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This article reviews the efficacy and safety data of tirzepatide, a once-weekly, novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1) receptor agonist approved in the United States, the European Union, and other regions for the treatment of type 2 diabetes. All doses of tirzepatide demonstrated superiority in reducing A1C and body weight from baseline versus placebo or active comparators. The safety profile of tirzepatide was consistent with that of the GLP-1 receptor agonist class, with mild to moderate and transient gastrointestinal side effects being the most common adverse events. With clinically and statistically significant reductions in A1C and body weight without increased risk of hypoglycemia in various populations, tirzepatide has demonstrated potential as a first-in-class treatment option for many people with type 2 diabetes.

Renewable fuels (drop-in replacement fuels made from renewable electricity) are one option to reduce environmental impacts in transportation. To support the use of renewable fuels, this study identifies early adopters in commercial transportation. We also examine requirements for user acceptance. Finally, we present policy recommendations to increase user acceptance of these fuels. To answer these research questions, we utilize three group discussions with commercial fleet operators of companies operating in urban areas as well as national and international transportation. By discussing on acceptance-building measures, barriers as well as their perception of branches comparatively most appropriate to renewable fuels’ characteristics. The empirical results show that long-distance trucking is the most likely early adopter of renewable fuels. Within long-distance trucking, large logistics and transportation firms in particular are identified as most suitable. Small and medium sized firms, however, are not seen as early adopters. This is due the numerous technical options they have (e.g., renewable fuels, electric vehicles), price uncertainty of renewable fuels, and volatile political decisions regarding vehicles. In our analysis we further identify three acceptance objects: aspects of practical use of renewable fuels (e.g., vehicle technology readiness levels and knowledge), secondary effects of renewable fuel production (e.g., upstream environmental burdens), and the relationship of renewable fuels to electric vehicles. Finally, we provide policy recommendations to support of renewable fuels. First, potential users require reliable and detailed information about planned government actions. In addition, there is a need for long-term funding for these new technologies. In particular, use-case specific (e.g., long-distance trucking) funding is important. Finally, consideration of and information about secondary effects (e.g., upstream environmental burdens) are crucial for user acceptance.

PurposeAnalyze how peer effects and social influences affect attitudes and responses to corruption in tax systems, identifying factors that improve tax morale.Design/methodology/approachLife in Transition Survey (LITS III, 2016) data are analyzed using ordered probit models of corrupt tax officials, Heckman-style selection models of the extent of corruption, probit models of reasons given for not reporting corruption and ordered probit models of the frequency of informal payments to tax officials.FindingsPeer effects and social influences significantly affect perceptions of and responses to corruption. Tax morale is supported in communities where people trust one another, where there is greater respect for the law and where people can achieve greater life satisfaction.Research limitations/implicationsResults are specific to transition countries represented in the data.Practical implicationsFindings can help improve tax morale and stabilize fiscal systems in transition countries.Social implicationsEnhanced tax morale can be facilitated by building inclusive, respectful and transparent institutions.Originality/valueThis study uses the latest LITS III data with a focus on peer effects and social influences, with improved empirical strategies.

Introduction: Hypoglycemia after BI initiation can negatively impact patient adherence to titration and glycemic target achievement. We report on 2 surveys to better understand patient and physician perspectives/experiences of hypoglycemia during BI titration. Methods: Adults with T2D and ≥2 claims (≥30 days apart in last 12 months) in the Optum Research Database who initiated BI (February-April 2021) , and physicians who treated ≥30 patients with T2D, ≥1 initiating BI (October 2020-March 2021) , completed a mailed survey. Results: Responders were 416 patients (51% male, 71% white, mean age 70 years, 72% >years T2D duration) and 386 physicians (45% general practice) . Most physicians reported discussing hypoglycemia signs/symptoms (93%) and how to titrate BI in response to blood glucose (BG) levels (81%) with patients. Among patients who experienced hypoglycemia (49%; Table) , 57% felt very/extremely confident titrating BI during hypoglycemia. Only 35% met fasting BG (FBG) targets. Diabetes Treatment Satisfaction Questionnaire hypoglycemia score (1.34/6) suggests patients felt hypoglycemia was infrequent. Conclusion: While physicians educate patients on hypoglycemia awareness and BI titration, nearly half of patients surveyed experienced hypoglycemia during titration, and only a third met FBG targets, suggesting new strategies and tools are needed for effective BI titration. Disclosure S.B.Harris: Consultant; Abbott, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Other Relationship; Abbott, AstraZeneca, Bayer Inc., Dexcom, Eli Lilly and Company, HLS Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; Applied Therapeutics Inc., AstraZeneca, Canadian Institutes of Health Research, Juvenile Diabetes Research Foundation (JDRF) , Novo Nordisk, Sanofi, The Lawson Foundation. K.Mohammedi: Board Member; Lilly, Novo Nordisk, Sanofi, Research Support; Cyclerion Therapeutics, Inc., Speaker's Bureau; Abbott, AstraZeneca. M.Bertolini: Employee; Sanofi. V.Walker: Consultant; Sanofi-Aventis U.S. M.H.Carlyle: None. F.L.Zhou: Employee; Sanofi, Stock/Shareholder; Sanofi. J.Seufert: Advisory Panel; Abbott, Sanofi-Aventis Deutschland GmbH, Research Support; Boehringer Ingelheim International GmbH, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. J.E.Anderson: Advisory Panel; Abbott Diabetes, Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gelesis, Novo Nordisk, Sanofi, Speaker's Bureau; Eli Lilly and Company. Funding Sanofi

Long-term risks of macro- and microvascular complications may be reduced in people with type 2 diabetes who achieve early and sustained glycemic control. Delays in attaining A1C goals are associated with poor long-term cardiovascular (CV) outcomes. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors are glucose-lowering therapies that act through complementary mechanisms of action with regard to the pathophysiologic defects of type 2 diabetes. Trials of agents in both drug classes have demonstrated improvements in CV and renal outcomes. This review discusses the rationale for combination therapy with a GLP-1 receptor agonist and an SGLT2 inhibitor, including early initiation of this combination in newly diagnosed patients. This combination may lead to timely glycemic control and potentially additive CV and renal benefits. Clinical studies of the combination have shown partially additive effects on A1C reduction, additive effects on weight reduction, and potentially synergistic effects on blood pressure reduction. Long-term studies are needed to determine whether the combination provides an additional effect on CV and renal outcomes compared with agents from either drug class when used alone.

Use of continuous glucose monitoring (CGM) improves clinical outcomes in type 1 diabetes, and significant benefits been demonstrated in patients with type 2 diabetes, including improved glycemic control, better treatment adherence, and an increased understanding of their treatment regimens. Currently, there are two types of CGM systems: real-time CGM (rtCGM) and flash CGM (FCGM). Retrospective analysis of CGM data allows patients and their clinicians to identify glycemic patterns that support and facilitate informed therapy decisions. With the increasing prevalence of diabetes, primary care physicians will be compelled to take on more responsibility for managing patients with diabetes. This article focuses on practical approaches and decision-making strategies for utilizing FCGM in primary care settings.

Despite ongoing advances in medications, insulin delivery systems, and glucose monitoring technologies, diabetes control remains suboptimal in many individuals with this disease.1 In addition to the clinical consequences resulting from poor control is the ever-increasing financial burden on individuals, health systems, and society.2 In its latest report, the American Diabetes Association (ADA) estimated the total estimated cost of diagnosed diabetes in 2017 to be $327 billion.2 Although the direct cost of treating complications (hospitalizations, emergency room visits, and nondiabetes prescription medications) and the indirect costs associated with lost/reduced productivity account for ∼73.1% of the total diabetes cost, many public and private payers continue to focus much of their cost-cutting efforts on reducing the costs of diabetes supplies, which account for only 1.1% of the total cost. Examples of these questionable efforts can be found in the restrictive eligibility criteria for coverage of continuous glucose monitoring (CGM). Specifically, the requirements are that eligible individuals must have type 1 diabetes (T1D) and be able to document routine performance of at least four fingerstick blood glucose tests per day. The Centers for Medicare and Medicaid Services (CMS) explicitly requires this level of testing for Medicare beneficiaries to qualify for CGM coverage, as do 11 of 36 state Medicaid programs that provide CGM coverage. Requiring documentation of >4 blood glucose tests per day is clearly enigmatic given that the Medicare coverage policy only pays for three test strips per day for insulin-treated beneficiaries. Although Medicare coverage includes both T1D and intensively treated type 2 diabetes (T2D), many state Medicaid programs do not match such coverage. A comprehensive Internet search found that 13 state programs limit CGM use to individuals with T1D and documented history of 4 × /day blood glucose testing (Table 1). Three programs cover both T1D and insulin-requiring T2D but with the minimum blood glucose monitoring restriction. Four programs cover T1D with no blood glucose monitoring restriction, and only one state covers both type 1 and insulin-requiring diabetes with no blood glucose restriction. Eligibility for CGM in the remaining 14 State Medicaid programs is not specified or accessible according to our Internet search. Table 1. Medicaid Coverage for Continuous Glucose Monitoring Use

With rapidly accelerating real estate prices in China, the government has used changes in deed tax rates to affect demand. Tax rates have been increased for buyers of large or multiple homes to discourage speculative demand. We analyze the effects of deed tax rates on real estate prices over the period 2004–2013, estimating traditional dynamic models and dynamic spatial models. Results indicate that deed tax rate increases have a negative effect on pre-tax prices for both residential units and land use rights. Spatial spillover effects are also found in the residential market, with larger effects in the long term.

Type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF)-along with their associated risk factors-have overlapping etiologies, and two or more of these conditions frequently occur in the same patient. Many recent cardiovascular outcome trials (CVOTs) have demonstrated the benefits of agents originally developed to control T2D, ASCVD, or CKD risk factors, and these agents have transcended their primary indications to confer benefits across a range of conditions. This evolution in CVOT evidence calls for practice recommendations that are not constrained by a single discipline to help clinicians manage patients with complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. The ultimate goal for these recommendations is to be comprehensive yet succinct and easy to follow by the nonexpert-whether a specialist or a primary care clinician. To meet this need, we formed a volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM Practice Recommendations, a multispecialty consensus on the comprehensive management of the patient with complicated metabolic disease. The task force recommendations are based on strong evidence and incorporate practical guidance that is clinically relevant and simple to implement, with the aim of improving outcomes in patients with DCRM. The recommendations are presented as 18 separate graphics covering lifestyle therapy, patient self-management education, technology for DCRM management, prediabetes, cognitive dysfunction, vaccinations, clinical tests, lipids, hypertension, anticoagulation and antiplatelet therapy, antihyperglycemic therapy, hypoglycemia, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), ASCVD, HF, CKD, and comorbid HF and CKD, as well as a graphical summary of medications used for DCRM.

Permafrost underlies one quarter of the northern hemisphere but is at increasing risk of thaw from climate warming. Recent studies across the Arctic have identified areas of rapid permafrost degradation from both top-down and lateral thaw. Of particular concern is thawing of ice rich high carbon content syngenetic yedoma permafrost like much of the permafrost in the region around Fairbanks, Alaska. With a mean annual temperature of −2 °C subtle differences in ecotype and permafrost ice and soil content control the near-surface permafrost thermal regime. Long-term measurements of the seasonally thawed active layer across central Alaska have identified an increase in permafrost thaw degradation that is expected to continue, and even accelerate, in coming decades. A major knowledge gap is relating belowground measurements of seasonal thaw, permafrost characteristics, and talik development with aboveground ecotype properties and thermokarst expansion that can readily quantify vegetation cover and track surface elevation changes over time. This study was conducted from 2013–2020 along four 400 to 500 m long transects near Fairbanks, Alaska. Repeat end of season active layer depths, near-surface permafrost temperature measurements, electrical resistivity tomography (ERT), deep (> 5 m) boreholes, and repeat airborne LiDAR were used to measure top down thaw and map thermokarst development at the sites. Our study confirms previous work using ERT to map surface thawed zones, however, our deep boreholes confirm the boundaries between frozen and thawed zones that are needed to model top down, lateral, and bottom-up thaw. At disturbed sites seasonal thaw increased up to 25 % between mid-August and early October and suggests active layer depths must be made as late in the fall season as possible because the projected increase in the summer season of just a few weeks could lead to significant additional thaw. At our sites, tussock tundra and spruce forest are associated with the lowest mean annual near-surface permafrost temperatures while mixed forest ecotypes are the warmest and exhibit the highest degree of recent temperature warming and thaw degradation. Thermokarst features and perennially thawed zones (taliks) have been identified at all sites. Our measurements, when combined with longer-term records from yedoma across the 500,000 km2 area of central Alaska show widespread initiation of near-surface permafrost thaw since roughly 2010. Using this partial area of the yedoma domain and projecting our thaw depth increases, by ecotype, across this domain we calculate 0.44 Gt of permafrost soil C have been thawed over the 7 year period, an amount equal to the yearly CO2 emissions of Australia. Since the yedoma permafrost and the variety of ecotypes at our sites represent much of the Arctic and subarctic land cover this study shows remote sensing measurements, top-down and bottom-up thermal modelling, and ground based surveys can be used predictively to identify areas of highest risk for permafrost thaw from projected future climate warming.

Introduction Basal-bolus (BB) regimens are generally used to intensify basal insulin therapy in patients with type 2 diabetes (T2D) not meeting glycemic targets. However, drawbacks include multiple injection burden and risk of weight gain and hypoglycemia. A once-daily titratable fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide (iGlarLixi) may provide a simple, well-tolerated, and efficacious alternative. We compared these treatments in a post hoc propensity score matched analysis using randomized trial data. Methods From the LixiLan-L study, 195 patients who had been randomized to iGlarLixi were matched for age, sex, race, T2D duration, baseline body mass index, glycated hemoglobin (HbA1c), fasting plasma glucose, insulin dose, and metformin use to 195 patients who had been randomized to a BB regimen in the GetGoal Duo-2 trial. Results At study end, estimated treatment differences for reduction in HbA1c and weight change, and ratio of hypoglycemia events per patient-year (BB vs iGlarLixi) were − 0.28% (standard error 0.08, P = 0.0002), − 1.32 kg (standard error 0.30, P

Purpose The purpose of this study is to test the hypothesis that real estate ownership contributes to life satisfaction in transition countries. Design/methodology/approach Life in Transition survey data are used to model reported life satisfaction using ordinary least squares, ordered probit, generalized ordered logit and bivariate probit models. The hypothesis tested is whether real estate ownership is associated with greater reported life satisfaction. Findings Empirical results from the variety of empirical models estimated strongly support the hypothesis that real estate ownership is associated with greater reported life satisfaction in transition countries. Research limitations/implications Analysis is limited because life satisfaction is self-reported and specifically for residents of transition countries. Practical implications Results confirm that ownership of a home, second home or land parcel is associated with greater life satisfaction. Social implications Real estate ownership can be an effective means to improve life satisfaction, especially in societies needing such improvements. Originality/value This is the first study of the link between real estate ownership and life satisfaction specifically in transition countries, and using a robust set of empirical models to address issues of ordinal dependent variables, varying coefficient estimates across dependent variable response categories, endogeneity and causality.

I examine how limited access to land and obstacles in gaining business licensing and permits are cited by businesses in transition economies as substantial impediments, feeding into cultures of bribery and corruption and impeding economic development. A theoretical model of limited access to land and permits is presented motivating empirical modeling. Using the EBRD-World Bank BEEPS V survey data for firms in transition economies, both country and firm-specific characteristics are used to explain the reported obstacles and requests for informal payments, or bribes, by government officials. Probit models of reported obstacles, models of the severity of those obstacles, and models of bribe requests by officials are estimated. To account for endogeneity, instrumental variable (IV) models are estimated explaining how predicted land access or permit obstacles influence the likelihood of firms reporting bribes paid to government officials to overcome those obstacles. Results indicate that government restrictions limiting access to land and permits have significant effects on the subjective views of firms. Both country and firm-specific characteristics influence firm responses. Limited access to land and/or business licensing and permits creates an environment in which firms report that they are much more likely to be asked to make informal payments, gifts, or bribes, to get things done.

Long-term therapeutic benefit of treatments for weight management in patients with overweight (also termed preobesity) or obesity may be limited by variable safety, tolerability, and efficacy profiles, and patient adherence to treatment regimens. There is a medical need for nonsystemic treatments that promote weight loss in patients with overweight or early obesity. This report reviews four different approaches of utilizing superabsorbent hydrogel technology for weight management at varying stages of preclinical and clinical development. The first is a nonsystemic, oral superabsorbent hydrogel created from naturally derived building blocks used in foods (cellulose-based), designed to mix homogenously with and change the properties of the ingested meal throughout the gastrointestinal tract (stomach and small intestine). This is the first-in-class to be cleared by the Food and Drug Administration (FDA) to aid in weight-management for adults with BMI of 25-40 kg/m

Many people with type 2 diabetes are treated with insulin with the goal of achieving a specific A1C target. The most prominent risk for people on insulin therapy is hypoglycemia. When basal insulin analogs are used appropriately, the risk of hypoglycemia can be reduced while still achieving individualized glycemic goals. In a series of short videos now available on the Clinical Diabetes website, the authors discuss approaches to optimizing basal insulin initiation and treatment in people with type 2 diabetes, including those at high risk such as individuals with renal impairment and older adults, with a focus on reaching A1C goals while mitigating the risk for hypoglycemia. This article is intended to briefly summarize those discussions, and readers are encouraged to view the videos in their entirety at https://clinical.diabetesjournals.org/content/basal-insulin-videos. ### Introduction (Available at https://bcove.video/2Q2Rb9b) Approximately 50% of people with type 2 diabetes have poorly controlled disease and are vulnerable to long-term micro- and macrovascular complications (1). As type 2 diabetes progresses, many patients will require insulin to maintain glycemic control. The appropriate use of insulin requires a balance between the need for tight glucose control and the potential risk for hypoglycemia. Definitions of hypoglycemia have evolved over time, and the American Diabetes Association (ADA) now uses a three-level classification of hypoglycemia severity (2). Mitigating the risk for hypoglycemia is crucial to the successful treatment of people with type 2 diabetes. In the following series of videos, the authors discuss the use of available insulin formulations in the context of hypoglycemia risk. ### Basal Insulin Therapy—Balancing Glycemic Control With Risk for Hypoglycemia (Available at https://bcove.video/3h3Y85h) The achievement of tight glycemic control reduces micro- and macrovascular complications, and adherence to treatment improves quality of life and decreases health care costs (3–9). The authors discuss the association between A1C reduction and microvascular complications, as reported in the UK …

The researchers combined two lists of 28 favorite “data science experts to follow on Twitter” to seed a Twitter network and analyze whether the recommended experts were indeed amongst the most influential “data science experts” on Twitter. They analyzed the resulting Twitter network to find the most important nodes in terms of popularity, quality of connections, types of roles played, such as bridges, and node ability to quickly spread information. They found that only some of the recommended experts appeared most influential given the network analysis. They also found that the experts on the list landed mainly in two sub-groups. Starting with a writer's favorite list of experts may be helpful in seeding a more comprehensive list.

Field collection of permafrost vegetation and seasonal thaw depth measurements are a time consuming and labor intensive procedure. To address this, in this study we assessed the capacity of airborne hyperspectral and LiDAR data for upscaling in-situ point data to map vegetation and summer thaw depth at an experimental site near Fairbanks, Alaska, USA. The site represents roughly three quarters of the most common vegetation in the boreal and taiga permafrost zones. An overall accuracy of 93% was achieved for mapping five different vegetation types, and a correlation coefficient (r) of 0.66 was produced for thaw depth modeling using a machine learning algorithm when two remote sensing data sources were combined. Object-based vegetation and thaw depth maps were produced. This study demonstrates that fine spatial resolution hyperspectral data could be valuable for permafrost characterization, while the contribution from LiDAR was marginal at the testing site.

Mean annual temperatures in interior Alaska, currently -1°C, are projected to increase as much as 5°C by 2100. An increase in mean annual temperatures is expected to degrade permafrost and alter hydrogeology, soils, vegetation, and microbial communities. Ice and carbon rich “yedoma type” permafrost in the area is ecosystem protected against thaw by a cover of thick organic soils and mosses. As such, interactions between vegetation, permafrost ice content, the snow pack, and the soil thermal regime are critical in maintaining permafrost. We studied how and where vegetation and soil surface characteristics can be used to identify subsurface permafrost composition. Of particular interest were potential relationships between permafrost ice content, the soil thermal regime, and vegetation cover. We worked along 400-500 m transects at sites that represent the variety of ecotypes common in interior Alaska. Airborne LiDAR imagery was collected from May 9-11, 2014 with a spatial resolution of 0.25 m. During the winters from 2013-2019 snow pack depths have been made at roughly 1 m intervals along site transects using a snow depth datalogger coupled with a GPS. In late summer from 2013-2019 maximum seasonal thaw depths have been measured at 4 m intervals along each transect. Electrical resistivity tomography measurements were collected across the site transects. A variety of machine learning geospatial analysis approaches were also used to identify relationships between ecosystem characteristics, seasonal thaw, and permafrost soil and ice composition. Wintertime measurements show a clear relationship between vegetation cover and snow depth. Interception (and shallow snow) was evident in the birch and white spruce forests and where dense shrubs are present while the open tussock and intermittent shrub regions yield the greatest snow depths. Results from repeat seasonal thaw depth measurements also show a strong relationship with vegetation where mixed birch and spruce forest is associated with the deepest seasonal thaw. The tussock/shrub and spruce forest zones consistently exhibited the shallowest seasonal thaw. Roughly 60% of the seasonal thaw along the transects occurred by mid-July and downward movement of the thaw front had mostly ceased by late August with little additional thaw between August 20 and early October. Summer precipitation shows a relationship with seasonal thaw depth with the wettest summers associated with the deepest thaw. Results from this study identify clear relationships between ecotype, permafrost composition, and seasonal thaw dynamics that can help identify how and where permafrost degradation can be expected in a warmer future arctic.

Importance Per the World Health Organization 2016 integrative classification, newly diagnosed glioblastomas are separated into isocitrate dehydrogenase gene 1 or 2 (IDH)–wild-type andIDH-mutant subtypes, with median patient survival of 1.2 and 3.6 years, respectively. Although maximal resection of contrast-enhanced (CE) tumor is associated with longer survival, the prognostic importance of maximal resection within molecular subgroups and the potential importance of resection of non–contrast-enhanced (NCE) disease is poorly understood. Objective To assess the association of resection of CE and NCE tumors in conjunction with molecular and clinical information to develop a new road map for cytoreductive surgery. Design, Setting, and Participants This retrospective, multicenter cohort study included a development cohort from the University of California, San Francisco (761 patients diagnosed from January 1, 1997, through December 31, 2017, with 9.6 years of follow-up) and validation cohorts from the Mayo Clinic (107 patients diagnosed from January 1, 2004, through December 31, 2014, with 5.7 years of follow-up) and the Ohio Brain Tumor Study (99 patients with data collected from January 1, 2008, through December 31, 2011, with a median follow-up of 10.9 months). Image accessors were blinded to patient groupings. Eligible patients underwent surgical resection for newly diagnosed glioblastoma and had available survival, molecular, and clinical data and preoperative and postoperative magnetic resonance images. Data were analyzed from November 15, 2018, to March 15, 2019. Main Outcomes and Measures Overall survival. Results Among the 761 patients included in the development cohort (468 [61.5%] men; median age, 60 [interquartile range, 51.6-67.7] years), younger patients withIDH–wild-type tumors and aggressive resection of CE and NCE tumors had survival similar to that of patients withIDH-mutant tumors (median overall survival [OS], 37.3 [95% CI, 31.6-70.7] months). Younger patients withIDH–wild-type tumors and reduction of CE tumor but residual NCE tumors fared worse (median OS, 16.5 [95% CI, 14.7-18.3] months). Older patients withIDH–wild-type tumors benefited from reduction of CE tumor (median OS, 12.4 [95% CI, 11.4-14.0] months). The results were validated in the 2 external cohorts. The association between aggressive CE and NCE in patients withIDH–wild-type tumors was not attenuated by the methylation status of the promoter region of the DNA repair enzyme O6-methylguanine-DNA methyltransferase. Conclusions and Relevance This study confirms an association between maximal resection of CE tumor and OS in patients with glioblastoma across all subgroups. In addition, maximal resection of NCE tumor was associated with longer OS in younger patients, regardless ofIDHstatus, and among patients withIDH–wild-type glioblastoma regardless of the methylation status of the promoter region of the DNA repair enzyme O6-methylguanine-DNA methyltransferase. These conclusions may help reassess surgical strategies for individual patients with newly diagnosed glioblastoma.

Battery electric vehicles (BEV) provide an opportunity to balance supply and demand in future power systems with high shares of fluctuating renewable energy. Compared to other storage systems such as pumped-storage hydroelectricity, electric vehicle energy demand is highly dependent on charging and connection choices of vehicle users. We present a model framework of a utility-based stock and flow model, a utility-based microsimulation of charging decisions, and an energy system model including respective interfaces to assess how the representation of battery electric vehicle charging affects energy system optimization results. We then apply the framework to a scenario study for controlled charging of nine million electric vehicles in Germany in 2030. Assuming a respective fleet power demand of 27 TWh, we analyze the difference between power-system-based and vehicle user-based charging decisions in two respective scenarios. Our results show that taking into account vehicle users’ charging and connection decisions significantly decreases the load shifting potential of controlled charging. The analysis of marginal values of equations and variables of the optimization problem yields valuable insights on the importance of specific constraints and optimization variables. Assumptions on fleet battery availability and a detailed representation of fast charging are found to have a strong impact on wind curtailment, renewable energy feed-in, and required gas power plant flexibility. A representation of fleet connection to the grid in high temporal detail is less important. Peak load can be reduced by 5% and 3% in both scenarios, respectively. Shifted load is robust across sensitivity analyses while other model results such as curtailment are more sensitive to factors such as underlying data years. Analyzing the importance of increased BEV fleet battery availability for power systems with different weather and electricity demand characteristics should be further scrutinized.

We estimate the responsiveness of state and local property, income, and sales tax revenues to state gross domestic product (GDP) changes using U.S. Census data over the period 1967–2012. Long-run a...

Quantifying end of summer season Active Layer Thickness (ALT) of permafrost is critical for understanding the effects of climate warming, disturbance, and hydrologic changes on permafrost. Current research mainly focuses on ALT estimation and mapping at large scales using process-based or statistical-empirical models with biophysical variables as predictors. Here we modeled multi-year ALT field measurements between 2014 and 2019 at a site in Interior Alaska using 1-m hyperspectral imaging data and an object-based ensemble approach at a local scale (1 km2), examined the efficacy of the multispectral sensor WorldView (WV)-2 for ALT estimation, and explored the potential of integrating single-date imaging data with multi-year in-situ measurements for mapping the spatial and temporal variation of ALT. Modeling results showed hyperspectral imaging was accurate for estimating ALT with a correlation coefficient (r) larger than 0.7, while application of WV-2 data produced an r around 0.4. Reasonable ALT patterns were generated, and the spatial and temporal variation of ALT was delineated between the shallowest (2015) and deepest (2019) years using hyperspectral data. This study suggests hyperspectral imaging is a promising tool for predicting field ALT measurements and monitoring ALT change at local scales. We expect this study will stimulate hyperspectral optical sensors for permafrost studies in general, and particularly for ALT upscaling.

Recent studies have demonstrated the clinical utility of continuous glucose monitoring (CGM) use in type 2 diabetes (T2D) patients who are treated with intensive insulin management. Large retrospective database analyses of T2D patients treated with less-intensive therapies have also shown that CGM use was associated with significant reductions in hemoglobin A1c levels and health resource utilization, including diabetes-related hospitalizations and emergency room care. Despite the growing body of evidence supporting CGM use in the broader T2D population, current eligibility criteria required by public and many private insurers are denying millions of individuals with T2D access to this valuable technology. In this article, we discuss an evidence-based rationale for modifying current eligibility requirements for CGM coverage.

Scottish Intercollegiate Guidelines Network (SIGN) guidelines require patients with colorectal cancer to wait no longer than 62 days from first referral to initiation of definitive treatment. We previously demonstrated that failure to meet with these guidelines did not appear to lead to poor outcomes in the short term. This study investigates whether this holds true over a longer period. The survival status of 1,012 patients treated for colorectal cancer between January 1999 and June 2005 was reviewed. As in the previous audit, patients were placed into four groups, standard met (elective), standard met (emergency), standard failed (elective) and standard failed (emergency). Parameters analysed were pathological staging, 30-day mortality, long-term survival and cause of death. Data was analysed using log rank and chi-squared tests. Operative mortality was higher in patients meeting the standard (7% elective, 20% emergency) compared to those who did not meet the standard (4% elective, 7% emergency). The proportion of early stage disease (Dukes’ A and B) was highest in elective patients who failed the standard (50%) and lowest in emergencies meeting the standard (30%). Long-term survival was greatest in elective patients who failed the standard with 52% alive in October 2011 compared to 34% of elective cases meeting the standard. The most common cause of recorded death was colorectal cancer in all groups. Patients who were not treated within the time frame set by the SIGN guidelines survived for longer following surgery. Reasons for this are likely to be multifactorial and include pathological cancer stage.

Silver is known to possess anti‐microbial properties that are of chemical origin. It is believed that either Ag atoms bind to thiol groups in bacterial enzymes or Ag(+) ions enter bacterial cells and denature the DNA molecule to kill bacteria. Silver nanorods, however, may kill bacteria by another mechanism: it is possible that the sharp tips of the nanorods puncture bacterial cells and kill bacteria via impalement—a physical mechanism. To test if this can indeed happen, we have compared the anti‐microbial properties of silver and CdS nanorods. No significant difference is found between the two even though CdS does not possess the chemical properties of silver. This indicates that the physical kill mechanism is indeed likely and therefore nanorods of any material may possess anti‐microbial properties. In that case, it is possible to overcome serious short‐ and long‐term health hazard issues which have been posed by silver nanoparticles by replacing them with nanorods of innocuous elements or compounds. A surface containing nanorods of varying heights presents an undulating bed of spikes to microbes and is most inhospitable to bacteria.

This paper examines how proximity to an ethanol plant influences land-use and crop choice among producers. We estimated a Tobit model of crop choice within parcels located in Central Nebraska in a 2014 sample period in order to analyze changes in land-use and crop choice. We employed Geographic Information System (GIS) databases to access relevant data on crop choice and other land uses in the study area parcels, in addition to detailed information on the location and capacity of irrigation wells. We utilized an instrumental variable approach to account for the endogeneity of crop choice with ethanol refinery locations in the study area. Our regional model also took into account specific characteristics of the local processing markets for grains, including animal food manufacturers and livestock as well as ethanol plants. Our estimates revealed that ethanol plants alter land-use in several ways. We found that proximity to an ethanol plant increases the share of land allocated to corn cultivation up to a distance of 30 miles and that the portion of land parcels allocated to corn production falls with distance from an ethanol plant in a non-linear pattern. We also find that land allocation to grassland and pasture rises with distance from ethanol plants.

Perceiving the dynamics of moving objects in complex scenarios is crucial for smart monitoring and safe navigation, thus a key enabler for intelligent supervision and autonomous driving. A variety of research has been developed to detect and track moving objects from data collected by optical sensors and/or laser scanners while most of them concentrate on certain type of objects or face the problem of lacking motion cues. In this thesis, we present a data-driven, model-free detection-based tracking approach for tracking moving objects in urban scenes from time sequential point clouds obtained via state-of-art Doppler LiDAR, which can not only collect spatial information (e.g. point clouds) but also Doppler images by using Doppler-shifted frequencies. In our approach, we first use Doppler images to detect moving points and determine the number of moving objects, which are then completely segmented via a region growing technique. The detected objects are then input to the tracking session which is based on Multiple Hypothesis Tracking (MHT) with two innovative extensions. One extension is that a new point cloud descriptor, Oriented Ensemble of Shape Function (OESF), is proposed to evaluate the structure similarity when doing object-to-track association in MHT. Another extension is that speed information from Doppler images is used to predict the dynamic state of the moving objects, which is integrated into MHT to improve the estimation of dynamic state of moving objects. The proposed approach has been tested on datasets collected by a terrestrial Doppler LiDAR and a mobile Doppler LiDAR separately. The quantitative evaluation of detection and tracking results shows the unique advantages of the Doppler LiDAR and the effectiveness of the proposed detection and tracking approach.

Background Ischemic cardiomyopathy (ICM) is a leading cause of cardiovascular mortality worldwide. It is defined as abnormal enlargement of the left ventricular (LV) cavity with poor LV function due to coronary artery disease. Currently available established treatments are palliative whereby blood supply is recovered to ischemic regions but fails to regenerate heart tissues. Mesenchymal stem cells (MSCs) offer a promising treatment for ICM given their regenerative and multipotent characteristics. This study aims to investigate the effect of MSCs infusion with concurrent revascularization in patients with severe ICM compared to receiving only revascularization procedure or MSCs infusion. Methods Twenty-seven patients with history of anterior myocardial infarction (MI) and baseline left ventricular ejection fraction (LVEF) of less than 35% were recruited into this study. Patients who are eligible for revascularization were grouped into group A (MSCs infusion with concurrent revascularization) or group B (revascularization only) while patients who were not eligible for revascularization were allocated in group C to receive intracoronary MSCs infusion. LV function was measured using echocardiography. Results Patients who received MSCs infusion (either with or without revascularization) demonstrated significant LVEF improvements at 3, 6 and 12 months post-infusion when compared to baseline LVEF within its own group. When comparing the groups, the magnitude of change in LVEF from baseline for third visits i.e., 12 months post-infusion was significant for patients who received MSCs infusion plus concurrent revascularization in comparison to patients who only had the revascularization procedure. Conclusions MSCs infusion significantly improves LV function in ICM patients. MSCs infusion plus concurrent revascularization procedure worked synergistically to improve cardiac function in patients with severe ICM.