Pan-tropical Sentinel-2 cloud-free annual composite datasets.

Sentinel-2 MSI is one of the core missions of the Copernicus Earth Observation programme of the European Union. This mission shows great potential to map the regional high-resolution spatio-temporal dynamics of land use and land cover. In tropical regions, despite the high revisiting time of 5 days including both Sentinel-2A and 2B satellites, the frequent presence of clouds, cloud-shadows, haze and other atmospheric contaminants are precluding the visibility of the Earth surface up to several months. In this paper we present four annual pan-tropical cloud-free composites computed and exported from Google Earth Engine (GEE) by making use of available Sentinel-2 L1C collection for the period spanning from 2015 to 2020. We furthermore propose empirical approaches to reduce the BRDF effect over tropical forest areas by showing pros and cons of image-based versus swath-based methodologies. Additionally, we provide a dedicated web-platform offering a fast and intuitive way to browse and explore the proposed annual composites as well as layers of potential annual changes as a ready-to-use means to visually identify and verify degradation and deforestation activities as well as other land cover changes.

MUFFIN-PTS trial, Micronized Purified Flavonoid Fraction for the Treatment of Post-Thrombotic Syndrome: protocol of a randomised controlled trial.

INTRODUCTION: After deep vein thrombosis, up to 50% of patients develop post-thrombotic syndrome (PTS). PTS is a chronic condition that reduces quality of life (QOL). Cornerstones of PTS treatment include the use of elastic compression stockings but this treatment is usually incompletely effective and is burdensome. Venoactive drugs have been reported to be effective to treat chronic venous insufficiency (CVI). However, the level of evidence supporting their use in CVI in general and in PTS in particular is low. METHODS AND ANALYSIS: The MUFFIN-PTS trial is an academic, publically funded, multicentre randomised placebo-controlled trial assessing the efficacy of micronised purified flavonoid fraction (MPFF, Venixxa), a venoactive drug, to treat PTS. Eighty-six patients with PTS (Villalta score (VS) ≥5) and experiencing at least two of the following PTS manifestations among daily leg heaviness, cramps, pain or oedema will be randomised to receive 1000 mg of oral MPFF or a similar appearing placebo for 6 months, in addition to their usual PTS treatment. Total study follow-up will be 9 months, with visits at inclusion/baseline, 3, 6 and 9 months. Primary outcome is the proportion of patients with improvement in VS in each group, where improvement is defined as a decrease of at least 30% in VS or a VS <5 in the PTS-affected leg. Main secondary outcomes include QOL and patient satisfaction. ETHICS AND DISSEMINATION: Primary ethics approval was received from Centre intégré universitaire de santé et de services sociaux (CIUSSS) West-Central Montreal Research Ethics Board. Results of the study will be disseminated via peer-reviewed publications and presentations at scientific conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03833024); Pre-results.

Adherence to, and outcomes of, a galactomannan screening protocol in high-risk hematology patients.

Background: A twice-weekly galactomannan (gm) screening protocol was implemented in high-risk hematology inpatients. Study objectives were to determine adherence to the protocol, use of selected resources, and patient outcomes. Methods: This retrospective cohort study compared outcomes of interest before and after implementation of gm screening. Adults undergoing matched related allogeneic hematopoietic stem-cell transplantation or induction chemotherapy for acute leukemia were eligible. Patients could be enrolled more than once and were evaluated as episodes. Adherence to the gm protocol was assessed in post-implementation episodes. Use of broad-spectrum antifungals (bsafs), consultations (infectious diseases, respirology), and diagnostic procedures (computed tomography imaging, bronchoalveolar lavage) were compared between phases, as were the patient outcomes of all-cause mortality and clinical success (alive and not taking a bsaf). Results: Of 182 episodes consecutively screened, 70 per phase were enrolled. Clinical characteristics and duration of assessment were similar for the phases. Full or partial adherence to the protocol was observed in 61 post-implementation episodes (87%), with full adherence in 40 episodes (57%). More episodes in the pre-implementation phase than in the post-implementation phase involved receipt of bsafs, consultations, and diagnostics (27% vs. 7%, p = 0.02; 46% vs. 26%, p = 0.014; and 46% vs. 31%, p = 0.083 respectively). Although mortality was similar in the two phases, clinical success at the final assessment was observed in fewer pre-implementation than post-implementation episodes (79% vs. 98%, p < 0.001). Conclusions: Implementation of a gm screening protocol was feasible and associated with significantly fewer episodes involving receipt of bsafs and consultations, and with significantly more episodes showing clinical success.

A prospective study of Rivaroxaban for central venous catheter associated upper extremity deep vein thrombosis in cancer patients (Catheter 2).

INTRODUCTION: Patients with cancer are at increased risk of thrombosis, particularly those with central venous catheter (CVC) placement, which may predispose to the development of upper extremity deep vein thrombosis (UEDVT). Standard treatment includes low molecular weight heparin (LMWH) or LMWH bridged to warfarin. The direct oral anticoagulants (DOACs) have become standard of care for uncomplicated venous thromboembolism (VTE), but research in patients with cancer is ongoing. OBJECTIVES: To assess rivaroxaban monotherapy in patients with cancer who develop UEDVT due to CVC for preservation of line function, and safety outcomes of VTE recurrence, bleeding risk and death. MATERIALS AND METHODS: Patients ≥18years of age with active malignancy and symptomatic proximal UEDVT with or without pulmonary embolism (PE), associated with a CVC, were eligible. Treatment included rivaroxaban 15mg oral twice daily for 3weeks, followed by 20mg oral daily for 9weeks. Patients were followed clinically for 12weeks to assess for line function, recurrent VTE and bleeding. RESULTS: Seventy patients (47 women) were included, with mean age 54.1years. The most common malignancy was breast cancer (41%). Preservation of line function was 100% at 12weeks. The risk of recurrent VTE at 12weeks was 1.43%, with one episode of fatal PE. 9 patients (12.9%) experienced 11 total bleeding episodes. CONCLUSIONS: Rivaroxaban showed promise in treating CVC-UEDVT in cancer patients, resulting in preserved line function. However, bleeding rates and a fatal pulmonary embolism on treatment are concerning safety outcomes necessitating further study before rivaroxaban can be recommended.

Clinical challenges in patients with cancer-associated thrombosis: Canadian expert consensus recommendations.

Venous thromboembolism is a common complication in cancer patients, and thromboembolism is the second most common cause of death after cancer progression. A number of clinical practice guidelines provide recommendations for the management of cancer-associated thrombosis. However, the guidelines lack recommendations covering commonly encountered clinical challenges (for example, thrombocytopenia, recurrent venous thromboembolism, etc.) for which little or no evidence exists. Accordingly, recommendations were developed to provide expert guidance to medical oncologists and other health care professionals caring for patients with cancer-associated thrombosis. The current expert consensus was developed by a team of 21 clinical experts. For each identified clinical challenge, the literature in medline, embase, and Evidence Based Medicine Reviews was systematically reviewed. The quality of the evidence was assessed, summarized, and graded. Consensus statements were generated, and the experts voted anonymously using a modified Delphi process on their level of agreement with the various statements. Statements were progressively revised through separate voting iterations and were then finalized. Clinicians using these recommendations and suggestions should tailor patient management according to the risks and benefits of the treatment options, patient values and preferences, and local cost and resource allocations.

Inflammation markers and their trajectories after deep vein thrombosis in relation to risk of post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT). OBJECTIVE: In the BioSOX study, we investigated whether inflammation markers predict the risk of PTS after DVT. METHODS: We measured C-reactive protein (CRP), ICAM-1, interleukin (IL)-6, and IL-10, at baseline, and 1 month and 6 months after a first proximal DVT, among 803 participants in the SOX trial. Participants were prospectively followed for 24 months for development of PTS. RESULTS: Median CRP levels at 1 month, ICAM-1 levels at baseline, 1 month and 6 months, IL-6 levels at 1 month and 6 months and IL-10 levels at 6 months were higher in patients who developed PTS than in those who did not. Multivariable regression with the median as a cutoff showed risk ratios (RRs) for PTS of 1.23 (95% confidence interval [CI] 1.05-1.45) and 1.25 (95% CI 1.05-1.48) for ICAM-1 at 1 month and 6 months, respectively, and 1.27 (95% CI 1.07-1.51) for IL-10 at 6 months. Quartile-based analysis demonstrated a dose-response association between ICAM-1 and PTS. ICAM-1 and IL-10 were also associated with PTS severity. Analysis of biomarker trajectories after DVT demonstrated an association between the highest-trajectory group of ICAM-1 and PTS. CONCLUSIONS: In this prospective study, ICAM-1 over time was most consistently associated with the risk of PTS. Further study is required to confirm these findings and assess their potential clinical relevance.

Rivaroxaban vs. low molecular weight heparin for the prevention of venous thromboembolism after hip or knee arthroplasty: a cohort study.

BACKGROUND: Rivaroxaban is increasingly used to prevent venous thromboembolism after hip or knee arthroplasty. Studies evaluating the effectiveness of rivaroxaban compared to low molecular weight heparin after orthopedic surgery in routine practice are scarce. PATIENTS AND METHODS: We conducted a retrospective cohort study in 121 hospitals in Ontario, Canada, between 2002 and 2012. We included patients aged 66 years or older (median age 73 years) who received an outpatient prescription for subcutaneous low molecular weight heparin (n = 11 471) or oral rivaroxaban (n = 12 850) on hospital discharge after a total knee or hip arthroplasty. The two coprimary outcomes assessed within 30 days of the prescription date were emergency department visit or hospitalization with venous thromboembolism (either deep vein thrombosis or pulmonary embolism; primary efficacy outcome) and a hospitalization with non-traumatic major hemorrhage (primary safety outcome). RESULTS: Rivaroxaban use increased over the study period. Compared to low molecular weight heparin, rivaroxaban was associated with a lower 30-day risk of hospitalization with venous thromboembolism (0.47% vs. 0.81%; relative risk 0.58; 95% confidence interval 0.42-0.81; P = 0.001) with no significant difference in hospitalizations for major bleeding (0.18% vs. 0.20%; relative risk 0.89; 95% confidence interval 0.50-1.59; P = 0.700). CONCLUSIONS: In routine practice, anticoagulant prophylaxis with rivaroxaban compared to low molecular weight heparin after hospital discharge from total hip or knee arthroplasty is associated with a lower risk of symptomatic venous thromboembolism with no difference in the risk of bleeding.

The effect of low molecular weight heparin on survival in cancer patients: an updated systematic review and meta-analysis of randomized trials.

BACKGROUND: Tumors may exploit the coagulation system to enhance the survival and dissemination of cancer cells. Some studies have suggested that heparin and low molecular weight heparin (LMWH) have antitumor effects. We reported a previous meta-analysis that suggested a modest improvement in overall survival with the use of LMWH in patients with cancer. Herein, we present the results of an updated systematic review and meta-analysis. OBJECTIVE: To evaluate the effect of LMWH as compared with placebo or no anticoagulant on the overall survival in patients with solid cancers. METHODS: We conducted a systematic review and meta-analysis of randomized trials evaluating the use of LMWH vs. placebo or no anticoagulant in cancer patients without venous thrombosis. A meta-analysis was conducted with a random-effects model, and data were analyzed by the use of odds ratios (ORs) and relative risks (RRs) calculated for 1-year overall mortality. RESULTS: We identified 724 potentially relevant studies, nine of which met our inclusion criteria, and reported data on 1-year overall mortality. Studies were heterogeneous regarding types of cancer and interventions, and included 5987 patients, 98.4% of whom had advanced-stage disease (III and IV). There was no discernible effect on mortality with the use of LMWH (pooled OR 0.87, 95% CI 0.70-1.08; RR 0.94, 95% CI 0.86-1.04). CONCLUSIONS: In contrast to the previous study, these results did not show a survival benefit in cancer patients receiving LMWH. The effect of LMWH on overall survival in patients with limited-stage disease still is unknown.

Patient preferences for stopping tyrosine kinase inhibitors in chronic myeloid leukemia.

BACKGROUND: We used an interview-assisted survey of patients with chronic myeloid leukemia (cml) at a single tertiary care centre to explore patient reactions to and preferences for, and the risk-acceptability of, stopping tyrosine kinase inhibitor (tki) treatment. METHODS: The study included patients with confirmed cml currently being treated with a tki. The survey was conducted by structured interview using a standard form. Patient preferences were explored in a case-based scenario using 0%-100% visual analog scales and 5-point Likert scales. Data were analyzed using proportions for dichotomous variables and medians and interquartile ranges for continuous variables. RESULTS: Of 63 patients approached, 56 completed the survey. Participant responses suggest that the idea of stopping tki use is appealing to many patients if there is a chance of long-term stable disease and a high probability of response upon restarting a tki. Participants were more likely to stop their tki as the risk of relapse decreased. Participants reported loss of disease control and failure of disease to respond to treatment as important concerns if they chose to stop their tki. CONCLUSIONS: Given the current 60% estimated rate of relapse after discontinuation of tki therapy, most patients with cml chose to continue with tki. However, at the lower relapse rates reported with second-generation tkis, participants were more undecided, demonstrating a basic understanding of risk. Contrary to our hypothesis, neither compliance nor occurrence of side effects significantly affected patient willingness to stop their tki.

Clinical performance of bleeding risk scores for predicting major and clinically relevant non-major bleeding events in patients receiving warfarin.

BACKGROUND: Oral anticoagulant therapy is associated with an increased risk of hemorrhage, which can be assessed by bleeding risk scores. We evaluated the performance of five validated scores for predicting major and clinically relevant non-major bleeding events in patients receiving warfarin. METHODS AND RESULTS: We conducted an ambispective, single-center cohort study of 321 consecutive patients enrolled in an academic anticoagulation clinic. The following scores were calculated: modified Outpatient Bleeding Risk Index, Contemporary Bleeding Risk Model, HEMORR(2)HAGES (Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly, Drugs/Alcohol). Main outcomes were major bleeding and a composite of major plus clinically relevant non-major bleeding. Incidence rates for all group were 3.8 (95% confidence interval [CI] 2.0-6.4) and 11.9 (95% CI 8.6-16.4) events per 100 patient-years for major bleeding and major plus clinically relevant non-major bleeding, respectively. Agreement among the five scores was low to moderate (Kendall's tau-b coefficients 0.22-0.54). For major bleeding, the c-statistics ranged from 0.606 to 0.735, whereas for major plus clinically relevant non-major bleeding, they ranged from 0.549 to 0.613. For all scores, the 95% CI for the c-statistics crossed 0.5 or was very close. Among high-risk patients, the hazard ratios for major bleeding ranged from 0.90 to 39.01, whereas for major plus clinically relevant non-major bleeding, they ranged from 1.52 to 8.71. For intermediate-risk patients, no score, except the Contemporary Bleeding Risk Model, produced statistically significant hazard ratios. CONCLUSION: The scores demonstrated poor agreement and low to moderate discriminatory ability. General clinical implementation of these scores cannot be recommended yet.

Superexchange-mediated ferromagnetic coupling in two-dimensional Ni-TCNQ networks on metal surfaces.

We investigate the magnetic coupling of Ni centers embedded in two-dimensional metal-coordination networks self-assembled from 7,7,8,8-tetracyanoquinodimethane (TCNQ) molecules on Ag(100) and Au(111) surfaces. X-ray magnetic circular dichroism measurements show that single Ni adatom impurities assume a spin-quenched configuration on both surfaces, while Ni atoms coordinating to TCNQ ligands recover their magnetic moment and exhibit ferromagnetic coupling. The valence state and the ferromagnetic coupling strength of the Ni coordination centers depend crucially on the underlying substrate due to the different charge state of the TCNQ ligands on the two surfaces. The results suggest a superexchange coupling mechanism via the TCNQ ligands.

Cisplatin and short-term 5-Fluorouracil infusion for paraneoplastic microangiopathic hemolytic anemia in gastric cancer: a case report and review of the literature.

Microangiopathic hemolytic anemia is a rare paraneoplastic syndrome accompanying adenocarcinoma of the stomach. We report on a patient presenting with anemia due to a combination of severe hemolysis and tumour bleeding, where the combination of cisplatin and 5-fluorouracil in a short course infusional regimen led to a complete response of the hematologic abnormalities in the first line setting. Relapse was successfully treated with second line docetaxel; however the response was relatively short-lived. Overall survival was 16 months from diagnosis, which compares favourably to the survival of other reported cases. The chemotherapy regimens used in previously reported similar cases are reviewed. We suggest that a regimen based on bolus 5-fluorouracil, possibly with a platinum, should be investigated as a possible regimen of choice.

Conservative perioperative anticoagulation management in patients with chronic venous thromboembolic disease: a cohort study.

BACKGROUND: Guidelines for perioperative warfarin management in patients with venous thromboembolic disease (VTE) are largely based on expert opinion. OBJECTIVES: To assess the effectiveness and safety of a conservative perioperative anticoagulation strategy in patients with VTE on chronic warfarin therapy. Our center uses a conservative bridging approach for chronic VTE patients consisting of withholding warfarin for 5 days preoperatively, with prophylactic low-molecular-weight heparin (LMWH) post-procedure only if patients are admitted to hospital. PATIENTS/METHODS: We performed a single-center retrospective cohort study. During the study period (1997-2011) there were 634 procedures in 416 patients that were reviewed for postoperative outcomes at 30 and 90 days. RESULTS: Of the 634 procedures, 156 procedures (24.6%) were completed as inpatients. Pre- and post-procedure LMWH bridging was used in 15 (2.4%) and 152 (24.0%) of all procedures, respectively. The 30-day VTE incidence was 0.32% (95% confidence interval [CI] 0.087-1.14), all non-fatal DVTs. The 30-day incidence of major and total bleeding events was 1.26% (95% CI 0.64-2.47) and 3.00% (95% CI 1.93-4.63), respectively. The all-cause mortality rate was 0.32% (95% CI 0.087-1.14) at 30 days; two patients died from arterial thrombosis events. CONCLUSIONS: A randomized controlled trial is needed to provide definitive conclusions but a conservative bridging approach appears promising.

Mixture-process variable approach to optimize a microemulsion electrokinetic chromatography method for the quality control of a nutraceutical based on coenzyme Q10.

In recent years, multivariate optimization has played an increasing role in analytical method development. ICH guidelines recommend using statistical design of experiments to identify the design space, in which multivariate combinations of composition variables and process variables have been demonstrated to provide quality results. Considering a microemulsion electrokinetic chromatography method (MEEKC), the performance of the electrophoretic run depends on the proportions of mixture components (MCs) of the microemulsion and on the values of process variables (PVs). In the present work, for the first time in the literature, a mixture-process variable (MPV) approach was applied to optimize a MEEKC method for the analysis of coenzyme Q10 (Q10), ascorbic acid (AA), and folic acid (FA) contained in nutraceuticals. The MCs (buffer, surfactant-cosurfactant, oil) and the PVs (voltage, buffer concentration, buffer pH) were simultaneously changed according to a MPV experimental design. A 62-run MPV design was generated using the I-optimality criterion, assuming a 46-term MPV model allowing for special-cubic blending of the MCs, quadratic effects of the PVs, and some MC-PV interactions. The obtained data were used to develop MPV models that express the performance of an electrophoretic run (measured as peak efficiencies of Q10, AA, and FA) in terms of the MCs and PVs. Contour and perturbation plots were drawn for each of the responses. Finally, the MPV models and criteria for the peak efficiencies were used to develop the design space and an optimal subregion (i.e., the settings of the mixture MCs and PVs that satisfy the respective criteria), as well as a unique optimal combination of MCs and PVs.

Fabrication of quasiperiodic nanostructures with EUV interference lithography.

We demonstrate the fabrication and analysis of well-ordered high-resolution quasiperiodic nanostructures with feature sizes down to a few tens of nanometers using extreme ultraviolet interference lithography. A well-controlled mask manufacturing process for producing high quality transmission diffraction masks enables simple and fast fabrication of highly ordered 2D quasiperiodic structures using 5- and 8-beam interference setups.

Heavy metals distribution in an Iowa suburban landscape.

This study investigated the degree to which human activities through urbanization influence heavy metal concentrations in a suburban landscape in Ankeny, IA. Residential areas from different years in nine time periods of development were identified from aerial photos. Soil cores were collected from the center of the front yard of 10 randomly selected homes. Cores were subdivided into 0- to 5-, 5- to 10-, and 10- to 20-cm increments from a composite of five cores. The soils were analyzed for organic C, pH, and total Cd, Co, Cr, Cu, Ni, Pb, and Zn. Results showed that organic C increased and pH decreased with time, and that there was a general decreasing trend in heavy metal concentrations from the pre-1939 period until 1983-1990, after which there was a sharp increase in the concentrations of most of the metals. The mean Cu concentration ranged from 21 mg kg(-1) for the pre-1939 time period of development to 14.9 mg kg(-1) for the recent period of development (2003-2005). Nickel concentrations increased significantly with depth with means of 21.3 mg kg(-1) at depth 0 to 5 cm, 22.5 mg kg(-1) at depth 5 to 10 cm, and 23.0 mg kg(-1) at depth 10 to 20 cm. The concentrations of heavy metals were significantly intercorrelated, except Zn, suggesting their coexistence as mineral constituents or common contamination source. The concentrations of Cu and Pb in some locations could be due to anthropogenic inputs or higher organic matter content in soils adjacent to older homes. There appears to have been a source that caused an increase in Cd, Cr, Co, Cu, Pb, and Ni concentrations in soil adjacent to homes built between 1983 and 1990.