How Dual-Energy Contrast-Enhanced Spectral Mammography Can Provide Useful Clinical Information About Prognostic Factors in Breast Cancer Patients: A Systematic Review of Literature

Introduction: In the past decade, a new technique derived from full-field digital mammography has been developed, named contrast-enhanced spectral mammography (CESM). The aim of this study was to define the association between CESM findings and usual prognostic factors, such as estrogen receptors, progesterone receptors, HER2, and Ki67, in order to offer an updated overview of the state of the art for the early differential diagnosis of breast cancer and following personalized treatments. Materials and methods: According to the PRISMA guidelines, two electronic databases (PubMed and Scopus) were investigated, using the following keywords: breast cancer AND (CESM OR contrast enhanced spectral mammography OR contrast enhanced dual energy mammography) AND (receptors OR prognostic factors OR HER2 OR progesterone OR estrogen OR Ki67). The search was concluded in August 2021. No restriction was applied to publication dates. Results: We obtained 28 articles from the research in PubMed and 114 articles from Scopus. After the removal of six replicas that were counted only once, out of 136 articles, 37 articles were reviews. Eight articles alone have tackled the relation between CESM imaging and ER, PR, HER2, and Ki67. When comparing radiological characterization of the lesions obtained by either CESM or contrast-enhanced MRI, they have a similar association with the proliferation of tumoral cells, as expressed by Ki-67. In CESM-enhanced lesions, the expression was found to be 100% for ER and 77.4% for PR, while moderate or high HER2 positivity was found in lesions with non-mass enhancement and with mass closely associated with a non-mass enhancement component. Conversely, the non-enhancing breast cancer lesions were not associated with any prognostic factor, such as ER, PR, HER2, and Ki67, which may be associated with the probability of showing enhancement. Radiomics on CESM images has the potential for non-invasive characterization of potentially heterogeneous tumors with different hormone receptor status. Conclusions: CESM enhancement is associated with the proliferation of tumoral cells, as well as to the expression of estrogen and progesterone receptors. As CESM is a relatively young imaging technique, a few related works were found; this may be due to the "off-label" modality. In the next few years, the role of CESM in breast cancer diagnostics will be more thoroughly investigated

CYP2D6 genotypes in revolving door patients with bipolar disorders: A case series

RATIONALE: In psychiatric disorders, interindividual differences in cytochrome P450 (CYP)2D6 (CYP2D6) enzymatic activity could be responsible of adverse drug reactions (ADRs) and therapeutic failures (TFs) for CYP2D6-metabolized drugs, contributing to the periodical hospital readmissions of the revolving door (RD) condition.PATIENT CONCERNS: We investigated CYP2D6 genotypes in a controlled series of 5 consecutive RD patients with Bipolar Disorder (BD).DIAGNOSES: Psychiatric patients affected by Bipolar Disorder.INTERVENTIONS: We defined TFs as a difference at the Brief Psychiatric Rating Scale score \u394BPRS\u200a<\u200a25% at each 1-week of stable treatment, and ADRs as the onset of extrapyramidal symptoms and/or metabolic impairment with weight gain.OUTCOMES: At 3 months, a mean number of 2.75\u200a\ub1\u200a1.26 ADR and a mean \u394BPRS score of 16.07\u200a\ub1\u200a0.05% were observed. At 6 months of follow-up, compared to the only patient without BD (\u394BPRS\u200a<\u200a32.10%), BD patients (n\u200a=\u200a4) showed TFs (\u394BPRS\u200a<\u200a25%). CYP2D6 genotyping revealed intermediate metabolizer phenotypes for BD patients and an extensive metabolizer phenotype for the patient without BD. In BD patients, the ratio of drugs maintained/discontinued for TFs or ADRs was 1.75 for non-CYP2D6 versus 0.33 for CYP2D6 interacting drugs, while the proportion of ADR:TF was 0:4 versus 6:3.LESSONS: Our findings may suggest that CYP2D6 clinically relevant genotypes may be involved in the unwanted outcomes observed in RD patients with BD

Critical Discourse Analysis of Media Texts

El volumen presenta una panorámica del Análisis Crítico del Discurso de los textos mediáticos. El Análisis Crítico del Discurso es un modelo que parte de la Lingüística Crítica, basada a su vez en la Gramática Funcional de M. A. K. Halliday. En el volumen se resumen los principales enfoques de esta teoría. El volumen está compuesto de diversos artículos en los que se analizan diferentes casos concretos de los discursos de los medios de comunicación de masas (discurso informativo, discurso publicitario, discurso televisivo y discurso fílmico)The volume presents an overview of Critical Discourse Analysis of media texts. Critical Discourse Analysis is a framework departing from Critical Linguistics, which is based, in turn, on Functional Grammar as developed by M. A. K. Halliday. In this volume several approaches to Critical Discourse Analysis are summed up. In addition, the volume is composed by several papers where diverse concrete cases of media discourses are analysed (news discourse, advertisement discourse, television discourse and filmic discourse

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10−12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10−14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10−103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10−49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10−93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10−23 and OR = 3.39, P = 5.2 × 10−82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20–37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population