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We develop a dynamic model of corporate investment and financing, in which shocks to the value of collateralizable assets generate variation in firms’ debt capacity. We show that the degree of similarity among firms’ financial flexibility forecasts cross-sectional variation in return correlation. We test the implications of the model with firm-level data in two empirical analyses using i) an instrumental variable approach based on shocks to the value of collateralizable corporate assets and ii) the outbreak of the COVID-19 crisis as an event study. We find that firms in the same percentile of the cross-sectional distribution of financial flexibility have 62% higher correlation in stock-return residuals than firms 50 percentiles apart.

Objective It is reported that recovery from COVID-19 chemosensory deficit generally occurs in a few weeks, although olfactory dysfunction may persist longer. Here, we provide a detailed follow-up clinical investigation in a very young female patient (17-year-old) with a long-lasting anosmia after a mild infection, with partial recovery 15 months after the onset. Methods Neuroimaging and neurophysiologic assessments as well as olfactory mucosa swabbing for microbiological and immunocytochemical analyses were performed. Olfactory and gustatory evaluations were conducted through validated tests. Results Chemosensory evaluations were consistent with anosmia associated with parosmia phenomena and gustatory impairment, the latter less persistent. Brain MRI (3.0 T) showed no microvascular injury in olfactory bulbs and brain albeit we cannot rule out slight structural abnormalities during the acute phase, and a high-density EEG was negative. Immunocytochemistry of olfactory mucosa swabs showed high expression of ACE2 in sustentacular cells and lower dot-like cytoplasmic positivity in neuronal-shaped cells. Discussion The occurrence of long-term persistent olfactory deficit in spite of the absence of structural brain and olfactory bulb involvement supports the view of a possible persistent dysfunction of both sustentacular cells and olfactory neurons. The gustatory dysfunction even if less persisting for the described features could be related to a primary gustatory system involvement. Future longitudinal studies are needed to investigate the persistence of chemosensory impairment, which could have a relevant impact on the daily life. Supplementary Information The online version contains supplementary material available at 10.1007/s10072-021-05635-y.

Objective: Vestibular schwannoma (VS) is a benign tumor of the lateral skull base. Different microscopic surgical techniques are described in literature: the retrosigmoid and translabyrinthine approaches are used to treat big tumors located in the cerebellopontine angle, and the middle cranial fossa approach is utilized for small tumors with good hearing preservation. The expanded transcanal transpromontorial (ExpTT) approach is a combined microscopic-endoscopic technique previously indicated for Koos stage I and II VS and now proposed for larger VS, up to 3 cm in diameter, with linear progression into the cerebellopontine angle and touching the brainstem. Study Design: The study was a retrospective case series of patients who underwent ExpTT surgery for VS in our ear, nose, and throat department. Setting: We reviewed the surgical videos and electrophysiologic data recorded during the surgical operations. Subjects and Methods: From January 2015 to January 2017, 20 patients affected by Koos stage II and III VS underwent surgery in our department with the ExpTT approach. This novel technique is described step by step, with a focus on the surgical procedure and anatomic landmarks; outcomes are detailed in terms of early and late complications. The mean follow-up was 15 months. Results: The ExpTT approach permitted, in all patients, gross total resection of the tumor without any complication and with preservation of facial nerve function. All patients had a good postoperative recovery. Conclusion: The ExpTT technique is a new approach that combines the advantages of a microscopic technique with the ones offered by the endoscope in removal of VS.

Introduction: Malocclusion is a pathology which has caused by multifactorial factores, being related to a lot of factors, as breastfeeding and deleterious oral habits. Objectives: The objective of this work was to verify the prevalence and association between time and type of breastfeeding with the installation of deleterious oral habits and consequential malocclusions. Materials and Methods: This is a transversal-type, observational, descriptive study, which evaluated 297 children, aged from three to five years, enrolled in municipal kindergartens. The first phase was carried out with a form directed to parents and guardians and collected information on the lactation period, presence of deleterious oral habits (DOH) and socioeconomic data. The second step consisted of the clinical occlusal examination of children whose parents or guardian had signed the Informed Consent Form and that were within the inclusion criteria of the survey. The data analysis was conducted at a level of significance of 5% through the tests χ2 and odds ratio, the OddsRatio were determined by formula OR = ad/bc, both processed in the software SPSS version 14.0. Results: Deleterious oral habits had a prevalence of 96.6% in the sample, the average time of exclusive breastfeeding was 4.57 months. The habit of highest incidence was the bottle suction, present in 69% of children, but the pacifier was the main responsible for developing malocclusions. Conclusion: The obtained data allow concluding that the breastfeeding time influenced directly the presence of deleterious oral habits and malocclusions in the primary dentition, and that digital sucking habits, pacifier sucking and baby’s bottle are associated with malocclusions in the studied population. Key words: Breastfeeding, Children, Habits, Malocclusion, Oral Health.

Objective: Complex middle and inner ear malformations are considered an important limitation for cochlear implant (CI) with traditional microscopic techniques. The aim of the present study is to describe the results of the endoscopic-assisted CI procedure in children with malformed ears. Study Design: Case series with chart review of consecutive patients. Setting: Two tertiary referral centers: University Hospital of Verona and University Hospital of Modena, Italy. Subjects and Methods: In total, 25 children underwent endoscopic-assisted cochlear implantation between January 2013 and January 2018. The audiologic and neuroradiologic assessment showed profound hearing loss and malformation of the middle and inner ear in all children. A complete review of anatomic features, surgical results, and audiologic outcomes was performed. The surgical technique is described step-by-step, and the outcomes are detailed. Results: All patients (mean age, 3.6 years; range, 2.8-9 years) underwent a transattical/endoscopic-assisted CI procedure. All children showed varying degrees of auditory benefit, as measured by routine audiometry, speech perception tests, and Categories of Auditory Performance scores (mean, 6). No immediate or late postoperative complications were noted. Conclusion: The endoscopic-assisted approach proved to be successful in cochlear implantation. The direct visualization and magnification allow (1) exploration of the tympanic cavity; (2) confirmation of all anatomic features, with strict control of the course of the facial nerve, round window area, and inner ear; and (3) performance of the cochleostomy with adequate insertion of the array.

Based on qualitative data collected for broader research on the transformation of hotel labour in Venice, Italy, this study explores how workers and unions have experienced outsourcing carried out through cooperatives of convenience (COC). The authors examine the impact of outsourcing on work processes, highlighting its link with growing standardisation and increased managerial control. In contrast to studies that underscore the critical effects of outsourcing on solidarity and the employment system, this article stresses that, even in a sector characterised by union weakness, workers, especially unorganised migrants, develop resistance strategies within the workplace as well as paths of mobilisation.

Objective The detection of prion seeding activity in CSF and olfactory mucosal brushings using real‐time quaking‐induced conversion assays allows highly accurate clinical diagnosis of sporadic Creutzfeldt–Jakob disease. To gauge transmission risks associated with these biospecimens and their testing, we have bioassayed prion infectivity levels in patients’ brain tissue, nasal brushings, and CSF, and assessed the pathogenicity of amplified products of real‐time quaking‐induced conversion assays seeded with Creutzfeldt–Jakob disease prions. Methods We obtained olfactory mucosal brushings and CSF from patients with a final diagnosis of sporadic Creutzfeldt–Jakob disease subtype MM1 (n = 3). Samples were inoculated intracerebrally into Tg66 transgenic mice that overexpress the homologous human 129M prion protein. The mice were evaluated for clinical, neuropathological, and biochemical evidence of prion infection. Results Patients’ brain tissue at 102 to 105 fold dilutions affected 47/48 Tg66 mice. In contrast, maximum acutely tolerable doses of insoluble pellets from their olfactory mucosa brushings caused evidence of prion disease in only 4/28 inoculated mice, and no effects were seen with 10‐fold dilutions. No clinical prion disease was observed in mice inoculated with antemortem CSF samples or prion‐seeded real‐time quaking‐induced conversion assay products. Interpretation Pellets from patients’ olfactory mucosa brushings had ≥10,000‐fold lower infectivity per unit volume than brain tissue, while CSF lacked detectable infectivity. Nonetheless, the results suggest that appropriate precautions may be warranted in surgical interventions involving the olfactory areas. The lack of pathogenic infectivity in the real‐time quaking‐induced conversion assay products provides evidence that the assay does not replicate biohazardous prions in vitro.

Genome-wide association studies (GWAS) and candidate pathway studies have identified low-penetrant genetic variants associated with cutaneous melanoma. We investigated the association of melanoma-risk variants with primary melanoma tumor prognostic characteristics and melanoma-specific survival. The Genes, Environment, and Melanoma Study enrolled 3285 European origin participants with incident invasive primary melanoma. For each of 47 melanoma-risk single nucleotide polymorphisms (SNPs), we used linear and logistic regression modeling to estimate, respectively, the per allele mean changes in log of Breslow thickness and odds ratios for presence of ulceration, mitoses, and tumor-infiltrating lymphocytes (TILs). We also used Cox proportional hazards regression modeling to estimate the per allele hazard ratios for melanoma-specific survival. Passing the false discovery threshold (p = 0.0026) were associations of IRF4 rs12203592 and CCND1 rs1485993 with log of Breslow thickness, and association of TERT rs2242652 with presence of mitoses. IRF4 rs12203592 also had nominal associations (p < 0.05) with presence of mitoses and melanoma-specific survival, as well as a borderline association (p = 0.07) with ulceration. CCND1 rs1485993 also had a borderline association with presence of mitoses (p = 0.06). MX2 rs45430 had nominal associations with log of Breslow thickness, presence of mitoses, and melanoma-specific survival. Our study indicates that further research investigating the associations of these genetic variants with underlying biologic pathways related to tumor progression is warranted.

Background For the detection of cardiac surgery-associated acute kidney injury (CS-AKI), the performance of urine tissue inhibitor of metalloproteinase 2 insulin-like growth factor-binding protein 7 (TIMP2 IGFBP7) has never been compared with that of very early changes in plasma creatinine (∆pCr). We hypothesized that, in the context of perioperative haemodilution, lack of postoperative decrease in pCr would be of honourable performance for the detection of CS-AKI. We therefore aimed at comparing these biomarkers and their kinetics (primary objective). As secondary objectives, we assessed plasma neutrophil gelatinase-associated lipocalin (pNGAL), cystatin C (pCysC) and urea (pUrea). We also determined the ability of these biomarkers to early discriminate persistent from transient CS-AKI. Methods Patients over 75 years-old undergoing aortic valve replacement with cardiopulmonary bypass (CPB) were included in this prospective observational study. Biomarkers were measured before/after CPB and at the sixth postoperative hour (H6). Results In 65 patients, CS-AKI occurred in 27 (42%). ∆pCr from post-CPB to H6 (∆pCrpostCPB-H6): outperformed TIMP2 IGFBP7 at H6 and its intra- or postoperative changes: area under the receiver operating characteristic curve (AUCROC) of 0.84 [95%CI:0.73–0.92] vs. ≤0.67 [95%CI:0.54–0.78], p ≤ 0.03. The AUCROC of pNGAL, pCysC and pUrea did not exceed 0.72 [95%CI:0.59–0.83]. Indexing biomarkers levels for blood or urine dilution did not improve their performance. Combining TIMP2 IGFBP7 and ∆pCrpostCPB-H6 was of no evident added value over considering ∆pCrpostCPB-H6 alone. For the early recognition of persistent CS-AKI, no biomarker outperformed ∆pCrpostCPB-H6 (AUCROC = 0.69 [95%CI:0.48–0.85]). Conclusions In this hypothesis-generating study mostly testing early detection of mild CS-AKI, there was no evident added value of the tested modern biomarkers over early minimal postoperative changes in pCr: despite the common perioperative hemodilution in the setting of cardiac surgery, if pCr failed to decline within the 6 h after CPB, the development of CS-AKI was likely. Confirmatory studies with more severe forms of CS-AKI are required.

Introducao A biosseguranca e um conjunto de medidas que busca reduzir os riscos inerentes a uma determinada atividade. Essa area de conhecimento e definida pela Agencia Nacional de Vigilância Sanitaria (Anvisa) como: “condicao de seguranca alcancada por um conjunto de acoes destinadas a prevenir, controlar, reduzir ou eliminar riscos inerentes as atividades que possam comprometer a saude humana, animal e o meio ambiente”. E relevante o entendimento das responsabilidades pertinentes para assegurar a cultura da biosseguranca e sua disseminacao tao quanto a valorizacao presente no ambiente laboratorial, visto que e a partir desta compreensao que surgem as modificacoes corretas nas atitudes, no comportamento e na reorganizacao do processo administrativo. O objetivo deste estudo foi avaliar a implementacao dos procedimentos de biosseguranca laboratorial nas Agencias Transfusionais (AT), os quais contribuirao para proporcionar um ambiente seguro para os funcionarios, clientes. Objetivo Avaliar e analisar os procedimentos de biosseguranca em AT. Material e metodos Foi realizado um estudo transversal com dados retrospectivos e analise dos dados contidos nos roteiros de inspecao da RDC 34/2014, realizados em ATs de uma regiao do nordeste brasileiro. Resultados Na analise realizada a partir dos roteiros de inspecao nas AT observou-se que os residuos biologicos sao depositados nas lixeiras com saco plastico de cor branca com o simbolo de infectante, e os residuos comuns armazenados em saco preto ou azul. Com relacao aos Equipamentos de Protecao Individuais (EPI's), sao disponibilizados e utilizados em todas AT, porem em 02 AT os oculos de protecao individual nao apresentavam boa vedacao periferica e boa adaptacao ao rosto. Ja no que concerne ao chuveiro de emergencia utilizado em acidente que envolvem o lancamento de uma grande quantidade de substâncias quimicas sobre o profissional nenhuma das agencias dispunham conforme tabela. Discussao Portanto, torna-se evidente as praticas de biosseguranca devido as exposicoes a agentes patogenos, superficies sujas com amostras biologicas, equipamentos contaminados, nos quais o profissional pode se contaminar e transferir essa contaminacao para outras pessoas. Dessa forma, faz-se necessario o acesso dos trabalhadores a informacoes sobre os riscos inerentes as suas atividades, alem de ter conhecimento sobre os EPIs e as medidas preventivas e corretivas. Conclusao Dessa forma, destaca-se a importância dos residuos biologicos da coleta sanguinea em ATs, no âmbito dos servicos de saude, e faz-se necessario o conhecimento sobre os conceitos, classicacao e gerenciamento desse tipo de residuo, uma vez que as condicoes de seguranca ambiental e ocupacional sao requisitos imprescindiveis a serem observados por todos os responsaveis pelos estabelecimentos de saude.

Introducao Uma das principais manifestacoes clinicas das hemofilias, especialmente as graves, sao os hematomas, principalmente as hemartroses. Elas sao de hemorragias intra-articulares que ocorrem desde os primeiros anos de vida. Estima-se que mais de 80% de todos os casos de hemorragias em portadores de hemofilia grave sejam intra-articulares. Ao longo do tempo, a recorrencia das hemartroses levam a ativacao de enzimas liticas e fibrose, gerando dano articular permanente, o que causa varios niveis de incapacidade fisica. Os demais sangramentos geralmente acontecem em episodios isolados, principalmente apos algum trauma ocorrido. OBJETIVO: O presente estudo teve como objetivo analisar as manifestacoes clinicas da hemofilia dos pacientes atendidos no ambulatorio de uma regiao do nordeste brasileiro. Material e metodos A pesquisa constitui-se de uma analise retrospectiva a partir de informacoes dos prontuarios de pacientes portadores de hemofilia A que foram atendidos no setor ambulatorial em uma regiao do nordeste brasileiro, durante o periodo de janeiro de 2018 a marco de 2020. Resultados Foram avaliados 100 prontuarios de pacientes portadores de hemofilia A atendidos no ambulatorio destes, foram selecionados 17% (17), levando-se em consideracao os pacientes que apresentam aloanticorpos inibidores do fator VIII. Dos pacientes diagnosticados, 18% (3) apresentam inibidores de alta titulacao e, dentre eles, 67% (2) apresentam a forma grave da doenca e 33% (1) apresentam a forma leve; dentre os 82% (14) dos pacientes que apresentam inibidores de baixa titulacao, por sua vez, 64% (9) tem a forma grave da doenca, 21% (3) tem a forma leve e 14% (2) apresentam a forma moderada (grafico 1). Dos sintomas apresentados pelos pacientes que apresentaram inibidores, todos apresentaram hemartrose e hematomas, e entre aqueles que desenvolveram algum tipo de artropatia: 80% (8) eram da forma grave e 20% (2) tinham hemofilia leve; enquanto isso, entre os que sofreram algum sangramento gengival: 60% (6) tinham a forma grave e 40% (4) tinham a leve. Discussao Uma das principais manifestacoes clinicas das hemofilias, especialmente as graves, sao os hematomas, principalmente as hermatroses. Elas sao de hemorragias intra-articulares que ocorrem desde os primeiros anos de vida. Estima-se que mais de 80% de todos os casos de hemorragias em portadores de hemofilia grave sejam intra-articulares. Ao longo do tempo, a recorrencia das hermatroses levam a ativacao de enzimas liticas e fibrose, gerando dano articular permanente, o que causa varios niveis de incapacidade fisica. Os demais sangramentos geralmente acontecem em episodios isolados, principalmente apos algum trauma ocorrido. Conclusao Nesse sentido, esta pesquisa pode ser utilizada como importante ferramenta para que a instituicao obtenha uma melhor compreensao acerca das manifestacoes clinicas dos pacientes portadores de hemofilia A atendidos.

The emergence of the new Brazilian variant of concern, P.1 lineage (Gamma), raised concern about its impact on the epidemiological profile of COVID-19 cases due to its higher transmissibility rate and immune evasion ability. Using 272 whole-genome sequences combined with epidemiological data, we showed that P.1 introduction in São José do Rio Preto, São Paulo, Brazil, was followed by the displacement of eight circulating SARS-CoV-2 variants and a rapid increase in prevalence two months after its first detection. Our findings support that the P.1 variant is associated with an increase in mortality risk and severity of COVID-19 cases in younger aged groups, which corresponds to the unvaccinated population at the time. Moreover, our data highlight the beneficial effects of vaccination indicated by a pronounced reduction of severe cases and deaths in immunized individuals, reinforcing the need for rapid and massive vaccination.

Primary hyperoxaluria (PH) is a rare disease, autosomal recessive inheritance disorder. This disease leads to overproduction of oxalates, and the excretation inability results in deposition of calcium oxalate crystals in almost all tissues presenting the oxalosis condition. The treatment is a combined liver and kidney transplantation (CLKT), which enables a better patient survival. Due to this survival, the patients had could present a several oral manifestations such as periodontal disease, root resorption, dental pain and increased tooth mobility. However, currently, there is a lack of information in the literature about all oral manifestations that this patient can present. Beside this, there are doubt and challenge about treatments to this patient in these different oral manifestations. The present study aims to report a case of a patient with hyperoxaluria type I with oxalosis oral manifestations. La hiperoxaluria primaria (HP) es una enfermedad rara, un trastorno hereditario autosómico recesivo. Esta enfermedad conduce a la sobreproducción de oxalatos y la incapacidad de excreción da como resultado el depósito de cristales de oxalato de calcio en casi todos los tejidos que presentan la condición de oxalosis. El tratamiento es un trasplante combinado de hígado y riñón (TCHR), que permite una mejor supervivencia del paciente. Debido a esta supervivencia los pacientes pudieron presentar diversas manifestaciones bucales como enfermedad periodontal, reabsorción radicular, dolor dentario y aumento de la movilidad dentaria. Sin embargo, hasta la fecha, existe una falta de información en la literatura sobre todas las manifestaciones bucales que puede presentar este paciente. Además de esto, tengo una duda y un desafío sobre los tratamientos a este paciente en estas diferentes manifestaciones orales. El presente estudio tiene como objetivo reportar el caso de un paciente con hiperoxaluria tipo I con manifestaciones orales de oxalosis. A hiperoxalúria primária (HP) é uma doença rara de herança autossômica recessiva. Essa doença leva à superprodução de oxalatos, e a incapacidade de excreção resulta na deposição de cristais de oxalato de cálcio em quase todos os tecidos que apresentam a condição de oxalose. O tratamento é o transplante combinado de fígado e rim (TCFR), que permite melhor sobrevida do paciente. Devido a esta sobrevida os pacientes puderam apresentar diversas manifestações bucais como doença periodontal, reabsorção radicular, dor dentária e aumento da mobilidade dentária. Porém, até o momento, faltam informações na literatura sobre todas as manifestações orais que esse paciente pode apresentar. Ao lado disso temos uma dúvida e um desafio quanto aos tratamentos a esse paciente nessas diferentes manifestações orais. O presente trabalho tem como objetivo relatar um caso de uma paciente com hiperoxalúria tipo I, apresentando manifestações orais de oxalose.

Introduction Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder persisting in adulthood in 40-60% of cases. Clinical and neuroimaging studies suggest that patients affected by both drug addiction and ADHD show higher rates of craving for drug than patients without ADHD. We designed a pilot open-label study to investigate the effects of ADHD on craving for heroin in methadone maintenance therapy patients. Method Patients were recruited from outpatient facilities in an addiction treatment unit in the municipality of Alba, Italy. They were assessed using the Structured Clinical Interview for DSM-5 (SCID-5), the SCID-5 for Personality Disorders (SCID-5-PD), the Diagnostic Interview for Adult ADHD, second edition (DIVA 2.0), and the Clinical Opiate Withdrawal Scale (COWS). Categorical variables were examined using the chi-square test, and continuous variables, the t-test and Mann-Whitney’s U test for normally and non-normally distributed data, respectively. Data distribution was evaluated using Shapiro-Wilk’s test. Significance was set at p=0.05. Bonferroni correction was applied (0.0063) to avoid type I error. Results A total of 104 patients were included in the study: 14 affected by ADHD (13.5%) and 90 were not affected (86.5%). Patients with ADHD showed higher intensity of craving for heroin than patients without ADHD in the absence of withdrawal symptoms. Conclusion Drug addiction and ADHD share various neurobiological mechanisms that mutually influence the evolution of both disorders. In particular, dopamine dysfunction within various brain circuits may influence impulsivity levels, motivation, inhibitory control, executive functions, and behavior and, consequently, the intensity of craving.

BRAF and NRAS mutations arise early in melanoma development, but their associations with low-penetrance melanoma susceptibility loci remain unknown. In the Genes, Environment and Melanoma Study, 1,223 European-origin participants had their incident invasive primary melanomas screened for BRAF/NRAS mutations and germline DNA genotyped for 47 single-nucleotide polymorphisms identified as low-penetrant melanoma-risk variants. We used multinomial logistic regression to simultaneously examine each single-nucleotide polymorphism's relationship to BRAF V600E, BRAF V600K, BRAF other, and NRAS+ relative to BRAF-/NRAS- melanoma adjusted for study features. IRF4 rs12203592*T was associated with BRAF V600E (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.43-0.79) and V600K (OR = 0.65, 95% CI = 0.41-1.03), but not BRAF other or NRAS+ melanoma. A global test of etiologic heterogeneity (Pglobal = 0.001) passed false discovery (Pglobal = 0.0026). PLA2G6 rs132985*T was associated with BRAF V600E (OR = 1.32, 95% CI = 1.05-1.67) and BRAF other (OR = 1.82, 95% CI = 1.11-2.98), but not BRAF V600K or NRAS+ melanoma. The test for etiologic heterogeneity (Pglobal) was 0.005. The IRF4 rs12203592 associations were slightly attenuated after adjustment for melanoma-risk phenotypes. The PLA2G6 rs132985 associations were independent of phenotypes. IRF4 and PLA2G6 inherited genotypes may influence melanoma BRAF/NRAS subtype development.

Integrated tunable lasers based on the co-integration of InP-based SOAs with low-loss Si3N4 dielectric waveguides have emerged as promising solutions in applications where the control of light phase is fundamental. Μicrowave photonics, coherent communications and LIDARs are only some of the applications where sub-KHz linewidths have already been achieved. Nevertheless, the majority of these demonstrations are based on Si3N4 platforms featuring thicknesses lower than 300nm and providing modes with effective indices below 1.6 imposing a major restriction on the achievable FSR values and devices’ footprint. In this work, we present the design of Vernier ring-inspired reflectors based on an 800nm- thick Si3N4 platform providing a TE fundamental mode with an effective index close to 1.71 for a width of 800nm, a group index close to 2.08 at λ=1550nm wavelength, and propagation losses as low as 0.2dB/cm. The proposed thick- Si3N4 designs are based on a simple dual ring Vernier configuration achieving an experimental FSR near 38nm and a 15dB side-mode suppression. These results are in close agreement with the ones obtained theoretically through a detailed Transfer Matrix Formulation verifying the accuracy of the presented semi-analytical model. This simulation model is then employed for the prediction of the performance of more advanced structures such as triple cascaded and high-order Vernier Ring designs, towards extending the achievable FSR and SMSR metrics.

In this work, we present the design process and experimental evaluation of a 1×2 asymmetric power splitters based on the self-imaging principle that is applied on an ultra-low-loss 800nm thick Si3N4 platform. The asymmetry in the multimode interference region is induced by removing a rectangular piece from the edge of the coupler, prompting a disruption at the interference pattern and adjusting accordingly the splitting power ratio. The design of the MMIs operating in the 1500- 1600nm wavelength region was realized through 3D-FDTD calculation method and the experimental results agree with theory providing an error of 5% in splitting ratio and less than -0.6dB insertion losses.

In an effort to understand the difference between melanomas diagnosed in Australia (New South Wales) and Canada, where the incidence in New South Wales is almost three times greater than in Canada, and mortality is twice as high although survival is slightly more favorable, we had one pathologist review 1,271 melanomas from British Columbia and Ontario, Canada, to compare these to melanomas in New South Wales, Australia. We hypothesized that histopathologic characteristics might provide insight into divergent pathways to melanoma development. We found a number of differences in risk factors and tumor characteristics between the two geographic areas. There were higher mole counts and darker phenotypes in the Canadian patients, while the Australian patients had greater solar elastosis, more lentigo maligna melanomas, and more tumor infiltrating lymphocytes. We hypothesize that the differences observed may illustrate different etiologies – the cumulative exposure pathway among Australian patients and the nevus pathway among Canadian patients. This is one of the largest studies investigating the divergent pathway hypothesis and is particularly robust due to the evaluation of all lesions by one dermatopathologist.

Introducao A HPN e um disturbio clonal causado por uma mutacao adquirida no gene PIGA das celulas-tronco hematopoieticas. O gene PIGA, localizado no cromossomo X, codifica uma proteina que e parte integral da formacao da âncora de glicosilfosfatidilinositol (GPI) para proteinas de membrana. Mutacoes no PIGA resultam na perda de todas as proteinas ancoradas no GPI, como a CD59, uma importante proteina reguladora do complemento, na superficie dos eritrocitos. Como consequencia, as celulas ficam suscetiveis a ativacao pelo complemento, levando a hemolise intravascular continua. Objetivo Relatar um caso de Anemia Aplastica, com a associacao a Hemoglobinuria Paroxistica Noturna (HPN), enfatizando os aspectos fisiopatologicos, clinicos, diagnosticos e tratamento. Material e metodos Trata-se de um estudo de carater exploratorio transversal por meio da analise dos prontuarios e resultados de exames. Resultados Paciente feminino de 54 anos, com diagnostico (AA) severa sintomatica (resposta da serie granulocitica e plaquetaria apos o uso de imunossupressor (ciclosporina), apresentando associado a anemia, DHL elevado, aumento da bilirrubina indireta e teste de coombs negativo, com citometria de fluxo positiva HPN, demonstrando que 33% das hemacias apresentam perda total de expressao de CD59 (populacao HPN III). Da mesma forma, 86% dos neutrofilos apresentam perda de expressao CD24 e aerolisina, em 91% dos monocitos apresentam perda de expressao de CD14 e aerolisina. Na ocasiao do tratamento a paciente teve necessidade transfusional (hemacias filtradas) em decorrer da AA. No decorrer do monitoramento apresentou diminuicao das plaquetas associada a astenia, sangramento retal, leucopenia, tendo necessidade transfusional para manter a homeostasia. Foi tratado com ciclosporina pelo quadro da anemia aplastica severa e em seguida foi administrado Eculizumabe em tratamento continuo de periodicidade semanal dentro de quatro semanas (fase de inducao) seguindo de periodo quinzenal apos a quinta semana (fase de manutencao) no tratamento especifico para HPN. Discussao A situacao da paciente e grave por caracteristica propria da doenca base, porem em resposta ao tratamento apresentou melhoras no quadro clinico e na qualidade de vida, obtendo melhoras da anemia sintomatica e amenizando o quadro de dor abdominal e necessidade transfusional, permitindo a paciente retomar as atividades domestica e laborais. Conclusao O conhecimento precoce da doenca (AA) e HPN, beneficiara o paciente no tratamento e na melhoria da qualidade de vida minimizando os riscos de sequelas graves.

Introducao Desde a percepcao do novo coronavirus (SARS-CoV-2), responsavel pela disseminacao do surto descoberto pela primeira vez na cidade de Wuhan, China, em dezembro de 2019, a raca humana tem vivenciado um dificil problema sanitario global, arrodeadas de exatidao no que diz respeito aos caracteres epidemiologicos, sorologicos e sua facilidade de se disseminar. As infeccoes relacionadas a assistencia a saude tem ocorrencia em varias em instituicoes assistenciais de saude, tanto em paises desenvolvidos como subdesenvolvidos, acometendo aproximadamente 1,4 milhoes de pacientes em todo o mundo, resultando em altos numeros morbimortalidade, prolongamento do tempo de internacao, resistencia de microrganismos e obitos. Apresentam diversas causas e tem varias relacoes multifatoriais. A higienizacao das maos retrata a conduta apartada primordial como tatica de minimizacao da incidencia das infeccoes ambulatoriais e hospitalares. Objetivo O objetivo deste estudo foi orientar os profissionais do setor de ambulatorio de um centro de Hemoterapia no periodo de 10 a 26 de fevereiro de 2020, com intuito de melhorar os metodos de limpeza e higienizacao e prevencao acerca da COVID-19. Material e metodos Foi realizado um treinamento teorico atraves do Google Met., que e um servico de comunicacao por video desenvolvido pelo Google. O treinamento foi realizado em cinco modulos com carga horaria 30h com os funcionarios envolvendo o preenchimento do check-list, baseado no manual Seguranca do Paciente em Servicos de Saude, Higienizacao das Maos da Agencia Nacional de Vigilância Sanitaria. Resultados Dos 32 funcionarios que executam suas atividades profissionais no setor de transfusao e ambulatorio que responderam o instrumento de pesquisa, 75% (24) eram do sexo feminino e 25% (08) do sexo masculino. O nivel de formacao academica variou entre os docentes: 9,3% (3) sao Enfermeiros, Farmaceuticos 6,2 (02), Tecnicos de Enfermagem 18,7% (06), Assistente administrativo 15,6% (05), Assistente social 3,1% (01), Psicologa 3,1% (01), Fisioterapeuta 3,1% (01), Dentista 6,2% (02), Estagiarios 34,3% (11). Discussao Neste estudo observou-se que a higienizacao e o uso de luvas associaram-se a uma menor velocidade de contaminacao das maos durante cuidados rotineiros nos setores laboratoriais e no ambulatorio evitando a contaminacao da maioria dos profissionais de saude. Conclusao Esta acao deve ser constantemente desenvolvida na pratica educacional, alem de abordagem aprofundada referente a prevencao e controle de infeccoes como estrategia de promocao da seguranca do paciente.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease characterized by progressive myocardial fibro-fatty replacement, arrhythmias and risk of sudden death. Its diagnosis is challenging and often it is achieved after disease onset or postmortem. In this study, we sought to identify circulating microRNAs (miRNAs) differentially expressed in ARVC patients compared to healthy controls. In the pilot study, we screened the expression of 754 miRNAs from 21 ARVC patients and 20 healthy controls. After filtering the miRNAs considering a log fold-change cut-off of ±1, p-value &lt, 0.05, we selected five candidate miRNAs for a subsequent validation study in which we used TaqMan-based real-time PCR to analyse samples from 37 ARVC patients and 30 healthy controls. We found miR-185-5p significantly upregulated in ARVC patients. Receiver operating characteristic analysis indicated an area under the curve of 0.854, corroborating the link of this miRNA and ARVC pathophysiology.

This work is aimed at illustrating the strict relationship between a general definition of concentration function appeared quite some time ago on this journal and a widely used measure of the diagnostic strength of a family of binary classifiers indexed by a threshold parameter, the so-called ROC curve. The ROC curve is a common work tool in Statistics, Machine Learning and Artificial Intelligence, appearing in many applications where a binary classification (diagnosis) procedure is of interest. Hence, it is worth remarking that diagnostic strength and concentration are two sides of the same coin: the higher the concentration of one probability measure with respect to another, the higher the diagnostic strength of the likelihood ratio classification rule.

We report a simple implementation of integrated polarization rotator for thick-film SiN platform for S-/C-/L- bands operation. The fabricated devices show high polarization conversion efficiency above 90% and broadband operation.

The aim of this paper is to extend discussion on subcontracted labour by focussing on the labour process and on the role of race and racialization within it. The existing literature has so far analysed the factors that have encouraged employer decisions to outsource labour, together with its effects on labour conditions and on industrial relations. Missing, however, has been any detailed analysis of the role of race and racialization processes, pivotal elements in the facilitation of subcontracting thereby accelerating the worsening of labour conditions. Based on qualitative empirical research on the meat industry in Northern Italy, this article highlights how the processes of outsourcing and racialization intersect to support the segmentation of labour within the workplace. In particular, we argue that, through contracting out work to racialized groups of migrant workers, outsourcing has been both facilitated and legitimized. Furthermore, the presence of in-plant contractors has fostered the implementation of racializing practices, which in turn have bolstered workforce fragmentation on racial lines. Notwithstanding this, our findings show that race can be a factor in the mobilization of subcontracted migrant labour through the production of pragmatic (racial) solidarities. These informal ties are a key component in the development of the everyday struggles and alliances that emerge within grass roots worker organisations as well as beyond their boundaries through hybrid forms of collective organisation.

Background The transcanal transpromontorial approach has been introduced to remove vestibular schwannomas. As with other techniques, preservation of the facial nerve (FN) is challenging. This pilot study described FN outcomes of patients preoperatively and postoperatively assessed with electromyography (EMG) and blink reflex (BR). Methods Between September 2017 and December 2018, 10 patients (5 men; 5 women; mean age, 59.8 years; age range, 25–77 years) underwent removal of vestibular schwannoma via the transcanal transpromontorial approach. FN assessment using EMG/BR and clinical evaluation with the House-Brackmann (HB) grading scale was performed preoperatively and 2 months postoperatively. If facial impairment was present postoperatively, further analysis was performed 6 months after surgery. Results All 10 patients had normal FN function on preoperative EMG/BR. After 2 months, 4 patients had normal FN function on EMG/BR, 4 patients showed a slight delay of FN responses, 1 patient had moderate dysfunction, and 1 patient had consistent damage. After 6 months, among the 6 patients with a pathologic neurophysiologic study, consistent EMG/BR improvement was shown, with complete recovery in 3 cases. At the last follow-up, 8 patients had HB grade I, 1 patient had HB grade II, and 1 patient had HB grade III in 1, showing progression toward healing in 9 of 10 cases. Conclusions The transcanal transpromontorial approach is an effective procedure for vestibular schwannoma removal. EMG/BR represents an objective evaluation method to verify FN recovery after surgery and confirms the low impact of this surgical procedure on the FN.

BackgroundThe excellent surgical results obtained with transnasal endoscopic approach to the anterior skull base (ASB) are universally recognized; less is known about the quality of life of patients after surgery.ObjectiveThe aim of this study is to analyze the quality of life of patients after endoscopic transnasal surgery for the treatment of neoplasms of the ASB.MethodsWe conducted a retrospective review of patients who underwent transnasal endoscopic surgery for treatment of ASB tumors at the Tertiary Referral Center University Hospital of Verona. All patients were asked to complete the Anterior Skull Base Questionnaire (ASBQ), the Skull Base Inventory (SBI), and the Sino-nasal Outcome Test – 22 Items (SNOT-22) after surgical treatment. The study population was divided into subgroups; a statistical analysis of the overall results and of the different questionnaire domains was performed.Results51 patients were enrolled in this study. The average score was 3.04 for ASBQ, 4.05 for SBI and 28.88 for SNOT-22. Analysis of the overall results for the ASBQ showed a lower quality of life in patients after recurrent surgery and in female patients. The SBI showed similar results in relation to recurrent surgery and radiotherapy. Similarly, the results for SNOT-22 highlighted the negative impact of recurrent surgery and radiotherapy.ConclusionOur results confirmed that the endoscopic transnasal approach shows excellent results not only in terms of surgical outcome, but also for the possibility of ensuring a good QoL after treatment. Recurrent surgery and radiation treatments were the most important negative prognostic factors.

Objectives Preoperative breast magnetic resonance imaging (MRI) can inform surgical planning but might cause overtreatment by increasing the mastectomy rate. The Multicenter International Prospective Analysis (MIPA) study investigated this controversial issue. Methods This observational study enrolled women aged 18–80 years with biopsy-proven breast cancer, who underwent MRI in addition to conventional imaging (mammography and/or breast ultrasonography) or conventional imaging alone before surgery as routine practice at 27 centers. Exclusion criteria included planned neoadjuvant therapy, pregnancy, personal history of any cancer, and distant metastases. Results Of 5896 analyzed patients, 2763 (46.9%) had conventional imaging only (noMRI group), and 3133 (53.1%) underwent MRI that was performed for diagnosis, screening, or unknown purposes in 692/3133 women (22.1%), with preoperative intent in 2441/3133 women (77.9%, MRI group). Patients in the MRI group were younger, had denser breasts, more cancers ≥ 20 mm, and a higher rate of invasive lobular histology than patients who underwent conventional imaging alone (p p p p Conclusions Clinicians requested breast MRI for women with a higher a priori probability of receiving mastectomy. MRI was associated with 11.3% more mastectomies, and with 3.2% fewer reoperations in the breast conservation subgroup. Key Points • In 19% of patients of the MIPA study, breast MRI was performed for screening or diagnostic purposes. • The current patient selection to preoperative breast MRI implies an 11% increase in mastectomies, counterbalanced by a 3% reduction of the reoperation rate. • Data from the MIPA study can support discussion in tumor boards when preoperative MRI is under consideration and should be shared with patients to achieve informed decision-making.

The procedure for salvage total laryngectomy (STL) is burdened by a high rate of postoperative complications as a result of delayed wound healing in previously irradiated tissue. Several observational studies have investigated the role of prophylactic vascularized flaps to aid pharyngeal closure after STL and prevent the development of PCF. The use of a temporoparietal fascia free flap (TFFF) as an overlay flap for STL has been described previously in two published studies and both sets of authors agreed that the most obvious benefit of the TFFF in STL is a reduced PCF rate with low site morbidity and good functional outcomes. The aim of this video is to illustrate the use of the temporoparietal fascia flap to provide an adjunctive reinforcement layer in the reconstruction of the pharynx.

In patients with suspected dementia with Lewy bodies, the detection of the disease-associated α-synuclein in easily accessible tissues amenable to be collected using minimally invasive procedures remains a major diagnostic challenge. This approach has the potential to take advantage of modern molecular assays for the diagnosis of α–synucleinopathy and, in turn, to optimize the recruitment and selection of patients in clinical trials, using drugs directed at counteracting α-synuclein aggregation. In this study, we explored the diagnostic accuracy of α-synuclein real-time quaking-induced conversion assay by testing olfactory mucosa and CSF in patients with a clinical diagnosis of probable (n = 32) or prodromal (n = 5) dementia with Lewy bodies or mixed degenerative dementia (dementia with Lewy bodies/Alzheimer’s disease) (n = 6). Thirty-eight patients with non-α-synuclein-related neurodegenerative and non-neurodegenerative disorders, including Alzheimer’s disease (n = 10), sporadic Creutzfeldt–Jakob disease (n = 10), progressive supranuclear palsy (n = 8), corticobasal syndrome (n = 1), fronto-temporal dementia (n = 3) and other neurological conditions (n = 6) were also included, as controls. All 81 patients underwent olfactory swabbing while CSF was obtained in 48 participants. At the initial blinded screening of olfactory mucosa samples, 38 out of 81 resulted positive while CSF was positive in 19 samples out of 48 analysed. After unblinding of the results, 27 positive olfactory mucosa were assigned to patients with probable dementia with Lewy bodies, five with prodromal dementia with Lewy bodies and three to patients with mixed dementia, as opposed to three out 38 controls. Corresponding results of CSF testing disclosed 10 out 10 positive samples in patients with probable dementia with Lewy bodies and six out of six with mixed dementia, in addition to three out of 32 for controls. The accuracy among results of real-time quaking-induced conversion assays and clinical diagnoses was 86.4% in the case of olfactory mucosa and 93.8% for CSF. For the first time, we showed that α-synuclein real-time quaking-induced conversion assay detects α-synuclein aggregates in olfactory mucosa of patients with dementia with Lewy bodies and with mixed dementia. Additionally, we provided preliminary evidence that the combined testing of olfactory mucosa and CSF raised the concordance with clinical diagnosis potentially to 100%. Our results suggest that nasal swabbing might be considered as a first-line screening procedure in patients with a diagnosis of suspected dementia with Lewy bodies followed by CSF analysis, as a confirmatory test, when the result in the olfactory mucosa is incongruent with the initial clinical diagnosis., Perra et al. detected α-synuclein aggregates in olfactory mucosa and CSF samples of patients with dementia with Lewy bodies, using real-time quaking-induced conversion assay. Positivity in unpaired olfactory mucosa and CSF samples was significantly concordant with the clinical diagnosis and nearly 100% in participants in whom paired samples were tested., Graphical Abstract Graphical Abstract

Isolated REM sleep behaviour disorder (RBD) is an early-stage α-synucleinopathy in most, if not all, affected subjects. Detection of pathological α-synuclein in peripheral tissues of patients with isolated RBD may identify those progressing to Parkinson’s disease, dementia with Lewy bodies or multiple system atrophy, with the ultimate goal of testing preventive therapies. Real-time quaking-induced conversion (RT-QuIC) provided evidence of α-synuclein seeding activity in CSF and olfactory mucosa of patients with α-synucleinopathies. The aim of this study was to explore RT-QuIC detection of α-synuclein aggregates in olfactory mucosa of a large cohort of subjects with isolated RBD compared to patients with Parkinson’s disease and control subjects. This cross-sectional case-control study was performed at the Medical University of Innsbruck, Austria, the Hospital Clinic de Barcelona, Spain, and the University of Verona, Italy. Olfactory mucosa samples obtained by nasal swab in 63 patients with isolated RBD, 41 matched Parkinson’s disease patients and 59 matched control subjects were analysed by α-synuclein RT-QuIC in a blinded fashion at the University of Verona, Italy. Median age of patients with isolated RBD was 70 years, 85.7% were male. All participants were tested for smell, autonomic, cognitive and motor functions. Olfactory mucosa was α-synuclein RT-QuIC positive in 44.4% isolated RBD patients, 46.3% Parkinson’s disease patients and 10.2% control subjects. While the sensitivity for isolated RBD plus Parkinson’s disease versus controls was 45.2%, specificity was high (89.8%). Among isolated RBD patients with positive α-synuclein RT-QuIC, 78.6% had olfactory dysfunction compared to 21.4% with negative α-synuclein RT-QuIC (P

Endoscopic ear surgery is a relatively new technique; as for all the surgical procedures on humans in general, it requires an adequate training of manual skills. These abilities should be improved during cadaveric dissection courses, before starting live surgery approaches. Training on cadaveric specimens during training courses enhances the dexterity of the surgeon and provides experience, which are mandatory for a successful performance during surgical procedures. Because of the limited availability of human cadaveric specimens, due to high costs and local regulations, the animal model represents a suitable, cheap, and reliable alternative. In our opinion, the ovine model is suitable to train and develop surgical skills in an education program for otologic surgeons, because it represents a great opportunity to improve instruments maneuvering and recreate a very similar model for the main steps of endoscopic middle ear surgery, if compared to humans.

The steep increase in incidence of cutaneous malignant melanoma in white populations mainly applies to thin lesions with good survival suggesting overdiagnosis. Based on population-based cancer registries (CRs), we have investigated changes in aggressive melanoma, selecting only cases who died within 1 or 3 years after diagnosis in 11 European countries between 1995 and 2012. Trends in fatal cases were analysed by period of diagnosis, sex, tumour thickness, histologic subtype of the lesion, tumour site and CR with a multivariate generalised linear mixed effects model, where geographical area was considered as a random effect. We collected data on 123 360 invasive melanomas, with 5133 fatal cases at 1 year (4%) and 12 330 (10%) at 3 years. The number of fatal cases showed a 16% decrease at 1 year and 8% at 3 years between the first (1995-2000) and the last (2007-2012) period. The highest proportion of fatal cases was seen for men, older age (≥65 years), thick lesions (>1 mm), nodular melanoma, melanoma on the trunk and for poorly documented cases, lacking information about thickness and histologic subtype. The mixed-effects model showed a remarkable variability among European countries. The majority of registries showed a decreasing trend in fatal cases, but a few registries showed an opposite pattern. Trends in fatal melanoma cases, highlighting real changes in risk not related to overdiagnosis, showed a decrease in most European countries, with a few exceptions. Stronger efforts for early detection could lead to a more efficient treatment of melanoma in general.

Open partial laryngectomies still play an important role in contemporary conservative management of laryngeal cancer. A comprehensive and systematic classification of open partial horizontal laryngectomies (OPHLs) was presented by the European Laryngological Society working committee in 2014. The aim of this video is to show the main surgical steps in OPHL using a cadaveric dissection and to explain the modular approach for removal of laryngeal tumors.

Background To enforce the evidence for causality between high-risk human papillomavirus (hrHPV) infections and neck squamous cell carcinoma from unknown primary (NSCCUP) and provide biological basis for treatment de-intensification, we searched for TP53 mutations in association with HPV status. Methods TP53 mutations were searched for by amplification of exons 4 to 10. Results Of the 70 NSCCUP, 27 (39%) harbored HPV infection. TP53 sequencing resulted in the identification of 19 patients harboring single mutations including 16 disruptive alterations (84%). The association of TP53 mutations and HPV could be evaluated in 48 NSCCUP including those with disruptive mutation in any exon (n = 16) and those without mutations but with complete sequence of exons 4 to 9 (n = 32): no disruptive mutations were found in the 17 HPV-driven NSCCUP but in 16 of the 31 non-HPV-driven NSCCUP (P = .0002). Conclusion In a fraction of cases, NSCCUP is an HPV-driven entity harboring wild-type TP53 gene or nondisruptive TP53 mutations. HPV-driven NSCCUP might benefit from treatment de-intensification.

The 2019 coronavirus disease (COVID-19) pandemic has stressed the health care system in Italy as well as around the world, with hospitals implementing their surge capacity to increase the number of available beds for patients positive to the virus.At the end of March, the Piemonte (Northern Italy) Government decided to build a temporary rapid-assembly emergency hospital for the treatment of mild and moderate COVID-19 patients, converting an existing concert hall in the city of Turin. The decision was prompted not only by the urgent need of hospital beds, but also by a forward-looking approach for the months immediately after the emergency, when it will be essential for conventional hospitals to return to a normal configuration.This paper documents the temporary hospital project, describing the site, the layout and the equipment, the idea behind structural choices, and the staff involved. The aim of the work is to share the experience and to provide some practical recommendations to other professionals who are fighting the COVID-19 pandemic worldwide.

Microcombs—optical frequency combs generated in microresonators—have advanced tremendously in the past decade, and are advantageous for applications in frequency metrology, navigation, spectroscopy, telecommunications, and microwave photonics. Crucially, microcombs promise fully integrated miniaturized optical systems with unprecedented reductions in cost, size, weight, and power. However, the use of bulk free-space and fiber-optic components to process microcombs has restricted form factors to the table-top. Taking microcomb-based optical frequency synthesis around 1550 nm as our target application, here, we address this challenge by proposing an integrated photonics interposer architecture to replace discrete components by collecting, routing, and interfacing octave-wide microcomb-based optical signals between photonic chiplets and heterogeneously integrated devices. Experimentally, we confirm the requisite performance of the individual passive elements of the proposed interposer—octave-wide dichroics, multimode interferometers, and tunable ring filters, and implement the octave-spanning spectral filtering of a microcomb, central to the interposer, using silicon nitride photonics. Moreover, we show that the thick silicon nitride needed for bright dissipative Kerr soliton generation can be integrated with the comparatively thin silicon nitride interposer layer through octave-bandwidth adiabatic evanescent coupling, indicating a path towards future system-level consolidation. Finally, we numerically confirm the feasibility of operating the proposed interposer synthesizer as a fully assembled system. Our interposer architecture addresses the immediate need for on-chip microcomb processing to successfully miniaturize microcomb systems and can be readily adapted to other metrology-grade applications based on optical atomic clocks and high-precision navigation and spectroscopy., Key steps towards photonic interposers for integrated optical synthesizers are shown: filters, mixers, linear processing of an octave-spanning microcomb, integration of microcomb and interposer layers, and a system-level feasibility analysis.

Contains fulltext : 225795.pdf (Publisher’s version ) (Closed access) Despite its high diagnostic performance, the use of breast MRI in the preoperative setting is controversial. It has the potential for personalized surgical management in breast cancer patients, but two of three randomized controlled trials did not show results in favor of its introduction for assessing the disease extent before surgery. Meta-analyses showed a higher mastectomy rate in women undergoing preoperative MRI compared to those who do not. Nevertheless, preoperative breast MRI is increasingly used and a survey from the American Society of Breast Surgeons showed that 41% of respondents ask for it in daily practice. In this context, a large-scale observational multicenter international prospective analysis (MIPA study) was proposed under the guidance of the European Network for the Assessment of Imaging in Medicine (EuroAIM). The aims were (1) to prospectively and systematically collect data on consecutive women with a newly diagnosed breast cancer, not candidates for neoadjuvant therapy, who are offered or not offered breast MRI before surgery according to local practice; (2) to compare these two groups in terms of surgical and clinical endpoints, adjusting for covariates. The underlying hypotheses are that MRI does not cause additional mastectomies compared to conventional imaging, while reducing the reoperation rate in all or in subgroups of patients. Ninety-six centers applied to a web-based call; 36 were initially selected based on volume and quality standards; 27 were active for enrollment. On November 2018, the target of 7000 enrolled patients was reached. The MIPA study is presently at the analytic phase. Key Points • Breast MRI has a high diagnostic performance but its utility in the preoperative setting is controversial. • A large-scale observational multicenter prospective study was launched to compare women receiving with those not receiving preoperative MRI. • Twenty-seven centers enrolled more than 7000 patients. The study is presently at the analytic phase.

Isolated REM sleep behaviour disorder is an early-stage α-synucleinopathy in most, if not all, affected subjects. Detection of pathological alpha-synuclein in peripheral tissues of isolated REM sleep behaviour disorder patients may identify those progressing to Parkinson’s disease, dementia with Lewy bodies or multiple system atrophy, with the ultimate goal of testing preventive therapies. Real-Time Quaking-Induced Conversion provided evidence of α-synuclein seeding activity in cerebrospinal fluid and olfactory mucosa of patients with α-synucleinopathies. Aim of this study was to explore Real-Time Quaking-Induced Conversion detection of α-synuclein aggregates in olfactory mucosa of large cohort of subjects with isolated REM sleep behavior disorder compared to Parkinson’s disease and controls.This prospective bicentric case-control study was performed between October 2017 and December 2018 at the Medical University of Innsbruck, Austria, and the Hospital Clinic de Barcelona, Spain. Olfactory mucosa samples obtained by nasal swab in 63 patients with isolated REM sleep behavior disorder, 31 matched Parkinson’s disease patients and 59 matched controls were analysed by α-synuclein Real-Time Quaking-Induced Conversion in a blinded fashion at the University of Verona, Italy. Median age of isolated REM sleep behavior disorder patients was 70 years, 85.7% were male. All participants were tested for smell, autonomic, cognitive and motor functions.Olfactory mucosa was α-synuclein Real-Time Quaking-Induced Conversion positive in 44.4% isolated REM sleep behavior disorder patients, 41.9% Parkinson’s disease and 10.2% controls. While the sensitivity for isolated REM sleep behavior disorder plus Parkinson’s disease versus controls was 40.9%, specificity was high (89.8%). Among isolated REM sleep behavior disorder patients with positive α-synuclein Real-Time Quaking-Induced Conversion, 78.6% had olfactory dysfunction as compared to 21.4% with negative α-synuclein Real-Time Quaking-Induced Conversion, pReal-Time Quaking-Induced Conversion olfactory mucosa isolated REM sleep behavior disorder patients (pWe provide evidence that α-synuclein Real-Time Quaking-Induced Conversion assay enables the molecular detection of neuronal α-synuclein aggregates in olfactory mucosa of patients with isolated REM sleep behavior disorder and Parkinson’s disease. Although the overall sensitivity was moderate in this study, nasal swabbing is attractive as simple, non-invasive test, with a potential of use as screening test to identify subjects in the prodromal stages of α-synucleinopathies. Further studies are needed to enhance sensitivity, and better understand the temporal dynamics of α-synuclein seeding in the olfactory mucosa and spreading to other brain areas during the progression from isolated REM sleep behavior disorder to overt α-synucleinopathy.

Importance The COVID-19 pandemic has resulted in more than 3.5 million cases and 245 thousand deaths worldwide as of May 6, 2020. Determining the extent of the presence of the virus on public surfaces is critical for understanding the potential risk of infection in these areas. Objective To evaluate the presence of SARS-CoV-2 RNA on public surfaces in a densely populated urban area in Brazil. Design and Setting A total of 101 samples were collected from different surfaces in public places in the region of Belo Horizonte with the highest number of COVID-19 cases. Samples were collected near the hospital and public transportation areas using sterile swabs, and then submitted to nucleic acid extraction and genomic detection and quantification by one-step qPCR. Results Seventeen of the 101 samples tested positive (16.8%) for SARS-CoV-2 RNA, including samples from bus stations/terminals, public squares, and sidewalks, including those near hospitals. Conclusions and Relevance Our data indicated the contamination of public surfaces by SARS-CoV-2, especially near hospital areas, highlighting the risk of infection for the population. Constant monitoring of the virus in urban areas is required as a strategy to fight the pandemic and prevent further infections. Key points Question Can SARS-CoV-2 be detected on surfaces in public areas used by a large proportion of the population? Findings SARS-CoV-2 RNA was detected in different locations, including bus stations/terminals, squares, and sidewalks, especially those near hospitals, in a densely populated area of Belo Horizonte, Brazil. Meaning This study highlights the need for constant monitoring for the presence of SARS-CoV-2 RNA in urban areas to support better strategies to fight the COVID-19 pandemic and prevent further infections.

Objective The objective of this study is to describe what we consider to be the state-of-the-art procedure for the treatment of tympanic membrane perforations, and to present the results attained in our institution. Study design A retrospective cohort study, using data of Verona University Hospital, Italy. This medical record includes the data of 98 patients who underwent 100 transcanal endoscopic type I tympanoplasties from November 2014 to October 2017. Setting Tertiary referral center University Hospital of Verona, Italy. Patients Were enrolled 109 patients, that underwent endoscopic type I tympanoplasty in the period considered. Out of the selected patients, 11 (10.1%) were lost to long-term follow-up, and were therefore excluded from our study. Other exclusion criteria were surgical approaches that included other procedures. Patients whose follow-up was shorter than 6 months were excluded from this study. Intervention The technique is based on an endoscopic placement of underlay graft of temporal fascia or tragal cartilage. We consider the data of four surgeons from Verona University ENT department. Main outcome measure In the study we considered the reduction of the Air Bone Gap as functional outcome and the integrity of the reconstruction as anatomical outcome of success. Results No major intraoperative complications were observed. The closure rate was 86%. The mean surgery time was 48.6 minutes. The air bone gap was improved within 20 DB HL in 89% of patient. Only 8% of patients needed revision surgery, and none needed a third surgical evaluation. Conclusion Endoscopic ear surgery is by now a reality that has replaced in many cases exclusive microscopic ear surgery. Transcanal endoscopic type I tympanoplasty can be considered nowadays as an alternative technique for tympanic membrane perforations.

We present a novel approach to generate a frequency comb based on Difference Frequency Generation (DFG). The frequency components required for the DFG process are generated in a Si3N4waveguide. A mode-locked 200 MHz oscillator is amplified in an Erbium-doped fiber, compressed to a duration of 42 fs and coupled into the waveguide. The power for generating the necessary spectral components in the waveguide is reduced by a factor of five compared to a setup based on highly nonlinear fiber.

The early and accurate in vivo diagnosis of sporadic Creutzfeldt&ndash, Jakob disease (sCJD) is essential in order to differentiate CJD from treatable rapidly progressive dementias. Diagnostic investigations supportive of clinical CJD diagnosis include magnetic resonance imaging (MRI), electroencephalogram (EEG), 14-3-3 protein detection, and/or real-time quaking-induced conversion (RT-QuIC) assay positivity in the cerebrospinal fluid (CSF) or in other tissues. The total CSF tau protein concentration has also been used in a clinical setting for improving the CJD diagnostic sensitivity and specificity. We analyzed 182 CSF samples and 42 olfactory mucosa (OM) brushings from patients suspected of having sCJD with rapidly progressive dementia (RPD), in order to determine the diagnostic accuracy of 14-3-3, the total tau protein, and the RT-QuIC assay. A probable and definite sCJD diagnosis was assessed in 102 patients. The RT-QuIC assay on the CSF samples showed a 100% specificity and a 96% sensitivity, significantly higher compared with 14-3-3 (84% sensitivity and 46% specificity) and tau (85% sensitivity and 70% specificity), however, the combination of RT-QuIC testing of the CSF and OM samples resulted in 100% sensitivity and specificity, proving a significantly higher accuracy of RT-QuIC compared with the surrogate biomarkers in the diagnostic setting of patients with RPD. Moreover, we showed that CSF blood contamination or high protein levels might interfere with RT-QuIC seeding. In conclusion, we provided further evidence that the inclusion of an RT-QuIC assay of the CSF and OM in the diagnostic criteria for sCJD has radically changed the clinical approach towards the diagnosis.

We demonstrate multiple silicon-nitride nanophotonic elements for on-chip processing of octave-spanning microresonator frequency combs. Dichroic filters, multimode interferometers, and tunable add-drop microring filters are shown along with soliton microcombs generated on a bilayer photonic chip. (C) 2020 The Author(s)

Traditionally, clinical studies relied on collecting data by hands in paper case report forms (CRFs), which were later entered into an electronic database for statistical analysis. Clearly, this method was time-consuming, prone to misinterpretation, and basically inefficient. These limitations can be currently avoided using electronic data capture (EDC) systems, powerful tools reducing study times and costs and, importantly, enhancing the quality of collected data. Generally, EDC systems use a web-based platform, accessible from any computer or mobile device connected to the Internet. Investigators of a multicenter clinical trial can access the system at any time and at any location, with only the possibility to enter patient data of their own center, being blinded to the other institutions’ data. The administrator has total access to all subjects enrolled by all centers, exclusive rights to extract patient data, and the ability to modify the content of any CRF at any time. EDC systems are still poorly used in breast imaging research and imaging research in general, as handling of images is still insufficiently supported. In this chapter, we provide an overview of the current information technology systems to gather data in the framework of a multicenter clinical trial. A working example is discussed in the specific setting of the use of magnetic resonance imaging (MRI) for breast cancer screening of high-risk women. In addition, the experience of a large international study on preoperative breast MRI is reported. Radiologists and imaging specialists, especially when carrying out spontaneous and/or low-budget research, should be aware of the possibilities offered by these systems.

A osteopatia crânio mandibular (OCM) é uma afecção óssea rara de caráter degenerativo, osteopetrótico, autolimitante, não neoplásico, sem predileção sexual, que acomete cães na fase pré-púbere. As raças mais predispostas são as Terries em destaque para o West Highland White Terrier. Os sinais clínicos são variáveis dependendo dos ossos alterados e do grau de acometimento. Dentre os mais comuns estão febre, dor ao abrir a boca, aumento de volume da mandíbula, hiporexia e sialorreia. Os ossos do crânio são os mais acometidos, em especial, os mandibulares, os das articulações temporomandibulares e as bulas timpânicas. O diagnóstico se baseia nos achados clínicos, radiográficos e histopatológicos. As alterações radiográficas mais comuns são aumento da radiopacidade e volume das mandíbulas e das bulas timpânicas. O tratamento é sintomático, tendo como ponto principal o controle de dor e suporte nutricional. O prognóstico é heterogêneo. Os pacientes podem passar pela remissão completa da afecção ou serem submetidos à eutanásia por anquilose da articulação temporomandibular.

To determine whether (1) computer-based self-training for CT colonography (CTC) improves interpretation performance of novice readers; (2) computer-aided detection (CAD) use during training affects learning. Institutional review board approval and patients’ informed consent were obtained for all cases included in this study. Twenty readers (17 radiology residents, 3 radiologists) with no experience in CTC interpretation were recruited in three centres. After an introductory course, readers performed a baseline assessment test (37 cases) using CAD as second reader. Then they were randomized (1:1) to perform either a computer-based self-training (150 cases verified at colonoscopy) with CAD as second reader or the same training without CAD. The same assessment test was repeated after completion of the training programs. Main outcome was per lesion sensitivity (≥ 6 mm). A generalized estimating equation model was applied to evaluate readers’ performance and the impact of CAD use during training. After training, there was a significant improvement in average per lesion sensitivity in the unassisted phase, from 74% (356/480) to 83% (396/480) (p < 0.001), and in the CAD-assisted phase, from 83% (399/480) to 87% (417/480) (p = 0.021), but not in average per patient sensitivity, from 93% (390/420) to 94% (395/420) (p = 0.41), and specificity, from 81% (260/320) to 86% (276/320) (p = 0.15). No significant effect of CAD use during training was observed on per patient sensitivity and specificity, nor on per lesion sensitivity. A computer-based self-training program for CTC improves readers’ per lesion sensitivity. CAD as second reader does not have a significant impact on learning if used during training. • Computer-based self-training for CT colonography improves per lesion sensitivity of novice readers. • Self-training program does not increase per patient specificity of novice readers. • CAD used during training does not have significant impact on learning.