Seeing Through the Blind: Belief about Treatment Randomization and Smoking Cessation Outcome among People with Current or Past Major Depressive Disorder who Smoke in a Placebo-Controlled Trial of Varenicline.

INTRODUCTION: Blinding participants to randomization is a cornerstone of science. However, participant beliefs about their allocation can influence outcomes. We examined blind integrity, the association between trial arm belief and cessation, and potential mechanisms linking treatment arm and treatment arm belief among people with major depressive disorder (MDD) who smoke receiving varenicline in a placebo-controlled trial. METHODS: 175 participants were asked at the end of treatment (EOT) if they thought they received placebo, varenicline, or were not sure. We assessed the relationship between treatment arm belief and actual treatment allocation, examined the association between treatment arm belief and EOT cessation, and evaluated changes in craving, withdrawal, side effects, depression symptoms, and smoking reward as mediators through which treatment arm was believed. RESULTS: Treatment arm belief was significantly associated with actual arm assignment (χ2(2)=13.0, p=0.002). Participants in the varenicline arm were >3 times as likely to believe they were taking varenicline, vs. "not sure" (RR=3.05 [1.41-6.60], p=0.005). Participants in the placebo arm were just as likely to believe they were taking placebo vs. "not sure" (χ2[2]=0.75, p=0.69). Controlling for treatment arm, belief that one received varenicline was significantly associated with an increase in cessation rate (OR=5.91 [2.06-16.92], p=0.001). Change in the rewarding experience of smoking may mediate participant ability to discern getting varenicline B=0.077 [0.002-0.192], p <0.05). CONCLUSIONS: Participants receiving varenicline can discern that they received varenicline and this belief is associated with higher cessation rates. Research is needed to continue to examine how participants correctly identify their allocation to varenicline.

The Mortality of Congenital Syphilis.

OBJECTIVES: To document the case-fatality rate (CFR) of congenital syphilis diagnosed by molecular tools and rabbit infectivity testing (RIT) of clinical specimens in addition to standard evaluation and to compare that with the CFR using the Centers for Disease Control and Prevention (CDC) surveillance case definition. STUDY DESIGN: Prospective, single site, cohort study of all cases of syphilis among mothers and their infants from 1984 to 2002. The diagnosis of congenital syphilis was determined using IgM immunoblotting, polymerase chain reaction, and RIT of fetal or infant specimens in addition to clinical, laboratory, and radiographic criteria. Data were retrospectively reviewed to ascertain fetal and neonatal mortality. RESULTS: During the 18-year study, there were 191 cases of congenital syphilis confirmed by abnormalities on clinical, laboratory, or radiographic evaluation and/or positive serum IgM immunoblot, blood polymerase chain reaction, or blood/cerebrospinal fluid RIT. Of the 191 cases, 59 died for a CFR of 31%. Of the 59 deaths, 53 (90%) were stillborn and 6 (10%) died in the neonatal period. The majority (74%, 39/53) of stillbirths occurred in the third trimester. The CDC surveillance case definition correctly identified all infants with congenital syphilis, but the CDC CFR was 10% which underestimated the CFR by more than 300%. CONCLUSIONS: Our findings corroborate the high sensitivity of the CDC surveillance definition for congenital syphilis but highlight its poor estimation of its associated mortality. The CFR among infected progeny of pregnant women with syphilis was 31%, due mostly to demise in the third trimester and as such highlights the need for detection and appropriate treatment of syphilis during pregnancy.

Effect of randomized prophylactic nitroglycerin on radial artery spasm during transradial catheterization: an analysis based on operator experience

One limitation to transradial access (TRA) is the occurrence of spasms (RAS), for which the use of prophylactic medications is recommended. Improvement in TRA material combined with the increase in operators' expertise, might mitigate this benefit. We assess the effect of preventive nitroglycerin on RAS during TRA, evaluating the role of the operator's experience. Patients received 500 µg nitroglycerin or placebo. The operator's expertise was classified as: inexperienced (I), intermediate (M), and experienced (E). 2040 patients were included. Prophylactic use of nitroglycerin did not reduce RAS (10.8% vs. 13.4% (placebo), p = 0.07). RAS incidence was 14.5% in I, 12.5% in M, and 9.7% in E (p = 0.01). In group I, nitroglycerin reduced RAS (17.4% vs. 11.1%, p = 0.04), which was not observed in other groups. Overall, nitroglycerin does not prevent RAS, which is more common among inexperienced operators. More experienced operators could abolish preventive nitroglycerin use.

Effect of randomized prophylactic nitroglycerin on radial artery spasm during transradial catheterization: An analysis based on operator experience.

One limitation to transradial access (TRA) is the occurrence of spasms (RAS), for which the use of prophylactic medications is recommended. Improvement in TRA material combined with the increase in operators' expertise, might mitigate this benefit. We assess the effect of preventive nitroglycerin on RAS during TRA, evaluating the role of the operator's experience. Patients received 500 µg nitroglycerin or placebo. The operator's expertise was classified as: inexperienced (I), intermediate (M), and experienced (E). 2040 patients were included. Prophylactic use of nitroglycerin did not reduce RAS (10.8% vs. 13.4% (placebo), p = 0.07). RAS incidence was 14.5% in I, 12.5% in M, and 9.7% in E (p = 0.01). In group I, nitroglycerin reduced RAS (17.4% vs. 11.1%, p = 0.04), which was not observed in other groups. Overall, nitroglycerin does not prevent RAS, which is more common among inexperienced operators. More experienced operators could abolish preventive nitroglycerin use.

COVID-19 Detection on Chest X-ray and CT Scan: A Review of the Top-100 Most Cited Papers.

Since the beginning of the COVID-19 pandemic, many works have been published proposing solutions to the problems that arose in this scenario. In this vein, one of the topics that attracted the most attention is the development of computer-based strategies to detect COVID-19 from thoracic medical imaging, such as chest X-ray (CXR) and computerized tomography scan (CT scan). By searching for works already published on this theme, we can easily find thousands of them. This is partly explained by the fact that the most severe worldwide pandemic emerged amid the technological advances recently achieved, and also considering the technical facilities to deal with the large amount of data produced in this context. Even though several of these works describe important advances, we cannot overlook the fact that others only use well-known methods and techniques without a more relevant and critical contribution. Hence, differentiating the works with the most relevant contributions is not a trivial task. The number of citations obtained by a paper is probably the most straightforward and intuitive way to verify its impact on the research community. Aiming to help researchers in this scenario, we present a review of the top-100 most cited papers in this field of investigation according to the Google Scholar search engine. We evaluate the distribution of the top-100 papers taking into account some important aspects, such as the type of medical imaging explored, learning settings, segmentation strategy, explainable artificial intelligence (XAI), and finally, the dataset and code availability.

Global Health Strategies in the Face of the COVID-19 Pandemic and Other Unprecedented Threats.

Global health is evolving as a discipline aiming at exploring needs and offering equitable health services for all people. Over the past four decades, several global initiatives have been introduced to improve the accessibility of primary health care (PHC) and solve most health issues at this level. Historically, the 1978 Alma-Ata and 2018 Astana Declarations were perhaps the most important documents for a comprehensive approach to PHC services across the world. With the introduction of the United Nations Sustainable Development Goals in 2015, developments in all spheres of human life and multi-sectoral cooperation became the essential action targets that could contribute to improved health, well-being, and safety of all people. Other global initiatives such as the Riyadh Declaration on Digital Health and São Paulo Declaration on Planetary Health called to urgent action to employ advanced digital technologies, improve health data processing, and invest more in research management. All these initiatives are put to the test in the face of the coronavirus disease 2019 (COVID-19) pandemic and other unprecedented threats to humanity.

Characterizing the Number of Kinesin Motors Bound to Microtubules in the Gliding Motility Assay Using FLIC Microscopy.

Intracellular transport by kinesin motors moving along their associated cytoskeletal filaments, microtubules, is essential to many biological processes. This active transport system can be reconstituted in vitro with the surface-adhered motors transporting the microtubules across a planar surface. In this geometry, the kinesin-microtubule system has been used to study active self-assembly, to power microdevices, and to perform analyte detection. Fundamental to these applications is the ability to characterize the interactions between the surface tethered motors and microtubules. Fluorescence Interference Contrast (FLIC) microscopy can illuminate the height of the microtubule above a surface, which, at sufficiently low surface densities of kinesin, also reveals the number, locations, and dynamics of the bound motors.

Hybrid systems using residual modeling for sea surface temperature forecasting.

The sea surface temperature (SST) is an environmental indicator closely related to climate, weather, and atmospheric events worldwide. Its forecasting is essential for supporting the decision of governments and environmental organizations. Literature has shown that single machine learning (ML) models are generally more accurate than traditional statistical models for SST time series modeling. However, the parameters tuning of these ML models is a challenging task, mainly when complex phenomena, such as SST forecasting, are addressed. Issues related to misspecification, overfitting, or underfitting of the ML models can lead to underperforming forecasts. This work proposes using hybrid systems (HS) that combine (ML) models using residual forecasting as an alternative to enhance the performance of SST forecasting. In this context, two types of combinations are evaluated using two ML models: support vector regression (SVR) and long short-term memory (LSTM). The experimental evaluation was performed on three datasets from different regions of the Atlantic Ocean using three well-known measures: mean square error (MSE), mean absolute percentage error (MAPE), and mean absolute error (MAE). The best HS based on SVR improved the MSE value for each analyzed series by [Formula: see text], [Formula: see text], and [Formula: see text] compared to its respective single model. The HS employing the LSTM improved [Formula: see text], [Formula: see text], and [Formula: see text] concerning the single LSTM model. Compared to literature approaches, at least one version of HS attained higher accuracy than statistical and ML models in all study cases. In particular, the nonlinear combination of the ML models obtained the best performance among the proposed HS versions.

Impact of Lung Segmentation on the Diagnosis and Explanation of COVID-19 in Chest X-ray Images.

COVID-19 frequently provokes pneumonia, which can be diagnosed using imaging exams. Chest X-ray (CXR) is often useful because it is cheap, fast, widespread, and uses less radiation. Here, we demonstrate the impact of lung segmentation in COVID-19 identification using CXR images and evaluate which contents of the image influenced the most. Semantic segmentation was performed using a U-Net CNN architecture, and the classification using three CNN architectures (VGG, ResNet, and Inception). Explainable Artificial Intelligence techniques were employed to estimate the impact of segmentation. A three-classes database was composed: lung opacity (pneumonia), COVID-19, and normal. We assessed the impact of creating a CXR image database from different sources, and the COVID-19 generalization from one source to another. The segmentation achieved a Jaccard distance of 0.034 and a Dice coefficient of 0.982. The classification using segmented images achieved an F1-Score of 0.88 for the multi-class setup, and 0.83 for COVID-19 identification. In the cross-dataset scenario, we obtained an F1-Score of 0.74 and an area under the ROC curve of 0.9 for COVID-19 identification using segmented images. Experiments support the conclusion that even after segmentation, there is a strong bias introduced by underlying factors from different sources.

Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR.

BACKGROUND: The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied. METHODS: We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding. RESULTS: A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11). CONCLUSIONS: In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).

A new genus and species of groundwater isopod of the family Protojaniridae (Isopoda: Asellota: Gnathostenetroidoidea) from southern Chile.

A new asellotan isopod of the family Protojaniridae Fresi, Idato Scipione, 1980 is described from freshwater springs in the Osorno province, Los Lagos region, southern Chile. Wiyufiloides osornoensis gen. sp. n. is the third South American protojanirid species and the first known groundwater isopod in Chile. The new genus and species is principally characterized by the presence of a vestigial antennal scale, a strongly subchelate pereiopod I and the absence of an apical lobe on the protopod of pleopod II. The new taxon is described in detail and figures are given.

Nanoarchitecture through Strained Molecules: Cubane-Derived Scaffolds and the Smallest Carbon Nanothreads.

Relative to the rich library of small-molecule organics, few examples of ordered extended (i.e., nonmolecular) hydrocarbon networks are known. In particular, sp3 bonded, diamond-like materials represent appealing targets because of their desirable mechanical, thermal, and optical properties. While many covalent organic frameworks (COFs)-extended, covalently bonded, and porous structures-have been realized through molecular architecture with exceptional control, the design and synthesis of dense, covalent extended solids has been a longstanding challenge. Here we report the preparation of a sp3-bonded, low-dimensional hydrocarbon synthesized via high-pressure, solid-state diradical polymerization of cubane (C8H8), which is a saturated, but immensely strained, cage-like molecule. Experimental measurements show that the obtained product is crystalline with three-dimensional order that appears to largely preserve the basic structural topology of the cubane molecular precursor and exhibits high hardness (comparable to fused quartz) and thermal stability up to 300 °C. Among the plausible theoretical candidate structures, one-dimensional carbon scaffolds comprising six- and four-membered rings that pack within a pseudosquare lattice provide the best agreement with experimental data. These diamond-like molecular rods with extraordinarily small thickness are among the smallest members in the carbon nanothread family, and calculations indicate one of the stiffest one-dimensional systems known. These results present opportunities for the synthesis of purely sp3-bonded extended solids formed through the strain release of saturated molecules, as opposed to only unsaturated precursors.

Big Data: uma nova fronteira na pesquisa e na prática médica / Big Data: a new frontier in research and medical practice

Espera-se que a integração contínua dos avanços tecnológicos e da digitalização revolucione os sistemas de saúde e a prestação de assistência ao paciente. Esses desen-volvimentos permitiram a geração de dados detalhados associados à assistência médica, os quais podem ser aproveitados, compilados e analisados com a ajuda de ferramentas sofisticadas. O ramo da ciência que lida com o armazenamento, processamento e imple-mentação desses grandes volumes de dados foi apropriadamente denominado "big data analytics" (BDA, Análise de grandes volumes de dados). Apesar do crescente interesse no potencial da BDA no campo da assistência médica, não há uma definição concisa, sendo que a BDA é descrita de acordo com o valor que ela pode fornecer. Como as ferramentas estatísticas tradicionais não estão equipadas para lidar com esses grandes e complexos conjuntos de dados, é preciso implementar ferramentas de inteligência artificial de alta di-mensão. A BDA foi explorada em várias vias em todo o espectro de serviços de saúde, desde a automação de tarefas, até ferramentas de previsão de risco, interpretação de imagens e realização de estudos clínicos. Contudo, como essas ferramentas são diferentes da medicina tradicional, existem várias preocupações referentes a implementação, uso e segurança e privacidade de dados. Todavia, a BDA detém imenso potencial para melhorar os serviços de saúde, sendo que todas as partes envolvidas devem envidar esforços deliberados para promover a aplicação dessa área emergente da medicina.

87Sr/86Sr and 14C evidence for peccary (Tayassuidae) introduction challenges accepted historical interpretation of the 1657 Ligon map of Barbados.

Contemporary West Indian biodiversity has been shaped by two millennia of non-native species introductions. Understanding the dynamics of this process and its legacy across extended temporal and spatial scales requires accurate knowledge of introduction timing and the species involved. Richard Ligon's 17th century account and celebrated map of early colonial Barbados records the translocation of several Old World species to the island in the post-contact era, including pigs (Sus scrofa) believed to have been released by passing sailors the century prior. Here we challenge this long-accepted historical narrative, presenting evidence that Ligon's "pigs" were in fact peccaries, a New World continental mammal often confused with wild boars. We document the first recorded instance of non-native peccary (Tayassuidae) on Barbados based on a securely identified mandibular specimen from a historic archaeological context. Results of specimen 87Sr/86Sr and AMS radiocarbon assays, along with newly reported data from Sr isotope environmental analyses, indicate a local origin dating to AD 1645-1670/1780-1800. These data support the presence of living peccary on Barbados some time during the first 175 years of English settlement, which, based on review of historical and archaeological data, most likely arises from 16th century peccary introduction from the Guianas/Trinidad by the Spanish or Portuguese. We argue dimorphic representations of "pigs" on Ligon's map reflect the co-occurrence of peccary and European domestic swine on historic Barbados. Our findings overturn conventional history and provide greater taxonomic and chronological resolution for Caribbean bioinvasion studies, helping to refine our understanding of potential ecological impacts. In addition, the new bioavailable 87Sr/86Sr data for Barbados reported here advance current efforts toward mapping the Caribbean Sr isoscape.

Earliest isotopic evidence in the Maya region for animal management and long-distance trade at the site of Ceibal, Guatemala.

This study uses a multiisotope (carbon, nitrogen, oxygen, and strontium) approach to examine early animal management in the Maya region. An analysis of faunal specimens across almost 2,000 years (1000 BC to AD 950) at the site of Ceibal, Guatemala, reveals the earliest evidence for live-traded dogs and possible captive-reared taxa in the Americas. These animals may have been procured for ceremonial functions based on their location in the monumental site core, suggesting that animal management and trade began in the Maya area to promote special events, activities that were critical in the development of state society. Isotopic evidence for animal captivity at Ceibal reveals that animal management played a greater role in Maya communities than previously believed.

Phylogenetic trophic specialization: a robust comparison of herbivorous guilds.

Resource specialization is a key concept in ecology, but it is unexpectedly difficult to parameterize. Differences in resource availability, sampling effort and abundances preclude comparisons of incompletely sampled biotic interaction webs. Here, we extend the distance-based specialization index (DSI) that measures trophic specialization by taking resource phylogenetic relatedness and availability into account into a rescaled version, DSI*. It is a versatile metric of specialization that expands considerably the scope and applicability, hence the usefulness, of DSI. The new metric also accounts for differences in abundance and sampling effort of consumers, which enables robust comparisons among distinct guilds of consumers. It also provides an abundance threshold for the reliability of the metric for rare species, a very desirable property given the difficulty of assessing any aspect of rare species accurately. We apply DSI* to an extensive dataset on interactions between insect herbivores from four folivorous guilds and their host plants in Papua New Guinean rainforests. We demonstrate that DSI*, contrary to the original DSI, is largely independent of sample size and weakly and non-linearly related with several host specificity measures that do not adjust for plant phylogeny. Thus, DSI* provides further insights into host specificity patterns; moreover, it is robust to the number and phylogenetic diversity of plant species selected to be sampled for herbivores. DSI* can be used for a broad range of comparisons of distinct feeding guilds, geographical locations and ecological conditions. This is a key advance in elucidating the interaction structure and evolution of highly diversified systems.

Rheumatoid arthritis-specific cardiovascular risk scores are not superior to general risk scores: a validation analysis of patients from seven countries.

Objectives: Cardiovascular disease (CVD) risk calculators developed for the general population do not accurately predict CVD events in patients with RA. We sought to externally validate risk calculators recommended for use in patients with RA including the EULAR 1.5 multiplier, the Expanded Cardiovascular Risk Prediction Score for RA (ERS-RA) and QRISK2. Methods: Seven RA cohorts from UK, Norway, Netherlands, USA, South Africa, Canada and Mexico were combined. Data on baseline CVD risk factors, RA characteristics and CVD outcomes (including myocardial infarction, ischaemic stroke and cardiovascular death) were collected using standardized definitions. Performance of QRISK2, EULAR multiplier and ERS-RA was compared with other risk calculators [American College of Cardiology/American Heart Association (ACC/AHA), Framingham Adult Treatment Panel III Framingham risk score-Adult Treatment Panel (FRS-ATP) and Reynolds Risk Score] using c-statistics and net reclassification index. Results: Among 1796 RA patients without prior CVD [mean ( s . d .) age: 54.0 (14.0) years, 74% female], 100 developed CVD events during a mean follow-up of 6.9 years (12430 person-years). Estimated CVD risk by ERS-RA [mean ( s . d .) 8.8% (9.8%)] was comparable to FRS-ATP [mean ( s . d .) 9.1% (8.3%)] and Reynolds [mean ( s . d .) 9.2% (12.2%)], but lower than ACC/AHA [mean ( s . d .) 9.8% (12.1%)]. QRISK2 substantially overestimated risk [mean ( s . d .) 15.5% (13.9%)]. Discrimination was not improved for ERS-RA (c-statistic = 0.69), QRISK2 or EULAR multiplier applied to ACC/AHA compared with ACC/AHA (c-statistic = 0.72 for all) or for FRS-ATP (c-statistic = 0.75). The net reclassification index for ERS-RA was low (-0.8% vs ACC/AHA and 2.3% vs FRS-ATP). Conclusion: The QRISK2, EULAR multiplier and ERS-RA algorithms did not predict CVD risk more accurately in patients with RA than CVD risk calculators developed for the general population.

Lead (Pb) Isotope Baselines for Studies of Ancient Human Migration and Trade in the Maya Region.

We examined the potential use of lead (Pb) isotopes to source archaeological materials from the Maya region of Mesoamerica. The main objectives were to determine if: 1) geologic terrains throughout the Maya area exhibit distinct lead isotope ratios (206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb), and 2) a combination of lead and strontium ratios can enhance sourcing procedures in the Mesoamerica region. We analyzed 60 rock samples for lead isotope ratios and a representative subset of samples for lead, uranium, and thorium concentrations across the Maya region, including the Northern Lowlands of the Mexican Yucatan Peninsula, the Southern Lowlands of Guatemala and Belize, the Volcanic Highlands, the Belizean Maya Mountains, and the Metamorphic Province/Motagua Valley. Although there is some overlap within certain sub-regions, particularly the geologically diverse Metamorphic Province, lead isotopes can be used to distinguish between the Northern Lowlands, the Southern Lowlands, and the Volcanic Highlands. The distinct lead isotope ratios in the sub-regions are related to the geology of the Maya area, exhibiting a general trend in the lowlands of geologically younger rocks in the north to older rocks in the south, and Cenozoic volcanic rocks in the southern highlands. Combined with other sourcing techniques such as strontium (87Sr/86Sr) and oxygen (δ18O), a regional baseline for lead isotope ratios can contribute to the development of lead isoscapes in the Maya area, and may help to distinguish among geographic sub-regions at a finer scale than has been previously possible. These isotope baselines will provide archaeologists with an additional tool to track the origin and movement of ancient humans and artifacts across this important region.