €13,203 (spinal cord compression). Early onset of bone metastasis (P = 0.03) and diagnosis of bone metastases at or after the occurrence of the first SRE (P < 0.001) were associated with higher SRE-treatment costs. CONCLUSION: These results reveal the high hospital SRE-treatment costs, highlighting the need for early diagnosis and treatment, and identify key factors determining the economic value of therapies for patients with skeletal metastases

Strengthening of three-leaf stone masonry walls: an experimental research

The paper summarizes the results of an experimental research carried out on three-leaf masonry walls of typical granite stone constructions from the North of Portugal. The research aimed at studying the behaviour under compression of this wall typology, as well as the improvements introduced by common strengthening techniques applied for the structural rehabilitation of masonry heritage buildings. Ten masonry specimens were tested, plain or strengthened by transversal tying of the external leaves, with GFRP bars, or/and by injection of the inner leaf, with a lime-based grout. The results obtained showed that these strengthening techniques were successful in increasing the compressive strength of the walls and in improving their behaviour under compressive loads.The authors would like to thank the technical staff of the Structural Laboratory of University of Minho for the help provided. Acknowledgements are also due to the companies Fradical, Mapei and Augusto de Oliveira Ferreira for providing raw materials and workmanship. Finally, the funding provided by the Portuguese Science and Technology Foundation, through the POCI/ECM/58987/2004 project, is gratefully acknowledged

Do adults with high functioning autism or Asperger Syndrome differ in empathy and emotion recognition?

The present study examined whether adults with high functioning autism (HFA) showed greater difficulties in (i) their self-reported ability to empathise with others and/or (ii) their ability to read mental states in others’ eyes than adults with Asperger syndrome (AS). The Empathy Quotient (EQ) and ‘Reading the Mind in the Eyes’ Test (Eyes Test) were compared in 43 adults with AS and 43 adults with HFA. No significant difference was observed on EQ score between groups, while adults with AS performed significantly better on the Eyes Test than those with HFA. This suggests that adults with HFA may need more support, particularly in mentalizing and complex emotion recognition, and raises questions about the existence of subgroups within autism spectrum conditions

Rapid Susceptibility Testing and Microcolony Analysis of Candida spp. Cultured and Imaged on Porous Aluminum Oxide

Contains fulltext : 124300.pdf (publisher's version ) (Open Access)BACKGROUND: Acquired resistance to antifungal agents now supports the introduction of susceptibility testing for species-drug combinations for which this was previously thought unnecessary. For pathogenic yeasts, conventional phenotypic testing needs at least 24 h. Culture on a porous aluminum oxide (PAO) support combined with microscopy offers a route to more rapid results. METHODS: Microcolonies of Candida species grown on PAO were stained with the fluorogenic dyes Fun-1 and Calcofluor White and then imaged by fluorescence microscopy. Images were captured by a charge-coupled device camera and processed by publicly available software. By this method, the growth of yeasts could be detected and quantified within 2 h. Microcolony imaging was then used to assess the susceptibility of the yeasts to amphotericin B, anidulafungin and caspofungin (3.5 h culture), and voriconazole and itraconazole (7 h culture). SIGNIFICANCE: Overall, the results showed good agreement with EUCAST (86.5% agreement; n = 170) and E-test (85.9% agreement; n = 170). The closest agreement to standard tests was found when testing susceptibility to amphotericin B and echinocandins (88.2 to 91.2%) and the least good for the triazoles (79.4 to 82.4%). Furthermore, large datasets on population variation could be rapidly obtained. An analysis of microcolonies revealed subtle effects of antimycotics on resistant strains and below the MIC of sensitive strains, particularly an increase in population heterogeneity and cell density-dependent effects of triazoles. Additionally, the method could be adapted to strain identification via germ tube extension. We suggest PAO culture is a rapid and versatile method that may be usefully adapted to clinical mycology and has research applications

Ferroelectric nanofibers with an embedded optically nonlinear benzothiazole derivative

We report measurements of the molecular first hyperpolarizability, thermal stability, photophysical, piezoelectric and ferroelectric properties of a benzothiazole derivative bearing an arylthiophene π-conjugated bridge both in solution and when embedded into a poly (L-lactic acid) (PLLA) matrix in the form of electrospun fibers with an average diameter of roughly 500 nm. The embedded nanocrystalline phenylthienyl-benzothiazole derivative, with crystal sizes of about 1.4 nm resulted in a good piezoelectric response from these functionalized electrospun fibers, indicative of a polar crystalline structure.Fundação para a Ciência e a Tecnologia (FCT

On the compressive strength prediction for concrete masonry prisms

The results of a combined experimental program and numerical modeling program to evaluate the behavior of ungrouted hollow concrete blocks prisms under uniaxial compression are addressed. In the numerical program, three distinct approaches have been considered using a continuum model with a smeared approach, namely plane-stress, plane-strain and three-dimensional conditions. The response of the numerical simulations is compared with experimental data of masonry prisms using concrete blocks specifically designed for this purpose. The elastic and inelastic parameters were acquired from laboratory tests on concrete and mortar samples that constitute the blocks and the bed joint of the prisms. The results from the numerical simulations are discussed with respect to the ability to reproduce the global response of the experimental tests, and with respect to the failure behavior obtained. Good agreement between experimental and numerical results was found for the peak load and for the failure mode using the three-dimensional model, on four different sets of block/mortar types. Less good agreement was found for plain stress and plain strain models.The authors would like to acknowledge FAPESP-Sao Paulo State Research Support Foundation-and CAPES-Brazilian Research Support Foundation-for the financial support given to this research

Influence of single and binary doping of strontium and lithium on in vivo biological properties of bioactive glass scaffolds

Effects of strontium and lithium ion doping on the biological properties of bioactive glass (BAG) porous scaffolds have been checked in vitro and in vivo. BAG scaffolds were prepared by conventional glass melting route and subsequently, scaffolds were produced by evaporation of fugitive pore formers. After thorough physico-chemical and in vitro cell characterization, scaffolds were used for pre-clinical study. Soft and hard tissue formation in a rabbit femoral defect model after 2 and 4 months, were assessed using different tools. Histological observations showed excellent osseous tissue formation in Sr and Li + Sr scaffolds and moderate bone regeneration in Li scaffolds. Fluorochrome labeling studies showed wide regions of new bone formation in Sr and Li + Sr doped samples as compared to Li doped samples. SEM revealed abundant collagenous network and minimal or no interfacial gap between bone and implant in Sr and Li + Sr doped samples compared to Li doped samples. Micro CT of Li + Sr samples showed highest degree of peripheral cancellous tissue formation on periphery and cortical tissues inside implanted samples and vascularity among four compositions. Our findings suggest that addition of Sr and/or Li alters physico-chemical properties of BAG and promotes early stage in vivo osseointegration and bone remodeling that may offer new insight in bone tissue engineering