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ABSTRACT: Background: Successful treatments for intractable chronic low back pain (CLBP) in patients who are not eligible for surgical interventions are scarce. The superior efficacy of differential target multiplexed spinal cord stimulation (DTM SCS) to conventional SCS (Conv-SCS) on the treatment of CLBP in patients with persistent spinal pain syndrome (PSPS) who have failed surgical interventions (PSPS-T2) motivated the evaluation of DTM SCS versus Conv-SCS on PSPS patients who are non-surgical candidates (PSPS-T1). Methods: This is a prospective, open label, crossover, post-market randomized controlled trial in 20 centers across the United States. Eligible patients were randomized to either DTM SCS or Conv-SCS in a 1:1 ratio. Primary endpoint was CLBP responder rate (percentage of subjects with ≥50% CLBP relief) at 3-month in randomized subjects who completed trialing (modified intention-to-treat population). Patients were followed up to 12 months. Secondary endpoints included change of CLBP and leg pain, responder rates, changes in disability, quality of life, patient satisfaction and global impression of change, and safety profile. An optional crossover was available at 6-month to all patients. Results: About 121 PSPS-T1 subjects with CLBP and leg pain mostly associated with degenerative disc disease and radiculopathy and who were not eligible for spine surgery were randomized. CLBP responder rate with DTM SCS (93.5%) was superior to Conv-SCS (36.4%) at the primary endpoint. Superior CLBP responder rates (88.1%–90.5%) were obtained with DTM SCS at all other timepoints. Mean CLBP reduction with DTM SCS (6.52 cm) was superior to that with Conv-SCS (3.01 cm) at the primary endpoint. Similar CLBP reductions (6.23–6.43 cm) were obtained with DTM SCS at other timepoints. DTM SCS provided significantly better leg pain reduction and responder rate, improvement of disability and quality of life, and better patient satisfaction and global impression of change. 90.9% of Conv-SCS subjects who crossed over were CLBP responders at completion of the study. Similar safety profiles were observed between the two groups. Conclusion: DTM SCS for chronic CLBP in nonsurgical candidates is superior to Conv-SCS. Improvements were sustained and provided significant benefits on the management of these patients.

Abstract GPKPDviz is a Shiny application (app) dedicated to real‐time simulation, visualization, and assessment of the pharmacokinetic/pharmacodynamic (PK/PD) models. Within the app, gPKPDviz is capable of generating virtual populations and complex dosing and sampling scenarios, which, together with the streamlined workflow, is designed to efficiently assess the impact of covariates and dosing regimens on PK/PD end points. The actual population data from clinical trials can be loaded into the app for simulation if desired. The app‐generated dosing regimens include single or multiple dosing, and more complex regimens, such as loading doses or intermittent dosing. When necessary, the dosing regimens can be defined externally and loaded to the app for simulation. Using mrgsolve as the simulation engine, gPKPDviz is typically used for population simulation, however, with a slight modification of the mrgsolve model, gPKPDviz is capable of performing individual simulations with individual post hoc parameters, individual dosing logs, and individual sampling timepoints through an external dataset. A built‐in text editor has a debugging feature for the mrgsolve model, providing the same error messages as model compilation in R. GPKPDviz has had stringent validation by comparing simulation results between the app and using mrgsolve in R. GPKPDviz is a member of the suite of Modeling and Simulation Shiny apps developed at Genentech to facilitate the typical modeling work in Clinical Pharmacology. For broader access to the Pharmacometric community, gPKPDviz has been published as an open‐source application in GitHub under the terms of GNU General Public License.

During the past decade, numerous postsecondary programs for students with intellectual disability have emerged as have standards to improve the quality of those programs. We used the Think College Standards for Inclusive Higher Education to develop a family survey to evaluate and improve programs. Overall, family responses were positive for most of the standards and indicated that students gained self-advocacy, technology and employment skills. Families indicated that we can improve on two standards: coordination/collaboration with adult services, and career development. Perspectives from families of current and past students provide critical information that enhances the quality of postsecondary programs for students with ID.

Hyperammonemia is a well-known adverse effect of valproate that can progress to a potentially fatal condition known as valproate-induced hyperammonemic encephalopathy (VHE). VHE is more common when valproate is used in combination therapy with other antiepileptic medications. A growing number of case reports have pointed to a possible interaction with the antipsychotic risperidone leading to an increased risk of VHE. We present a case of VHE in which a 20-year-old male patient with bipolar affective disorder developed VHE when on concomitant valproate, risperidone, and paliperidone palmitate. On the seventh day of treatment with oral risperidone, oral divalproex sodium was added. Intramuscular paliperidone palmitate was initiated on day 13, and oral risperidone was discontinued after the second loading dose on day 16. The following day, the patient displayed worsening psychomotor retardation, swaying gait, drowsiness, and vomiting. The patient was found to have hyperammonemia and transferred to the emergency department for treatment of suspected VHE.

Key Clinical Message Hydroa vacciniforme‐like lymphoproliferative disorder (HV‐LPD) is a rare cutaneous form of chronic active Epstein–Barr virus (CAEBV) that presents with vesicular lesions induced by sun‐exposure. Arterial aneurysm is a rare but potentially fatal complication of CAEBV and HV‐LPD.

Purpose: Non-small cell lung cancer (NSCLC) is a deadly malignancy that is frequently diagnosed in patients with significant medical comorbidities. When delivering local and regional therapy, an exceedingly narrow therapeutic window is encountered, which often precludes patients from receiving aggressive curative therapy. Radiation therapy advances including particle therapy have been employed in an effort to expand this therapeutic window. Here we report outcomes with the use of proton therapy with curative intent and immunotherapy to treat patients diagnosed with high-risk NSCLC. Methods and Materials: Patients were determined to be high risk if they had severe underlying cardiopulmonary dysfunction, history of prior thoracic radiation therapy, and/or large volume or unfavorable location of disease (eg, bilateral hilar involvement, supraclavicular involvement). As such, patients were determined to be ineligible for conventional x-ray–based radiation therapy and were treated with pencil beam scanning proton beam therapy (PBS-PBT). Patients who demonstrated excess respiratory motion (ie, greater than 1 cm in any dimension noted on the 4-dimensional computed tomography simulation scan) were deemed to be ineligible for PBT. Toxicity was reported using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Overall survival and progression-free survival were calculated using the Kaplan-Meier method. Results: A total of 29 patients with high-risk NSCLC diagnoses were treated with PBS-PBT. The majority (55%) of patients were defined as high risk due to severe cardiopulmonary dysfunction. Most commonly, patients were treated definitively to a total dose of 6000 cGy (relative biological effectiveness) in 30 fractions with concurrent chemotherapy. Overall, there were a total of 6 acute grade 3 toxicities observed in our cohort. Acute high-grade toxicities included esophagitis (n = 4, 14%), dyspnea (n = 1, 3.5%), and cough (n = 1, 3.5%). No patients developed grade 4 or higher toxicity. The majority of patients went on to receive immunotherapy, and high-grade pneumonitis was rare. Two-year progression-free and overall survival was estimated to be 51% and 67%, respectively. COVID-19 was confirmed or suspected to be responsible for 2 patient deaths during the follow-up period. Conclusions: Radical PBS-PBT treatment delivered in a cohort of patients with high-risk lung cancer with immunotherapy is feasible with careful multidisciplinary evaluation and rigorous follow-up.

Abstract Background Given the high risk of COVID‐19 mortality, patients with cancer may be vulnerable to fear of COVID‐19, adverse psychological outcomes, and health care delays. Methods This longitudinal study surveyed the pandemic's impact on patients with cancer (N= 1529) receiving Patient Advocate Foundation services during early and later pandemic. Generalized estimating equation with repeated measures was conducted to assess the effect of COVID‐19 on psychological distress. Logistic regression with repeated measures was used to assess the effect of COVID‐19 on any delays in accessing health care (e.g., specialty care doctors, laboratory, or diagnostic testing, etc.). Results Among 1199 respondents, 94% considered themselves high risk for COVID‐19. Respondents with more fear of COVID‐19 had a higher mean psychological distress score (10.21; 95% confidence intervals [CI] 9.38–11.03) compared to respondents with less fear (7.55; 95% CI 6.75–8.36). Additionally, 47% reported delaying care. Respondents with more fear of COVID‐19 had higher percentages of delayed care than those with less (56; 95% CI 39%–72% vs. 44%; 95% CI 28%–61%). These relationships persisted throughout the pandemic. For respondents with a COVID‐19 diagnosis in their household (n = 116), distress scores were similar despite higher delays in care (58% vs. 27%) than those without COVID‐19. Conclusions Fear of COVID‐19 is linked to psychological distress and delays in care among patients with cancer. Furthermore, those who are personally impacted see exacerbated cancer care delays. Timely psychosocial support and health care coordination are critical to meet increased care needs of patients with cancer during the COVID‐19 pandemic.

BackgroundDespite the use of interventions (e.g., monetary incentives, educational campaigns, on-site workplace vaccination) to increase COVID-19 vaccination, differences in uptake persist by poverty level, insurance status, geography, race, and ethnicity, suggesting that these interventions may not be adequately addressing the barriers faced by these populations. Among a sample of resource-limited individuals with chronic illnesses, we (1) described the prevalence of different types of barriers to the COVID-19 vaccination and (2) identified associations between patients' sociodemographic characteristics and barriers to vaccination.MethodsWe surveyed a national sample of patients with chronic illness and demonstrated healthcare affordability and/or access challenges about barriers to COVID-19 vaccination in July 2021. We categorized participant responses into cost, transportation, informational, and attitudinal barrier domains and assessed the prevalence of each domain, both overall and by self-reported vaccination status. Using logistic regression models, we examined unadjusted and adjusted associations between respondent characteristics (sociodemographic, geographic, and healthcare access) and self-reported barriers to vaccination.ResultsOf 1,342 respondents in the analytic sample, 20% (264/1,342) reported informational barriers and 9% (126/1,342) reported attitudinal barriers to COVID-19 vaccination. Transportation and cost barriers were reported much less commonly, by only 1.1% (15/1,342) and 0.7% (10/1,342) of the sample, respectively. Controlling for all other characteristics, respondents with either a specialist as their usual source of care or no usual source of care had an 8.4 (95% CI: 1.7–15.1) and 18.1 (95% CI: 4.3–32.0) percentage point higher predicted probability, respectively, of reporting informational barriers to care. Compared to females, males had an 8.4% point (95% CI: 5.5–11.4) lower predicted probability of reporting attitudinal barriers. Only attitudinal barriers were associated with COVID-19 vaccine uptake.ConclusionAmong a sample of adults with chronic illnesses who had received financial assistance and case management services from a national non-profit, informational and attitudinal barriers were more commonly reported than logistical or structural access barriers (i.e., transportation and cost barriers). Interventions should target attitudinal barriers among patients with chronic illness, who may have particular concerns about the interaction of the vaccine with ongoing medical care. Additionally, interventions targeting informational barriers are particularly needed among individuals without a usual source of care.

As postsecondary programs grow for students with intellectual and developmental disabilities (SwIDD), there is an increased focus on program evaluation and effectiveness, specifically related to impact on employment outcomes. Ohio’s Statewide Consortium (OSC) of postsecondary programs for individuals with intellectual and developmental disabilities interviewed seventeen current employer partners to determine to what degree they perceive OSC programs demonstrate quality indicators, as outlined in the eight Think College Standards for Inclusive Higher Education (TCSIHE). Results indicate OSC programs are providing high-quality, positive work-based learning experiences for SwIDD and their employer partners that align to TCSIHE. Key components of quality partnerships are highlighted as well as aspects of work-based learning experiences critical to skill development for SwIDD, and barriers to post-graduation employment outcomes.

Van der Waals (vdW) magnets have allowed researchers to explore the two dimensional limit of magnetisation; however experimental challenges have hindered analysis of magnetic domains. Here, using an NV centre based probe, the authors analyse the nature of magnetic domains in the vdW magnet, CrBr3.

ObjectiveTo establish the extent to which Rugby Union was a compulsory physical education activity in state-funded secondary schools in England and to understand the views of Subject Leaders for Physical Education with respect to injury risk.MethodA cross-sectional research study using data obtained under the Freedom of Information Act (2000) from 288 state-funded secondary schools.ResultsRugby Union was delivered in 81% (n = 234 of 288) of state-funded secondary school physical education curricula, including 83% (n = 229 of 275) of state-funded secondary school boys' and 54% (n = 151 of 282) of girls' physical education curricular. Rugby Union was compulsory in 91% (n = 208 of 229) of state-funded secondary schools that delivered it as part of the boys' physical education curriculum and 54% (n = 82 of 151) of state-funded secondary schools that delivered contact Rugby Union as part of the girls' physical education curriculum. Subject Leaders for Physical Education also perceived Rugby Union to have the highest risk of harm of the activities they delivered in their school physical education curriculum.ConclusionNotwithstanding discussions of appropriate measures (i.e., mandatory concussion training, Rugby Union specific qualifications and CPD) to reduce injury risk, it is recommended that Rugby Union should not be a compulsory activity given that it has a perceived high risk of injury and is an unnecessary risk for children in physical education.

Uninsured or underinsured individuals with cancer are likely to experience financial hardship, including forgoing healthcare or non-healthcare needs such as food, housing, or utilities. This study evaluates the association between health insurance coverage and financial hardship among cancer survivors during the COVID-19 pandemic. This cross-sectional analysis used Patient Advocate Foundation (PAF) survey data from May to July 2020. Cancer survivors who previously received case management or financial aid from PAF self-reported challenges paying for healthcare and non-healthcare needs during the COVID-19 pandemic. Associations between insurance coverage and payment challenges were estimated using Poisson regression with robust standard errors, which allowed for estimation of adjusted relative risks (aRR). Of 1,437 respondents, 74% had annual household incomes

The purpose of this study was to explore the understandings and perceptions of risk related to brain trauma amongst parents of children that play contact rugby. A qualitative approach was taken, using semi-structured interviews with 7 mothers and 27 fathers of children that participate in contact rugby. A thematic analysis of data suggests that parents used two primary cognitive strategies to process the risk they consented to with their children’s participation in rugby; (1) minimalizing rugby risk to be equivalent to less injurious sports; and (2) elevating physical and social advantages above what they think other sports are capable of providing. From the findings it is suggested that parents who permit their children to play contact rugby are both aware of the high risks of injury in the sport, but simultaneously utilize two cognitive distortion techniques to rectify the dissonance caused between their choice to have their children play, and the salient number of concussions they observe. These results suggest that it will take properly informed consent, inclusive of concussion rates compared to other sports, in order to reduce cognitive distortion and effectively communicate risks associated with participation in contact rugby.

PurposeStereotactic body radiation therapy (SBRT) is considered standard of care for medically inoperable early stage non-small cell lung cancer (ES-NSCLC). Central tumor location is a known risk factor for severe SBRT related toxicity. Bronchoscopy allows for visualization of the central airways prior to treatment. Five fraction SBRT approaches have been advocated to mitigate treatment induced toxicity. In this report, we examine the mature clinical outcomes of a diverse cohort of ES-NSCLC patients with both peripheral and central tumors treated with a conservative 5 fraction SBRT approach and evaluate the role of lobar gross endobronchial disease (LGED) in predicting overall survival and treatment-related death.MethodsMedically inoperable biopsy-proven, lymph node-negative ES-NSCLC patients were treated with SBRT. Bronchoscopy was completed prior to treatment in all centrally located cases. The Kaplan-Meier method was used to estimate overall survival (OS), local control (LC), regional control (RC), distant metastasis free survival (DMFS) and disease-free survival (DFS). Overall survival was stratified based on clinical stage, histology, tumor location and LGED. Toxicities were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0.ResultsFrom December 2010 to December 2015, 50 consecutive patients were treated uniformly with a 50 Gy in 5 fraction SBRT approach (tumor BED10 ≥ 100 Gy) and followed for a minimum of 5 years or until death. At a median follow up of 42 months for all patients, 3-year OS was 50%. Three-year OS did not statistically differ between stage I and stage II disease (51% vs. 47%; p=0.86), adenocarcinoma and squamous cell carcinoma (50% vs. 45%; p=0.68), or peripheral and central tumors (56% vs. 45%; p=0.46). Five central tumors were found to have LGED, and 3-year OS for this cohort was quite poor at 20%. Cox regression analysis identified LGED as a predictor of OS while controlling for age, stage and location (OR:4.536, p-value=0.038). Despite the relatively low dose delivered, treatment likely contributed to the death of 4 patients with central tumors. Lobar gross endobronchial disease was an independent predictor for grade 5 pulmonary toxicity (n=4, p=0.007). Specifically, 3 of the 5 patients with LGED developed fatal radiation-induced bronchial stricture. Three-year LC, RC, DMFS and DFS results for the group were similar to contemporary studies at 90%, 90%, 82% and 65%.ConclusionsCentral location of ES-NSCLC is a well-established predictor for severe SBRT-related toxicity. Here we identify LGED as a significant predictor of poor overall survival and grade 5 pulmonary toxicity. The relatively high rates of severe treatment-related toxicity seen in patients with central ES-NSCLC may be due in part to LGED. Underlying LGED may cause irreparable damage to the lobar airway, unmitigated by SBRT treatment thus increasing the risk of severe treatment-related toxicity. These findings should be verified in larger data sets. Future prospective central ES-NSCLC clinical trials should require staging bronchoscopy to identify LGED and further assess its clinical significance.

IntroductionCancer-related employment disruption contributes to financial toxicity and associated clinical outcomes through income loss and changes in health insurance and may not be uniformly experienced. We examined racial/ethnic differences in the financial consequences of employment disruption.MethodsWe surveyed a national sample of cancer patients employed at diagnosis who had received assistance from a national nonprofit about the impact of cancer diagnosis and treatment on employment. We used logistic regression models to examine racial/ethnic differences in income loss and changes in health insurance coverage.ResultsOf 619 cancer patients included, 63% identified as Non-Hispanic/Latinx (NH) White, 18% as NH Black, 9% as Hispanic/Latinx, 5% as other racial/ethnic identities, and 5% unreported. Over 83% reported taking a significant amount of time off from work during cancer diagnosis and treatment, leading to substantial income loss for 64% and changes in insurance coverage for 31%. NH Black respondents had a 10.2 percentage point (95% CI: 4.8 – 19.9) higher probability of experiencing substantial income loss compared to NH White respondents, and Hispanic or Latinx respondents had a 12.4 percentage point (95% CI: 0.3 – 24.5) higher probability compared to NH White respondents, controlling for clinical characteristics (i.e., cancer type, stage and age at diagnosis, and time since diagnosis). Similarly, NH Black respondents had a 9.3 percentage point (95% CI: -0.7 – 19.3) higher probability of experiencing changes in health insurance compared to NH White respondents, and Hispanic or Latinx respondents had a 10.0 percentage point (95% CI: -3.0 – 23.0) higher probability compared to NH White respondents.DiscussionCompared with NH White respondents, NH Black and Hispanic/Latinx respondents more commonly reported employment-related income loss and health insurance changes. Given documented racial/ethnic differences in job types, benefit generosity, and employment protections as a result of historic marginalization, policies to reduce employment disruption and its associated financial impact must be developed with a racial equity lens.

Emotional states are thought to influence athletic performance. Emotions characterized by high arousal enhance exercise performance. Extant research has focused on the valence and arousal dimensions of emotions, but not whether the motivational dimension (the extent to which the emotion engenders approach or avoidance behaviors) influences exercise performance. Two studies aimed to determine whether films and music chosen to induce approach- (i.e., anger), avoidance- (i.e., fear), and neutral-oriented emotions would successfully induce their intended emotional states (Study 1) and whether anger and fear emotion inductions would influence 2-mile time trial performance (Study 2). In Study 1, the films and music successfully induced their intended emotions. In Study 2, run time and perceived level of exertion did not differ between emotions across all participants or among faster running participants per a median split. However, among slower running participants, the anger induction increased the 2-mile running speed relative to the neutral induction. These findings suggest that emotions eliciting approach-related motivational states may improve exercise performance, particularly in slower runners.

Objectives: Heart disease is the leading cause of death in American Indians (AIs). For AI patients with severe coronary artery disease requiring coronary artery bypass graft (CABG) surgery, little data exist. The purpose of this study was to evaluate short-term outcomes of Northern Plains AI undergoing CABG and identify variations in patient presentation. Methods: All patients undergoing isolated CABG between June 2012 and June 2017 were studied. Seventy-four AI and 1236 non-American Indian (non-AI) patients were identified. Risk factors, preoperative characteristics, cardiac status, procedural information, and outcomes were collected. Univariate analysis comparing short-term clinical outcomes between AI and non-AI populations was performed. Multivariable logistic regression models were constructed and outcome differences assessed. Unadjusted Kaplan?Meier survival estimates were produced using 5-year survival data. Results: AI patients presented with increased risk factors, including higher rates of diabetes mellitus (AI 63.5% vs. non-AI 38.7% p=< 0.001) and smoking/tobacco use (AI 60.8% vs. non-AI 20.0% p=> 0.001). Seventy-nine percent of AI patients resided on or near federal reservations and presented from rural locations. Internal mammary artery (IMA) graft use in both groups was high (AI 95.9% vs. non-AI 94.9% p=0.904), and multiarterial grafting with left internal mammary artery and radial artery use was common in both groups (AI 67.6% vs. non-AI 69.6% p=0.814). No significant differences in unadjusted 30-day mortality or short-term outcomes were detected. Adjusted Kaplan?Meier survival curves were similar between race groups up through 5 years after CABG (p-value=0.38). Conclusion: AIs presented with significantly more risk factors for cardiovascular disease compared with the general population, with especially high rates of insulin-dependent diabetes and active tobacco use. Despite this, outcomes were similar between groups. In propensity-matched groups, AIs were at decreased risk for prolonged length of stay and combined morbidity/mortality. In contrast to previous reports, AI racial identity did not adversely affect survival up to 5 years after CABG.

Abstract Purpose/objective Local treatment options for patients with in-field non-small cell lung cancer (NSCLC) recurrence following conventionally fractionated external beam radiation therapy (CF-EBRT) are limited. Stereotactic body radiation therapy (SBRT) is a promising modality to achieve reasonable local control, although toxicity remains a concern. Materials/methods Patients previously treated with high-dose CF-EBRT (≥59.4 Gy, ≤3 Gy/fraction) for non-metastatic NSCLC who underwent salvage SBRT for localized ultra-central in-field recurrence were included in this analysis. Ultra-central recurrences were defined as those abutting the trachea, mainstem bronchus, or esophagus and included both parenchymal and nodal recurrences. The Kaplan-Meier method was used to estimate local control and overall survival. Durable local control was defined as ≥12 months. Toxicity was scored per the CTC-AE v4.0. Results Twenty patients were treated with five-fraction robotic SBRT for ultra-central in-field recurrence following CF-EBRT. Fifty percent of recurrences were adenocarcinoma, while 35% of tumors were classified as squamous cell carcinoma. The median interval between the end of CF-EBRT and SBRT was 23.3 months (range: 2.6 – 93.6 months). The median CF-EBRT dose was 63 Gy (range: 59.4 – 75 Gy), the median SBRT dose was 35 Gy (range: 25 – 45 Gy), and the median total equivalent dose in 2 Gy fractions (EQD2) was 116 Gy (range: 91.3 – 136.7 Gy). At a median follow-up of 12 months for all patients and 37.5 months in surviving patients, the majority of patients (90%) have died. High-dose SBRT was associated with improved local control (p

People, livelihoods, and infrastructure in Myanmar suffer from devastating monsoonal flooding on a frequent basis. Quick and effective management of flood risk relies on planning and preparedness to ensure the availability of supplies, shelters and emergency response personnel. The mandated government agency Department of Disaster Management (DDM) as well as local and international organizations play roles in producing, disseminating, and using accurate and timely information on flood risk. Currently, systematic flood risk maps are lacking, which leaves DDM to rely on inconsistent historic reports and local knowledge to inform their emergency planning. Although these types of knowledge are critical, they can be complemented to reduce bias and human error to planning processes and decisions. As such, the present situation has led to ineffective distribution of emergency response resources prior to flooding, leaving vulnerable populations less-than-prepared for inevitable flood events. Given these issues, we have developed a flood risk decision-support tool in collaboration with DDM. The tool uses surface water maps developed by the Joint Research Center (JRC), which were derived from more than 30 years of Landsat imagery. We have also incorporated population data, land cover data, and other information on flood exposure and vulnerability to create the first scalable and replicable Flood Risk Index (FRI) for flood risk reduction in Myanmar.

Land cover maps are a critical component to make informed policy, development, planning, and resource management decisions. However, technical, capacity, and institutional challenges inhibit the creation of consistent and relevant land cover maps for use in developing regions. Many developing regions lack coordinated capacity, infrastructure, and technologies to produce a robust land cover monitoring system that meets land management needs. Local capacity may be replaced by external consultants or methods which lack long-term sustainability. In this study, we characterize and respond to the key land cover mapping gaps and challenges encountered in the Lower Mekong (LMR) and Hindu Kush-Himalaya (HKH) region through a needs assessment exercise and a collaborative system design. Needs were assessed using multiple approaches, including focus groups, user engagement workshops, and online surveys. Efforts to understand existing limitations and stakeholder needs resulted in a co-developed and modular land cover monitoring system which utilizes state-of-the-art cloud computing and machine learning which leverages freely available Earth observations. This approach meets the needs of diverse actors and is a model for transnational cooperation.

The phase 4 ABOUND.70+ trial assessed the safety and efficacy of nab-paclitaxel/carboplatin continuously or with a 1-week break between cycles in elderly patients with advanced non-small cell lung cancer (NSCLC). Patients ≥70 years with locally advanced/metastatic NSCLC were randomized 1:1 to first-line nab-paclitaxel days 1, 8, 15 plus carboplatin day 1 of a 21-day cycle (21d) or the same nab-paclitaxel/carboplatin regimen with a 1-week break between cycles (21d + break; 28d). The primary endpoint was the percentage of patients with grade ≥ 2 peripheral neuropathy (PN) or grade ≥ 3 myelosuppression. Other key endpoints included progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). A total of 143 patients were randomized (71 to 21d, 72 to 21d + break). The percentage of patients with grade ≥ 2 PN or grade ≥ 3 myelosuppression was similar between the 21d and 21d + break arms (76.5 and 77.1%; P = 0.9258). Treatment exposure was lower in the 21d arm compared with the 21d + break arm. Median OS was 15.2 and 16.2 months [hazard ratio (HR) 0.72, 95% CI 0.44–1.19; P = 0.1966], median PFS was 3.6 and 7.0 months (HR 0.48, 95% CI 0.30–0.76; P

This article provides an overview of the changing nature ofmasculinities in several English speaking cultures. The evidence andtheory come from numerous investigations into masculinities amongboth gay and straight male youths in the United States, UnitedKingdom, Canada and Australia. Collectively, I show that culturalhomophobia is rapidly decreasing among young men in these cultures, and that this is particularly true of teamsport athletes. I suggest that thedominant way of theorizing masculinities over the previous quartercentury, hegemonic masculinity theory, is incapable of explaining thesechanges. Thus, I introduce a new theory, inclusive masculinity theory, and the new heuristic concept of homohysteria, to make sense of thechanging nature of young men’s masculinities.