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Aims: It is unclear whether activated partial thromboplastin time (aPTT) or anti‐Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti‐Xa in MCS patients and identifies predictors of discordance. Methods and results: aPTT and anti‐Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti‐Xa levels were 60–100 s and 0.3–0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning random forest model and a multivariate regression model were applied to patient demographics, device type, and 14 laboratory variables; 23 001 pairs of simultaneously measured aPTT/anti‐Xa were collected from 699 MCS patients. aPTT and anti‐Xa were concordant in 35.5% of paired observations and discordant in 64.5% (aPTT > antiXa 61.5%; aPTT < antiXa 3.0%). Discordance with a high aPTT relative to anti‐Xa (aPTT > antiXa) was associated with high INR, eGFR, and total bilirubin, as well as low platelets, haemoglobin, pre‐albumin, white blood cell count, and haptoglobin. Total artificial heart and durable ventricular assist devices were more likely to be associated with aPTT > anti‐Xa than temporary MCS devices. Conclusions: aPTT and anti‐Xa were frequently discordant in MCS patients receiving heparin anticoagulation. Clinical conditions common in MCS patients such as concurrent warfarin use, malnutrition, haemolysis, and thrombocytopenia, as well as durable type of MCS devices were associated with a high aPTT relative to anti‐Xa. [ABSTRACT FROM AUTHOR]

Friction stir welding (FSW) produces a gradient microstructure with distinct metallurgical zones. The present study focuses on characterizing the fracture behavior during uniaxial loading across thick‐section FSW joint in nonheat‐treatable 5083 aluminum alloy. The hardness variation is linked to microstructural features across the weld zones through correlative microscopy. Notably, the heat‐affected zone (HAZ) exhibits a lower hardness of 75 HV, while the thermomechanically affected zone (TMAZ) and stir zones (SZ) display a hardness of around 79HV. A marginal difference in hardness in HAZ prompts strain localization in HAZ on the advancing side of the weld, resulting in offset in fracture from the SZ, which is captured through in situ monitoring of the tensile test. Further, the postdeformation analysis reveals crack propagation along the maximum shear stress plane due to the coalescence of microvoids resulting from the fracturing and debonding of second‐phase particles. Overall, this study provides valuable insight for optimizing the FSW process of AA 5083 alloy for thick‐section applications. [ABSTRACT FROM AUTHOR]

Background: Hispanics and American Indians (AI) have high kidney cancer incidence and mortality rates in Arizona. This study assessed: (1) whether racial and ethnic minority patients and patients from neighborhoods with high social vulnerability index (SVI) experience a longer time to surgery after clinical diagnosis, and (2) whether time to surgery, race and ethnicity, and SVI are associated with upstaging to pT3/pT4, disease‐free survival (DFS), and overall survival (OS). Methods: Arizona Cancer Registry (2009–2018) kidney and renal pelvis cases (n = 4592) were analyzed using logistic regression models to assess longer time to surgery and upstaging. Cox‐regression hazard models were used to test DFS and OS. Results: Hispanic and AI patients with T1 tumors had a longer time to surgery than non‐Hispanic White patients (median time of 56, 55, and 45 days, respectively). Living in neighborhoods with high (≥75) overall SVI increased odds of a longer time to surgery for cT1a (OR 1.54, 95% CI: 1.02–2.31) and cT2 (OR 2.32, 95% CI: 1.13–4.73). Race and ethnicity were not associated with time to surgery. Among cT1a patients, a longer time to surgery increased odds of upstaging to pT3/pT4 (OR 1.95, 95% CI: 0.99–3.84). A longer time to surgery was associated with PFS (HR 1.52, 95% CI: 1.17–1.99) and OS (HR 1.63, 95% CI: 1.26–2.11). Among patients with cT2 tumor, living in high SVI neighborhoods was associated with worse OS (HR 1.66, 95% CI: 1.07–2.57). Conclusions: High social vulnerability was associated with increased time to surgery and poor survival after surgery. [ABSTRACT FROM AUTHOR]

Background: Myocardial feature tracking (FT) provides a comprehensive analysis of myocardial deformation from cine balanced steady‐state free‐precession images (bSSFP). However, FT remains time‐consuming, precluding its clinical adoption. Purpose: To compare left‐ventricular global radial strain (GRS) and global circumferential strain (GCS) values measured using automated DeepStrain analysis of short‐axis cine images to those calculated using manual commercially available FT analysis. Study Type: Retrospective, single‐center. Population: A total of 30 healthy subjects and 120 patients with cardiac disease for DeepStrain development. For evaluation, 47 healthy subjects (36 male, 53 ± 5 years) and 533 patients who had undergone a clinical cardiac MRI (373 male, 59 ± 14 years). Field Strength/Sequence: bSSFP sequence at 1.5 T (Phillips) and 3 T (Siemens). Assessment: Automated DeepStrain measurements of GRS and GCS were compared to commercially available FT (Circle, cvi42) measures obtained by readers with 1 year and 3 years of experience. Comparisons were performed overall and stratified by scanner manufacturer. Statistical Tests: Paired t‐test, linear regression slope, Pearson correlation coefficient (r). Results: Overall, FT and DeepStrain measurements of GCS were not significantly different (P = 0.207), but measures of GRS were significantly different. Measurements of GRS from Philips (slope = 1.06 [1.03 1.08], r = 0.85) and Siemens (slope = 1.04 [0.99 1.09], r = 0.83) data showed a very strong correlation and agreement between techniques. Measurements of GCS from Philips (slope = 0.98 [0.98 1.01], r = 0.91) and Siemens (slope = 1.0 [0.96 1.03], r = 0.88) data similarly showed a very strong correlation. The average analysis time per subject was 4.1 ± 1.2 minutes for FT and 34.7 ± 3.3 seconds for DeepStrain, representing a 7‐fold reduction in analysis time. Data Conclusion: This study demonstrated high correlation of myocardial GCS and GRS measurements between freely available fully automated DeepStrain and commercially available manual FT software, with substantial time‐saving in the analysis. Evidence Level: 3 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) plays an increasingly important role in the diagnosis and prognosis of neurodegenerative diseases. One field of extensive clinical use of MRI is the accurate and automated classification of degenerative disorders. Most of current classification studies either do not mirror medical practice where patients may exhibit early stages of the disease, comorbidities, or atypical variants, or they are not able to produce probabilistic predictions nor account for uncertainty. Also, the spatial heterogeneity of the brain alterations caused by neurodegenerative processes is not usually considered, despite the spatial configuration of the neuronal loss is a characteristic hallmark for each disorder. In this article, we propose a classification technique that incorporates uncertainty and spatial information for distinguishing between healthy subjects and patients from four distinct neurodegenerative diseases: Alzheimer's disease, mild cognitive impairment, Parkinson's disease, and Multiple Sclerosis. We introduce a spatially informed Bayesian neural network (SBNN) that combines a three‐dimensional neural network to extract neurodegeneration features from MRI, Bayesian inference to account for uncertainty in diagnosis, and a spatially informed MRI image using hidden Markov random fields to encode cerebral spatial information. The SBNN model demonstrates that classification accuracy increases up to 25% by including a spatially informed MRI scan. Furthermore, the SBNN provides a robust probabilistic diagnosis that resembles clinical decision‐making and can account for the heterogeneous medical presentations of neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Background: Although adherence to the American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity for Cancer Prevention associates with lower risk of obesity-related cancer (ORC) incidence and mortality, evidence in Black and Latina women is limited. This association was examined in Black and Latina participants in the Women's Health Initiative (WHI).Methods: Semi-Markov multistate model examined the association between ACS guideline adherence and ORC incidence and mortality in the presence of competing events, combined and separately, for 9301 Black and 4221 Latina postmenopausal women. Additionally, ACS guideline adherence was examined in a subset of less common ORCs and potential effect modification by neighborhood socioeconomic status and smoking.Results: Over a median of 11.1, 12.5, and 3.7 years of follow-up for incidence, nonconditional mortality, and conditional mortality, respectively, 1191 ORCs (Black/Latina women: 841/269), 1970 all-cause deaths (Black/Latina women: 1576/394), and 341 ORC-related deaths (Black/Latina women: 259/82) were observed. Higher ACS guideline adherence was associated with lower ORC incidence for both Black (cause-specific hazard ratio [CSHR]highvs.low : 0.72; 95% CI, 0.55-0.94) and Latina (CSHRhighvs.low : 0.58, 95% CI, 0.36-0.93) women; but not conditional all-cause mortality (Black hazard ratio [HR]highvs.low : 0.86; 95% CI, 0.53-1.39; Latina HRhighvs.low : 0.81; 95% CI, 0.32-2.06). Higher adherence was associated with lower incidence of less common ORC (Ptrend  = .025), but conditional mortality events were limited. Adherence and ORC-specific deaths were not associated and there was no evidence of effect modification.Conclusions: Adherence to the ACS guidelines was associated with lower risk of ORCs and less common ORCs but was not for conditional ORC-related mortality.Lay Summary: Evidence on the association between the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and cancer remains scarce for women of color. Adherence to the guidelines and risk of developing one of 13 obesity-related cancers among Black and Latina women in the Women's Health Initiative was examined. Women who followed the lifestyle guidelines had 28% to 42% lower risk of obesity-related cancer. These findings support public health interventions to reduce growing racial/ethnic disparities in obesity-related cancers. [ABSTRACT FROM AUTHOR]

Background: Anticoagulation requires urgent reversal in cases of life-threatening bleeding or invasive procedures.Study Design and Methods: Network meta-analysis for comparing the safety and efficacy of warfarin reversal strategies including plasma and prothrombin complex concentrates (PCCs).Results: Seven studies including 594 subjects using reversal agents plasma, 3-factor-PCC (Uman Complex and Konyne), and 4-factor-PCC (Beriplex/KCentra, Octaplex, and Cofact) met inclusion criteria. Compared with plasma, patients receiving Cofact probably have a higher rate of international normalized ratio (INR) correction (risk difference [RD] 499 more per 1000 patients, 95% confidence interval [CI], 176-761, low certainty[LC]); higher reversal of bleeding (323 more per 1000 patients, 11-344 more, LC); and fewer transfusion requirements (0.96 fewer units, 1.65-0.27 fewer, LC). Patients receiving Beriplex/KCentra probably have a higher rate of INR correction (476 more per 1000 patients, 332-609 more, LC); higher reversal of bleeding (127 more per 1000 patients, 43 fewer to 236 more); and similar transfusion requirements (0.01 fewer units, 0.31 fewer to 0.28 more, high/moderate certainty). Patients receiving Octaplex probably have a higher rate of INR correction (RD 579 more per 1000 patients, 189-825 more, LC).Conclusions: PCCs probably provide an advantage in INR reversal compared to plasma. There was no added risk of adverse events with PCCs. [ABSTRACT FROM AUTHOR]

The overall 5-year relative survival rate for all cancers combined is now 68%, and there are over 16.9 million survivors in the United States. Evidence from laboratory and observational studies suggests that factors such as diet, physical activity, and obesity may affect risk for recurrence and overall survival after a cancer diagnosis. The purpose of this American Cancer Society guideline is to provide evidence-based, cancer-specific recommendations for anthropometric parameters, physical activity, diet, and alcohol intake for reducing recurrence and cancer-specific and overall mortality. The audiences for this guideline are health care providers caring for cancer survivors as well as cancer survivors and their families. The guideline is intended to serve as a resource for informing American Cancer Society programs, health policy, and the media. Sources of evidence that form the basis of this guideline are systematic literature reviews, meta-analyses, pooled analyses of cohort studies, and large randomized clinical trials published since 2012. Recommendations for nutrition and physical activity during cancer treatment, informed by current practice, large cancer care organizations, and reviews of other expert bodies, are also presented. To provide additional context for the guidelines, the authors also include information on the relationship between health-related behaviors and comorbidities, long-term sequelae and patient-reported outcomes, and health disparities, with attention to enabling survivors’ ability to adhere to recommendations. Approaches to meet survivors’ needs are addressed as well as clinical care coordination and resources for nutrition and physical activity counseling after a cancer diagnosis. [ABSTRACT FROM AUTHOR]

Objective: An international multidisciplinary initiative, jointly supported by the American College of Rheumatology and European Alliance of Associations for Rheumatology, is underway to develop new rigorous classification criteria to identify patients with high likelihood of antiphospholipid syndrome (APS) for research purposes. The present study was undertaken to apply an evidence‐ and consensus‐based approach to identify candidate criteria and develop a hierarchical organization of criteria within domains. Methods: During phase I, the APS classification criteria steering committee used systematic literature reviews and surveys of international APS physician scientists to generate a comprehensive list of items related to APS. In phase II, we reviewed the literature, administered surveys, formed domain subcommittees, and used Delphi exercises and nominal group technique to reduce potential APS candidate criteria. Candidate criteria were hierarchically organized into clinical and laboratory domains. Results: Phase I generated 152 candidate criteria, expanded to 261 items with the addition of subgroups and candidate criteria with potential negative weights. Using iterative item reduction techniques in phase II, we initially reduced these items to 64 potential candidate criteria organized into 10 clinical and laboratory domains. Subsequent item reduction methods resulted in 27 candidate criteria, hierarchically organized into 6 additive domains (laboratory, macrovascular, microvascular, obstetric, cardiac, and hematologic) for APS classification. Conclusion: Using data‐ and consensus‐driven methodology, we identified 27 APS candidate criteria in 6 clinical or laboratory domains. In the next phase, the proposed candidate criteria will be used for real‐world case collection and further refined, organized, and weighted to determine an aggregate score and threshold for APS classification. [ABSTRACT FROM AUTHOR]

Key points: We report a novel method for the transient expression of SARS‐CoV‐2 envelope (E) protein in intracellular organelles and the plasma membrane of mammalian cells and Xenopus oocytes.Intracellular expression of SARS‐CoV‐2 E protein increases intra‐Golgi pH.By targeting the SARS‐CoV‐2 E protein to the plasma membrane, we show that it forms a cation channel, viroporin, that is modulated by changes of pH.This method for studying the activity of viroporins may facilitate screening for new antiviral drugs to identify novel treatments for COVID‐19. The envelope (E) protein of coronaviruses such as SARS‐CoV‐1 is proposed to form an ion channel or viroporin that participates in viral propagation and pathogenesis. Here we developed a technique to study the E protein of SARS‐CoV‐2 in mammalian cells by directed targeting using a carboxyl‐terminal fluorescent protein tag, mKate2. The wild‐type SARS‐CoV‐2 E protein can be trafficked to intracellular organelles, notably the endoplasmic reticulum–Golgi intermediate complex, where its expression increases pH inside the organelle. We also succeeded in targeting SARS‐CoV‐2 E to the plasma membrane, which enabled biophysical analysis using whole‐cell patch clamp recording in a mammalian cell line, HEK 293 cells, and two‐electrode voltage clamp electrophysiology in Xenopus oocytes. The results suggest that the E protein forms an ion channel that is permeable to monovalent cations such as Na+, Cs+ and K+. The E current is nearly time‐ and voltage‐independent when E protein is expressed in mammalian cells, and is modulated by changes of pH. At pH 6.0 and 7.4, the E protein current is activated, whereas at pH 8.0 and 9.0, the amplitude of E protein current is reduced, and in oocytes the inward E current fades at pH 9 in a time‐ and voltage‐dependent manner. Using this directed targeting method and electrophysiological recordings, potential inhibitors of the E protein can be screened and subsequently investigated for antiviral activity against SARS‐CoV‐2 in vitro and possible efficacy in treating COVID‐19. Key points: We report a novel method for the transient expression of SARS‐CoV‐2 envelope (E) protein in intracellular organelles and the plasma membrane of mammalian cells and Xenopus oocytes.Intracellular expression of SARS‐CoV‐2 E protein increases intra‐Golgi pH.By targeting the SARS‐CoV‐2 E protein to the plasma membrane, we show that it forms a cation channel, viroporin, that is modulated by changes of pH.This method for studying the activity of viroporins may facilitate screening for new antiviral drugs to identify novel treatments for COVID‐19. [ABSTRACT FROM AUTHOR]

Supplemental oxygen and mechanical ventilation commonly used in premature infants may lead to chronic lung disease of prematurity, which is characterized by arrested alveolar development and dysmorphic vascular development. Hyperoxia is also known to dysregulate p53, senescence, and metabolism. However, whether these changes in p53, senescence, and metabolism are intertwined in response to hyperoxia is still unknown. Given that the lung epithelium is the first cell to encounter ambient oxygen during a hyperoxic exposure, we used mouse lung epithelial cells (MLE‐12), surfactant protein expressing type II cells, to explore whether hyperoxic exposure alters senescence and glycolysis. We measured glycolytic rate using a Seahorse Bioanalyzer assay and senescence using a senescence‐associated β galactosidase activity assay with X‐gal and C12FDG as substrates. We found that hyperoxic exposure caused senescence and increased glycolysis as well as reduced proliferation. This was associated with increased double stranded DNA damage, p53 phosphorylation and nuclear localization. Furthermore, hyperoxia‐induced senescence was p53‐dependent, but not pRB‐dependent, as shown in p53KO and pRBKO cell lines. Despite the inhibitory effects of p53 on glycolysis, we observed that glycolysis was upregulated in hyperoxia‐exposed MLE‐12 cells. This was attributable to a subpopulation of highly glycolytic senescent cells detected by C12FDG sorting. Nevertheless, inhibition of glycolysis did not prevent hyperoxia‐induced senescence. Therapeutic strategies modulating p53 and glycolysis may be useful to mitigate the detrimental consequences of hyperoxia in the neonatal lung. [ABSTRACT FROM AUTHOR]

Background: Subject motion in positron emission tomography (PET) studies leads to image blurring and artifacts; simultaneously acquired magnetic resonance imaging (MRI) data provides a means for motion correction (MC) in integrated PET/MRI scanners.Purpose: To assess the effect of realistic head motion and MR-based MC on static [18 F]-fluorodeoxyglucose (FDG) PET images in dementia patients.Study Type: Observational study.Population: Thirty dementia subjects were recruited.Field Strength/sequence: 3T hybrid PET/MR scanner where EPI-based and T1 -weighted sequences were acquired simultaneously with the PET data.Assessment: Head motion parameters estimated from high temporal resolution MR volumes were used for PET MC. The MR-based MC method was compared to PET frame-based MC methods in which motion parameters were estimated by coregistering 5-minute frames before and after accounting for the attenuation-emission mismatch. The relative changes in standardized uptake value ratios (SUVRs) between the PET volumes processed with the various MC methods, without MC, and the PET volumes with simulated motion were compared in relevant brain regions.Statistical Tests: The absolute value of the regional SUVR relative change was assessed with pairwise paired t-tests testing at the P = 0.05 level, comparing the values obtained through different MR-based MC processing methods as well as across different motion groups. The intraregion voxelwise variability of regional SUVRs obtained through different MR-based MC processing methods was also assessed with pairwise paired t-tests testing at the P = 0.05 level.Results: MC had a greater impact on PET data quantification in subjects with larger amplitude motion (higher than 18% in the medial orbitofrontal cortex) and greater changes were generally observed for the MR-based MC method compared to the frame-based methods. Furthermore, a mean relative change of ∼4% was observed after MC even at the group level, suggesting the importance of routinely applying this correction. The intraregion voxelwise variability of regional SUVRs was also decreased using MR-based MC. All comparisons were significant at the P = 0.05 level.Data Conclusion: Incorporating temporally correlated MR data to account for intraframe motion has a positive impact on the FDG PET image quality and data quantification in dementia patients.Level Of Evidence: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1288-1296. [ABSTRACT FROM AUTHOR]

This study presents the determination of electrochemical properties of active steel in mortar, based on inverse numerical modeling that focuses on their dependency on chloride content. An experimental campaign, consisting of galvanic coupling tests between anode samples contaminated with different chloride concentrations and cathode samples without chlorides, was carried out. Cathode polarization tests allowed for directly determining passive steel electrochemical parameters. Anode polarization tests coupled with a numerical optimization were then performed for quantifying active steel parameters and focusing on chloride's effect on the iron anodic Tafel coefficient. Furthermore, the steel electrochemical properties were successfully used as input parameters to model the galvanic experiments. [ABSTRACT FROM AUTHOR]

Culturally Responsive and Equitable Evaluation requires evaluators to understand the social and intersectional identity experienced by Hispanic/Latino/Latinx communities, inclusive of immigrants in the United States. This chapter introduces relevant issues for evaluators to consider when working with Latinx immigrants. Evaluators must simultaneously address biases that people have toward Latinx immigrants; heed intergroup diversity among Latino immigrants, and increase Latinx immigrants' knowledge about their existing environment and their ability to advocate for themselves. Likewise, they must advocate for change in policies and practices of public, private, and nonprofit institutions to be more welcoming and responsive to Latinx immigrants' needs; build social support and foster a shared sense of community between immigrants and their communities, and transform the way multiple institutions with related goals and services work together to provide more seamless support to Latinx immigrants. Furthermore, stakeholders must be involved in the change process, with data made available at the stakeholder level to incite change. Therefore, evaluators must spend adequate time during the design phase to align their understanding, expectations, and strategies. Evaluators working collaboratively with diverse Latinx immigrants ensures these perspectives are integrated throughout the process and to address unanticipated challenges. [ABSTRACT FROM AUTHOR]

A portable paper‐based organic redox flow primary battery using sustainable quinone chemistry is presented. The compact prototype relies on the capillary forces of the paper matrix to develop a quasi‐steady flow of the reactants through a pair of porous carbon electrodes without the need of external pumps. Co‐laminar capillary flow allows operation Under mixed‐media conditions, in which an alkaline anolyte and an acidic catholyte are employed. This feature enables higher electrochemical cell voltages during discharge operation and the utilization of a wider range of available species and electrolytes and provides the advantage to form a neutral or near‐neutral pH as the electrolytes neutralize at the absorbent pad, which allows a safe disposal after use. The effects of the device design parameters have been studied to enhance battery features such as power output, operational time, and fuel utilization. The device achieves a faradaic efficiency of up to 98 %, which is the highest reported in a capillary‐based electrochemical power source, as well as a cell capacity of up to 11.4 Ah L−1 cm−2, comparable to state‐of‐the‐art large‐scale redox flow cells. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES: While breast cancer and associated therapies can influence physical function (PF), findings for breast cancer's effects on PF among postmenopausal women are not consistent. This research evaluates the effect of breast cancer on change in PF. DESIGN: Longitudinal cohort study analyzed using difference‐in‐differences (DID) method to compare the changes in PF over time between women with and without breast cancer, by invasive status, stage, and age. SETTING AND PARTICIPANTS: Women's Health Initiative participants, aged 50 to 79 years at baseline, with four completed functional status assessments were eligible for inclusion (mean age = 62.1 ± 6.9 years). Women with breast cancer diagnosed between the 3rd and 11th enrollment year (n = 1636) were compared to women without breast cancer (n = 35 660). MEASUREMENTS: PF was measured using the Medical Outcomes Study Short Form 36 at baseline and years 3, 11, and 12. RESULTS: Compared with women without breast cancer, women with breast cancer experienced greater PF decline (P <.0001), after adjustment for age, race, education, income, study/trial arm, and body mass index. Overall, functional declines were greatest among women with invasive breast cancer (DID = −4.87; 95% confidence interval = −7.12 to −2.62). In stratified analyses, the breast cancer effect on PF was greater among women in older age groups. CONCLUSION: Women diagnosed with breast cancer experienced a significant decline in PF beyond what is observed in typical aging in this cohort. To optimally address survivorship issues, disease sequelae need to be distinguished from normal aging in studies incorporating a cancer‐free comparison group. J Am Geriatr Soc 68:1029–1036, 2020 [ABSTRACT FROM AUTHOR]

Background: Randomized controlled trials (RCTs) have demonstrated that low-dose direct oral anticoagulants (DOACs), including rivaroxaban and apixaban, may help reduce the incidence of cancer-associated venous thromboembolism (VTE).Methods: A cost-utility analysis was performed from the health sector perspective using a Markov state-transition model in patients with cancer who are at intermediate-to-high risk for VTE. Transition probability, relative risk, cost, and utility inputs were obtained from a meta-analysis of the RCTs and relevant epidemiology studies. Differences in cost, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) per patient were calculated over a lifetime horizon. One-way, probabilistic, and scenario sensitivity analyses were conducted.Results: In patients with cancer at intermediate-to-high risk for VTE, treatment with low-dose DOAC thromboprophylaxis for 6 months, compared with placebo, was associated with 32 per 1000 fewer VTE and 11 per 1000 more major bleeding episodes over a lifetime. The incremental cost and QALY increases were $1445 and 0.12, respectively, with an ICER of $11,947 per QALY gained. Key drivers of ICER variations included the relative risks of VTE and bleeding as well as drug cost. This strategy was 94% cost effective at the threshold of $50,000 per QALY. The selection of patients with Khorana scores ≥3 yielded the greatest value, with an ICER of $5794 per QALY gained.Conclusions: Low-dose DOAC thromboprophylaxis for 6 months appears to be cost-effective in patients with cancer who are at intermediate-to-high risk for VTE. The implementation of this strategy in patients with Khorana scores ≥3 may lead to the highest cost-benefit ratio. [ABSTRACT FROM AUTHOR]

Obesity and type 2 diabetes disproportionately impact U.S. racial and ethnic minority communities and low‐income populations. Improvements in implementing efficacious interventions to reduce the incidence of type 2 diabetes are underway (i.e., the National Diabetes Prevention Program), but challenges in effectively scaling‐up successful interventions and reaching at‐risk populations remain. In October 2017, the National Institutes of Health convened a workshop to understand how to (1) address socioeconomic and other environmental conditions that perpetuate disparities in the burden of obesity and type 2 diabetes; (2) design effective prevention and treatment strategies that are accessible, feasible, culturally relevant, and acceptable to diverse population groups; and (3) achieve sustainable health improvement approaches in communities with the greatest burden of these diseases. Common features of guiding frameworks to understand and address disparities and promote health equity were described. Promising research directions were identified in numerous areas, including study design, methodology, and core metrics; program implementation and scalability; the integration of medical care and social services; strategies to enhance patient empowerment; and understanding and addressing the impact of psychosocial stress on disease onset and progression in addition to factors that support resiliency and health. [ABSTRACT FROM AUTHOR]

Can the noun 'beauty' be repurposed as a verb? Can beauty manifest itself in the act of making architecture to become a 'doing word'? David A Garcia thinks so. His notion of beauty is illustrated through his recent work as Associate Professor at the Royal Danish Academy of Fine Arts (KADK) and with his practice MAP Architects, which uses art and technology to produce architecture in extreme arctic environments. [ABSTRACT FROM AUTHOR]

Objective: To characterize [11 C]-PBR28 brain uptake using positron emission tomography (PET) in people with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). We have previously shown increased [11 C]-PBR28 uptake in the precentral gyrus in a small group of ALS patients. Herein, we confirm our initial finding, study the longitudinal changes, and characterize the gray versus white matter distribution of [11 C]-PBR28 uptake in a larger cohort of patients with ALS and PLS.Methods: Eighty-five participants including 53 with ALS, 11 with PLS, and 21 healthy controls underwent integrated [11 C]-PBR28 PET-magnetic resonance brain imaging. Patients were clinically assessed using the Upper Motor Neuron Burden (UMNB) and the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). [11 C]-PBR28 uptake was quantified as standardized uptake value ratio (SUVR) and compared between groups. Cortical thickness and fractional anisotropy were compared between groups and correlated with SUVR and the clinical data. [11 C]-PBR28 uptake and ALSFRS-R were compared longitudinally over 6 months in 10 ALS individuals.Results: Whole brain voxelwise, surface-based, and region of interest analyses revealed increased [11 C]-PBR28 uptake in the precentral and paracentral gyri in ALS, and in the subcortical white matter for the same regions in PLS, compared to controls. The increase in [11 C]-PBR28 uptake colocalized and correlated with cortical thinning, reduced fractional anisotropy, and increased mean diffusivity, and correlated with higher UMNB score. No significant changes were detected in [11 C]-PBR28 uptake over 6 months despite clinical progression.Interpretation: Glial activation measured by in vivo [11 C]-PBR28 PET is increased in pathologically relevant regions in people with ALS and correlates with clinical measures. Ann Neurol 2018;83:1186-1197. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies have associated Attention‐Deficit/Hyperactivity Disorder (ADHD) with a maturational lag of brain functional networks. Functional connectivity of the human brain changes from primarily local to more distant connectivity patterns during typical development. Under the maturational lag hypothesis, we expect children with ADHD to exhibit increased local connectivity and decreased distant connectivity compared with neurotypically developing (ND) children. We applied a graph‐theory method to compute local and distant connectivity levels and cross‐sectionally compared them in a sample of 120 children with ADHD and 120 age‐matched ND children (age range = 7–17 years). In addition, we measured if potential group differences in local and distant connectivity were stable across the age range considered. Finally, we assessed the clinical relevance of observed group differences by correlating the connectivity levels and ADHD symptoms severity separately for each group. Children with ADHD exhibited more local connectivity than age‐matched ND children in multiple brain regions, mainly overlapping with default mode, fronto‐parietal and ventral attentional functional networks (p < .05‐ threshold free‐cluster enhancement–family‐wise error). We detected an atypical developmental pattern of local connectivity in somatomotor regions, that is, decreases with age in ND children, and increases with age in children with ADHD. Furthermore, local connectivity within somatomotor areas correlated positively with clinical severity of ADHD symptoms, both in ADHD and ND children. Results suggest an immature functional state of multiple brain networks in children with ADHD. Whereas the ADHD diagnosis is associated with the integrity of the system comprising the fronto‐parietal, default mode and ventral attentional networks, the severity of clinical symptoms is related to atypical functional connectivity within somatomotor areas. Additionally, our findings are in line with the view of ADHD as a disorder of deviated maturational trajectories, mainly affecting somatomotor areas, rather than delays that normalize with age. [ABSTRACT FROM AUTHOR]

The objective of this work is to address the issue of using the human hand as an antenna, the hantenna. The method used is based on an experiment involving a wireless link between a traditional antenna and the human hand functioning as an antenna. Measurements were performed over six subjects in an anechoic chamber. The results show very clear trends. In the frequency band 800 MHz–2 GHz the human hand does improve the link performance, mainly by providing a better matching to the feeding cable. The main conclusion is that expressed in realised gain, the improvement of the link may go up to 15–20 dB, which is very considerable. The significance of the work is that it shows how to use the human hand as an antenna in certain non-critical telecom applications. [ABSTRACT FROM AUTHOR]

Abstract: Importance: Electronic consultation (e‐consult) is an important component of care for patients in the Veterans Health Administration who require subspecialty consultation but not urgent face‐to‐face evaluation. Monoclonal gammopathy of undetermined significance (MGUS) is a common reason for e‐consult. While often benign, MGUS requires careful evaluation and persistent surveillance over time. Objective: To identify areas to improve MGUS care delivery by e‐consult. Methods: We performed a retrospective review of our e‐consult database and identified a cohort of 152 MGUS patients triaged for e‐consult over a 5‐year period (2010‐2014). Results: The median time to completion of an e‐consult was 2 days. Ninety‐six percent of MGUS e‐consults had a hemoglobin >10 g/dL, and 90% had a creatinine <2 mg/dL. While the majority of e‐consults were low risk, paraprotein surveillance varied over time and tracked with consult utilization. With a median follow‐up of 44 months, there were 6 documented progression events, representing a mean rate of progression of 1% per year. Conclusions: E‐consult is a helpful mechanism for the evaluation of MGUS, reducing the need for outpatient appointments. However, timely risk stratification and persistent surveillance over time are critical for e‐consult to work well. [ABSTRACT FROM AUTHOR]

Objectives: To compare the value of clinically measured gait speed with that of the self‐reported Medical Outcomes Study 36‐item Short‐Form Survey Physical Function Index (SF‐36 PF) in predicting future preclinical mobility disability (PCMD) in older women. Design: Prospective cohort study. Setting: Forty clinical centers in the United States. Participants: Women aged 65 to 79 enrolled in the Women's Health Initiative Clinical Trials with gait speed and SF‐36 assessed at baseline (1993–1998) and follow‐up Years 1, 3, and 6 (N = 3,587). Measurements: Women were categorized as nondecliners or decliners based on changes (from baseline to Year 1) in gait speed and SF‐36 PF scores. Logistic regression models were used to estimate incident PCMD (gait speed <1.0 m/s) at Years 3 and 6. Area under the receiver operating characteristic curve (AUC) was used to compare the predictive value of SF‐36 PF with that of measured gait speed. Results: Slower baseline gait speed and lower SF‐36 PF scores were associated with higher adjusted odds of PCMD at Years 3 and 6 (all P < .001). For gait speed, decliners were 2.59 times as likely to have developed PCMD as nondecliners by Year 3 and 2.35 times as likely by Year 6. Likewise, for SF‐36, decliners were 1.42 times as likely to have developed PCMD by Year 3 and 1.49 times as likely by Year 6. Baseline gait speed (AUC = 0.713) was nonsignificantly better than SF‐36 (AUC = 0.705) at predicting PCMD over 6 years (P = .21); including measures at a second time point significantly improved model discrimination for predicting PCMD (all P < .001). Conclusion: Gait speed identified PCMD risk in older women better than the SF‐36 PF did, although the results may be limited given that gait speed served as a predictor and to define the PCMD outcome. Nonetheless, monitoring trajectories of change in mobility are better predictors of future mobility disability than single measures. [ABSTRACT FROM AUTHOR]

Objectives To examine prospective associations between changes in physical activity ( PA) and changes in physical performance measures ( PPMs) over 6 years in older women. Design Prospective cohort study. Setting Forty clinical centers in the United States. Participants Women aged 65 and older (mean age 69.8) enrolled in the Women's Health Initiative Clinical Trials with gait speed, timed chair stand, grip strength, and self-reported recreational PA data assessed at baseline (1993-98) and follow-up Years 1, 3, and 6 (N = 5,092). Measurements Mixed-effects linear regression models were used to determine the association between time-varying PA and change in each PPM. Potential interactions between time-varying PA and age (<70, ≥70) were also tested. Results Significan, dose-response associations between PA and improvements in all PPMs were observed over the 6 years of follow-up after adjusting for important covariates. High PA groups (≥1,200 metabolic equivalent ( MET)-min/wk) had stronger grip strength (0.48 kg greater; P < .01), more chair stands (0.35 more; P < .001), and faster gait speeds (0.06 m/s faster; P < .001) than sedentary women (<100 MET-min/wk). Higher PA levels were associated with a greater increase in chair stands over time in women aged 70 and older ( P < .001) than in those younger than 70 ( Pinteraction for age = .01). Conclusion In postmenopausal women, maintaining high PA levels over time is associated with better lower extremity function. These data support the view that regular PA plays an important role in maintaining functional status during aging in older women. [ABSTRACT FROM AUTHOR]

The pervasive presence of online media in our society has transferred a significant part of political deliberation to online forums and social networking sites. This article examines popularity, reputation, and social influence on Twitter using large-scale digital traces from 2009 to 2016. We process network information on more than 40 million users, calculating new global measures of reputation that build on the D-core decomposition and the bow-tie structure of the Twitter follower network. We integrate our measurements of popularity, reputation, and social influence to evaluate what keeps users active, what makes them more popular, and what determines their influence. We find that there is a range of values in which the risk of a user becoming inactive grows with popularity and reputation. Popularity in Twitter resembles a proportional growth process that is faster in its strongly connected component, and that can be accelerated by reputation when users are already popular. We find that social influence on Twitter is mainly related to popularity rather than reputation, but that this growth of influence with popularity is sublinear. The explanatory and predictive power of our method shows that global network metrics are better predictors of inactivity and social influence, calling for analyses that go beyond local metrics like the number of followers. [ABSTRACT FROM AUTHOR]

Aims We aimed to define the clinicopathological characteristics of 29 primary sinonasal diffuse large B cell lymphoma ( DLBCLsn) in a series of 240 cases of DLBCL not otherwise specified [ DLBCLall ( NOS)], including DLBCLsn training set ( n = 11) and validation set ( n = 18), and DLBCLnon-sn ( n = 211). Methods and results In the training set, 82% had a non-germinal center B-cell-like (Hans' Classifier) (non- GCB) phenotype and 18% were Epstein-Barr virus-encoded small RNAs ( EBER)+. The genomic profile showed gains(+) of 1q21.3q31.2 (55%), 10q24.1 (46%), 11q14.1 (46%) and 18q12.1q23 (46%); losses(−) of 6q26q27 (55%) and 9p21.3 (64%); and copy number neutral loss of heterozygosity (LOH) (acquired uniparental disomy, UPD) at 6p25.3p21.31 (36%). This profile is comparable to DLBCLNOS ( GSE11318, n = 203.) and closer to non- GCB/activated B-cell-like subtype ( ABC). Nevertheless, +1q31, −9p21.3 and −10q11.1q26.2 were more characteristic of DLBCLsn ( P < 0.001). Array results were verified successfully by fluorescence in situ hybridization ( FISH) on +1q21.3 ( CKS1B), −6q26 ( PARK2), +8q24.21 ( MYC), −9p21.3 ( MTAP, CDKN2A/B), −17p13.1 ( TP53) and +18q21.33 ( BCL2) with 82-91% agreement. Minimal common regions included biologically relevant genes of MNDA (+1q23.1), RGS1 and RGS13 (+1q31.2), FOXP1 (+3p13), PRDM1 (BLIMP1) and PARK2 (−6q21q26) , MYC ( +8q24.21), CDKN2A (−9p21.3), PTEN (−10q23.31), MDM2 (+12q15), TP53 (−17p13.1) and BCL2 (+18q21.33). Correlation between DNA copy number and protein immunohistochemistry was confirmed for RGS1, RGS13, FOXP1, PARK2 and BCL2. The microenvironment had high infiltration of M2-like tumour associated macrophages ( TAMs) and CD8+T lymphocytes that associated with higher genomic instability. The DLBCLsn validation set confirmed the clinicopathological characteristics, all FISH loci and immunohistochemistry ( IHC) for RGS1. RGS1, one of the most frequently altered genes, was analysed by IHC in DLBCLall and high RGS1 expression associated with non- GCB, EBER+ and unfavourable overall survival (hazard ratio = 1.794; P = 0.016). Conclusions DLBCLsn has a characteristic genomic profile. High RGS1 IHC expression associates with poor overall survival in DLBCLall ( NOS). [ABSTRACT FROM AUTHOR]

Objective: In multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with 11 C-PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions, and normal-appearing WM (NAWM) to investigate the in vivo pathological and clinical relevance of neuroinflammation.Methods: Fifteen secondary-progressive MS (SPMS) patients, 12 relapsing-remitting MS (RRMS) patients, and 14 matched healthy controls underwent 11 C-PBR28 MR-PET. MS subjects underwent 7T T2*-weighted imaging for cortical lesion segmentation, and neurological and cognitive evaluation. 11 C-PBR28 binding was measured using normalized 60- to 90-minute standardized uptake values and volume of distribution ratios.Results: Relative to controls, MS subjects exhibited abnormally high 11 C-PBR28 binding across the brain, the greatest increases being in cortex and cortical lesions, thalamus, hippocampus, and NAWM. MS WM lesions showed relatively modest TSPO increases. With the exception of cortical lesions, where TSPO expression was similar, 11 C-PBR28 uptake across the brain was greater in SPMS than in RRMS. In MS, increased 11 C-PBR28 binding in cortex, deep GM, and NAWM correlated with neurological disability and impaired cognitive performance; cortical thinning correlated with increased thalamic TSPO levels.Interpretation: In MS, neuroinflammation is present in the cortex, cortical lesions, deep GM, and NAWM, is closely linked to poor clinical outcome, and is at least partly linked to neurodegeneration. Distinct inflammatory-mediated factors may underlie accumulation of cortical and WM lesions. Quantification of TSPO levels in MS could prove to be a sensitive tool for evaluating in vivo the inflammatory component of GM pathology, particularly in cortical lesions. Ann Neurol 2016;80:776-790. [ABSTRACT FROM AUTHOR]

We evaluated the efficacy of an instructional procedure to teach young children with autism to evacuate settings and notify an adult during a fire alarm. A multiple baseline design across children showed that an intervention that included modeling, rehearsal, and praise was effective in teaching fire safety skills. Safety skills generalized to novel settings and maintained during a 5-week follow-up in both training and generalization settings. [ABSTRACT FROM AUTHOR]

Objective: Studies evaluating the relationship between body mass index (BMI) and mortality demonstrate a U-shaped association. To expand, this study evaluated the relationship between adiposity indices, a body shape index (ABSI) and body adiposity index (BAI), and mortality in 77,505 postmenopausal women.Methods: A prospective cohort analysis was conducted in the Women's Health Initiative to ascertain the independent relationships between adiposity indices and mortality in order to inform on the clinical usefulness of alternate measures of mortality risk. ABSI (waist circumference (cm)/[BMI(2/3) × height (cm)(1/2) ]), BAI (hip circumference (cm)/[height (m)(1.5) ] - 18), weight, BMI, and waist circumference (WC) were evaluated in relation to mortality risk using adjusted Cox proportional hazards regression models.Results: ABSI showed a linear association with mortality (HR, 1.37; 95% CI, 1.28-1.47 for quintile 5 vs. 1) while BMI and BAI had U-shaped relationships with HR of 1.30; 95% CI, 1.20-1.40 for obesity II/III BMI and 1.06, 95% CI, 0.99-1.13 for BAI. Higher WC (HR, 1.21; 95% CI, 1.13-1.29 for quintile 5 vs. 1) showed relationships similar to BMI.Conclusions: ABSI appears to be a clinically useful measure for estimating mortality risk, perhaps more so than BAI and BMI in postmenopausal women. [ABSTRACT FROM AUTHOR]

This study presents the experimental and modeling results of CO2 injection and transport in the vadose zone performed in PISCO2 facilities at the ES.CO2 center in Ponferrada (North Spain). During 46 days of experiments, 62.10 kg of CO2 were injected through 16 micro-injectors in a 35 m3 experimental unit filled with sandy material. Monitoring and mapping of surface CO2 flux were performed periodically to assess the evolution of CO2 migration through the soil and to the atmosphere. Numerical simulations were run using TOUGH2 code with EOS7CA research module considering two phases (gas and liquid) and three components (H2O, CO2, air). Two layers (sand, gravel) and atmosphere boundary were implemented taking into account heterogeneous soils, homogeneous soil, rainfall, temperature, and liquid saturation to allow a better understanding of CO2 behavior in the vadose zone. This combined experimental and modeling approach shows that CO2 leakage in the vadose zone quickly comes out through preferential migration pathways and spots with the ranges of fluxes in the ground/surface interface from 2.5 to 600 g·m−2·day−1. This gas channeling is mainly related to soil compaction and climatic perturbation. This has significant implications for design-adapted detection and monitoring strategies of early leakage in commercial CO2 storage. © 2015 Society of Chemical Industry and John Wiley & Sons, Ltd [ABSTRACT FROM AUTHOR]

Political polarization is traditionally analyzed through the ideological stances of groups and parties, but it also has a behavioral component that manifests in the interactions between individuals. We present an empirical analysis of the digital traces of politicians in politnetz.ch, a Swiss online platform focused on political activity, in which politicians interact by creating support links, comments, and likes. We analyze network polarization as the level of intra-party cohesion with respect to inter-party connectivity, finding that supports show a very strongly polarized structure with respect to party alignment. The analysis of this multiplex network shows that each layer of interaction contains relevant information, where comment groups follow topics related to Swiss politics. Our analysis reveals that polarization in the layer of likes evolves in time, increasing close to the federal elections of 2011. Furthermore, we analyze the internal social network of each party through metrics related to hierarchical structures, information efficiency, and social resilience. Our results suggest that the online social structure of a party is related to its ideology, and reveal that the degree of connectivity across two parties increases when they are close in the ideological space of a multi-party system. [ABSTRACT FROM AUTHOR]

The BAR (Bin/Amphiphysin/Rvs) domain proteins arfaptin1 and arfaptin2 are localized to the trans-Golgi network (TGN) and, by virtue of their ability to sense and/or generate membrane curvature, could play an important role in the biogenesis of transport carriers. We report that arfaptins contain an amphipathic helix (AH) preceding the BAR domain, which is essential for their binding to phosphatidylinositol 4-phosphate (PI(4)P)-containing liposomes and the TGN of mammalian cells. The binding of arfaptin1, but not arfaptin2, to PI(4)P is regulated by protein kinase D (PKD) mediated phosphorylation at Ser100 within the AH. We also found that only arfaptin1 is required for the PKD-dependent trafficking of chromogranin A by the regulated secretory pathway. Altogether, these findings reveal the importance of PI(4)P and PKD in the recruitment of arfaptins at the TGN and their requirement in the events leading to the biogenesis of secretory storage granules. [ABSTRACT FROM AUTHOR]

The use of generic drugs has become increasingly common in clinical practice. However, for drugs with a narrow therapeutic index, such as warfare, there may be some concern regarding the definition of bioequivalence. Clinical studies that compared brand name and generic warfare products provided conflicting results. Therefore, we performed a systematic review of the literature to better assess the characteristics of each generic warfare product. Several sources were searched, including MEDLINE and EMBASE, electronic records of meetings' abstracts, and reference lists of included articles. Articles were considered relevant if they were original studies, enrolled patients receiving oral anticoagulant treatment, and compared any approved generic warfare with brand name warfare in at least one clinical, laboratory, or management outcome. Eleven studies, with a total of more than 40,000 patients, were included; five were randomized controlled trials, and six were observational studies. In three crossover trials evaluating the mean difference of the international normalized ratio (IN) after switching to the alternate formulation of warfare, no statistically significant difference was found between patients randomly assigned to receive brand name or generic warfare. The two other randomized trials found no significant differences in the magnitude or number of dosage changes between patients switched to brand name or generic warfare. The results of the observational studies are more conflicting, suggesting different features for different generic warfare products. In these observational studies, the time in the therapeutic range and the number of thromboses and hemorrhagic complications were similar in studies that compared the anticoagulation control before and after the switch to a generic warfare product. In one observational study, however, a change in therapeutic IN control after the switch to generic warfare was reported at the individual patient level. The results of our systematic review suggest that generic warfare products may be as safe and effective as brand name products and that patients may be safely treated with these products. However, closer monitoring may be reasonable when switching brands, as variations in individual IN response may be seen. [ABSTRACT FROM AUTHOR]

The role of the plasma level of homocysteine (Hcy), as a primary outcome, and the effect of silent cerebrovascular lesions and genetic variants related to Hcy metabolism, as secondary outcomes, in the cognitive decline and dementia in Parkinson's disease (PD) were studied. This case-control study focused on 89 PD patients of minimum 10 years of evolution and older than 60 years, who were neuropsychologically classified either as cognitively normal (n = 37), having mild cognitive impairment (Petersen criteria) (n = 22), or suffering from dementia (DSM-IV) (n = 30), compared with cognitively normal age-matched control subjects (n = 30). Plasma levels of Hcy, vitamins B12 and B6, folic acid, polymorphisms in genes related to Hcy metabolism ( MTHFR, MTR, MTRR, and CBS) and silent cerebrovascular events were analyzed. Plasma levels of Hcy were increased in PD patients ( P = 0.0001). There were no differences between the groups of patients. The brain vascular burden was similar among PD groups. There was no association between polymorphisms in the studied genes and the Hcy plasma levels or cognitive status in PD patients. We found no evidence for a direct relationship between Hcy plasma levels and cognitive impairment and dementia in PD. No indirect effect through cerebrovascular disease or genetic background was found either. © 2009 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Study Objective. To quantify the absolute risk of thromboembolism associated with a significant subtherapeutic international normalized ratio (INR) in patients with previously stable anticoagulation while receiving warfarin. Design. Retrospective, matched cohort analysis. Setting. Centralized anticoagulation service in an integrated health care delivery system. Patients. A total of 2597 adult patients receiving warfarin from January 1998-December 2005; 1080 patients were in the low INR cohort and were matched to 1517 patients in the therapeutic INR cohort based on index INR date, indication for warfarin, and age. Measurements and Main Results. Stable, therapeutic anticoagulation was defined as two INR values, measured at least 2 weeks apart, within or above the therapeutic range. The low INR cohort included patients with a third INR value of 0.5 or more units below their therapeutic range. The therapeutic INR cohort included patients with a third therapeutic INR value and no INR value 0.2 or more units below their target INR range in the ensuing 90 days. The primary outcome was anticoagulation-related thromboembolism during the 90 days after the index INR. Secondary outcomes were times to the first occurrence of anticoagulation-related complications (bleeding, thromboembolism, or death) in the 90 days after the index INR. Four thromboembolic events (0.4%) occurred in the low INR cohort and one event (0.1%) in the therapeutic INR cohort (p=0.214). The differences in the proportions of thromboembolism, bleeding, or death were not significant between the cohorts (p>0.05). No significant differences were noted in the hazard of thromboembolism, bleeding, or death between the cohorts (p>0.05). Conclusion. Patients with stable INRs while receiving warfarin who experience a significant subtherapeutic INR value have a low risk of thromboembolism in the ensuing 90 days. The risk was similar to that observed in a matched control population in whom therapeutic anticoagulation was maintained. These findings do not support the practice of anticoagulant bridge therapy for patients stabilized on warfarin therapy to reduce their risk for thromboembolism during isolated periods of subtherapeutic anticoagulation. [ABSTRACT FROM AUTHOR]

Precise placement of the electrodes for stimulation of the subthalamic nucleus (STN) in Parkinson's disease (PD) is crucial for the therapeutic benefit. As a result of the mistargeting and misplacement of the electrodes during surgery in 2 patients with PD, we have characterized the neuronal firing in the red nucleus (RN) and observed the effects of stimulation of this nucleus. Although the neuronal firing (mean ± SD) of the RN (34 ± 4.4 Hz) resembles that described for the STN (33.1 ± 16.6 Hz), a higher proportion of cells responded to the movement of the contralateral limbs (70-80%). Stimulation in the area of the RN-induced intolerable side effects without motor improvement. We conclude that the STN and RN have some similar neurophysiological features but can be distinguished intraoperatively. This initial description of the physiological characteristics of the RN in humans will draw attention to the possibility of confusing the RN and STN during intraoperative recording. © 2008 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Objectives. The purpose of this study is to assess if students enter charter schools at an academic disadvantage compared to students who make other types of school-choice decisions, such as transferring between district schools, from a charter to a district school, or staying in the same school. We assess the demographic and academic characteristics of students prior to choosing to attend a charter school in comparison to students who made other types of school-choice decisions and broaden the operational definition of a “disadvantaged” student when exploring differences between charter and district students to include academic achievement prior to entering a school. Methods. The analysis is conducted with student-level panel data and a progressive series of ANCOVA models that were estimated using ordinary least squares (OLS) regression. This methodology allows for a comparison of the mean differences in academic achievement among students who made different types of school-choice decisions while controlling for student-level covariates. Results. Students who transferred from district to charter schools had the lowest levels of prior academic achievement compared to students who made other types of choice decisions. Conclusions. When Arizona charter authorizers face the deluge of renewal decisions that are approaching, the quality of education available to the next generation of charter school students is at stake. Renewal decisions will impact what choices are available going forward and, given the comparative academic disadvantage of charter school students prior to entering, those decisions should take into consideration the starting point for students entering charter schools. [ABSTRACT FROM AUTHOR]