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BACKGROUND: Detecting antibody responses following infection with SARS-CoV-2 is necessary for sero-epidemiological studies and assessing the role of specific antibodies in disease, but serum or plasma sampling is not always viable due to logistical challenges. Dried blood spot sampling (DBS) is a cheaper, simpler alternative and samples can be self-collected and returned by post, reducing risk for SARS-CoV-2 exposure from direct patient contact. The value of large-scale DBS sampling for the assessment of serological responses to SARS-CoV-2 has not been assessed in depth and provides a model for examining the logistics of using this approach to other infectious diseases. The ability to measure specific antigens is attractive for remote outbreak situations where testing may be limited or for patients who require sampling after remote consultation. METHODS: We compared the performance of SARS-CoV-2 anti-spike and anti-nucleocapsid antibody detection from DBS samples with matched serum collected by venepuncture in a large population of asymptomatic young adults (N = 1070) living and working in congregate settings (military recruits, N = 625); university students, N = 445). We also compared the effect of self-sampling (ssDBS) with investigator-collected samples (labDBS) on assay performance, and the quantitative measurement of total IgA, IgG and IgM between DBS eluates and serum. RESULTS: Baseline seropositivity for anti-spike IgGAM antibody was significantly higher among university students than military recruits. Strong correlations were observed between matched DBS and serum samples in both university students and recruits for the anti-spike IgGAM assay. Minimal differences were found in results by ssDBS and labDBS and serum by Bland Altman and Cohen kappa analyses. LabDBS achieved 82.0% sensitivity and 98.2% specificity and ssDBS samples 86.1% sensitivity and 96.7% specificity for detecting anti-spike IgGAM antibodies relative to serum samples. For anti-SARS-CoV-2 nucleocapsid IgG there was qualitatively 100% agreement between serum and DBS samples and weak correlation in ratio measurements. Strong correlations were observed between serum and DBS-derived total IgG, IgA, and IgM. CONCLUSIONS: This is the largest validation of DBS against paired serum for SARS-CoV-2 specific antibody measurement and we have shown that DBS retains performance from prior smaller studies. There were no significant differences regarding DBS collection methods, suggesting that self-collected samples are a viable sampling collection method. These data offer confidence that DBS can be employed more widely as an alternative to classical serology.
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COVID-19 , Humanos , Adulto Jovem , COVID-19/diagnóstico , SARS-CoV-2 , Anticorpos Antivirais , Teste em Amostras de Sangue Seco , Imunoglobulina G , Imunoglobulina A , Imunoglobulina M , Sensibilidade e EspecificidadeRESUMO
Haematopoietic stem cell transplant (HSCT) recipients have deficiencies in their adaptive immunity against vaccine preventable diseases. National and International guidance recommends that HSCT recipients are considered 'never vaccinated' and offered a comprehensive course of revaccination. This position statement aims to draw upon the current evidence base and existing guidelines, and align this with national vaccine availability and licensing considerations in order to recommend a pragmatic and standardised re-vaccination schedule for adult and paediatric HSCT recipients in the UK.
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Transplante de Células-Tronco Hematopoéticas , Leucemia , Adulto , Criança , Humanos , Medula Óssea , Transplantados , Vacinação , VacinasRESUMO
BACKGROUND: Being diagnosed with cancer is challenging. Many patients wish to be actively involved in treatment and contribute to therapy, but the patients' coping abilities and desire for involvement differ. The individual level of resilience seems to play a major role. Our study aims to learn more about the associations of resilience and factors as demographics and psychological factors. METHODS: This multicentric cross-sectional study was conducted in ten oncological centers in Germany in summer 2021. The questionnaire collected information on demographics, resilience, self-efficacy, general satisfaction with life, and sense of coherence. Considered lifestyle-aspects were diet and physical activity. 416 patients were included in the analyses. RESULTS: A moderate mean resilience score was achieved (M = 69). Significant correlations in demographics were found for resilience and education (r = 0.146, p = 0.003), income (r = 0.205, p = 0.001), and time since receiving diagnosis (r = - 0.115, p = 0.021). Resilience and self-efficacy correlated on a high level (r = 0.595, p < 0.001), resilience and sense of coherence, and resilience and general satisfaction with life in a moderate way (r = 0.339, p < 0.001; r = 0.461, p = 0.001). CONCLUSIONS: Resilience portrays an important aspect in cancer treatment. Detecting patients at risk, stabilizing, or improving resilience are important to focus on and strengthen them accordingly. Possible negatively influencing factors (e.g., low self-efficacy) need to be considered. Factors affecting resilience but difficult to influence, as educational background, should be screened for. Also, the combination of low resilience and low income seems to describe a vulnerable patient group.
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Neoplasias , Resiliência Psicológica , Humanos , Estudos Transversais , Adaptação Psicológica , Neoplasias/epidemiologia , Estilo de Vida , Demografia , Inquéritos e QuestionáriosRESUMO
Introduction: Pelvic floor trauma in the form of partial or complete avulsions of the levator ani muscle (LAM) affects 6-42% of women after vaginal birth and can cause tremendous long-term morbidity. Many studies assessed morphological pelvic floor trauma after childbirth but lacked to evaluate women's associated short-term complaints. A proper assessment of trauma and subjective complaints after birth could help to assess possible associations between them and their relevance to women's daily life. Therefore, we aimed to assess women's complaints within the first months after birth in association to their LAM trauma. Materials and Methods: Between 3/2017 and 4/2019, we prospectively evaluated vaginal births of 212 primiparous women with singletons in vertex presentation ≥ 36 + 0 gestational weeks for levator ani muscle (LAM) trauma by translabial ultrasound, for pelvic organ prolapse by clinical examination, and for urogynecological complaints using questionnaires 1-4 days (P1), 6-10 weeks (P2), and 6-9 months (P3) after birth. The questionnaires were self-designed but oriented to and modified from validated questionnaires. Women's complaints were evaluated for P1-P3 according to their LAM trauma state. Results: At P1, 67% of women showed an intact LAM, whereas 14.6% presented a hematoma, 6.6% a partial avulsion (PAV), and 11.8% a complete avulsion (CAV). At P2, 75.9% showed an intact LAM, 9.9% a PAV, and 14.2% a CAV. At P3, 72.9% of women with a LAM trauma in P1 and/or P2 were assessed with 21.6% being intact and 39.2% having a PAV and CAV, respectively. Obstetrical and baseline characteristics differed slightly between the groups. When comparing the time before and during pregnancy with the time after childbirth, birth itself affected women's complaints in all LAM state groups, but the presence of a LAM trauma, especially a CAV, had more negative effects. Conclusions: Vaginal birth changes the anatomical structure of the maternal birth canal and genital tract, and it alters women's perceptions and body function. In our study, LAM trauma did not change these effects tremendously within the first months. Therefore, other maternal, fetal, and obstetrical factors need consideration for the explanation of maternal complaints, in addition to long-term effects of trauma and dysfunction of the LAM and other birth canal structures.
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Diafragma da Pelve , Prolapso de Órgão Pélvico , Feminino , Humanos , Parto , Diafragma da Pelve/diagnóstico por imagem , Diafragma da Pelve/lesões , Prolapso de Órgão Pélvico/etiologia , Gravidez , Estudos Prospectivos , VaginaRESUMO
Observations of key gaseous trace pollutants, namely NO, NOy, CO, SO2 and O3, performed at several curb, residential, industrial, background and free-troposphere sites were analyzed to assess the temporal and spatial variability of pollution in Cyprus. Notably, the analysis utilized one of the longest datasets of 17 years of measurements (2003-2019) in the East Mediterranean and the Middle East (EMME). This region is considered a regional hotspot of ozone and aerosol pollution. A trend analysis revealed that at several stations, a statistically significant decrease in primary pollutant concentration is recorded, most likely due to pollution control strategies. In contrast, at four stations, a statistically significant increase in ozone levels, ranging between 0.36 ppbv y-1 and 0.82 ppbv y-1, has been observed, attributed to the above strategies targeting the reduction of nitrogen oxides (NOx) but not that of Volatile Organic Compounds (VOCs). The NO and NOy, and CO levels at the Agia Marina regional background station were two orders of magnitude and four times lower, respectively, than the ones of the urban centers. The latter denotes that local emissions are not negligible and control a large fraction of the observed interannual and diurnal variability. Speciation analysis showed that traffic and other local emissions are the sources of urban NO and NOy. At the same time, 46 % of SO2 and 40 % of CO, on average, originate from long-range regional transport. Lastly, a one-year analysis of tropospheric NO2 vertical columns from the TROPOMI satellite instrument revealed a west-east low-to-high gradient over the island, with all major hotspots, including cities and powerplants, being visible from space. With the help of an unsupervised machine learning approach, it was found that these specific hotspots contribute overall around 10 % to the total NO2 tropospheric columns.
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Poluentes Atmosféricos , Poluição do Ar , Ozônio , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Chipre , Monitoramento Ambiental , Dióxido de Nitrogênio/análise , Ozônio/análiseRESUMO
BACKGROUND: In patients with axial spondyloarthritis (axSpA), magnetic resonance imaging (MRI) is used to detect bone marrow edema (BME) in sacroiliac joints (SIJ) but SIJ BME are also detected in the population. Not much is known about sex differences in that regard. OBJECTIVE: To explore sex-specific differences associated with the extent of BME in the SIJ suggestive of axSpA in a general population cohort study. METHODS: Taking advantage of 793 recently evaluated MRIs of subjects < 45 years taking part in the SHIP cohort, we used negative-binomial (NB) count data regression to analyze factors associated with the extent of SIJ BME. Predictors were explored by model-based boosting (MBB), a machine learning approach. RESULTS: Estimates of NB regression showed strong effects of sex in interaction with age, BMI, back pain, and particularly HLA-B27. The NB regression model showed incidence rate ratios (IRR) for the main effect of sex (females vs. males): 0.94 [95% CI: 0.63; 1.41], HLA-B27: 4.32 [2.09; 9.8], and for the interaction of sex to HLA-B27: 0.22 [0.06; 0.75]. According to MBB, HLA-B27 positivity, BMI, current smoking, back pain in the last 3 months, the interaction of sex and HLA-B27, and delivery in the last 12 months were of highest importance to explain the extent of SIJ BME. CONCLUSIONS: Different factors were associated with the extent of SIJ BME in females and males. Most importantly, HLA-B27 was relevant only in males but not in females in whom a postpartal state was important. This finding may be relevant for the pathogenesis of axSpA.
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Articulação Sacroilíaca , Espondilartrite , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Articulação Sacroilíaca/diagnóstico por imagem , Articulação Sacroilíaca/patologia , Caracteres Sexuais , Espondilartrite/diagnósticoRESUMO
PURPOSE: Advanced testicular germ cell tumours (GCT) generally have a good prognosis owing to their unique sensitivity towards cisplatin-based chemotherapies. However, cisplatin-resistant GCT have a poor outcome. Further studies are mandatory to better understand resistance mechanisms and develop therapeutic strategies for refractory GCTs. METHODS: Protein levels in cisplatin-resistant GCT cell lines of NTERA-2, NCCIT and 2102EP were analyzed by quantitative proteomic mass spectrometry (MS) in combination with stable isotope labelling by amino acids in cell culture (SILAC). Differentially abundant protein markers of acquired cisplatin resistance were validated by Western blotting. Comprehensive bioinformatical annotation using gene set enrichment analyses (GSEA) and STRING interaction analysis were performed to identify commonly affected pathways in cisplatin resistance and the data were compared to the GCT cohort of the 'The Cancer Genome Atlas'. RESULTS: A total of 4375 proteins were quantified by MS, 144 of which were found to be differentially abundant between isogenic resistant and sensitive cell line pairs (24 proteins for NTERA-2, 60 proteins for NCCIT, 75 proteins for 2102EP). Western blotting confirmed regulation of key resistance-associated proteins (CBS, ANXA1, LDHA, CTH, FDXR). GSEA revealed a statistically significant enrichment of DNA repair-associated proteins in all three resistant cell lines and specific additional processes for individual cell lines. CONCLUSION: High resolution MS combined with SILAC is a powerful tool and 144 significantly deregulated proteins were found in cisplatin-resistant GCT cell lines. Our study provides the largest proteomic in vitro library for cisplatin resistance in GCT, yet, enabling further studies to develop new treatment options for patients with refractory GCT.
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Antineoplásicos , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Espectrometria de Massas , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Proteômica , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologiaRESUMO
This article presents how, based on the availability of new imaging methods and medications, objectives regarding the rheumatic disease axial spondyloarthritis (axSpA) have developed over the course of more than two decades into a rheumatologic research group. During recent years, cooperation with the Study of Health in Pomerania (SHIP) cohort has given rise to new fundamental aspects. This involved intensive cooperation between the Ruhr University Bochum (Rheumazentrum Ruhrgebiet) and the Greifswald University Hospital (Community Medicine research collective). The design of the SHIP cohort was published 10 years ago and the cohort approach presented in the Bundesgesundheitsblatt, which also described central methodologic questions in detail. In 2014, a cooperation project between the Ruhr Rheumatology Center/Ruhr University Bochum and the SHIP Department of Clinical and Epidemiologic Research (Klinisch-Epidemiologische Forschung, KEF; SHIP-KEF) was established, which has already resulted in publication of interesting results in high-ranking journals. In order to stress the potential of such corporations, important contents thereof are presented herein, with a focus on MRI and consideration of historical aspects.
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Artrite Reumatoide , Espondiloartrite Axial , Sacroileíte , Espondilartrite , Espondilite Anquilosante , Estudos de Coortes , Humanos , Imageamento por Ressonância Magnética , Sacroileíte/diagnóstico , Espondilartrite/diagnóstico , Espondilartrite/epidemiologia , Espondilite Anquilosante/diagnósticoRESUMO
The validity of the Brink-Axel hypothesis, which is especially important for numerous astrophysical calculations, is addressed for ^{116,120,124}Sn below the neutron separation energy by means of three independent experimental methods. The γ-ray strength functions (GSFs) extracted from primary γ-decay spectra following charged-particle reactions with the Oslo method and with the shape method demonstrate excellent agreement with those deduced from forward-angle inelastic proton scattering at relativistic beam energies. In addition, the GSFs are shown to be independent of excitation energies and spins of the initial and final states. The results provide a critical test of the generalized Brink-Axel hypothesis in heavy nuclei, demonstrating its applicability in the energy region of the pygmy dipole resonance.
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Borderline personality disorder (BPD) is associated with an elevated mortality risk that is partially attributed to suicide, but few studies examined other possible causes of premature death. The present study compared epicardial adipose tissue (EAT) volume as a known early predictor of premature cardiovascular morbidity, cardiovascular risk indices, and adrenal gland volume (AGV) as an indicator for chronic hypothalamus-pituitary-adrenal (HPA) axis activation in females with borderline personality disorder (BPD), major depressive disorder (MDD) and in healthy individuals. Twenty-eight patients with BPD comorbid with MDD (BPD/MDD), 22 MDD patients and 26 healthy females (CTRL) of comparable age were included. EAT and AGV were assessed by magnetic resonance tomography; 10-year cardiovascular risk and diabetes risk were determined by PROCAM and FINDRISK score; metabolic syndrome was defined following National Cholesterol Education Adult Treatment Panel III R (NCEP/ATP III) criteria. MADRS was used to assess depression severity. After adjustment for age, body mass index (BMI), and physical activity, EAT and AGV were significantly increased in BPD/MDD compared to MDD and CTRL. EAT and AGV displayed a positive correlation. Finally, diabetes risk in BPD/MDD was elevated compared to CTRL and MDD. The present study highlights the increased cardiometabolic risk of BPD patients. We identify EAT accumulation as an early predictor and potential mediator of cardiovascular disease in BPD that appears to be driven at least in part by HPA axis dysregulation. Therefore, interventions that reduce EAT volume (i.e. exercise and diet) should be considered in the clinical management of BPD.
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Transtorno da Personalidade Borderline , Transtorno Depressivo Maior , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , Adulto , Transtorno da Personalidade Borderline/complicações , Transtorno da Personalidade Borderline/diagnóstico por imagem , Transtorno da Personalidade Borderline/epidemiologia , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismoRESUMO
In order to obtain entirely soft bio-inspired robots, fully soft electronic circuits are needed. Dielectric elastomers (DEs) are electroactive polymers that have demonstrated multifunctionality. The same material can achieve different tasks like actuation, sensing, or energy harvesting. It has been shown that basic logic and memory functions can be realized with similar soft structures by combining multiple DE actuators and DE switches. Thus it would be possible to build, with the same materials and processes, a soft structure that mimics a biological being with all these capabilities. This contribution is focused on the modelling of the aforementioned soft electro-mechanical circuit networks. It is here reported the building process of a comprehensive SIMULINK model including the electro-mechanical behaviour of DE logic units and their interconnections. Conventional models deal with a single aspect of DEs, generating complex finite-element simulations. This contribution, based on a former model for an inverter-based DEO, shows how to integrate these various mathematical models and, with the help of direct measurements, create a software representation of DE circuit networks. This work is intended to demonstrate the validity of a recently introduced model and apply it to more complex circuit networks that have a higher number of components. Since, at the present state, the building processes are by hand, adding components generates more variability due to sample-to-sample variation and human error. Despite this, the model still shows a qualitatively good prediction of the devices' behaviour. Furthermore, the introduction of new materials and automatic processes will help to reduce this variability, allowing the model to reach even better performance.
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Biomimética , Robótica , Elastômeros , Eletrônica , Humanos , PolímerosRESUMO
B-cell chronic lymphocytic leukaemia (CLL) is associated with immunosuppression and patients are at increased clinical risk following SARS-CoV-2 infection. Covid-19 vaccines offer the potential for protection against severe infection but relatively little is known regarding the profile of the antibody response following first or second vaccination. We studied spike-specific antibody responses following first and/or second Covid-19 vaccination in 299 patients with CLL compared with healthy donors. 286 patients underwent extended interval (10-12 week) vaccination. 154 patients received the BNT162b2 mRNA vaccine and 145 patients received ChAdOx1. Blood samples were taken either by venepuncture or as dried blood spots on filter paper. Spike-specific antibody responses were detectable in 34% of patients with CLL after one vaccine (n = 267) compared to 94% in healthy donors with antibody titres 104-fold lower in the patient group. Antibody responses increased to 75% after second vaccine (n = 55), compared to 100% in healthy donors, although titres remained lower. Multivariate analysis showed that current treatment with BTK inhibitors or IgA deficiency were independently associated with failure to generate an antibody response after the second vaccine. This work supports the need for optimisation of vaccination strategy in patients with CLL including the potential utility of booster vaccines.
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Anticorpos Antivirais , Formação de Anticorpos/efeitos dos fármacos , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Leucemia Linfocítica Crônica de Células B , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacina BNT162 , COVID-19/sangue , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
Dental care professionals (DCPs) are thought to be at enhanced risk of occupational exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, robust data to support this from large-scale seroepidemiological studies are lacking. We report a longitudinal seroprevalence analysis of antibodies to SARS-CoV-2 spike glycoprotein, with baseline sampling prior to large-scale practice reopening in July 2020 and follow-up postimplementation of new public health guidance on infection prevention control (IPC) and enhanced personal protective equipment (PPE). In total, 1,507 West Midlands DCPs were recruited into this study in June 2020. Baseline seroprevalence was determined using a combined IgGAM enzyme-linked immunosorbent assay and the cohort followed longitudinally for 6 mo until January/February 2021 through the second wave of the coronavirus disease 2019 pandemic in the United Kingdom and vaccination commencement. Baseline seroprevalence was 16.3%, compared to estimates in the regional population of 6% to 7%. Seropositivity was retained in over 70% of participants at 3- and 6-mo follow-up and conferred a 75% reduced risk of infection. Nonwhite ethnicity and living in areas of greater deprivation were associated with increased baseline seroprevalence. During follow-up, no polymerase chain reaction-proven infections occurred in individuals with a baseline anti-SARS-CoV-2 IgG level greater than 147.6 IU/ml with respect to the World Health Organization international standard 20-136. After vaccination, antibody responses were more rapid and of higher magnitude in those individuals who were seropositive at baseline. Natural infection with SARS-CoV-2 prior to enhanced PPE was significantly higher in DCPs than the regional population. Natural infection leads to a serological response that remains detectable in over 70% of individuals 6 mo after initial sampling and 9 mo from the peak of the first wave of the pandemic. This response is associated with protection from future infection. Even if serological responses wane, a single dose of the Pfizer-BioNTech 162b vaccine is associated with an antibody response indicative of immunological memory.
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COVID-19 , Vacinas , Assistência Odontológica , Humanos , SARS-CoV-2 , Estudos Soroepidemiológicos , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Frequently SARS-CoV-2 results in mild or moderate disease with potentially lower concentrations of antibodies compared to those that are hospitalised. Here, we validated an ELISA using SARS-CoV-2 trimeric spike glycoprotein, with targeted detection of IgG, IgA and IgM (IgGAM) using serum and dried blood spots (DBS) from adults with mild or moderate disease. METHODS: Targeting the SARS-CoV-2 trimeric spike, a combined anti-IgG, IgA and IgM serology ELISA assay was developed using 62 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 624 COVID-19 negative samples. The assay was validated using 73 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 359 COVID-19 negative serum samples with an additional 81 DBSs. The assay was further validated in 226 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 426 COVID-19 negative clinical samples. RESULTS: A sensitivity and specificity of 98.6% (95% CI, 92.6-100.0), 98.3% (95% CI, 96.4-99.4), respectively, was observed following validation of the SARS-CoV-2 ELISA. No cross-reactivities with endemic coronaviruses or other human viruses were observed, and no change in results were recorded for interfering substances. The assay was stable at temperature extremes and components were stable for 15 days once opened. A matrix comparison showed DBS to correlate with serum results. Clinical validation of the assay reported a sensitivity of 94.7% (95% CI, 90.9-97.2%) and a specificity of 98.4% (95% CI, 96.6-99.3%). CONCLUSIONS: The human anti-IgGAM SARS-CoV-2 ELISA provides accurate and sensitive detection of SARS-CoV-2 antibodies in non-hospitalised adults with mild or moderate disease. The use of dried blood spots makes the assay accessible to the wider community.
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Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19 , COVID-19 , SARS-CoV-2/metabolismo , Adulto , COVID-19/sangue , COVID-19/diagnóstico , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
In the journal Nature, under the headline "Retire statistical significance", Amrhein et al. called for the concept of statistical significance to be abolished. This appeal, which was signed by about 800 other researchers, triggered a controversial discussion. One reason for the deliberately provocative call is the scientific practice in which the concept of statistical significance is often applied in an incorrect way for yes/no decisions. The criticism is not new and has been repeatedly expressed over the last 50 years. We refer to current and previously published caveats, give an overview of different applications of the concept of statistical significance as well as possible alternatives. We agree in principle with the criticism of the concept expressed by Amrhein et al. but in the absence of agreed alternatives and insufficient consideration of the many different applications of the concept of statistical significance, we consider the demand for its abolition to be exaggerated. A more pragmatic approach to the problem, supported by targeted instructions for scientists and reviewers, seems to be a more appropriate way forward.
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Interpretação Estatística de Dados , Reumatologia , HumanosRESUMO
BACKGROUND: Depression and the experience of early adversity are associated with impairments in interpersonal and social cognitive functioning. The neural mechanisms involved in these impairments remain insufficiently understood. METHODS: In a sample of 48 depressed and 50 healthy participants, we explored seed-to-voxel functional connectivity (FC) during the recall of formative relationship episodes using functional magnetic resonance imaging. RESULTS: While depressive symptoms were associated with increased FC of brain regions that form an introspective socio-affective network, such as the precuneus, bilateral anterior insula, dorsal anterior cingulate cortex, left amygdala, and medial prefrontal cortex, early adversity linked to decreased FC of brain regions mediating emotion processing such as the bilateral anterior insula and increased FC of the bilateral parahippocampal gyrus. LIMITATIONS: We report both results that are corrected for the number of seeds tested in FC analyses using strict Bonferroni adjustments and unadjusted results as part of an exploratory analysis. DISCUSSION: Our findings suggest that depression and early adversity are associated with differential FC patterns in the brain during the recall of formative relationship episodes. Hyperconnectivity of an introspective socio-affective network associated with depressive symptoms may link to enhanced self-focus and emotional reactivity. Patterns of neural activation associated with early adversity may underpin numbed affective states or enhanced affective memory regulation. Overall, these findings inform about the neural underpinnings of a reflective ability that is predictive of the adaptation to depression and to early adversity and relevant for psychotherapy outcomes.
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Mapeamento Encefálico , Depressão , Encéfalo/diagnóstico por imagem , Depressão/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Rememoração MentalRESUMO
Natural motion types found in skeletal and muscular systems of vertebrate animals inspire researchers to transfer this ability into engineered motion, which is highly desired in robotic systems. Dielectric elastomer actuators (DEAs) have shown promising capabilities as artificial muscles for driving such structures, as they are soft, lightweight, and can generate large strokes. For maximum performance, dielectric elastomer membranes need to be sufficiently pre-stretched. This fact is challenging, because it is difficult to integrate pre-stretched membranes into entirely soft systems, since the stored strain energy can significantly deform soft elements. Here, we present a soft robotic structure, possessing a bioinspired skeleton integrated into a soft body element, driven by an antagonistic pair of DEA artificial muscles, that enable the robot bending. In its equilibrium state, the setup maintains optimum isotropic pre-stretch. The robot itself has a length of 60 mm and is based on a flexible silicone body, possessing embedded transverse 3D printed struts. These rigid bone-like elements lead to an anisotropic bending stiffness, which only allows bending in one plane while maintaining the DEA's necessary pre-stretch in the other planes. The bones, therefore, define the degrees of freedom and stabilize the system. The DEAs are manufactured by aerosol deposition of a carbon-silicone-composite ink onto a stretchable membrane that is heat cured. Afterwards, the actuators are bonded to the top and bottom of the silicone body. The robotic structure shows large and defined bimorph bending curvature and operates in static as well as dynamic motion. Our experiments describe the influence of membrane pre-stretch and varied stiffness of the silicone body on the static and dynamic bending displacement, resonance frequencies and blocking forces. We also present an analytical model based on the Classical Laminate Theory for the identification of the main influencing parameters. Due to the simple design and processing, our new concept of a bioinspired DEA based robotic structure, with skeletal and muscular reinforcement, offers a wide range of robotic application.
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We report on the experimental realization of a flat, superconducting microwave resonator, a microwave billiard, with partially violated time-reversal (T) invariance, induced by inserting a ferrite into the cavity and magnetizing it with an external magnetic field perpendicular to the resonator plane. In order to prevent its expulsion caused by the Meissner-Ochsenfeld effect, we used a cavity of which the top and bottom plate were made from niobium, a superconductor of type II, and cooled it down to liquid-helium temperature T_{LHe}≃4 K. The cavity had the shape of a chaotic Africa billiard. Superconductivity rendered possible the accurate determination of complete sequences of the resonance frequencies and of the widths and strengths of the resonances, an indispensable prerequisite for the unambiguous detection of T invariance violation, especially when it is only partially violated. This allows for the first time the precise specification of the size of T invariance violation from the fluctuation properties of the resonance frequencies and from the strength distribution, which actually depends sensitively on it and thus provides a most suitable measure. For this purpose we derived an analytical expression for the latter which is valid for isolated resonances in the range from no T invariance violation to complete violation.
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Microscopy techniques are widely used in life sciences to study cells and tissues. Fluorescence microscopy, for example, is a very common method in many laboratories. While reliable and strong fluorescence signals are a clear advantage of this method, the labelling procedure with fluorescent dyes, the availability of required antibodies or the potentially necessary genetic modifications of the studied organism all introduce potential complications. By contrast, confocal Raman microscopy is a label-free and non-destructive imaging technique. In contrast to infrared microscopy, it is easily applicable in aqueous environments. Different microscope setups and combinations allow for the examination of various solid and liquid samples, even in their typical environments. The article demonstrates the analyzing capability of confocal Raman microscopy and correlative techniques through application examples of eukaryotic and prokaryotic cells, and cancerous and normal tissues and shows how confocal Raman microscopy provides valuable information for a more comprehensive understanding of the investigated sample.