Development and validation of a self-updating gout register from electronic health records data.

OBJECTIVE: To develop an automatic gout register from electronic health records (EHRs) data. METHODS: We analysed the EHR of all patients >18 years old from a tertiary academic hospital (2013-2022) based on six criteria: International Classification of Diseases 10 gout diagnosis, urate-lowering therapy prescription, monosodium urate crystals in joint aspiration and gout-related terms in problem lists, clinical or imaging reports. We assessed the positive and negative predictive value (PPV and NPV) of the query by chart reviews. RESULTS: Of 2 110 902 outpatients and inpatients, 10 289 had at least one criterion for gout. The combination of joint aspiration OR diagnostic in the problem list OR≥2 other criteria created a register of 5138 patients, with a PPV of 92.4% (95% CI 88.5% to 95.0%) and an NPV of 94.3% (95% CI 91.9% to 96.0%). PPV and NPV were similar among outpatients and inpatients. Incidence was 2.9 per 1000 person-year and dropped by 30% from the COVID-19 pandemic onward. Patients with gout were on average 71.2 years old (SD 14.9), mainly male (76.5%), overweight (69.5%) and polymorbid (mean number of comorbidities of 3, IQR 1-5). More than half (57.4%) had received a urate-lowering treatment, 6.7% had a gout that led to a hospitalisation or ≥2 flares within a year and 32.9% received a rheumatology consultation. CONCLUSION: An automatic EHR-based gout register is feasible, valid and could be used to evaluate and improve gout management. Interestingly, the register uncovered a marked underdiagnosis or under-reporting of gout since the COVID-19 pandemic.

Validation of French versions of the 15-item picker patient experience questionnaire for adults, teenagers, and children inpatients.

Objectives: No French validated concise scales are available for measuring the experience of inpatients in pediatrics. This study aims to adapt the adult PPE-15 to a pediatric population, and translating it in French, as well as to establish reference values for adults, teenagers, and parents of young children. Methods: Cultural adaptation involved forward and backward translations, along with pretests in all three populations. Dimensional structure and internal consistency were assessed using principal component analysis, exploratory factor analysis, and Cronbach's alpha. Construct validity was assessed by examining established associations between patient satisfaction and inpatient variables, including length of stay, and preventable readmission. Results: A total of 25,626 adults, 293 teenagers and 1,640 parents of young children completed the French questionnaires. Factor analysis supported a single dimension (Cronbach's alpha: adults: 0.85, teenagers: 0.82, parents: 0.80). Construct validity showed the expected pattern of association, with dissatisfaction correlating with patient- and stay-related factors, notably length of stay, and readmission. Conclusion: The French versions of the PPE-15 for adults, teenagers and parents of pediatric patients stand as valid and reliable instruments for gauging patient satisfaction regarding their hospital stay after discharge.

A female woolly mammoth's lifetime movements end in an ancient Alaskan hunter-gatherer camp.

Woolly mammoths in mainland Alaska overlapped with the region's first people for at least a millennium. However, it is unclear how mammoths used the space shared with people. Here, we use detailed isotopic analyses of a female mammoth tusk found in a 14,000-year-old archaeological site to show that she moved ~1000 kilometers from northwestern Canada to inhabit an area with the highest density of early archaeological sites in interior Alaska until her death. DNA from the tusk and other local contemporaneous archaeological mammoth remains revealed that multiple mammoth herds congregated in this region. Early Alaskans seem to have structured their settlements partly based on mammoth prevalence and made use of mammoths for raw materials and likely food.

A hydrogen isoscape for tracing the migration of herbivorous lepidopterans across the Afro-Palearctic range.

RATIONALE: Many insect species undertake multigenerational migrations in the Afro-tropical and Palearctic ranges, and understanding their migratory connectivity remains challenging due to their small size, short life span and large population sizes. Hydrogen isotopes (δ2 H) can be used to reconstruct the movement of dispersing or migrating insects, but applying δ2 H for provenance requires a robust isotope baseline map (i.e. isoscape) for the Afro-Palearctic. METHODS: We analyzed the δ2 H in the wings (δ2 Hwing ) of 142 resident butterflies from 56 sites across the Afro-Palearctic. The δ2 Hwing values were compared to the predicted local growing-season precipitation δ2 H values (δ2 HGSP ) using a linear regression model to develop an insect wing δ2 H isoscape. We used multivariate linear mixed models and high-resolution and time-specific remote sensing climate and environmental data to explore the controls of the residual δ2 Hwing variability. RESULTS: A strong linear relationship was found between δ2 Hwing and δ2 HGSP values (r2 = 0.53). The resulting isoscape showed strong patterns across the Palearctic but limited variation and high uncertainty for the Afro-tropics. Positive residuals of this relationship were correlated with dry conditions for the month preceding sampling whereas negative residuals were correlated with more wet days for the month preceding sampling. High intra-site δ2 Hwing variance was associated with lower relative humidity for the month preceding sampling and higher elevation. CONCLUSION: The δ2 Hwing isoscape is applicable for tracing herbivorous lepidopteran insects that migrate across the Afro-Palearctic range but has limited geolocation potential in the Afro-tropics. The spatial analysis of uncertainty using high-resolution climatic data demonstrated that many African regions with highly variable evaporation rates and relative humidity have δ2 Hwing values that are less related to δ2 HGSP values. Increasing geolocation precision will require new modeling approaches using more time-specific environmental data and/or independent geolocation tools.

[Management of gout in the inpatient setting]. / Prise en charge hospitalière de la goutte.

Gout is a common complication occurring among inpatients, as factors affecting urate levels in blood and tissues are often modified by acute conditions. The control of chronic uricemia within recommended target values helps reduce the risk of flares. Joint aspiration is the gold standard for diagnosis, but ultrasound and dual-energy CT scan are reasonable alternatives. Acute and chronic treatments do not differ from those provided in outpatient care, although the increased prevalence of organ failures often require treatment adjustments. Active patient engagement, including therapeutic education during hospitalization, is essential for long-term disease control.

Lors d'un séjour hospitalier, les facteurs impactant la concentration sanguine et tissulaire d'urate sont souvent modifiés, augmentant le risque d'une crise de goutte. Le maintien de l'uricémie dans les cibles reconnues grâce à la poursuite des traitements contribue à réduire ce risque. La ponction articulaire est la méthode de référence pour établir le diagnostic, mais l'ultrason et le scanner à double énergie sont des alternatives fiables pour diagnostiquer une goutte. Les traitements aigu et chronique ne diffèrent pas de ceux pratiqués en ambulatoire, mais la fréquence augmentée d'insuffisances d'organes peut nécessiter l'adaptation des traitements. Pour assurer un contrôle de la maladie sur le long terme, il est essentiel d'impliquer le patient dans sa prise en charge, notamment par l'éducation thérapeutique dispensée pendant l'hospitalisation.

Applying Machine Learning to investigate metal isotope variations at the watershed scale: A case study with lithium isotopes across the Yukon River Basin.

Constraining the multiple climatic, lithological, topographic, and geochemical variables controlling isotope variations in large rivers is often challenging with standard statistical methods. Machine learning (ML) is an efficient method for analyzing multidimensional datasets, resolving correlated processes, and exploring relationships between variables simultaneously. We tested four ML algorithms to elucidate the controls of riverine δ7Li variations across the Yukon River Basin (YRB). We compiled (n = 102) and analyzed new samples (n = 21), producing a dataset of 123 river water samples collected across the basin during the summer including δ7Li and extracted environmental, climatological, and geological characteristics of the drainage area for each sample from open-access geospatial databases. The ML models were trained, tuned, and tested under multiple scenarios to avoid issues such as overfitting. Random Forests (RF) performed best at predicting δ7Li across the basin, with the median model explaining 62 % of the variance. The most important variables controlling δ7Li across the basin are elevation, lithology, and past glacial coverage, which ultimately influence weathering congruence. Riverine δ7Li has a negative dependence on elevation. This reflects congruent weathering in kinetically-limited mountain zones with short residence times. The consistent ranking of lithology, specifically igneous and metamorphic rock cover, as a top feature controlling riverine δ7Li modeled by the RFs is unexpected. Further study is required to validate this finding. Rivers draining areas that were extensively covered during the last glacial maximum tend to have lower δ7Li due to immature weathering profiles resulting in short residence times, less secondary mineral formation and therefore more congruent weathering. We demonstrate that ML provides a fast, simple, visualizable, and interpretable approach for disentangling key controls of isotope variations in river water. We assert that ML should become a routine tool, and present a framework for applying ML to analyze spatial metal isotope data at the catchment scale.

COVID-19 Vaccination Rate under Different Political Incentive: A Counterfactual Trend Approach Using Nationwide Data.

(1) Background: France implemented a COVID-19 certificate in July 2021 to incentivize the population to uptake COVID-19 vaccines. However, little is known about the variation in its impact across age groups and its dependence on socio-demographic, economic, logistic, or political factors. (2) Methods: Using France's weekly first dose vaccination rate, a counterfactual trend approach allowed for the estimation of the vaccination rate across age groups at a small geographical level before and after the implementation of the health pass. The effect of the health pass was operationalized as the vaccination rate among those who would not be vaccinated without it. (3) Results: Vaccination before the health pass varied greatly among age groups and was mainly influenced by territory (lower in rural and overseas territories when compared to urban and metropolitan ones), political beliefs, and socio-economic disparities. Vaccine logistics played a minor but significant role, while the impact of COVID-19 did not affect the vaccination rate. The health pass increased the vaccination overall but with varying efficiency across groups. It convinced mainly young people politically close to the governmental vaccination strategy and living in urban metropolitan areas with low socio-economical discrepancies. The selected variables explained most of the variability of the vaccination rate before the health pass; they explained, at most, a third of the variation in the health pass effect on vaccination. (4) Conclusions: From a public health perspective, the French health pass increased the overall vaccination, but failed to promote preventive behaviours in all segments of society, particularly in vulnerable communities.

The Afrotropical breeding grounds of the Palearctic-African migratory painted lady butterflies (Vanessa cardui).

Migratory insects are key players in ecosystem functioning and services, but their spatiotemporal distributions are typically poorly known. Ecological niche modeling (ENM) may be used to predict species seasonal distributions, but the resulting hypotheses should eventually be validated by field data. The painted lady butterfly (Vanessa cardui) performs multigenerational migrations between Europe and Africa and has become a model species for insect movement ecology. While the annual migration cycle of this species is well understood for Europe and northernmost Africa, it is still unknown where most individuals spend the winter. Through ENM, we previously predicted suitable breeding grounds in the subhumid regions near the tropics between November and February. In this work, we assess the suitability of these predictions through i) extensive field surveys and ii) two-year monitoring in six countries: a large-scale monitoring scheme to study butterfly migration in Africa. We document new breeding locations, year-round phenological information, and hostplant use. Field observations were nearly always predicted with high probability by the previous ENM, and monitoring demonstrated the influence of the precipitation seasonality regime on migratory phenology. Using the updated dataset, we built a refined ENM for the Palearctic-African range of V. cardui. We confirm the relevance of the Afrotropical region and document the missing natural history pieces of the longest migratory cycle described in butterflies.

Cellular and molecular features related to exceptional therapy response and extreme long-term survival in glioblastoma.

Glioblastoma Multiforme (GBM) remains the most common malignant primary brain tumor with a dismal prognosis that rarely exceeds beyond 2 years despite extensive therapy, which consists of maximal safe surgical resection, radiotherapy, and/or chemotherapy. Recently, it has become clear that GBM is not one homogeneous entity and that both intra-and intertumoral heterogeneity contributes significantly to differences in tumoral behavior which may consequently be responsible for differences in survival. Strikingly and in spite of its dismal prognosis, small fractions of GBM patients seem to display extremely long survival, defined as surviving over 10 years after diagnosis, compared to the large majority of patients. Although the underlying mechanisms for this peculiarity remain largely unknown, emerging data suggest that still poorly characterized both cellular and molecular factors of the tumor microenvironment and their interplay probably play an important role. We hereby give an extensive overview of what is yet known about these cellular and molecular features shaping extreme long survival in GBM.

Structural and functional analysis of natural capsid variants suggests sialic acid-independent entry of BK polyomavirus.

BK polyomavirus (BKPyV) is an opportunistic pathogen that uses the b-series gangliosides GD1b and GT1b as entry receptors. Here, we characterize the impact of naturally occurring VP1 mutations on ganglioside binding, VP1 protein structure, and virus tropism. Infectious entry of single mutants E73Q and E73A and the triple mutant A72V-E73Q-E82Q (VQQ) remains sialic acid dependent, and all three variants acquire binding to a-series gangliosides, including GD1a. However, the E73A and VQQ variants lose the ability to infect ganglioside-complemented cells, and this correlates with a clear shift of the BC2 loop in the crystal structures of E73A and VQQ. On the other hand, the K69N mutation in the K69N-E82Q variant leads to a steric clash that precludes sialic acid binding. Nevertheless, this mutant retains significant infectivity in 293TT cells, which is not dependent on heparan sulfate proteoglycans, implying that an unknown sialic acid-independent entry receptor for BKPyV exists.

Small-scale mobility fostering the interaction networks of Patagonian (Argentina) hunter-gatherers during the Late Holocene: Perspectives from strontium isotopes and exotic items.

During the Late Holocene, hunter-gatherer interaction networks significantly grew in intensity and extension across Patagonia. Although this growth is evidenced by the increased flow of exotic items across the region, the mechanisms behind these strengthening social networks remain unclear. Since evidence suggests that some individuals might have performed long-distance trips, this article aims to address the potential relationship between these individuals and the flows of exotic items in North Patagonia. We analyzed 54 enamel teeth for strontium isotopes and reconstructed their probable mobility using mixed-effect models and isotope-based geographic assignments. We inferred population and individual mobility trends and compared them against the flow of exotic items built from a standardized compilation. Our results indicate that most individuals have isotopic composition compatible with residence within their burial and surrounding areas. However, a few individuals show isotopic composition incompatible with their burial areas, which suggests axes -from the burial location to the most likely isotope integration area- of extraordinary mobility. At the same time, the flows of exotic items overlap with these axes around the eastern sector of the study area suggesting that this location could have been a central point of convergence for people and items. We argue that small-scale socially driven mobility could have played a relevant role as a general mechanism of interaction that fostered and materialized Patagonian interaction networks during the Late Holocene.

Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial.

Importance: Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed. Objective: To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma. Design, Setting, and Participants: This phase 3, prospective, externally controlled nonrandomized trial compared overall survival (OS) in patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) treated with DCVax-L plus SOC vs contemporaneous matched external control patients treated with SOC. This international, multicenter trial was conducted at 94 sites in 4 countries from August 2007 to November 2015. Data analysis was conducted from October 2020 to September 2021. Interventions: The active treatment was DCVax-L plus SOC temozolomide. The nGBM external control patients received SOC temozolomide and placebo; the rGBM external controls received approved rGBM therapies. Main Outcomes and Measures: The primary and secondary end points compared overall survival (OS) in nGBM and rGBM, respectively, with contemporaneous matched external control populations from the control groups of other formal randomized clinical trials. Results: A total of 331 patients were enrolled in the trial, with 232 randomized to the DCVax-L group and 99 to the placebo group. Median OS (mOS) for the 232 patients with nGBM receiving DCVax-L was 19.3 (95% CI, 17.5-21.3) months from randomization (22.4 months from surgery) vs 16.5 (95% CI, 16.0-17.5) months from randomization in control patients (HR = 0.80; 98% CI, 0.00-0.94; P = .002). Survival at 48 months from randomization was 15.7% vs 9.9%, and at 60 months, it was 13.0% vs 5.7%. For 64 patients with rGBM receiving DCVax-L, mOS was 13.2 (95% CI, 9.7-16.8) months from relapse vs 7.8 (95% CI, 7.2-8.2) months among control patients (HR, 0.58; 98% CI, 0.00-0.76; P < .001). Survival at 24 and 30 months after recurrence was 20.7% vs 9.6% and 11.1% vs 5.1%, respectively. Survival was improved in patients with nGBM with methylated MGMT receiving DCVax-L compared with external control patients (HR, 0.74; 98% CI, 0.55-1.00; P = .03). Conclusions and Relevance: In this study, adding DCVax-L to SOC resulted in clinically meaningful and statistically significant extension of survival for patients with both nGBM and rGBM compared with contemporaneous, matched external controls who received SOC alone. Trial Registration: ClinicalTrials.gov Identifier: NCT00045968.

Multi-isotopes in human hair: A tool to initiate cross-border collaboration in international cold-cases.

Unidentified human remains have historically been investigated nationally by law enforcement authorities. However, this approach is outdated in a globalized world with rapid transportation means, where humans easily move long distances across borders. Cross-border cooperation in solving cold-cases is rare due to political, administrative or technical challenges. It is fundamental to develop new tools to provide rapid and cost-effective leads for international cooperation. In this work, we demonstrate that isotopic measurements are effective screening tools to help identify cold-cases with potential international ramifications. We first complete existing databases of hydrogen and sulfur isotopes in human hair from residents across North America by compiling or analyzing hair from Canada, the United States (US) and Mexico. Using these databases, we develop maps predicting isotope variations in human hair across North America. We demonstrate that both δ2H and δ34S values of human hair are highly predictable and display strong spatial patterns. Multi-isotope analysis combined with dual δ2H and δ34S geographic probability maps provide evidence for international travel in two case studies. In the first, we demonstrate that multi-isotope analysis in bulk hair of deceased border crossers found in the US, close to the Mexico-US border, help trace their last place of residence or travel back to specific regions of Mexico. These findings were validated by the subsequent identification of these individuals through the Pima County Office of the Medical Examiner in Tucson, Arizona. In the second case study, we demonstrate that sequential multi-isotope analysis along the hair strands of an unidentified individual found in Canada provides detailed insights into the international mobility of this individual during the last year of life. In both cases, isotope data provide strong leads towards international travel.

Comparison of electrical and optical transduction modes of DNA-wrapped SWCNT nanosensors for the reversible detection of neurotransmitters.

In this study, we compare the electrical and optical signal transduction of nanoscale biosensors based on single-walled carbon nanotubes (SWCNTs). Solution processable single-stranded (ss) DNA-wrapped SWCNTs were used for the fabrication of the distinct sensors. For electrical measurements, SWCNTs were assembled from solution onto pre-patterned electrodes by electric-field-assisted assembly in field-effect transistor (FET) configuration. A combination of micro- and nano-fabrication and microfluidics enabled the integration into a sensing platform that allowed real-time and reversible detection. For optical measurements, the near-infrared (NIR) fluorescence of the SWCNTs was acquired directly from solution. The detection of important biomolecules was investigated in high-ionic strength solution (0.5xPBS). Increase in fluorescence intensities correlated with a decrease in the SWCNTs electrical current and enabled detection of the important biomolecules dopamine, epinephrine, and ascorbic acid. For riboflavin, however, a decrease in the fluorescence intensity could not be associated with changes in the SWCNTs electrical current, which indicates a different sensing mechanism. The combination of SWCNT-based electrical and optical transduction holds great potential for selective detection of biomarkers in next generation portable diagnostic assays.

Seasonal Growth of the Purple Sea Urchin Heliocidaris crassispina Revealed by Sequential Fluorochrome Tagging.

Many studies have applied fluorochrome tagging to examine the growth of animals with calcified skeletons, but most of them have used only a single tag to determine the annual growth rate. We used sequential fluorochrome tagging to study the seasonal growth of the purple sea urchin Heliocidaris crassispina in Hong Kong waters from February 2012 to February 2013. Sea urchins ranging from 18.9 to 42.7 mm in test diameter had a yearly growth from 0.6 to 13.0 mm. During that year, the sea urchins grew from 0.6 to 5.0 mm in test diameter during the first six months, and from 0.4 to 10.2 mm in test diameter in the second six months. The seasonal differences in growth were confirmed using the von Bertalanffy model. The growth was clear for young sea urchins, especially for individuals less than 5 years old, but was not evident for sea urchins older than 7 years. The seasonal differences in growth were probably related to the reproductive cycle and the seasonal differences in environmental conditions. Our empirical results provide the first evidence of seasonal changes in growth for H. crassispina, demonstrating the usefulness of sequential fluorochrome tagging in studying the growth of sea urchins in the field. We also identify the problem of low recovery of tagged individuals and provide recommendations to improve the tagging procedure.

The last battle of Anne of Brittany: Solving mass grave through an interdisciplinary approach (paleopathology, biological anthropology, history, multiple isotopes and radiocarbon dating).

Mass graves are usually key historical markers with strong incentive for archeological investigations. The identification of individuals buried in mass graves has long benefitted from traditional historical, archaeological, anthropological and paleopathological techniques. The addition of novel methods including genetic, genomic and isotopic geochemistry have renewed interest in solving unidentified mass graves. In this study, we demonstrate that the combined use of these techniques allows the identification of the individuals found in two Breton historical mass graves, where one method alone would not have revealed the importance of this discovery. The skeletons likely belong to soldiers from the two enemy armies who fought during a major event of Breton history: the siege of Rennes in 1491, which ended by the wedding of the Duchess of Brittany with the King of France and signaled the end of the independence of the region. Our study highlights the value of interdisciplinary approaches with a particular emphasis on increasingly accurate isotopic markers. The development of the sulfur isoscape and testing of the triple isotope geographic assignment are detailed in a companion paper [13].

Triple sulfur-oxygen-strontium isotopes probabilistic geographic assignment of archaeological remains using a novel sulfur isoscape of western Europe.

Sulfur isotope composition of organic tissues is a commonly used tool for gathering information about provenance and diet in archaeology and paleoecology. However, the lack of maps predicting sulfur isotope variations on the landscape limits the possibility to use this isotopic system in quantitative geographic assignments. We compiled a database of 2,680 sulfur isotope analyses in the collagen of archaeological human and animal teeth from 221 individual locations across Western Europe. We used this isotopic compilation and remote sensing data to apply a multivariate machine-learning regression, and to predict sulfur isotope variations across Western Europe. The resulting model shows that sulfur isotope patterns are highly predictable, with 65% of sulfur isotope variations explained using only 4 variables representing marine sulfate deposition and local geological conditions. We used this novel sulfur isoscape and existing strontium and oxygen isoscapes of Western Europe to apply triple isotopes continuous-surface probabilistic geographic assignments to assess the origin of a series of teeth from local animals and humans from Brittany. We accurately and precisely constrained the origin of these individuals to limited regions of Brittany. This approach is broadly transferable to studies in archaeology and paleoecology as illustrated in a companion paper (Colleter et al. 2021).

Corrigendum to "Clinical Presentation, Natural History, and Therapeutic Approach in Patients with Solitary Fibrous Tumor: A Retrospective Analysis".

[This corrects the article DOI: 10.1155/2020/1385978.].