Planning for the Regeneration of Towns and Cities

This chapter looks at urban regeneration in the UK and the challenges it presents. It introduces an overview of the concept of urban regeneration, trying to define what that field of policy has come to mean, what actions it implies and what issues it raises, considering that it is mostly delivered by private-led development operations. The second section of the chapter looks at two key challenges for planners involved in regeneration: the capture of development value to pay for public goods and social and economic policy objectives, as well as participation and accountability. It concludes with reflections about the skills required from those involved to make urban regeneration effective and fair

Initial experience with targeted axillary dissection after neoadjuvant therapy in breast cancer patients

Background: Targeted axillary dissection (TAD) combines sentinel node biopsy (SNB) with the removal of the previously marked metastatic node. TAD is a promising concept for axillary restaging in node-positive breast cancer patients with pathological complete response (pCR) to neoadjuvant therapy (NAT). We aimed to evaluate TAD feasibility in this context. Methods: A prospective observational study was conducted in biopsy-confirmed cN1 patients. The removal of the clipped node (CN) was guided by intraoperative ultrasound. SNB used indocyanine green and patent blue V dye. If the CN or sentinel lymph nodes (SLN) had any metastatic foci, or the TAD procedure was unsuccessful, the patient underwent axillary lymph node dissection (ALND). Results: Thirty-seven patients were included. TAD and SNB identification rates were 97.3%. Every retrieved CN was also a SLN. At the individual level, SNB identification rate was 89.2% with indocyanine green and 85.5% with patent blue V dye. The CN identification rate was 81.1%, being higher when the CN was localized on the intraoperative ultrasound (84.4% vs 60.0%). Nodal pCR was achieved by 54.1% of our patients and was more frequent in HER2-positive and triple-negative tumors (p = 0.039). Nineteen patients were spared from ALND. Conclusion: TAD with intraoperative ultrasound-guided excision of the CN and SNB with indocyanine green and patent blue V dye is a feasible concept to identify patients without axillary residual disease after NAT, that can be spared from ALND, although the need for marking the biopsied node should be further investigated. © 2022, The Author(s), under exclusive licence to The Japanese Breast Cancer Society

Phred-Phrap package to analyses tools: a pipeline to facilitate population genetics re-sequencing studies

BACKGROUND: Targeted re-sequencing is one of the most powerful and widely used strategies for population genetics studies because it allows an unbiased screening for variation that is suitable for a wide variety of organisms. Examples of studies that require re-sequencing data are evolutionary inferences, epidemiological studies designed to capture rare polymorphisms responsible for complex traits and screenings for mutations in families and small populations with high incidences of specific genetic diseases. Despite the advent of next-generation sequencing technologies, Sanger sequencing is still the most popular approach in population genetics studies because of the widespread availability of automatic sequencers based on capillary electrophoresis and because it is still less prone to sequencing errors, which is critical in population genetics studies. Two popular software applications for re-sequencing studies are Phred-Phrap-Consed-Polyphred, which performs base calling, alignment, graphical edition and genotype calling and DNAsp, which performs a set of population genetics analyses. These independent tools are the start and end points of basic analyses. In between the use of these tools, there is a set of basic but error-prone tasks to be performed with re-sequencing data. RESULTS: In order to assist with these intermediate tasks, we developed a pipeline that facilitates data handling typical of re-sequencing studies. Our pipeline: (1) consolidates different outputs produced by distinct Phred-Phrap-Consed contigs sharing a reference sequence; (2) checks for genotyping inconsistencies; (3) reformats genotyping data produced by Polyphred into a matrix of genotypes with individuals as rows and segregating sites as columns; (4) prepares input files for haplotype inferences using the popular software PHASE; and (5) handles PHASE output files that contain only polymorphic sites to reconstruct the inferred haplotypes including polymorphic and monomorphic sites as required by population genetics software for re-sequencing data such as DNAsp. CONCLUSION: We tested the pipeline in re-sequencing studies of haploid and diploid data in humans, plants, animals and microorganisms and observed that it allowed a substantial decrease in the time required for sequencing analyses, as well as being a more controlled process that eliminates several classes of error that may occur when handling datasets. The pipeline is also useful for investigators using other tools for sequencing and population genetics analyses

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

Effects of the functional HOTAIR rs920778 and rs12826786 genetic variants in glioma susceptibility and patient prognosis

Abnormal expression of the long non-coding RNA HOX transcript antisense intergenic RNA (HOTAIR) is oncogenic in several human cancers, including gliomas. The HOTAIR single nucleotide polymorphisms (SNPs) rs920778 (C > T) and rs12826786 (C > T) present in the intronic enhancer and promoter regions of HOTAIR, respectively, are associated with expression, cancer susceptibility, and patient prognosis in some tumor types. However, the relevance of these HOTAIR SNPs has not been studied in glioma. Here, we report a case-control study comprising 177 Portuguese glioma patients and 199 cancer-free controls. All subjects were genotyped by PCR and restriction fragment length polymorphism (RFLP). No statistically significant differences were found in the genotype or allele distributions of either rs920778 or rs12826786 between glioma patients and controls, suggesting these SNPs are not associated with glioma risk. No significant associations were found between rs920778 variants and HOTAIR expression levels, while rs12826786 CT genotype was associated with increased intratumoral HOTAIR RNA levels when compared to TT genotype (p-value = 0.04). Univariate (Log-rank) and multivariate (Cox proportional) analyses showed both rs920778 CT and rs12826786 CT genotypes were significantly associated with longer overall survival of WHO grade III anaplastic oligodendroglioma patients. Our results suggest that HOTAIR SNPs rs920778 and rs12826786 do not play a significant role in glioma susceptibility, but may be important prognostic factors in anaplastic oligodendroglioma patients. Future studies are warranted to validate and expand these findings, and to further dissect the importance of these SNPs in glioma.info:eu-repo/semantics/publishedVersio

Feeding spectra and activity of the freshwater crab Trichodactylus kensleyi (Decapoda: Brachyura: Trichodactylidae) at La Plata basin

Background: In inland water systems, it is important to characterize the trophic links in order to identify the ‘trophic species’ and, from the studies of functional diversity, understand the dynamics of matter and energy in these environments. The aim of this study is to analyze the natural diet of Trichodactylus kensleyi of subtropical rainforest streams and corroborate the temporal variation in the trophic activity during day hours. Results: A total of 15 major taxonomic groups were recognized in gut contents. The index of relative importance identified the following main prey items in decreasing order of importance: vegetal remains, oligochaetes, chironomid larvae, and algae. A significant difference was found in the amount of full stomachs during day hours showing a less trophic activity at midday and afternoon. The index of relative importance values evidenced the consumption of different prey according to day moments. Results of the gut content indicate that T. kensleyi is an omnivorous crab like other trichodactylid species. Opportunistic behavior is revealed by the ingestion of organisms abundant in streams such as oligochaetes and chironomid larvae. The consumption of allochthonous plant debris shows the importance of this crab as shredder in subtropical streams. However, the effective assimilation of plant matter is yet unknown in trichodactylid crabs. Conclusions: This research provides knowledge that complements previous studies about trophic relationships of trichodactylid crabs and supported the importance of T. kensleyi in the transference of energy and matter from benthic community and riparian sources to superior trophic levels using both macro- and microfauna.Fil: Williner, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Humanidades y Ciencias; ArgentinaFil: de Azevedo Carvalho, Debora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Collins, Pablo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin

Effect of binder on performance of intumescent coatings

This study investigates the role of the polymeric binder on the properties and performance of an intumescent coating. Waterborne resins of different types (vinylic, acrylic, and styrene-acrylic) were incorporated in an intumescent paint formulation, and characterized extensively in terms of thermal degradation behavior, intumescence thickness, and thermal insulation. Thermal microscopy images of charred foam development provided further information on the particular performance of each type of coating upon heating. The best foam expansion and heat protection results were obtained with the vinyl binders. Rheological measurements showed a complex evolution of the viscoelastic characteristics of the materials with temperature. As an example, the vinyl binders unexpectedly hardened significantly after thermal degradation. The values of storage moduli obtained at the onset of foam blowing (melamine decomposition) were used to explain different intumescence expansion behaviors.Funding for this work was provided by FCT-Fundacao para a Ciencia e Tecnologia (Project PTDC/EQU-EQU/65300/2006), and by FEDER/QREN (project RHED) in the - framework of Programa Operacional Factor de Competitividade-COMPETE. Joana Pimenta thanks FCT for PhD Grant SFRH/BDE/33431/2008

Abnormal NK cell lymphocytosis detected after splenectomy: association with repeated infections, relapsing neutropenia, and persistent polyclonal B-cell proliferation

Abnormal NK cell lymphocytosis detected after splenectomy: association with repeated infections, relapsing neutropenia, and persistent polyclonal B-cell proliferation. Granjo E, Lima M, Fraga M, Santos F, Magalhães C, Queirós ML, Moreira I, Rocha S, Silva AS, Rebelo I, Quintanilha A, Ribeiro ML, Candeias J, Orfão A. Department of Hematology, Hospital S. João, Porto, Portugal. [email protected] Abstract We report the case of a boy with hereditary spherocytosis who presented with mild microcytic hypochromic anemia and recurrent leg ulcers that had been present since childhood. Chronic natural killer (NK) cell and B-cell lymphocytosis was detected 1 year after therapeutic splenectomy during investigation of recurrent episodes of neutropenia and persistent lymphocytosis. NK cells proved to be abnormal at immunophenotyping studies, and B-cells were polyclonal and displayed a normal immunophenotype. Genotypic analysis of T-cell receptor (TCR)-beta and TCR-gamma genes showed a germ-line pattern. The clinical course of this patient was characterized by multiple pulmonary infections and amygdalitis. We discuss the potential roles of persistent immune stimulation due to chronic hemolysis and severe leg ulcers and of splenectomy in the origin of NK cell lymphocytosis and the relationship between NK cells and recurrent infections, relapsing neutropenia, and polyclonal B-cell response