Search

This study explores factors influencing the extent of engagement of international faculty in developing local research capacity. Drawing on ideas from research on knowledge sharing and on "intellectual commons," we found that while the faculty share explicit knowledge in publications and tacit knowledge by providing apprenticeship opportunities for their students, they remain disengaged from building capacity of local academics. We argue that the main reasons for this disengagement is ambiguity in interpretation of the social contract, ineffective reward structures, and the lack of tenure contracts.

Building local research capacity is an enduring challenge that confronts many higher education systems particularly when aspirations for a knowledge economy dominate policymaking. While research capacity has received tremendous attention among international development agencies and scholars, the discourse is largely oriented towards infrastructure, skills training and best practices. This study interrogates the concept of "local research capacity building" as a dynamic process. By contrasting the policy rhetoric with the lived experiences of academics based in Kazakhstan, we propose a conceptual model to illustrate the diverse levels of research capacity building: resources, locality, relevance, human capital and culture. This study examines research capacity building in the context of the internationalisation of higher education as researchers become increasingly mobile. We argue that investing in infrastructure and human capital are insufficient for capacity building. Rather, sustainable capacity building requires research that is relevant to the local context and a cultural environment that can nurture a vibrant research community.

Schools are increasingly being encouraged to teach vocational skills to middle and high school students. Although extensive research exists demonstrating the benefits of fluency instruction when teaching academic skills to this population of students, few studies have examined the importance of fluency training when teaching vocational skills. Using an alternating treatments design, the present study examined the effects of fluency versus accuracy training on 4 students' fluency in completing 2 vocational tasks. Following the training phase, students completed each task during 20- and 40-min work sessions to assess endurance and retention of the trained skills. Overall, results suggest that the fluency condition produced greater work productivity.

Breaking infection chains requires not just behaviours that allow individuals to stay healthy and uninfected (i.e. health protective behaviours) but also for those who are possibly infected to protect others from their harboured infection risk (i.e. socially responsible behaviours). However, socially responsible behaviours entail costs without clear, immediate benefits to the individual, such that public health‐risking lapses occur from time to time. In this important yet understudied area, the current exploratory study sought to identify possible psychological factors that may affect people's likelihood of engaging in socially responsible behaviours. Assuming that self‐perceived infection should provide an impetus to engage in socially responsible behaviours, we contend that lapses could occur in two scenarios: discounting of possible infection or prioritizing self‐interest over collective good. Through a vignette portraying COVID‐19 relevant symptoms presented to culturally diverse participants (Singapore and United States; N = 645), we found dispositional denialism (an ego defence mechanism) to exert a negative indirect effect on likelihood of engaging in socially responsible behaviours through its negative association with perceived infection status. Further, social value orientation and cultural orientation appeared to significantly moderate the positive association between perceived infection status and the likelihood of engaging in socially responsible behaviours, such that the positive association held only when individuals espouse both a prosocial value orientation and a collectivistic cultural orientation. Further analyses also point toward a possible attenuation of this positive association when individuals espouse a vertical cultural orientation. Future directions and implications for public health management are discussed. [ABSTRACT FROM AUTHOR]

Objective: Interstitial lung diseases (ILDs) are a heterogeneous group of disorders that can develop in patients with connective tissue diseases. Establishing autoimmunity in ILD impacts prognosis and treatment. Patients with ILD are screened for autoimmunity by measuring antinuclear autoantibodies, rheumatoid factors, and other nonspecific tests. However, this approach may miss autoimmunity that manifests as autoantibodies to tissue antigens not previously defined in ILD. Methods: We use Phage Immunoprecipitation‐Sequencing (PhIP‐Seq) to conduct an autoantibody discovery screen of patients with ILD and controls. We screened for novel autoantigen candidates using PhIP‐Seq. We next developed a radio‐labeled binding assay and validated the leading candidate in 398 patients with ILD recruited from two academic medical centers and 138 blood bank individuals that formed our reference cohort. Results: PhIP‐Seq identified 17 novel autoreactive targets, and machine learning classifiers derived from these targets discriminated ILD serum from controls. Among the 17 candidates, we validated CDHR5 and found CDHR5 autoantibodies in patients with rheumatologic disorders and importantly, patients not previously diagnosed with autoimmunity. Using survival and transplant free–survival data available from one of the two centers, patients with CDHR5 autoantibodies showed worse survival compared with other patients with connective tissue disease ILD. Conclusion: We used PhIP‐Seq to define a novel CDHR5 autoantibody in a subset of select patients with ILD. Our data complement a recent study showing polymorphisms in the CDHR5‐IRF7 gene locus strongly associated with titer of anticentromere antibodies in systemic sclerosis, creating a growing body of evidence suggesting a link between CDHR5 and autoimmunity. [ABSTRACT FROM AUTHOR]

Author(s): Wilson X Mai [1]; Laura Gosa [1]; Veerle W Daniels [2]; Lisa Ta [1]; Jonathan E Tsang [1]; Brian Higgins [3]; W Blake Gilmore [1]; Nicholas A Bayley [1]; [...], Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [[sup.18]F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies.

Author(s): Salma Kassem [1]; Alan T. L. Lee [1]; David A. Leigh (corresponding author) [1]; Vanesa Marcos [1]; Leoni I. Palmer [1]; Simone Pisano [1] It has been convincingly argued [...]

Vascular and haematopoietic cells organize into specialized tissues during early embryogenesis to supply essential nutrients to all organs and thus play critical roles in development and disease. At the top [...]

Acute skeletal muscle damage triggers a transient phase of extracellular matrix (ECM) remodeling (1), the prompt termination of which is crucial to avoiding pathological fibrosis and consequent tissue degeneration. Recent [...], Depending on the inflammatory milieu, injury can result either in a tissue's complete regeneration or in its degeneration and fibrosis, the latter of which could potentially lead to permanent organ failure. Yet how inflammatory cells regulate matrixproducing cells involved in the reparative process is unknown. Here we show that in acutely damaged skeletal muscle, sequential interactions between multipotent mesenchymal progenitors and infiltrating inflammatory cells determine the outcome of the reparative process. We found that infiltrating inflammatory macrophages, through their expression of tumor necrosis factor (TNF), directly induce apoptosis of fibro/adipogenic progenitors (FAPs). In states of chronic damage, however, such as those in mdx mice, macrophages express high levels of transforming growth factor [beta]1 (TGF-[beta]1), which prevents the apoptosis of FAPs and induces their differentiation into matrix- producing cells. Treatment with nilotinib, a kinase inhibitor with proposed anti-fibrotic activity, can block the effect of TGF-[beta]1 and reduce muscle fibrosis in mdx mice. Our findings reveal an unexpected anti-fibrotic role of TNF and suggest that disruption of the precisely timed progression from a TNF- rich to a TGF-[beta]-rich environment favors fibrotic degeneration of the muscle during chronic injury.

Research involving international research communities has been advocated in the field of behavior analysis (Dymond et al., 2000; Martin et al., 2016). The purpose of the present study was to report the status of behavioral research in mainland China, Hong Kong, and Taiwan, in terms of number of publications, types of research, and frequency of collaboration with international researchers. Fifteen behavioral journals were selected from the list by Cooper et al. (2020). These were searched by hand to find publications conducted in or authored by researchers from mainland China, Hong Kong, and Taiwan dating from each journal's inception to December 2021. The earliest publication we found appeared in 1980 in The Psychological Record. Over the following four decades (1980–1989; 1990–1999; 2000–2009; 2010–2021), the number of publications per decade increased dramatically and continues in recent years to rise. Publications include research reports, review papers, and conceptual articles, with the majority being basic research reports published in Behavioral Processes. Approximately half the publications involve collaboration with international researchers, mostly in North America. Implications for behavioral research, practice, and policy in mainland China, Hong Kong, and Taiwan are discussed. [ABSTRACT FROM AUTHOR]

Introduction 5'-AMP-activated protein kinase (AMPK) is a serine/threonine kinase that acts as a 'cellular fuel gauge,' owing to its ability to increase energy producing pathways, and to inhibit energy consuming [...], Glucose uptake and glycolysis are increased in the heart during ischemia, and this metabolic alteration constitutes an important contributing factor towards ischemic injury. Therefore, it is important to understand glucose uptake regulation in the ischemic heart. There are primarily 2 glucose transporters controlling glucose uptake into cardiac myocytes: GLUT1 and GLUT4. In the non-ischemic heart, insulin stimulates GLUT4 translocation to the sarcolemmal membrane, while both GLUT1 and GLUT4 translocation can occur following AMPK stimulation. Using a newly developed technique involving [³H]2-deoxyglucose, we measured glucose uptake in H9c2 ventricular myoblasts, and demonstrated that while insulin has no detectable effect on glucose uptake, phenformin-induced AMPK activation increases glucose uptake 2.5-fold. Furthermore, insulin treatment produced no discernible effect on either Akt serine 473 phosphorylation or AMPKα threonine 172 phosphorylation, while treatment with phenformin results in an increase in AMPKα threonine 172 phosphorylation, and a decrease in Akt serine 473 phosphorylation. Visualization of a dsRed-GLUT4 fusion construct in H9c2 cells by laser confocal microscopy showed that unlike insulin, AMPK activation did not redistribute GLUT4 to the sarcolemmal membrane, suggesting that AMPK may regulate glucose uptake via another glucose transporter. These studies suggest that AMPK is a major regulator of glucose uptake in cardiac myocytes. Key words: AMPK, glucose uptake, GLUT4, glycolysis, metabolism, cardiac myocyte, 2-deoxyglucose. La captation de glucose et laglycolyse sont accrues dans le cceur lors de l'ischemie, et cette modification metabolique constitue un facteur contributif important vers le dommage ischemique. En consequence, il est important de comprendre la regulation de la captation du glucose dans le cceur ischemique. Il existe 2 transporteurs de glucose qui controlent la captation de glucose dans les myocytes cardiaques, GLUT1 et GLUT4. Dans le ccur non ischemique, l'insuline stimule la translocation de GLUT4 vers la membrane du sarcolemme, alors que la translocation de GLUT1 et GLUT4 peut survenir a la suite de la stimulation de l'AMPK. Nous avons mesure la captation de glucose dans les myoblastes ventriculaires H9c2 a l'aide d'une nouvelle technique impliquant le [³H]2-deoxyglucose, et nous avons demontre que, alors que l'insuline n'exerce pas d'effet detectable sur la captation de glucose, l'activation de l'AMPK par la phenformine accroit la captation de glucose de 2.5 fois. De plus, le traitement a l'insuline ne produisait par d'effet detectable sur la phosphorylation d'Akt sur la serine 473 ou de l'AMPKα sur la threonine 172, alors que le traitement a la phenformine resultait en une augmentation de la phosphorylation de l'AMPKα sur la threonine 172, et en une diminution de la phosphorylation d'Akt sur la serine 473. L'observation en microscopie confocale au laser d'une construction impliquant une fusion dsRed-GLUT4 chez les cellules H92c a montre que contrairement a l'insuline, l'activation de l'AMPK ne produit pas de redistribution de GLUT4 a la membrane du sarcolemme, suggerant que l'AMPK peut reguler la captation de glucose par l'intermediaire d'un autre transporteur de glucose. Ces etudes suggerent que l'AMPK est un regulateur cle de la captation de glucose dans les myocytes cardiaques. [Traduit par la Redaction] Mots-cles: AMPK, captation de glucose, GLUT4, glycolyse, metabolisme, myocytes cardiaques, 2-deoxyglucose.

Introduction: The growing practice of living liver donation requires comprehensive understanding of the financial implications for living liver donors. While obtaining and maintaining insurance is important to financial health, little is known about the impact of liver donation on future insurability. Research Questions: The purpose of this study was to evaluate the donors' experiences with insurance following donation and identify the insurance provider-driven factors that contribute to donor insurability. Design: A two center cohort of living donors with donation between January 2000 and December 2018 (N = 442) were surveyed about postdonation insurance experiences. To understand insurance provider practices towards liver donors, life (n = 11) and disability (n = 4) insurance underwriters were asked to provide policy quotes for a standardized living liver donor profile. Results: Responses (N = 101) were received by August 2020 (response rate = 22.9%). Living liver donors reported owning life (58%), disability (35%), and medical (87%) insurance at rates comparable to the general population with low proportions reporting difficulty obtaining these insurance types (9%, 9%, 4%, respectively). Post-donation life insurance ownership was associated with post-donation employment (P = 0.01). Underwriter responses indicate life and disability insurability were adversely affected up to 12 months following donation. Conclusions: Living liver donors did not have difficulty maintaining insurance in the long-term but should be counseled to purchase insurance prior to surgery as short-term insurability may be affected. Perception of difficulty obtaining insurance following donation remains of significant concern among living donors. Further collaboration between the transplant community and insurance companies is warranted. [ABSTRACT FROM AUTHOR]

In animals, maternal gene products drive early development in a transcriptionally silent embryo, and are responsible for ZGA. ZGA occurs during the MZT, when developmental control transfers to the embryonic [...], After fertilization, maternal factors direct development and trigger zygotic genome activation (ZGA) at the maternal-to-zygotic transition (MZT). In zebrafish, ZGA is required for gastrulation and clearance of maternal messenger RNAs, which is in part regulated by the conserved microRNA miR-430. However, the factors that activate the zygotic program in vertebrates are unknown. Here we show that Nanog, Pou5f1 (also called Oct4) and SoxB1 regulate zygotic gene activation in zebrafish. We identified several hundred genes directly activated by maternal factors, constituting the first wave of zygotic transcription. Ribosome profiling revealed that nanog, sox19b and pou5f1 are the most highly translated transcription factors pre-MZT. Combined loss of these factors resulted in developmental arrest before gastrulation and a failure to activate > 75% of zygotic genes, including miR-430. Our results demonstrate that maternal Nanog, Pou5f1 and SoxB1 are required to initiate the zygotic developmental program and induce clearance of the maternal program by activating miR-430 expression.

The suppression of tumorigenicity 2/IL-33 (ST2/IL-33) pathway has been implicated in several immune and inflammatory diseases. ST2 is produced as 2 isoforms. The membrane-bound isoform (ST2L) induces an immune response [...]

Although recent studies have revealed that heart cells are generated in adult mammals, the frequency of generation and the source of new heart cells are not yet known. Some studies [...]

MIMS combines ion microscopy with secondary ion mass spectrometry (SIMS), stable isotope reporters and intensive computation (Supplementary Fig. 1). MIMS allows imaging and measuring of stable isotope labels in cell [...], Mass spectrometry with stable isotope labels has been seminal in discovering the dynamic state of living matter (1,2), but is limited to bulk tissues or cells. We developed multi-isotope imaging mass spectrometry (MIMS) that allowed us to view and measure stable isotope incorporation with submicrometre resolution (3,4). Here we apply MIMS to diverse organisms, including Drosophila, mice and humans. We test the 'immortal strand hypothesis', which predicts that during asymmetric stem cell division chromosomes containing older template DNA are segregated to the daughter destined to remain a stem cell, thus insuring lifetime genetic stability. After labelling mice with [sup.15]N-thymidine from gestation until post-natal week 8, we find no [sup.15]N label retention by dividing small intestinal crypt cells after a four-week chase. In adult mice administered [sup.15]N-thymidine pulse-chase, we find that proliferating crypt cells dilute the [sup.15]N label, consistent with random strand segregation. We demonstrate the broad utility of MIMS with proof-of-principle studies of lipid turnover in Drosophila and translation to the human haematopoietic system. These studies show that MIMS provides high-resolution quantification of stable isotope labels that cannot be obtained using other techniques and that is broadly applicable to biological and medical research.

Introduction The clinical profile of ischemic heart disease has changed profoundly over the last decade, with a growing prevalence of systemic metabolic disorders. As the metabolic syndrome can decrease the [...], Classic therapeutics for ischemic heart disease are less effective in individuals with the metabolic syndrome. As the prevalence of the metabolic syndrome is increasing, better understanding of cardiac metabolism is needed to identify potential new targets for therapeutic intervention. Thioredoxin-interacting protein (Txnip) is a regulator of metabolism and an inhibitor of the antioxidant thioredoxins, but little is known about its roles in the myocardium. We examined hearts from Txnip-KO mice by polony multiplex analysis of gene expression and an independent proteomic approach; both methods indicated suppression of genes and proteins participating in mitochondrial metabolism. Consistently, Txnip-KO mitochondria were functionally and structurally altered, showing reduced oxygen consumption and ultrastructural derangements. Given the central role that mitochondria play during hypoxia, we hypothesized that Txnip deletion would enhance ischemia-reperfusion damage. Surprisingly, Txnip-KO hearts had greater recovery of cardiac function after an ischemia-reperfusion insult. Similarly, cardiomyocyte-specific Txnip deletion reduced infarct size after reversible coronary ligation. Coordinated with reduced mitochondrial function, deletion of Txnip enhanced anaerobic glycolysis. Whereas mitochondrial ATP synthesis was minimally decreased by Txnip deletion, cellular ATP content and lactate formation were higher in Txnip-KO hearts after ischemia-reperfusion injury. Pharmacologic inhibition of glycolytic metabolism completely abolished the protection afforded the heart by Txnip deficiency under hypoxic conditions. Thus, although Txnip deletion suppresses mitochondrial function, protection from myocardial ischemia is enhanced as a result of a coordinated shift to enhanced anaerobic metabolism, which provides an energy source outside of mitochondria.

XCI has been reliably modelled in female mouse ES cells, which carry two active X chromosomes but will inactivate one when induced to differentiate into embryoid bodies ex vivo. Given [...], Pluripotency of embryonic stem (ES) cells is controlled by defined transcription factors (1,2). During differentiation, mouse ES cells undergo global epigenetic reprogramming, as exemplified by X-chromosome inactivation (XCI) in which one female X chromosome is silenced to achieve gene dosage parity between the sexes (3-5). Somatic XCI is regulated by homologous X-chromosome pairing (6,7) and counting (8-10), and by the random choice of future active and inactive X chromosomes. XCI and cell differentiation are tightly coupled (11), as blocking one process compromises the other (8,12) and dedifferentiation of somatic cells to induced pluripotent stem cells is accompanied by X chromosome reactivation (2). Recent evidence suggests coupling of Xist expression to pluripotency factors occurs (13), but how the two are interconnected remains unknown. Here we show that Oct4 (also known as Pou5f1) (14) lies at the top of the XCI hierarchy, and regulates XCI by triggering X-chromosome pairing and counting. Oct4 directly binds Tsix and Xite, two regulatory noncoding RNA genes of the X-inactivation centre (15,16), and also complexes with XCI trans-factors, Ctcf and Yy1 (ref. 17), through protein--protein interactions. Depletion of Oct4 blocks homologous X-chromosome pairing and results in the inactivation of both X chromosomes in female cells. Thus, we have identified the first trans-factor that regulates counting, and ascribed new functions to Oct4 during X-chromosome reprogramming.

Muscular dystrophies are often caused by mutations in cytoskeletal proteins that render cells more susceptible to strain-induced injury in mechanically active tissues such as skeletal or cardiac muscle. In this [...]

ST2 is an IL-1 receptor family member with transmembrane (ST2L) and soluble (sST2) isoforms. sST2 is a mechanically induced cardiomyocyte protein, and serum sST2 levels predict outcome in patients with [...]

Objective: Auditory verbal hallucinations (AVHs) likely result from disorders, as yet unspecified, of the neural mechanisms of language. Here we examine the functional neuroanatomy of single-word reading in patients with [...]

Does the ethnic and immigrant composition of a community and existence of immigrant enclaves or barrios influence community level drug violence? This study explores the relationship between these and other factors in Miami and San Diego census tracts. We employ data about the distribution of Cubans, Central Americans, Haitians, Mexicans and Southeast Asians, controlling for social and economic influences of drug versus non-drug violence. We also analyze the impact of various waves of immigration and immigrant communities to understand the circumstances under which drug violence occurs or is limited at the census tract level. The findings lend some support to the positive and negative aspects of Portes and Rumbaut's (2001) segmented assimilation hypothesis in Miami and San Diego neighborhoods. The strength of this conclusion varies and is contingent upon ethnic composition, new versus old immigration, and the all-encompassing effects of economic deprivation, In recent years, drug violence has been a source of anxiety in many communities across urban America (Baumer et al., 1998; Blumstein, 1995). This anxiety centers on the fact that [...]

Insufficiency stress fractures often occur in older patients who have underlying metabolic bone disease, such as osteopenia and osteoporosis. Our case report describing an older woman with foot pain serves [...]

This paper describes the development and validation of the Emotional Labour Scale (ELS) as tested on samples of 296 and 238 respondents. The ELS is a 15-item self-report questionnaire that measures six facets of emotional display in the workplace, including the frequency, intensity and variety of emotional display, the duration of interaction, and surface and deep acting. Estimates of internal consistency for the subscales ranged from .74 to .91. Confirmatory factor analysis results provided support for the existence of six unidimensional subscales. Evidence was also provided for convergent and discriminant validity., Much of what workers do on the job entails the management of emotions in their interactions with others. The display of emotions or the use of feelings to accomplish their [...]

Since its discovery over a decade ago, the family of ABC transporter proteins has grown dramatically to well over a thousand examples with known sequences. ABC transporters now form the [...], The ABC transporters are ubiquitous membrane proteins that couple adenosine triphosphate (ATP) hydrolysis to the translocation of diverse substrates across cell membranes. Clinically relevant examples are associated with cystic fibrosis and with multidrug resistance of pathogenic bacteria and cancer cells. Here, we report the crystal structure at 3.2 angstrom resolution of the Escherichia coli BtuCD protein, an ABC transporter mediating vitamin [B.sub.12] uptake. The two ATP-binding cassettes (BtuD) are in close contact with each other, as are the two membrane-spanning subunits (BtuC); this arrangement is distinct from that observed for the E. coli lipid flippase MsbA. The BtuC subunits provide 20 transmembrane helices grouped around a translocation pathway that is closed to the cytoplasm by a gate region whereas the dimer arrangement of the BtuD subunits resembles the ATP-bound form of the Rad50 DNA repair enzyme. A prominent cytoplasmic loop of BtuC forms the contact region with the ATP-binding cassette and appears to represent a conserved motif among the ABC transporters.

Background: A number of circulating plasma biomarkers have been shown to predict survival in patients with idiopathic pulmonary fibrosis (IPF), but most were identified before the use of antifibrotic (AF) therapy in this population. Because pirfenidone and nintedanib have been shown to slow IPF progression and may prolong survival, the role of such biomarkers in AF-treated patients is unclear.Research Question: To determine whether plasma concentration of cancer antigen 125 (CA-125), C-X-C motif chemokine 13 (CXCL13), matrix metalloproteinase 7 (MMP7), surfactant protein D (SP-D), chitinase-3-like protein-1 (YKL-40), vascular cell adhesion protein-1 (VCAM-1), and osteopontin (OPN) is associated with differential transplant-free survival (TFS) in AF-exposed and nonexposed patients with IPF.Study Design and Methods: A pooled, multicenter, propensity-matched analysis of IPF patients with and without AF exposure was performed. Optimal thresholds for biomarker dichotomization were identified in each group using iterative Cox regression. Longitudinal biomarker change was assessed in a subset of patients using linear mixed regression modeling. A clinical-molecular signature of IPF TFS was then derived and validated in an independent IPF cohort.Results: Three hundred twenty-five patients were assessed, of which 68 AF-exposed and 172 nonexposed patients were included after propensity matching. CA-125, CXCL13, MMP7, YKL-40, and OPN predicted differential TFS in AF-exposed patients but at higher thresholds than in AF-nonexposed individuals. Plasma biomarker level generally increased over time in nonexposed patients but remained unchanged in AF-exposed patients. A clinical-molecular signature predicted decreased TFS in AF-exposed patients (hazard ratio [HR], 5.91; 95% CI, 2.25-15.5; P < .001) and maintained this association in an independent AF-exposed cohort (HR, 3.97; 95% CI, 1.62-9.72; P = .003).Interpretation: Most plasma biomarkers assessed predicted differential TFS in AF-exposed patients with IPF, but at higher thresholds than in nonexposed patients. A clinical-molecular signature of IPF TFS may provide a reliable predictor of outcome risk in AF-treated patients but requires additional research for optimization and validation. [ABSTRACT FROM AUTHOR]

Nonadherence to oral anticancer medications (OAMs) in the United States is as low as 33% for some cancers. The reasons for nonadherence to these lifesaving medications are multifactorial, yet the majority of studies focus on patient-level factors influencing uptake and adherence. Individually based interventions to increase patient adherence have not been effective, and this warrants attention to factors at the payor, pharmaceutical, and clinical systems levels. Based on the authors' research and clinical experiences, this commentary brings fresh attention to the long-standing issue of OAM nonadherence, a growing quality-of-care issue, from a systems perspective. In this commentary, the key driving factors in pharmaceutical and payor systems (state and federal laws, payor/insurance companies, and pharmaceutical companies), clinical systems (hospitals and providers), and patient contexts that have trickle-down effects on patient adherence to OAMs are outlined. In the end, the authors' recommendations include examining the influence of laws governing OAM drug pricing, OAM supply, and provider reimbursement; reducing the need for prior authorization of long-approved OAMs; identifying cost-effective ways for providers to monitor nonadherence; examining issues of provider bias in OAM prescriptions; and further elucidating in which contexts patients are likely to be able to adhere. These recommendations offer a starting point for an examination of the chain of systems influencing patient adherence and may help to finally resolve persistently high levels of OAM nonadherence. [ABSTRACT FROM AUTHOR]

Background: The National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, collected alongside the clinician-reported Common Terminology Criteria for Adverse Events, enables comparisons of patient and clinician reports on treatment toxicity.Methods: In a multisite study of women receiving chemotherapy for early-stage breast cancer, symptom reports were collected on the same day from patients and their clinicians for 17 symptoms; their data were not shared with each other. The proportions of moderate, severe, or very severe patient-reported symptom severity were compared with the proportions of clinician-rated grade 2, 3, or 4 toxicity. Patient-clinician agreement was assessed via κ statistics. Chi-square tests investigated whether patient characteristics were associated with patient-clinician agreement.Results: Among 267 women, the median age was 58 years (range, 24-83 years), and 26% were nonwhite. There was moderate scoring agreement (κ = 0.413-0.570) for 53% of symptoms, fair agreement for 41% (κ = 0.220-0.378), and slight agreement for 6% (κ = 0.188). For example, patient-reported and clinician-rated percentages were 22% and 8% for severe or very severe fatigue, 41% and 46% for moderate fatigue, 32% and 39% for mild fatigue, and 6% and 7% for none. Clinician severity scores were lower for nonwhite patients in comparison with white patients for peripheral neuropathy, nausea, arthralgia, and dyspnea.Conclusions: Although clinician reporting of symptoms is common practice in oncology, there is suboptimal agreement with the gold standard of patient self-reporting. These data provide further evidence supporting the integration of patient-reported outcomes into oncological clinical research and clinical practice to improve monitoring of symptoms as well as timely interventions for symptoms. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety and effectiveness of the MANTA percutaneous vascular closure device in patients undergoing percutaneous endovascular aneurysm repair (PEVAR) or thoracic endovascular aortic repair (TEVAR). Materials and Methods: The SAFE MANTA Study (ClinicalTrials.gov identifier NCT02908880) was a prospective, single-arm, multicenter trial in patients undergoing endovascular interventions using large-bore sheaths (transcatheter aortic valve replacement, PEVAR, or TEVAR) at 20 sites in North America. Patient selection intended to test the MANTA device in populations without morbid obesity, severe calcification, or a severely scarred femoral access area. Of the 263 patients enrolled in the primary analysis cohort, 53 (20.2%) patients (mean age 74.9±8.9 years; 41 men) underwent PEVAR (n=51) or TEVAR (n=2) procedures and form the cohort for this subgroup analysis. Per protocol a single MANTA device was deployed in all PEVAR/TEVAR cases. Results: The mean time to hemostasis in the PEVAR/TEVAR cohort was 35±91 seconds, with a median time of 19 seconds vs 24 seconds in the overall SAFE MANTA population. The MANTA device met the definition for technical success in 52 (98%) of 53 PEVAR/TEVAR cases compared with 97.7% in the overall SAFE MANTA population. One (1.9%) major complication (access-site stenosis) occurred in this subgroup compared to 14 (5.3%) events in the SAFE population. In the PEVAR/TEVAR group, 1 pseudoaneurysm was noted prior to discharge, another at 30-day follow-up, and one at 60 days. One (1.9%) of the 3 minor pseudoaneurysms was treated with ultrasound-guided compression and the other 2 required no treatment. Conclusion: The MANTA device demonstrated a short time to hemostasis and low complication rates compared with published literature results of other percutaneous closure devices. Time to hemostasis and complication rates were comparable between the PEVAR/TEVAR patients and the full SAFE MANTA study cohort. The MANTA device provides reliable closure with a single percutaneous device for PEVAR/TEVAR procedures. [ABSTRACT FROM AUTHOR]

Although evidence points to the benefits of continuity of care after detoxification (detox), especially when continuity of care occurs within a short time after discharge from a detox episode, the rate at which clients engage in continued treatment after detox remains low. The goal of the study was to develop and deploy a specially trained workforce, called recovery support navigators (RSNs), to increase the likelihood of clients continuing onto treatment after detox. Continuity of care is defined as receiving any substance use disorder (SUD) treatment service within 14 days of discharge from the index detox. We examined whether clients in the RSN Intervention group were more likely to meet the continuity of care after detox criteria than clients in the treatment-as-usual (TAU) group. A quasi-experimental intervention versus comparison group study was conducted. Data were from the Massachusetts Behavioral Health Partnership (MBHP), a Beacon Health Options company that manages behavioral health benefits for a subset of Medicaid beneficiaries in the state. Inclusion in the analytic sample (N = 4,236) required that the client's index admission to detox was between 3/29/13 and 3/31/15. RSN Intervention versus TAU status was assigned based on provider organization where the index detox occurred. Analyses were conducted on an intent-to-treat basis. Overall, the continuity of care rate across all study groups was 42%. The rate by study group was 38% for the TAU and 45% for the RSN group. Clients who were in the RSN group were significantly more likely to have continuity of care after discharge from detox than those in the TAU (OR = 1.233, p < .05, 95% CI = 1.044, 1.455). Clients who entered detox at a site that provided specialized training to RSN, which included motivational interviewing and educational sessions related to treatment issues, and allowing them to bill with a flexible daily case rate instead of the usual fee-for-service billing, were more likely to have continuity of care after discharge from detox compared to clients in the TAU group. [ABSTRACT FROM AUTHOR]

The [sup 18]O([sup 1]D)+[sup 44]CO[sub 2] oxygen isotope exchange reaction has been studied using a crossed molecular beam apparatus at a collision energy of 7.7 kcal/mol. Two different reaction channels are observed, both proceeding via a relatively long-lived CO[sub 3] complex. Electronic quenching of O([sup 1]D) is the major channel, accounting for 68% of all isotope exchange, while 32% occurs without quenching. These results are the first experimental evidence that isotope exchange can occur through a long-lived CO[sub 3] intermediate without subsequent crossing to the triplet surface, and could prove important for atmospheric models of oxygen isotope exchange between CO[sub 2] and O[sub 3]. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Globalization has opened access to distant regions of the world and increased awareness of global health disparities [1-3]. This heightened awareness, coupled with the rapid expansion of treatment to over [...]

Introduction Inorganic arsenic (iAs) is a toxicant and carcinogen common in groundwater and certain foods (e.g., rice, grains) (EFSA 2009). Evidence from Taiwan, Bangladesh, and Mexico supports an association of [...], Background: High arsenic exposure has been related to diabetes, but at low-moderate levels the evidence is mixed. Arsenic metabolism, which is partly genetically controlled and may rely on certain B vitamins, plays a role in arsenic toxicity. OBJECTIVE: We evaluated the prospective association of arsenic exposure and metabolism with type 2 diabetes and insulin resistance. Methods: We included 1,838 American Indian men and women free of diabetes (median age, 36 y). Arsenic exposure was assessed as the sum of inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) urine concentrations ([summation]As). Arsenic metabolism was evaluated by the proportions of iAs, MMA, and DMA over their sum (iAs%, MMA%, and DMA%). Homeostasis model assessment for insulin resistance (HOMA2-IR) was measured at baseline and follow-up visits. Incident diabetes was evaluated at follow-up. Results: Median [summation]As, iAs%, MMA%, and DMA% was 4.4 [micro]g/g creatinine, 9.5%, 14.4%, and 75.6%, respectively. Over 10,327 person-years of follow-up, 252 participants developed diabetes. Median HOMA2-IR at baseline was 1.5. The fully adjusted hazard ratio [95% confidence interval (CI)] for incident diabetes per an interquartile range increase in [summation]As was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. [summation]As was positively associated with HOMA2-IR at baseline but negatively with HOMA2-IR at follow-up. Increased MMA% was associated with lower HOMA2-IR when either iAs% or DMA% decreased. The association of arsenic metabolism with HOMA2-IR differed by B-vitamin intake and AS3MT genetics variants. Conclusions: Among participants without baseline prediabetes, arsenic exposure was associated with incident diabetes. Low MMA% was cross-sectional and prospectively associated with higher HOMA2-IR. Research is needed to confirm possible interactions of arsenic metabolism with B vitamins and AS3MT variants on diabetes risk. https://doi.org/10.1289/EHP2566

The FAO of the UN convened an Expert Working Group meeting to provide recommendations related to protein quality evaluation of Follow-up Formula for Young Children (FUF-YC) and Ready-to-Use Therapeutic Foods (RUTFs). The protein and amino acid (AA) scoring patterns for the target age groups were defined and recommendations provided on the use of currently available protein and indispensable AA digestibility data. For FUF-YC, an age category of 1-2.9 y was identified, and a matching protein requirement of 0.86 g · kg-1 · d-1 with corresponding AA requirements were recommended. For RUTF, the protein requirement recommended was 2.82 g · kg-1 · d-1, to achieve a catch-up weight gain of 10 g · kg-1 · d-1 in children recovering from severe acute malnutrition. The AA requirements were factorially derived based on the adult protein requirement for maintenance and tissue AA composition. A flowchart was proposed for the best available methods to estimate digestibility coefficients (of either protein or AAs), in the following order: human, growing pig, and rat true ileal AA digestibility values. Where this is not possible, fecal protein digestibility values should be used. The Expert Working Group recommends the use of the Protein Digestibility Corrected Amino Acid Score (PDCAAS), with existing protein digestibility values, or the Digestible Indispensable Amino Acid Score provided that individual AA digestibility values are available for protein quality evaluation using the latter score. The Group also recommends the use of ileal digestibility of protein or of AAs for plant-based protein sources, recognizing the possible effects of antinutritional factors and impaired gut function. A PDCAAS score of ≥90% can be considered adequate for these formulations, whereas with a score <90%, the quantity of protein should be increased to meet the requirements. Regardless of the protein quality score, the ability of formulations to support growth in the target population should be evaluated. Future research recommendations are also proposed based on the knowledge gaps identified. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to compare the cosmesis and recurrence rates of conventional excision (CE), Mohs micrographic surgery (MMS), external-beam radiation therapy (EBRT), or brachytherapy (BT), for basal cell carcinoma and squamous cell carcinoma of the skin.Methods: Population, Intervention, Control, Outcome, Study Design (PICOS), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and Meta-Analyses of Observational Studies in Epidemiology (MOOSE) methods were used to identify studies on PubMed (from 1985 to 2018), including patients with American Joint Committee on Cancer (AJCC) T1-T2N0 basal cell carcinomas and squamous cell carcinomas and ≥10 months follow-up who received CE, MMS, EBRT, or BT. The primary endpoint was cosmesis, classified as "good," "fair," or "poor." The secondary endpoint was 1-year recurrence. Fixed-effects and random-effects meta-analyses were performed to evaluate primary and secondary outcomes with respect to treatment modality.Results: In total, 18,095 studies met initial search criteria. There were 24 CE, 13 MMS, 19 EBRT, and 7 BT studies included with a total of 21,371 patients. The summary effect size for "good" cosmesis was 81% (95% CI, 70.6%-89.6%), 74.6% (95% CI, 63%-84.6%), and 97.6% (95% CI, 91.3%-100%) for CE, EBRT, and BT, respectively. Good cosmesis was 96.0% in the only MMS study that reported cosmesis. BT had improved "good" cosmesis over EBRT (P = .0025) and was similar to CE and MMS. No significant differences were seen for "fair" or "poor" cosmesis. One-year recurrence rates were low throughout at 0.8% (95% CI, 0.3%-1.6%), 0.2% (95% CI, 0%-0.6%), 2% (95% CI, 1.3%-2.7%), and 0% (95% CI, 0%-0.5%) for CE, MMS, EBRT, and BT, respectively.Conclusions: For T1-T2N0 skin cancers, BT and MMS have improved cosmesis over EBRT and CE. It is unclear whether this is because of treatment superiority or selection and reporting bias. Local control is similar among all modalities at 1 year. [ABSTRACT FROM AUTHOR]

We contribute to the field of immigration and crime research by conducting one of the first contemporary examinations of Afro-Caribbean homicides. Despite the growth of immigration across urban America, social [...]