Natural History of Patients With Ischemia and No Obstructive Coronary Artery Disease: The CIAO-ISCHEMIA Study.

BACKGROUND: Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. METHODS: CIAO-ISCHEMIA (Changes in Ischemia and Angina over One Year in ISCHEMIA Trial Screen Failures With INOCA) was an international cohort study conducted from 2014 to 2019 involving angina assessments (Seattle Angina Questionnaire) and stress echocardiograms 1 year apart. This was an ancillary study that included patients with a history of angina who were not randomly assigned in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease status, and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between the changes in the Seattle Angina Questionnaire angina frequency score and changes in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and we compared CIAO participants with ISCHEMIA participants with obstructive coronary artery disease who had stress echocardiography before enrollment, as CIAO participants did. RESULTS: INOCA participants in CIAO were more often female (66% of 208 versus 26% of 865 ISCHEMIA participants with obstructive coronary artery disease, P<0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [interquartile range, 3-5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO (P=0.46) or ISCHEMIA stress echocardiography participants (P=0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants, and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over 1 year was not significantly correlated with change in angina (ρ=0.029). CONCLUSIONS: Improvement in ischemia and angina were common in INOCA but not correlated. Our INOCA cohort had a degree of inducible wall motion abnormalities similar to concurrently enrolled ISCHEMIA participants with obstructive coronary artery disease. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02347215.

A rapid and cost-effective pipeline for digitization of museum specimens with 3D photogrammetry.

Natural history collections are yielding more information as digitization brings specimen data to researchers, connects specimens across museums, and as new technologies allow for more large-scale data collection. Therefore, a key goal in specimen digitization is developing methods that both increase access and allow for the highest yield of phenomic data. 3D digitization is increasingly popular because it has the potential to meet both aspects of that key goal. However, current methods overlook or do not prioritize some of the most sought-after phenotypic traits, those involving the external appearance of specimens, especially color. Here, we introduce an efficient and cost-effective pipeline for 3D photogrammetry to capture the external appearance of natural history specimens and other museum objects. 3D photogrammetry aligns and compares sets of dozens, hundreds, or even thousands of photos to create 3D models. The hardware set-up requires little physical space and around $3,000 in initial investment, while the software pipeline requires $1,400/year for proprietary software subscriptions (with open-source alternatives). The creation of each 3D model takes 1-2 hours/specimen and much of the software pipeline is automated with minimal supervision required, including the onerous step of mesh processing. We showcase the method by creating 3D models for most of the type specimens in the Moore Laboratory of Zoology bird collection and show that digital bill measurements are comparable to hand-taken measurements. Color data, while not included as part of this pipeline, is easily extractable from the models and one of the most promising areas of data collection. Future advances can adapt the method for ultraviolet reflectance capture and increased efficiency and model quality. Combined with genomic data, phenomic data from 3D models including photogrammetry will open new doors to understanding organismal evolution.

Boosting natural history research via metagenomic clean-up of crowdsourced feces.

Biodiversity is in crisis due to habitat destruction and climate change. The conservation of many noncharismatic species is hampered by the lack of data. Yet, natural history research-a major source of information on noncharismatic species-is in decline. We here suggest a remedy for many mammal species, i.e., metagenomic clean-up of fecal samples that are "crowdsourced" during routine field surveys. Based on literature data, we estimate that this approach could yield natural history information for circa 1,000 species within a decade. Metagenomic analysis would simultaneously yield natural history data on diet and gut parasites while enhancing our understanding of host genetics, gut microbiome, and the functional interactions between traditional and new natural history data. We document the power of this approach by carrying out a "metagenomic clean-up" on fecal samples collected during a single night of small mammal trapping in one of Alfred Wallace's favorite collecting sites.

¿Están justificadas las consultas externas de medicina intensiva? / Are outpatient clinics justified in intensive care medicine?

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A blood tumor marker combination assay produces high sensitivity and specificity for cancer according to the natural history.

Diagnosis using a specific tumor marker is difficult because the sensitivity of this detection method is under 20%. Herein, a tumor marker combination assay, combining growth-related tumor marker and associated tumor marker (Cancer, 73(7), 1994), was employed. This double-blind tumor marker combination assay (TMCA) showed 87.5% sensitivity as the results, but a low specificity, ranging from 30 to 76%. To overcome this low specificity, we exploited complex markers, a multivariate analysis and serum fractionation by biochemical biopsy. Thus, in this study, a combination of new techniques was used to re-evaluate these serum samples. Three serum panels, containing 90, 120, and 97 samples were obtained from the Mayo Clinic. The final results showed 80-90% sensitivity, 84-85% specificity, and 83-88% accuracy. We demonstrated a notable tumor marker combination assay with high accuracy. This TMCA should be applicable for primary cancer detection and recurrence prevention.

Hígado graso no alcohólico: una pandemia poco conocida / Non-alcoholic fatty liver disease: A poorly known pandemic

El hígado graso no alcohólico (HGNA, Nonalcoholic Fatty Liver Disease [NAFLD]) consiste en el depósito excesivo de grasa en el hígado que puede acabar generando inflamación, fibrosis e incluso cirrosis y sus complicaciones, incluido el carcinoma hepatocelular. El HGNA se ha convertido en la enfermedad hepática crónica más prevalente del mundo. Su incidencia ha ido aumentando en paralelo con la epidemia de obesidad, diabetes y síndrome metabólico, siendo además una de las principales causas de indicación de trasplante hepático. Su diagnóstico ha sido clásicamente histológico, pero el desarrollo de métodos no invasivos está ayudando a simplificar el manejo de estos pacientes en la práctica clínica. Las únicas estrategias terapéuticas disponibles son las enfocadas en la pérdida de peso (cambios de estilo de vida y/o cirugía bariátrica). Todavía no hay fármacos aprobados para el tratamiento del HGNA, pero existen numerosas moléculas en fases avanzadas de desarrollo (AU)

Non-alcoholic fatty liver disease (NAFLD) consists of an excessive depositing of fat in the liver, which can end up by causing inflammation, fibrosis and also cirrhosis with the corresponding complications including liver cancer. NAFLD has become the most common liver disease worldwide. The incidence has increased in parallel with the obesity, diabetes and metabolic syndrome epidemic, thus resulting in becoming one of the main indications for liver transplant. The diagnosis has principally been through histology but with the development of non-invasive methods, these have helped in simplifying the management of these patients in clinical practice. The only therapeutic strategies currently available are focused on weight loss (lifestyle changes or bariatric surgery). There is still no approved pharmacological option for the treatment of NAFLD, however there are a number of molecular studies in advanced stages of development (AU)

Diffuse low-grade glioma: a review on the new molecular classification, natural history and current management strategies

The management of diffuse supratentorial WHO grade II glioma remains a challenge because of the infiltrative nature of the tumor, which precludes curative therapy after total or even supratotal resection. When possible, functional-guided resection is the preferred initial treatment. Total and subtotal resections correlate with increased overall survival. High-risk patients (age >40, partial resection), especially IDH-mutated and 1p19q-codeleted oligodendroglial lesions, benefit from surgery plus adjuvant chemoradiation. Under the new 2016 WHO brain tumor classification, which now incorporates molecular parameters, all diffusely infiltrating gliomas are grouped together since they share specific genetic mutations and prognostic factors. Although low-grade gliomas cannot be regarded as benign tumors, large observational studies have shown that median survival can actually be doubled if an early, aggressive, multi-stage and personalized therapy is applied, as compared to prior wait-and-see policy series. Patients need an honest long-term therapeutic strategy that should ideally anticipate neurological, cognitive and histopathologic worsening (AU)

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A Comparison of the Natural History of HPV Infection and Cervical Abnormalities among HIV-Positive and HIV-Negative Women in Senegal, Africa.

Background: There is evidence of an interaction between HIV and human papillomavirus (HPV) resulting in increased HPV-associated morbidity and cancer mortality among HIV-positive women. This study aims to determine how the natural history of cervical HPV infection differs by HIV status.Methods: A total of 1,320 women (47% were positive for HIV-1 and/or HIV-2) were followed for an average of two years in Senegal, West Africa between 1994 and 2010. Cytology (with a sub-sample of histology) and HPV DNA testing were performed at approximately 4-month intervals yielding data from over 7,900 clinic visits. Competing risk modeling was used to estimate rates for transitioning between three clinically relevant natural history stages: Normal, HPV, and HSIL (high-grade squamous intraepithelial lesions). Among HIV-positive women, exploratory univariate analyses were conducted examining the impact of HPV type, infection with multiple HPV types, HIV type, CD4+ count, and age.Results: HIV-positive women had higher rates of progression and lower rates of regression compared with HIV-negative women (i.e., adverse transitions). HIV-positive women had a 2.55 [95% confidence interval (CI), 1.69-3.86; P < 0.0001] times higher rate of progression from HPV to HSIL than HIV-negative women (with 24-month absolute risks of 0.18 and 0.07, respectively). Among HIV-positive women, HPV-16/18 infection and CD4+ count <200/mm3 were associated with adverse transitions.Conclusions: Adverse HIV effects persist throughout HPV natural history stages.Impact: In the limited-resource setting of sub-Saharan Africa where cervical cancer screening is not widely available, the high-risk population of HIV-positive women may be ideal for targeted screening. Cancer Epidemiol Biomarkers Prev; 26(6); 886-94. ©2017 AACR.

Management of chronic spontaneous urticaria in routine clinical practice: a Delphi-method questionnaire among specialists to test agreement with current European guidelines statements

BACKGROUND: Chronic spontaneous urticaria (CSU) is a frequent clinical entity that often presents a diagnostic and therapeutic challenge. OBJECTIVE: To explore the degree of agreement that exists among the experts caring for patients with CSU diagnosis, evaluation, and management. METHODS: An online survey was conducted to explore the opinions of experts in CSU, address controversial issues, and provide recommendations regarding its definition, natural history, diagnosis, and treatment. A modified Delphi method was used for the consensus. RESULTS: The questionnaire was answered by 68 experts (dermatologists, allergologists, and primary care physicians). A consensus was reached on 54 of the 65 items posed (96.4%). The experts concluded that CSU is a difficult-to-control disease of unpredictable evolution. Diagnostic tests should be limited and based on clinical history and should not be indiscriminate. Autoinflammatory syndromes and urticarial vasculitis must be ruled out in the differential diagnosis. A cutaneous biopsy is only recommended when wheals last more than 24h, to rule out urticarial vasculitis. The use of specific scales to assess the severity of the disease and the quality of life is recommended. In patients with severe and resistant CSU, second-generation H1-antihistamines could be used at doses up to four times the standard dose before giving second-line treatments. Omalizumab is a safe and effective treatment for CSU that is refractory to H1-antihistamines treatment. In general, diagnosis and treatment recommendations given for adults could be extrapolated to children. CONCLUSIONS: This work offers consensus recommendations that may be useful in the management of CSU

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Natural history and clinical characteristics of inhibitors in previously treated haemophilia A patients: a case series.

BACKGROUND: Development of inhibitors is the most serious complication in haemophilia A treatment. The assessment of risk for inhibitor formation in new or modified factor concentrates is traditionally performed in previously treated patients (PTPs). However, evidence on risk factors for and natural history of inhibitors has been generated mostly in previously untreated patients (PUPs). The purpose of this study was to examine cases of de novo inhibitors in PTPs reported in the scientific literature and to the EUropean HAemophilia Safety Surveillance (EUHASS) programme, and explore determinants and course of inhibitor development. METHODS: We used a case series study design and developed a case report form to collect patient level data; including detection, inhibitor course, treatment, factor VIII products used and events that may trigger inhibitor development (surgery, vaccination, immune disorders, malignancy, product switch). RESULTS: We identified 19 publications that reported 38 inhibitor cases and 45 cases from 31 EUHASS centres. Individual patient data were collected for 55/83 (66%) inhibitor cases out of 12 330 patients. The median (range) peak inhibitor titre was 4.4 (0.5-135.0), the proportion of transient inhibitors was 33% and only two cases of 12 undergoing immune tolerance induction failed this treatment. In the two months before inhibitor development, surgery was reported in nine (22%) cases, and high intensity treatment periods reported in seven (17%) cases. CONCLUSIONS: By studying the largest cohort of inhibitor development in PTPs assembled to date, we showed that inhibitor development in PTPs, is on average, a milder event than in PUPs.

Fibrosis pulmonar idiopática / Idiopathic pulmonary fibrosis

La fibrosis pulmonar idiopática es una neumonía intersticial fibrosante asociada al patrón radiológico y/o histológico de la neumonía intersticial usual. No se conoce su etiología, aunque es probable que consista en la acción de diversos factores microambientales exógenos y/o endógenos en sujetos con predisposición genética. El diagnóstico se basa en los hallazgos característicos en la tomografía axial computarizada de alta resolución y biopsia pulmonar en ausencia de enfermedades pulmonares intersticiales de otras causas. La evolución es variable, aunque la supervivencia media es de 2-5 años desde el inicio de los síntomas. Los pacientes con fibrosis pulmonar idiopática pueden presentar complicaciones y comorbilidades, que modifican el curso clínico y el pronóstico. En la enfermedad leve-moderada el tratamiento consiste en la administración de fármacos antifibróticos, y en la enfermedad grave, la mejor opción terapéutica es el trasplante pulmonar. En el presente artículo, se revisan los aspectos diagnósticos y terapéuticos de la enfermedad (AU)

Idiopathic pulmonary fibrosis is a fibrosing interstitial pneumonia associated with the radiological and/or histological pattern of usual interstitial pneumonia. Its aetiology is unknown, but probably comprises the action of endogenous and exogenous micro-environmental factors in subjects with genetic predisposition. Its diagnosis is based on the presence of characteristic findings of high-resolution computed tomography scans and pulmonary biopsies in absence of interstitial lung diseases of other aetiologies. Its clinical evolution is variable, although the mean survival rate is 2-5 years as of its clinical presentation. Patients with idiopathic pulmonary fibrosis may present complications and comorbidities which modify the disease’s clinical course and prognosis. In the mild-moderate disease, the treatment consists of the administration of anti-fibrotic drugs. In severe disease, the best therapeutic option is pulmonary transplantation. In this paper we review the diagnostic and therapeutic aspects of the disease (AU)

The transcontinental birth of a species: scientific discussions and natural history museums in the second half of the nineteenth century

This article is a case study of the scientific discussions on the birth of a zoological species that eventually came to be known as Arctocephalus philippii (Peters, 1866). It also examines the movement of the remains of a sea lion specimen from Chile to Germany and the discussions that arose in regard to its taxonomic definition. The paper argues that the material properties of this mobilized specimen, the circumstances of how it was hunted, transported and stored at the different museums, as well as the material aspects that later allowed it to be compared and analyzed, influenced the international debates on its classification between naturalists in England, Germany, Chile and Argentina. The first part reconstructs the context of sea lion’s capture, transportation and transformation, while the second examines the discussion around this particular specimen - a controversy hinged partly upon the issue of the conditions in which it was graphically reproduced and preserved at the museum (AU)

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Survival in glioblastoma: a review on the impact of treatment modalities

Glioblastoma (GBM) is the most common and lethal tumor of the central nervous system. The natural history of treated GBM remains very poor with 5-year survival rates of 5 %. Survival has not significantly improved over the last decades. Currently, the best that can be offered is a modest 14-month overall median survival in patients undergoing maximum safe resection plus adjuvant chemoradiotherapy. Prognostic factors involved in survival include age, performance status, grade, specific markers (MGMT methylation, mutation of IDH1, IDH2 or TERT, 1p19q codeletion, overexpression of EGFR, etc.) and, likely, the extent of resection. Certain adjuncts to surgery, especially cortical mapping and 5-ALA fluorescence, favor higher rates of gross total resection with apparent positive impact on survival. Recurrent tumors can be offered re-intervention, participation in clinical trials, anti-angiogenic agent or local electric field therapy, without an evident impact on survival. Molecular-targeted therapies, immunotherapy and gene therapy are promising tools currently under research (AU)

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Revealing Invisible Beauty, Ultra Detailed: The Influence of Low Cost UV Exposure on Natural History Specimens in 2D+ Digitization.

Digitization of the natural history specimens usually occurs by taking detailed pictures from different sides or producing 3D models. Additionally this is normally limited to imaging the specimen while exposed by light of the visual spectrum. However many specimens can see in or react to other spectra as well. Fluorescence is a well known reaction to the ultraviolet (UV) spectrum by animals, plants, minerals etc. but rarely taken into account while examining natural history specimens. Our tests show that museum specimens still fluoresce when exposed to UV light of 395 nm and 365 nm, even after many years of preservation. When the UV exposure is used in the digitization of specimens using our low cost focus stacking (2D+) setup, the resulting pictures reveal more detail than the conventional 2D+ images. Differences in fluorescence using 395 nm or 365 nm UV lights were noticed, however there isn't a preferred wavelength as some specimens react more to the first, while others have better results with the latter exposure. Given the increased detail and the low cost of the system, UV exposure should be considered while digitizing natural history museum collections.

Relaciones ocultas a fines del siglo XVIII: la specimen florae americae meridionalis (1780) del Real Jardim Botânico da ajuda y los diseños científicos de la Real Expedición Botánica al virreinato peruano / Hidden relationships in late eighteen century: the specimen florae americae meridionalis (1780) of the Real Jardim Botânico da Ajuda and the scientific drawings of the Royal Botanical expedition to the Peru viceroyalty

Este artículo muestra que en las décadas finales del siglo XVIII, más allá de las relaciones diplomáticas y los conflictos militares entre Portugal y España, existieron importantes conexiones científicas, que han sido poco estudiadas. Teniendo como punto de partida la casi desconocida Specimen Florae Americae Meridionalis (1780), una obra botánica compuesta de cuatro volúmenes, producida en el Real Museu da Ajuda (Lisboa), exploraremos el interés que suscitó en los círculos de estudiosos y aficionados a la botánica en Lisboa la llegada de más de doscientos dibujos de plantas procedentes de la Real Expedición Botánica al Virreinato del Perú (1777-1788). Considerando las personalidades portuguesas, españolas e inglesas que estuvieron implicadas en la presencia de estos diseños en Portugal, recuperaremos algunas de las prácticas que posibilitaban en este período la circulación de conocimientos científicos y el adelanto de la botánica. En este sentido, este estudio pretende realizar una aportación novedosa a la Historia de la Botánica en Portugal y España y apuntar caminos para futuras investigaciones (AU)

This paper shows that in the final decades of the eighteenth century, beyond the diplomatic and military conflicts between Portugal and Spain, there were important scientific connections, which have been little studied. Having as a starting point the almost unknown Specimen Florae Americae Meridionalis (1780), a four volumes botanical work produced in Real Museu da Ajuda (Lisbon), we will explore the interest aroused in the circles of scholars and amateur botanists the arrival in Lisbon of over two hundred drawings of plants from the Royal Botanical Expedition to the Viceroyalty of Peru (1777-1788). Considering the Portuguese, Spanish and English personalities who were involved in the presence of these drawings in Portugal we will recover some of the practices that made possible in this period the circulation of scientific knowledge and the advancement of botany. In this sense, this study aims to make a novel contribution to the History of Botany in Portugal and Spain, and point paths for future research (AU)

Widespread mistaken identity in tropical plant collections.

Specimens of plants and animals preserved in museums are the primary source of verifiable data on the geographical and temporal distribution of organisms. Museum datasets are increasingly being uploaded to aggregated regional and global databases (e.g. the Global Biodiversity Information Facility; GBIF) for use in a wide range of analyses. Thus, digitisation of natural history collections is providing unprecedented information to facilitate the study of the natural world on a global scale. The digitisation of this information utilises information provided on specimen labels, and assumes they are correctly identified. Here we evaluate the accuracy of names associated with 4,500 specimens of African gingers from 40 herbaria in 21 countries. Our data show that at least 58% of the specimens had the wrong name prior to a recent taxonomic study. A similar pattern of wrongly named specimens is also shown for Dipterocarps and Ipomoea (morning glory). We also examine the number of available plant specimens worldwide. Our data demonstrate that, while the world's collections have more than doubled since 1970, more than 50% of tropical specimens, on average, are likely to be incorrectly named. This finding has serious implications for the uncritical use of specimen data from natural history collections.

Inselect: Automating the Digitization of Natural History Collections.

The world's natural history collections constitute an enormous evidence base for scientific research on the natural world. To facilitate these studies and improve access to collections, many organisations are embarking on major programmes of digitization. This requires automated approaches to mass-digitization that support rapid imaging of specimens and associated data capture, in order to process the tens of millions of specimens common to most natural history collections. In this paper we present Inselect-a modular, easy-to-use, cross-platform suite of open-source software tools that supports the semi-automated processing of specimen images generated by natural history digitization programmes. The software is made up of a Windows, Mac OS X, and Linux desktop application, together with command-line tools that are designed for unattended operation on batches of images. Blending image visualisation algorithms that automatically recognise specimens together with workflows to support post-processing tasks such as barcode reading, label transcription and metadata capture, Inselect fills a critical gap to increase the rate of specimen digitization.

Impact of the age of diagnosis on the natural history of ulcerative colitis

BACKGROUND: Ulcerative colitis (UC) has a recognized phenotypic heterogeneity. Some studies suggest that age at diagnosis may influence features and natural history of the disease. AIM: This study aimed to compare patients', disease's and treatment's features between Portuguese patients diagnosed before and after the age of 40-years-old. METHODS: Retrospective single-center study that included 310 patients with UC, divided in two groups: Those diagnosed before the age of 40-years-old (early onset UC) and those diagnosed later than that (late onset UC). In each group features of the patients (gender, family history, smoking), of the disease (duration, extension, severity, clinical course, hospitalization, extraintestinal manifestations), and of treatment (oral aminosalicylates, systemic steroids or immunomodulators) were analyzed. Statistical analysis was performed using SPSSv22.0. Univariate and multivariate analyses were performed to assess factors associated with early and late onset UC. RESULTS: From the analyzed patients, 207 had UC diagnosed before the age of 40 years old (43.5% men; mean age at diagnosis 29.4 ± 6.9 years) and 103 were diagnosed after that age (61.2% men; mean age at diagnosis 51.8 ± 8.1 years). In the group diagnosed before 40 years old, female gender (p = 0.003), severe disease (p = 0.002), chronic intermittent clinical course (p = 0.026), and hospitalizations (p = 0.001) were significantly more frequent. The use of oral aminosalicylates (p = 0.032), systemic steroids (p = 0.003) and immunomodulators (p = 0.012) were also more common in the early onset UC group. No differences between groups were found in family history, smoking, disease's extension, extraintestinal manifestations, and use of biological agents. Multivariate analysis pointed early onset UC to be significantly associated with female gender (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.08- 2.91; p = 0.024), chronic intermittent symptoms (OR, 2.34; 95% CI, 1.17-4.70; p = 0.016), and need of hospitalization (OR, 2.89; 95% CI, 1.46-5.72; p = 0.002). CONCLUSIONS: When diagnosed before the age of 40-yearsold, UC preferably affects women and manifests as a more severe disease, with more frequent hospitalizations and chronic intermittent symptoms. These facts might have implications in planning timely and individualized future therapeutic strategies

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