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The study examines the associations between socioeconomic status (SES) and noncognitive development in first year college students, distinguish-ing between objective (or absolute) and subjective (or relative) measures of SES. The analyses draw from longitudinal data capturing college students(N = 2,488) at the start of the first year of college and again towards the end of the same academic year, across 25 public four-year colleges and universities within a single state higher education system. Results highlight the importance of subjective status, over and above objective status, and suggest strategies that may inform college and university support.

To evaluate the prognostic significance of the new index designed by formulating neutrophil, lymphocyte, and platelet counts in patients with metastatic disease receiving immune checkpoint inhibitors (ICI) and its effect on the immune-related adverse events (irAEs).Cohort study.Department of Medical Oncology, University of Manisa Celal Bayar, University of Aydin Adnan Menderes, and University of Ege, and Izmir Kent Hospital, Turkey, from January 2016 to April 2020.Patients with metastatic disease receiving ICI sufficient follow-up data were included. Patients, who had received treatment for a minimum of 3 months, were evaluated for the response. Systemic immune-inflammation index (SII) was calculated as neutrophil (/L) × (lymphocyte (/L) / platelet (/L). The cut-off value was determined by examining the area under the receiver operating characteristic (ROC) curve for the SII value. The endpoints of this study included overall survival (OS) and progression-free survival (PFS).A total of 168, patients who received ICI in the metastatic stage, were evaluated. The OS of the patients with low SII scores was 110.8 months (95% CI, 88.2-133.5), while patients with high SII scores were 36.0 months (95% CI, 28.4-43.6) and reached statistical significance (p0.001). The results of univariate (HR=3.376, 95% CI, 1.986-5.739, p0.001 and multivariate (HR=2.792, 95% CI, 1.495-5.215, p=0.011) analyses were statistically significant as well.The SII score in patients with metastatic disease receiving ICI was closely related to the prognosis. Patients with a high SII score are associated with a worse prognosis, these patients develop fewer irAEs.Systemic immune inflammation index, Overall survival, Progression-free survival, İmmune checkpoint inhibitor, Pembrolizumab, Nivolumab.

As opioid prescribing has declined, it is unclear how the landscape of prescription pain treatment across the U.S. has changed. We used nationally-representative data from the Medical Expenditure Health Survey, 2014 to 2018 to examine trends in prescriptions for opioid and non-opioid pain medications, including acetaminophen, non-steroidal anti-inflammatory drugs, gabapentinoids, and antidepressants among U.S. adults with self-reported pain. Overall, from 2014 to 2018, the percentage of participants receiving a prescription for opioids declined, (38.8% vs 32.8%), remained stable for non-steroidal anti-inflammatory drugs (26.8% vs 27.7%), and increased for acetaminophen (1.6% vs 2.3%), antidepressants (9.6% vs 12.0%) and gabapentinoids (13.2% vs 19.0%). In this period, the adjusted odds of receiving an opioid prescription decreased (aOR=.93, 95% CI=.90-.96), while the adjusted odds of receiving antidepressant, gabapentinoid and acetaminophen prescriptions increased (antidepressants: aOR=1.08, 95% CI=1.03-1.13 gabapentinoids: aOR=1.11, 95% CI=1.06-1.17; acetaminophen: aOR=1.10, 95% CI: 1.02-1.20). Secondary analyses stratifiying within the 2014 to 2016 and 2016 to 2018 periods revealed particular increases in prescriptions for gabapentinoids (aOR=1.13, 95% CI=1.05-1.21) and antidepressants (aOR=1.23, 95% CI=1.12-1.35) since 2016. PERSPECTIVE: These data demonstrate that physicians are increasingly turning to CDC-recommended non-opioid medications for pain management, particularly antidepressants and gabapentinoids. However, evidence for these medications' efficacy in treating numerous common pain conditions, including low back pain, remains limited.

OBJECTIVE Healthcare disparities are widely described in adults, but barriers affecting access to care for pediatric patients with moyamoya disease (MMD) are unknown. Understanding socioeconomic factors impacting hospital access and outcomes is necessary to address pediatric healthcare disparities. METHODS In this cross-sectional observational study, the Kids’ Inpatient Database was used to identify patients admitted with a primary diagnosis of MMD from 2003 to 2016. Patients ≤ 18 years with a primary diagnosis of MMD based on International Classification of Diseases (ICD) codes were included. Hospital admissions were queried for use of cerebral revascularization based on ICD procedure codes. RESULTS Query of the KID yielded 1449 MMD hospitalizations. After multivariable regression, Hispanic ethnicity (OR 0.52 [95% CI 0.33–0.81], p = 0.004) was associated with lack of surgical revascularization. Private insurance (OR 1.56 [95% CI 1.15–2.13], p = 0.004), admissions at medium- and high-volume centers (OR 2.01 [95% CI 1.42–2.83], p < 0.001 and OR 2.84 [95% CI 1.95–4.14], p < 0.001, respectively), and elective hospitalization (OR 3.37 [95% CI 2.46–4.64], p < 0.001) were positively associated with revascularization. Compared with Caucasian race, Hispanic ethnicity was associated with increased mean (± SEM) length of stay by 2.01 ± 0.70 days (p = 0.004) and increased hospital charges by $24,333.61 ± $7918.20 (p = 0.002), despite the decreased utilization of surgical revascularization. Private insurance was associated with elective admission (OR 1.50 [95% CI 1.10–2.05], p = 0.01) and admission to high-volume centers (OR 1.90 [95% CI 1.26–2.88], p = 0.002). African American race was associated with the development of in-hospital complications (OR 2.52 [95% CI 1.38–4.59], p = 0.003). CONCLUSIONS Among pediatric MMD hospitalizations, multiple socioeconomic factors were associated with access to care, whether surgical treatment is provided, and whether in-hospital complications occur. These results suggest that socioeconomic factors are important drivers of healthcare disparities in children with MMD and warrant further study.

We review and compare different fluid-structure interaction (FSI) numerical methods in the context of heart modeling, aiming at assessing their computational ef-ficiency for cardiac numerical simulations and selecting the most appropriate method for heart FSI. Blood dynamics within the human heart is characterized by active mus-cular action, during both contraction and relaxation phases of the heartbeat. The effi-cient solution of the FSI problem in this context is challenging, due to the added-mass effect (caused by the comparable densities of fluid and solid, typical of biomechan-ics) and to the complexity, nonlinearity and anisotropy of cardiac consitutive laws. In this work, we review existing numerical coupling schemes for FSI in the two classes of strongly-coupled partitioned and monolithic schemes. The schemes are compared on numerical tests that mimic the flow regime characterizing the heartbeat in a hu-man ventricle, during both systole and diastole. Active mechanics is treated in both the active stress and active strain frameworks. Computational costs suggest the use of a monolithic method. We employ it to simulate a full heartbeat of a human ventricle, showing how it allows to efficiently obtain physiologically meaningful results.

The Achilles tendon is the strongest tendon in the human body but its mechanical behaviour during failure has been little studied and the basis of its high tensile strength has not been elucidated in detail. In the present study, healthy, human, Achilles tendons were loaded to failure in an anatomically authentic fashion while the local deformation and strains were studied in real time, with very high precision, using digital image correlation (DIC). The values determined for the strength of the Achilles tendon were at the high end of those reported in the literature, consistent with the absence of a pre-existing tendinopathy in the samples, as determined by careful gross inspection and histology. Early in the loading cycle, the proximal region of the tendon accumulated high lateral strains while longitudinal strains remained low. However, immediately before rupture, the mid-substance of the Achilles tendon, its weakest part, started to show high longitudinal strains. These new insights advance the understanding of the mechanical behaviour of tendons as they are stretched to failure.

The dissolution of sulfide minerals can lead to hazardous arsenic levels in groundwater. This study investigates the oxidative dissolution of natural As-bearing sulfide minerals and the related release of arsenic under flow-through conditions. Column experiments were performed using reactive As-bearing sulfide minerals (arsenopyrite and löllingite) embedded in a sandy matrix and injecting oxic solutions into the initially anoxic porous media to trigger the mineral dissolution. Noninvasive oxygen measurements, analyses of ionic species at the outlet, and scanning electron microscopy allowed tracking the propagation of the oxidative dissolution fronts, the mineral dissolution progress, and the change in mineral surface composition. Process-based reactive transport simulations were performed to quantitatively interpret the geochemical processes. The experimental and modeling outcomes show that pore-water acidity exerts a key control on the dissolution of sulfide minerals and arsenic release since it determines the precipitation of secondary mineral phases causing the sequestration of arsenic and the passivation of the reactive mineral surfaces. The impact of surface passivation strongly depends on the flow velocity and on the spatial distribution of the reactive minerals. These results highlight the fundamental interplay of reactive mineral distribution and hydrochemical and hydrodynamic conditions on the mobilization of arsenic from sulfide minerals in flow-through systems.

Introduction: Since the beginning of the pandemic, factors associated with mortality in patients with corona virus infection disease 2019 (COVID-19) have been investigated. Comorbidities and increased age have been frequently reported to be associated with mortality. We aimed to evaluate the factors associated with unfavorable outcome of patients with COVID-19 at an early period of the pandemic. Methodology: This single center, retrospective, observational study was conducted among laboratory confirmed COVID-19 patients hospitalized between March 11 and May 5, 2020, at Umraniye Training and Research Hospital, Istanbul, Turkey. The effects of the severity of illness, comorbidities, symptoms, and laboratory findings on the clinical outcome were evaluated. Factors associated with unfavorable outcome (necessity of mechanical ventilation or death) were examined using Cox proportional hazards models. Results: Out of a total of 728 patients, 53.8% were men and median age 54 years. The 30-day mortality rate was 4.9% among all hospitalized patients. A logistic regression model identified six predictors of unfavorable clinical outcome: age, severity of illness, the numbers of comorbidities, lymphopenia, high levels of C-reactive protein, and procalcitonin. Conclusions: The mortality rate was lower among the patients with COVID-19, hospitalized during the early period of the pandemic. Older age, higher severity score on admission, the numbers of comorbidities, higher levels of C-reactive protein, procalcitonin, and lymphopenia were identified to be associated with unfavorable outcome of the hospitalized patients with COVID-19.

The study investigated the existing guidelines on the quality and frequency of the follow-up visits after total hip replacement surgery and assessed the level of evidence of these recommendations. The review process was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Additional works were retrieved by direct investigation of the available guidelines of the most important orthopedic societies and regulatory agencies. The current systematic review of the literature resulted in zero original papers, four guidelines for routine follow-up and three guidelines for special cases. Concerning the quality of evidence behind them, these guidelines were not evidence based but drafted from expert consensus. The most important finding of this review is the large variation of recommendations in the follow-up schedule after total hip arthroplasty and the lack of evidence-based indications. Indeed, all the above-reported guidelines are the result of a consensus among experts in the field (level of recommendation class D ‘very low’) and not based on clinical studies.

OBJECTIVES This study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction. BACKGROUND The estimated treatment effects of various combinations of contemporary HF medical therapies are not well characterized. METHODS We performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between January 1987 and January 2020. We included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers (BB), mineralocorticoid receptor antagonists (MRAs), digoxin, hydralazine-isosorbide dinitrate, ivabradine, angiotensin receptor-neprilysin inhibitors (ARNi), sodium glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv-mecarbil. The primary outcome was all-cause death. We estimated the life-years gained in 2 HF populations (BIOSTAT-CHF [BIOlogy Study to TAilored Treatment in Chronic Heart Failure] and ASIAN-HF [Asian Sudden Cardiac Death in Heart Failure Registry]). RESULTS We identified 75 relevant trials representing 95,444 participants. A combination of ARNi, BB, MRA, and SGLT2i was most effective in reducing all-cause death (HR: 0.39; 95% CI: 0.31-0.49); followed by ARNi, BB, MRA, and vericiguat (HR: 0.41; 95% CI: 0.32-0.53); and ARNi, BB, and MRA (HR: 0.44; 95% CI: 0.36-0.54). Results were similar for the composite outcome of cardiovascular death or first hospitalization for HF (HR: 0.36; 95% CI: 0.29-0.46 for ARNi, BB, MRA, and SGLT2i; HR: 0.44; 95% CI: 0.35-0.56 for ARNi, BB, MRA, and omecamtiv-mecarbil; and HR: 0.43; 95% CI: 0.34-0.55 for ARNi, BB, MRA, and vericiguat). The estimated additional number of life-years gained for a 70-year-old patient on ARNi, BB, MRA, and SGLT2i was 5.0 years (2.5-7.5 years) compared with no treatment in secondary analyses. CONCLUSIONS In patients with HF with reduced ejection fraction, the estimated aggregate benefit is greatest for a combination of ARNi, BB, MRA, and SGLT2i. (J Am Coll Cardiol HF 2022;10:73-84) (c) 2022 by the American College of Cardiology Foundation.

OBJECTIVES This study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction. BACKGROUND The estimated treatment effects of various combinations of contemporary HF medical therapies are not well characterized. METHODS We performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between January 1987 and January 2020. We included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers (BB), mineralocorticoid receptor antagonists (MRAs), digoxin, hydralazine-isosorbide dinitrate, ivabradine, angiotensin receptor-neprilysin inhibitors (ARNi), sodium glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv-mecarbil. The primary outcome was all-cause death. We estimated the life-years gained in 2 HF populations (BIOSTAT-CHF [BIOlogy Study to TAilored Treatment in Chronic Heart Failure] and ASIAN-HF [Asian Sudden Cardiac Death in Heart Failure Registry]). RESULTS We identified 75 relevant trials representing 95,444 participants. A combination of ARNi, BB, MRA, and SGLT2i was most effective in reducing all-cause death (HR: 0.39; 95% CI: 0.31-0.49); followed by ARNi, BB, MRA, and vericiguat (HR: 0.41; 95% CI: 0.32-0.53); and ARNi, BB, and MRA (HR: 0.44; 95% CI: 0.36-0.54). Results were similar for the composite outcome of cardiovascular death or first hospitalization for HF (HR: 0.36; 95% CI: 0.29-0.46 for ARNi, BB, MRA, and SGLT2i; HR: 0.44; 95% CI: 0.35-0.56 for ARNi, BB, MRA, and omecamtiv-mecarbil; and HR: 0.43; 95% CI: 0.34-0.55 for ARNi, BB, MRA, and vericiguat). The estimated additional number of life-years gained for a 70-year-old patient on ARNi, BB, MRA, and SGLT2i was 5.0 years (2.5-7.5 years) compared with no treatment in secondary analyses. CONCLUSIONS In patients with HF with reduced ejection fraction, the estimated aggregate benefit is greatest for a combination of ARNi, BB, MRA, and SGLT2i. (J Am Coll Cardiol HF 2022;10:73-84) (c) 2022 by the American College of Cardiology Foundation.

The integration of sensory inputs in the motor cortex is crucial for dexterous movement. We recently demonstrated that a closed-loop control based on the feedback provided through intraneural multichannel electrodes implanted in the median and ulnar nerves of a participant with upper limb amputation improved manipulation skills and increased prosthesis embodiment. Here we assessed, in the same participant, whether and how selective intraneural sensory stimulation also elicits a measurable cortical activation and affects sensorimotor cortical circuits. After estimating the activation of the primary somatosensory cortex evoked by intraneural stimulation, sensorimotor integration was investigated by testing the inhibition of primary motor cortex (M1) output to transcranial magnetic stimulation, after both intraneural and perineural stimulation. Selective sensory intraneural stimulation evoked a low-amplitude, 16 ms-latency, parietal response in the same area of the earliest component evoked by whole-nerve stimulation, compatible with fast-conducting afferent fibre activation. For the first time, we show that the same intraneural stimulation was also capable of decreasing M1 output, at the same time range of the short-latency afferent inhibition effect of whole-nerve superficial stimulation. The inhibition generated by the stimulation of channels activating only sensory fibres was stronger than that due to intraneural or perineural stimulation of channels activating mixed fibres. We demonstrate in a human subject that the cortical sensorimotor integration inhibiting M1 output previously described after the experimental whole-nerve stimulation is present also with a more ecological selective sensory fibre stimulation. KEY POINTS: Cortical integration of sensory inputs is crucial for dexterous movement. Short-latency somatosensory afferent inhibition of motor cortical output is typically produced by peripheral whole-nerve stimulation. We exploited intraneural multichannel electrodes used to provide sensory feedback for prosthesis control to assess whether and how selective intraneural sensory stimulation affects sensorimotor cortical circuits in humans. Activation of the primary somatosensory cortex (S1) was explored by recording scalp somatosensory evoked potentials. Sensorimotor integration was tested by measuring the inhibitory effect of the afferent stimulation on the output of the primary motor cortex (M1) generated by transcranial magnetic stimulation. We demonstrate in humans that selective intraneural sensory stimulation elicits a measurable activation of S1 and that it inhibits the output of M1 at the same time range of whole-nerve superficial stimulation.

Although stem cell-derived extracellular vesicles (EVs) have remarkable therapeutic potential for various diseases, the therapeutic efficacy of EVs is limited due to their degradation and rapid diffusion after administration, hindering their translational applications. Here, we developed a new generation of collagen-binding EVs, by chemically conjugating a collagen-binding peptide SILY to EVs (SILY-EVs), which were designed to bind to collagen in the extracellular matrix (ECM) and form an EV-ECM complex to improve EVs' in situ retention and therapeutic efficacy after transplantation. Methods: SILY was conjugated to the surface of mesenchymal stem/stromal cell (MSC)-derived EVs by using click chemistry to construct SILY-EVs. Nanoparticle tracking analysis (NTA), ExoView analysis, cryogenic electron microscopy (cryo-EM) and western-blot analysis were used to characterize the SILY-EVs. Fluorescence imaging (FLI), MTS assay, ELISA and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to evaluate the collagen binding and biological functions of SILY-EVs in vitro. In a mouse hind limb ischemia model, the in vivo imaging system (IVIS), laser doppler perfusion imaging (LDPI), micro-CT, FLI and RT-qPCR were used to determine the SILY-EV retention, inflammatory response, blood perfusion, gene expression, and tissue regeneration. Results:In vitro, the SILY conjugation significantly enhanced EV adhesion to the collagen surface and did not alter the EVs' biological functions. In the mouse hind limb ischemia model, SILY-EVs presented longer in situ retention, suppressed inflammatory responses, and significantly augmented muscle regeneration and vascularization, compared to the unmodified EVs. Conclusion: With the broad distribution of collagen in various tissues and organs, SILY-EVs hold promise to improve the therapeutic efficacy of EV-mediated treatment in a wide range of diseases and disorders. Moreover, SILY-EVs possess the potential to functionalize collagen-based biomaterials and deliver therapeutic agents for regenerative medicine applications.

The present study was conducted to determine the possibility of the employed of jute (Corchorus olitorius L.), a natural fiber used as geotextile cover material, under saline soilless culture conditions, which constitute of the biggest problems in agriculture. The effect of the jute material employed in Mexican marigold (Tagetes erecta) cultivation under saline soilless conditions was determined. For this purpose, the Mexican marigold cultivation was tested in a pot experiment under greenhouse conditions for two growth periods in Izmir, Turkey. The salinity levels in the experiment were compared based on whether the treatment included the jute material (G1) or did not include jute material (G0). The measured salinity level of Hoagland nutrient solution employed the irrigation and fertilization of plants was one of the studied factors and was considered as control (S1). The measured EC (electrical conductivity) level of Hoagland nutrient solution was increased by 1 dS m-1 (S2) and 2 dS m-1 (S3) with stock NaCl solution, and 3 salinity factors were tested. According to the results of the present study the highest salinity was observed in the G0 group without jute cover. It was demonstrated that the jute cover on the pot media reduced the mean salinity concentration in growth medium by 22.56%. This finding was associated with the ability of the jute material to hold the salt in the nutrient solution, preventing spread of the salinity around the root zone.

The Supporting Information is available free of charge at: https://pubs.acs.org/doi/10.1021/acs.est.1c08722., Several problems associated with the presence of lipids in wastewater treatment plants are usually overcome by removing them ahead of the biological treatment. However, because of their high energy content, waste lipids are interesting yet challenging pollutants in anaerobic wastewater treatment and codigestion processes. The maximal amount of waste lipids that can be sustainably accommodated, and effectively converted to methane in anaerobic reactors, is limited by several problems including adsorption, sludge flotation, washout, and inhibition. These difficulties can be circumvented by appropriate feeding, mixing, and solids separation strategies, provided by suitable reactor technology and operation. In recent years, membrane bioreactors and flotation-based bioreactors have been developed to treat lipid-rich wastewater. In parallel, the increasing knowledge on the diversity of complex microbial communities in anaerobic sludge, and on interspecies microbial interactions, contributed to extend the knowledge and to understand more precisely the limits and constraints influencing the anaerobic biodegradation of lipids in anaerobic reactors. This critical review discusses the most important principles underpinning the degradation process and recent key discoveries and outlines the current knowledge coupling fundamental and applied aspects. A critical assessment of knowledge gaps in the field is also presented by integrating sectorial perspectives of academic researchers and of prominent developers of anaerobic technology., This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of the UIDB/04469/2020 unit and by the CCDR-N − Comissao de Coordenac ̃ a̧ o e Desenvolvimento Regional do ̃ Norte, NORTE2020, Portugal 2020, and ESIF − European Structural and Investment Funds with the funding given under the Program NORTE-45-2020-75 to the BIOECONORTE project (NORTE-01-0145-FEDER-000070). Our work was also financially supported by grants from the Irish Research Council (EBPP 2012), the Enterprise Ireland Technology Centres Programme (TC/2014/0016), and Science Foundation Ireland (14/IA/2371 and 16/RC/3889). M. A. Szabo-Corbacho would like to express gratitude for the Ph.D. Fellowship award provided by ANII-Uruguay, IHE Delft Institute for Water Education and Latitud − Fundación LATU. The research of A. J. M. Stams is supported by ERC Grant (323009) and by the Gravitation Grant (024.002.002) of The Netherlands Ministry of Education, Culture and Science., info:eu-repo/semantics/publishedVersion

The poolr package provides an implementation of a variety of methods for pooling (i.e., combining) p values, including Fisher's method, Stouffer's method, the inverse chisquare method, the binomial test, the Bonferroni method, and Tipp ett's method. More importantly, the methods can be adjusted to account for dependence among the tests from which the p values have been derived assuming multivariate normality among the test statistics. All methods can be adjusted based on an estimate of the effective number of tests or by using an empirically-derived null distribution based on pseudo replicates that mimics a proper permutation test. For the Fisher, Stouffer, and inverse chi-square methods, the test statistics can also be directly generalized to account for dependence, leading to Brown's method, Strube's method, and the generalized inverse chi-square method. In this paper, we describe the various methods, discuss their implementation in the package, illustrate their use based on several examples, and compare the poolr package with several other packages that can be used to combine p values.

BACKGROUND: Patients with symptomatic carotid stenosis are at high risk for recurrent stroke. The decision for carotid endarterectomy currently mainly relies on degree of stenosis (cutoff value >50% or 70%). Nevertheless, also, patients with mild-to-moderate stenosis still have a considerable recurrent stroke risk. Increasing evidence suggests that carotid plaque composition rather than degree of stenosis determines plaque vulnerability; however, it remains unclear whether this also provides additional information to improve clinical decision making. OBJECTIVES: The PARISK (Plaque At RISK) study aimed to improve the identification of patients at increased risk of recurrent ischemic stroke using multimodality carotid imaging. METHODS: The authors included 244 patients (71% men; mean age, 68 years) with a recent symptomatic mild-to-moderate carotid stenosis in a prospective multicenter cohort study. Magnetic resonance imaging (carotid and brain) and computed tomography angiography (carotid) were performed at baseline and after 2 years. The clinical endpoint was a recurrent ipsilateral ischemic stroke or transient ischemic attack (TIA). Cox proportional hazards models were used to assess whether intraplaque hemorrhage (IPH), ulceration, proportion of calcifications, and total plaque volume in ipsilateral carotid plaques were associated with the endpoint. Next, the authors investigated the predictive performance of these imaging biomarkers by adding these markers (separately and simultaneously) to the ECST (European Carotid Surgery Trial) risk score. RESULTS: During 5.1 years follow-up, 37 patients reached the clinical endpoint. IPH presence and total plaque volume were associated with recurrent ipsilateral ischemic stroke or TIA (HR: 2.12 [95% CI: 1.02-4.44] for IPH; HR: 1.07 [95% CI: 1.00-1.15] for total plaque volume per 100 µL increase). Ulcerations and proportion of calcifications were not statistically significant determinants. Addition of IPH and total plaque volume to the ECST risk score improved the model performance (C-statistics increased from 0.67 to 0.75-0.78). CONCLUSIONS: IPH and total plaque volume are independent risk factors for recurrent ipsilateral ischemic stroke or TIA in patients with mild-to-moderate carotid stenosis. These plaque characteristics improve current decision making. Validation studies to implement plaque characteristics in clinical scoring tools are needed. (PARISK: Validation of Imaging Techniques [PARISK]; NCT01208025). ispartof: JACC-CARDIOVASCULAR IMAGING vol:15 issue:10 pages:1715-1726 ispartof: location:United States status: published

Arthrodesis of the proximal interphalangeal (PIP) joint of the finger is an established procedure for advanced osteoarthritis. As there are different techniques of fusion, it seems necessary to evaluate the results. Primary outcome of this review was to evaluate different arthrodesis methods of the PIP joint and describe different numbers of non-unions. Secondary outcome was to evaluate time to consolidation. Respective complications, if mentioned, were listed additionally. The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The selected databases were PubMed, Medline, Embase, Google Scholar and Cochrane Library. Studies reporting outcomes of the arthrodesis with a defined technique and radiological consolidation were included. Complication rates and types were recorded. In total, 6162 articles could be identified, 159 full-texts were assessed and 64 studies were included. Methodological quality was assessed using Methodological Index for Non-Randomized Studies. A total of 1923 arthrodeses of the PIP joint could be identified. Twelve different surgical techniques were described, four of these techniques with compression at the arthrodesis site. The most frequently used techniques were K-wires (n = 743, 14 studies), tension-band (n = 313, 15 studies) and compression screws (n = 233, 12 studies). The lowest rate of described non-unions in compression techniques was 3.9% with the compression screw. The highest non-union rate of 8.6% was achieved by interosseous wiring. All the described techniques can achieve the goal of fusing an osteoarthritic joint. There is a tendency in the more recent literature for the use of compression techniques.

Arthrodesis of the proximal interphalangeal (PIP) joint of the finger is an established procedure for advanced osteoarthritis. As there are different techniques of fusion, it seems necessary to evaluate the results. Primary outcome of this review was to evaluate different arthrodesis methods of the PIP joint and describe different numbers of non-unions. Secondary outcome was to evaluate time to consolidation. Respective complications, if mentioned, were listed additionally. The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The selected databases were PubMed, Medline, Embase, Google Scholar and Cochrane Library. Studies reporting outcomes of the arthrodesis with a defined technique and radiological consolidation were included. Complication rates and types were recorded. In total, 6162 articles could be identified, 159 full-texts were assessed and 64 studies were included. Methodological quality was assessed using Methodological Index for Non-Randomized Studies. A total of 1923 arthrodeses of the PIP joint could be identified. Twelve different surgical techniques were described, four of these techniques with compression at the arthrodesis site. The most frequently used techniques were K-wires (n = 743, 14 studies), tension-band (n = 313, 15 studies) and compression screws (n = 233, 12 studies). The lowest rate of described non-unions in compression techniques was 3.9% with the compression screw. The highest non-union rate of 8.6% was achieved by interosseous wiring. All the described techniques can achieve the goal of fusing an osteoarthritic joint. There is a tendency in the more recent literature for the use of compression techniques.

Errors have been conceptualized as internal forms of threat that can cause harm in unpredictable ways. An index of error processing is the error-related negativity (ERN), an event-related potential reflecting variability in the sensitivity to errors. Prior work has shown the relationship between psychopathology symptoms and the ERN is unclear, and may be moderated by intolerance of uncertainty (IU), a trait that captures how people react to unpredictability. IU includes two subfactors of prospective IU (active seeking of predictability) and inhibitory IU (behavioral paralysis). In the present study, 188 undergraduates performed an Eriksen flanker task designed to elicit the ERN, while brain activity was recorded using electroencephalography (EEG). Participants completed the Intolerance of Uncertainty Scale, Short Form (IUS-12), and other measures of anxiety, depression and worry. Total IU explained 5 % of the variance in correct-response negativity (CRN), but was not associated with the ERN in our sample. In contrast to previous findings, the IU subfactors did not predict the ERN or post-error slowing (PES), nor did total IU and depression interact to predict the ERN. Exploratory analyses also showed that total IU did not moderate the relationship between trait anxiety and the ERN. Small samples may have previously exaggerated the links between self-reported IU and the ERN. As such, further high-powered replications are required to confirm if, and how, they are related.

Purpose: To date, population-based studies reporting associations between dry eye disease and medications were hypothesis-driven, did not take into account underlying comorbidities, and did not investigate individual drugs. The purpose of this study was to clarify the association of dry eye symptoms with medication classes and in-dividual drugs, using a hypothesis-free approach. Methods: 79,606 participants (age 20-97 years, 59.2% female) from the population-based Lifelines cohort in the Netherlands were cross-sectionally assessed for dry eye symptoms using the Womens' Health Study dry eye questionnaire. All medications used were coded with the ATC classification system. Logistic regression was used to assess the risk of the 59 most-used therapeutic/pharmacological subgroups and the 99 most-used individual drugs (all n > 200) on dry eye symptoms, correcting for age, sex, body mass index, and 48 comorbidities associated with dry eye. Results: Thirty-eight (64%) medication subgroups and fifty-two (53%) individual drugs were associated with dry eye symptoms (P < 0.05), after correction for age and sex only. A multivariable model correcting for comor-bidities revealed highly significant associations between dry eye symptoms and drugs for peptic ulcer (partic-ularly proton pump inhibitors (PPIs)), antiglaucoma and anticholinergic medications. Conclusions: This study underlines that medication use is highly informative of risk of dry eye symptoms. Correction for underlying comorbidities is critical to avoid confounding effects. This study confirms suggested associations between medications and dry eye symptoms at a population level and shows several new associa-tions. The novel link between PPIs and dry eye symptoms deserves particular attention given how commonly they are prescribed.

Mental healthcare disparities are routinely documented, yet they remain wider than in most other areas of healthcare services and common mental disorders (depression and anxiety) continue to be one of the highest health burdens for older people of color. To address disparities in mental health services for older people of color, the narrative must move beyond simply documenting these inequities and attain a better understanding of the internalized, interpersonal, systemic, and medical racism that have harmed these communities and excluded them from its services in the first place. It is imperative that researchers, clinicians, and policymakers acknowledge the realities of racism and discrimination as leading causes of mental healthcare disparities. Therefore, this review is a call-to-action. Authors adopt an antiracist and health equity lens in evaluating the differing needs of Blacks/African-Americans, Asian Americans, and Latinos by exploring psychiatric comorbidity, experiences with seeking, accessing, and engaging in treatment, and the unique cultural and psychosocial factors that affect treatment outcomes for these diverse groups. Further, authors offer researchers and practitioners tangible tools for developing and implementing culturally-sensitive, mental health focused interventions for older people of color with special attention placed on cultural adaptations, models of care, prevention, and practical strategies that can be implemented to reduce disparities and increase equity in mental healthcare.

Purpose ― Mishkin’s hypothesis suggests that globalization appears to be a vital factor in stimulating the development of the financial system. The study examines this hypothesis for the Turkish economy from 1970 to 2017. It focuses on the link between financial globalization and financial development by integrating economic growth, inflation, and natural resource rent as additional determinants into the financial development specification. Methods ― The Ng-Perron and Vogelsang-Perron unit root tests are used to check the stationarity of variables. The cointegration analysis is performed using the Hatemi-J and ARDL bounds testing procedures. Findings ― The main empirical results show that the series are cointegrated under structural breaks; in the long run, financial globalization and economic growth increase financial development while inflation and natural resource rent negatively affect financial development. A unidirectional causality exists from financial globalization and economic growth to financial development. At the same time, there is bidirectional causality between inflation and financial development, natural resource rent, and financial development. Implications ― The empirical findings can present important recommendations for policymakers. Originality ― Very few time-series studies include Turkey’s economy and structural breaks.

BACKGROUND The association between the change in vessel inflammation, as quantified by perivascular adipose tissue (PVAT) density, and the progression of coronary atherosclerosis remains to be determined.OBJECTIVES The purpose of this study was to explore the association between the change in PVAT density and the progression of total and compositional plaque volume (PV). METHODS Patients were selected from a prospective multinational registry. Patients who underwent serial coronary computed tomography angiography studies with $2-year intervals and were scanned with the same tube voltage at baseline and follow-up were included. Total and compositional PV and PVAT density at baseline and follow-up were quantitatively analyzed for every lesion. Multivariate linear regression models using cluster analyses were constructed.RESULTS A total of 1,476 lesions were identified from 474 enrolled patients (mean age 61.2 +/- 9.3 years; 65.0% men). The mean PVAT density was-74.1 +/- 11.5 HU, and total PV was 48.1 +/- 83.5 mm3 (19.2 +/- 44.8 mm3 of calcified PV and 28.9 +/- 51.0 mm3 of noncalcified PV). On multivariate analysis (adjusted for clinical risk factors, medication use, change in lipid levels, total PV at baseline, luminal HU attenuation, location of lesions, and tube voltage), the increase in PVAT density was positively associated with the progression of total PV (estimate = 0.275 [95% CI: 0.004-0.545]; P = 0.047), driven by the association with fibrous PV (estimate = 0.245 [95% CI: 0.070-0.420]; P = 0.006). Calcified PV progression was not associated with the increase in PVAT density (P > 0.050). CONCLUSIONS Increase in vessel inflammation represented by PVAT density is independently associated with the progression of the lipid component of coronary atherosclerotic plaques. (Progression of AtheRosclerotic PlAque Deter-mIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411) (J Am Coll Cardiol Img 2022;15:1760-1767) (c) 2022 by the American College of Cardiology Foundation.

BACKGROUND Nonischemic cardiomyopathy patients referred for catheter ablation of ventricular arrhythmias (VAs) typically have either inferolateral (ILS) or anteroseptal (ASS) VA substrate locations, with poorer outcomes for ASS. Sympathetic denervation is an important determinant of arrhythmogenicity. Its relation to nonischemic fibrosis in general and to the different VA substrates is unknown.OBJECTIVES This study sought to evaluate the association between VA substrates, myocardial fibrosis, and sympa-thetic denervation. METHODS Thirty-five patients from the Leiden Nonischemic Cardiomyopathy Study, who underwent electroanatomic voltage mapping and iodine-123 metaiodobenzylguanidine imaging between 2011 and 2018 were included. Late gadolinium-enhanced cardiac magnetic resonance data were collected when available. The relation between global cardiac sympathetic innervation and area-weighted unipolar voltage (UV) as a surrogate for diffuse fibrosis was evalu-ated. For regional analysis, patients were categorized as ASS or ILS. The distribution of low UV, sympathetic denervation, and late gadolinium enhancement (LGE) scar were compared using the 17-segment model.RESULTS Median area-weighted UV was 12.3 mV in patients with normal sympathetic innervation and 8.7 mV in patients with sympathetic denervation. Global sympathetic denervation correlated with diffuse myocardial fibrosis (R = 0.53; P = 0.02). ILS (n = 13) matched with low UV, sympathetic denervation, and LGE scar in all patients, whereas ASS (n = 11) matched with low UV in all patients, with LGE scar in 63% (P = 0.20), but with sympathetic denervation in only 27% of patients (P = 0.0002).CONCLUSIONS Global cardiac sympathetic denervation is related to fibrosis in nonischemic cardiomyopathy patients with VA. The mismatch between regional fibrosis and preserved innervation for ASS may contribute to a VA substrate difficult to control by catheter ablation. (J Am Coll Cardiol EP 2022;8:1234-1245)(c) 2022 by the American College of Cardiology Foundation.

Background The COVID-19 pandemic represents one of the greatest ever challenges for healthcare. In the UK and beyond, acute medical units (AMUs) are the first point of assessment and care for the majority of medical inpatients. By their design and systems, they inevitably played an important role in the COVID-19 response but to date little has been published on how the COVID-19 pandemic has affected how AMUs have reorganised their resources, processes and structure. Methods This retrospective study in August 2020 of 10 AMUs across Europe and Australasia used a standardised questionnaire to investigate existing practice and structure of AMUs, the national context of local hospital experience, changes to practice during the COVID-19 pandemic and views regarding future practice. Results Changes to AMU structure, process and organisation are described in two contexts: preventing and controlling the spread of COVID-19 and adding value to the patient9s acute care journey in the local context. We describe novel practices that have arisen and highlight areas of concern. Conclusions The AMUs were able to adapt to meet the demands of acute care delivery during the first wave of the COVID-19 pandemic. Operational planning and prioritisation of resources must be optimised to ensure sustainability of these services for future waves.

Virtual reality has been recognized as a potent tool for creating more natural and intuitive human-computer interfaces and has been found to be beneficial in so many applications. However, the inability to interact in a virtual environment through touch compromises its realism and usefulness. Haptic interfaces with intermittent contacts allow users to reach out and touch the virtual objects physically to simulate contact between the user and the environment with use of tactile sensation to increase the realism of interaction. They allow a wide range of physical interactions throughout the user's workspace, with a physical input that resembles reality.These devices are faced with challenges such as cost, a small workspace, limited speed and user safety. In this thesis, we developed a haptic interface using a cooperative robot to address these challenges. Several motion strategies, a trajectory generation scheme and user interaction techniques to ensure safety were developed and evaluated. Two case studies were used as application areas. The first is an industrial application for analysis of the interior material of the car during the early stages of development while the second one is a haptic interface for upper limb rehabilitation training. User studies were conducted to evaluate the efficacy of the motion strategies in improving device speed, response, and user safety.; La réalité virtuelle a été reconnue comme un outil puissant pour créer des interfaces homme-machine plus naturelles et intuitives et s'est avérée bénéfique dans de nombreuses applications. Cependant, l'incapacité d'interagir dans un environnement virtuel par le toucher compromet son réalisme et son utilité. Les interfaces haptiques avec des contacts intermittents permettent aux utilisateurs d'atteindre et de toucher physiquement les objets virtuels pour simuler le contact entre l'utilisateur et l'environnement en utilisant la sensation tactile pour augmenter le réalisme de l'interaction. Ils permettent un large éventail d'interactions physiques dans l'espace de travail de l'utilisateur, avec une entrée physique qui ressemble à la réalité. Ces appareils sont confrontés à des défis tels que le coût, un petit espace de travail, une vitesse limitée et la sécurité des utilisateurs.Dans cette thèse, nous avons développé une interface haptique utilisant un robot coopératif pour relever ces défis. Plusieurs stratégies de mouvement, un schéma de génération de trajectoire et des techniques d'interaction avec l'utilisateur pour assurer la sécurité ont été développés et évalués. Deux études de cas ont été utilisées comme domaines d'application. Le premier est une application industrielle pour l'analyse du matériau intérieur de la voiture pendant les premières phases de développement tandis que le second est une interface haptique pour l'entraînement en rééducation des membres supérieurs. Des études d'utilisateurs ont été menées pour évaluer l'efficacité des stratégies de mouvement dans l'amélioration de la vitesse, de la réponse et de la sécurité de l'utilisateur.

To develop a reliable 2-compartment population pharmacokinetic (PK) model for unbound ceftriaxone in a critically ill population and determine an optimal dosing regimen.This was a prospective, single-center, observational study of critically ill patients treated with ceftriaxone. Unbound serum ceftriaxone concentrations were measured using validated ultrafiltration and ultra-performance liquid chromatography-tandem mass spectrometry. PK analysis and dosing simulations were performed using an iterative 2-stage Bayesian fitting procedure and Monte Carlo simulations. The PK/pharmacodynamics (PD) target was attained when unbound serum ceftriaxone concentrations exceeded 4 times the minimum inhibitory concentration (MIC) for ≥ 60% of the dosing interval (ƒT91 patients were enrolled, and 173 unbound ceftriaxone concentrations were acquired. The population PK parameter estimates were hepatic clearance 5.2 ± 0.9 L/h/1.85mWe developed a reliable population PK model for unbound ceftriaxone in a critically ill population. Dosing simulations revealed ƒT

BackgroundWith rising United States health care expenditure, estimating current spending for patients with heart failure (HF) informs the value of preventative health interventions.ObjectivesThe purpose of this study was to estimate current health care expenditure growth for patients with HF in the United States.MethodsThe authors pooled MEPS (Medical Expenditure Panel Survey) data from 2009-2018 to calculate totalHF-related expenditure across clinical settings in the United States. A 2-part model adjusted for demographics,comorbidities, and year was used to estimate annual mean and incremental expenditures associated with HF.ResultsIn the United States, an average of $28,950 (2018 inflation-adjusted dollars) is spent per year for health care-related expenditure for individuals with HF compared with $5,727 for individuals without HF. After adjusting for demographics and comorbidities, a diagnosis of HF was associated with $3,594 in annual incremental expenditure compared with those without HF. HF-related expenditure increased from $26,864 annual per person in 2009-2010 to $32,955 in 2017-2018, representing a 23% rise over 10 years. In comparison, expenditure on myocardial infarction, type 2 diabetes mellitus, and cancer grew by 16%, 28%, and 16%, respectively. Most of the cost was related to hospitalization: $12,569 per year. Outpatient office-based care and prescription medications saw the greatest growth in cost over the period, 41% and 24%, respectively. Estimated incremental national expenditure for HF per year was $22.3 billion; total annual expenditure for adults with HF was $179.5 billion.ConclusionsHF is a costly condition for which expenditure is growing faster than that of other chronic conditions.

© 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), Objectives: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. Materials and methods: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. Results: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. Conclusions: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors., The study was funded by the Helsinki and Uusimaa Hospital District, Academy of Finland, University of Helsinki, and Sahlgrenska University Hospital.

Golgi membrane protein 1 (GOLM1) is a Golgi-resident type 2 transmembrane protein known to be overexpressed in several cancers, including he-patocellular carcinoma (HCC), as well as in viral in-fections. However, the role of GOLM1 in lipid metabolism remains enigmatic. In this study, we employed siRNA-mediated GOLM1 depletion in Huh -7 HCC cells to study the role of GOLM1 in lipid metabolism. Mass spectrometric lipidomic analysis in GOLM1 knockdown cells showed an aberrant accu-mulation of sphingolipids, such as ceramides, hex-osylceramides, dihexosylceramides, sphinganine, sphingosine, and ceramide phosphate, along with cholesteryl esters. Furthermore, we observed a reduction in phosphatidylethanolamines and lyso-phosphatidylethanolamines. In addition, Seahorse extracellular flux analysis indicated a reduction in mitochondrial oxygen consumption rate upon GOLM1 depletion. Finally, alterations in Golgi struc-ture and distribution were observed both by electron microscopy imaging and immunofluorescence mi-croscopy analysis. Importantly, we found that GOLM1 depletion also affected cell proliferation and cell cycle progression in Huh-7 HCC cells. The Golgi structural defects induced by GOLM1 reduction might potentially affect the trafficking of proteins and lipids leading to distorted intracellular lipid ho-meostasis, which may result in organelle dysfunction and altered cell growth. In conclusion, we demon-strate that GOLM1 depletion affects sphingolipid metabolism, mitochondrial function, Golgi structure, and proliferation of HCC cells.

BackgroundThe sex differences in use, safety outcomes, and health-care resource use of patients with pulmonary embolism (PE) undergoing percutaneous pulmonary artery thrombectomy are not well characterized.Research questionWhat are the sex differences in outcomes for patients diagnosed with PE who undergo percutaneous pulmonary artery thrombectomy?Study design and methodsThis retrospective cross-sectional study used national inpatient claims data to identify patients in the United States with a discharge diagnosis of PE who underwent percutaneous thrombectomy between January 2016 and December 2018. We evaluated the demographics, comorbidities, safety outcomes (in-hospital mortality), and health-care resource use (discharge to home, length of stay, and hospital charges) of patients with PE undergoing percutaneous thrombectomy.ResultsAmong 1,128,904 patients with a diagnosis of PE between 2016 and 2018, 5,160 patients (0.5%) underwent percutaneous pulmonary artery thrombectomy. When compared with male patients, female patients showed higher procedural bleeding (16.9%vs11.2%; P< .05), required more blood transfusions (11.9%vs5.7%; P< .05), and experienced more vascular complications (5.0%vs1.5%; P< .05). Women experienced higher in-hospital mortality (16.9%vs9.3%; adjusted OR, 1.9; 95%CI, 1.2-3.0; P= .003) when compared with men. Although length of stay and hospital charges were similar to those of men, women were less likely to be discharged home after surviving hospitalization (47.9%vs60.3%; adjusted OR, 0.7; 95%CI, 0.50-0.99; P= .04).InterpretationIn this large nationwide cohort, women with PE who underwent percutaneous thrombectomy showed higher morbidity and in-hospital mortality compared with men.

As high readout channel density and compact design become the norm for HEP detectors so is the detector cooling at temperatures below the experimental site dewpoint. This increases the importance of humidity and temperature monitoring systems that are also adapted to the detector environment. The proposed systems for temperature and humidity monitoring are developed targeting compactness, cost, and seamless integration to the CMS DSS/DCS systems. Therefore, this paper presents a novel design for a standalone system, able to condition up to 24 temperature sensors. The proposed temperature monitoring system is aimed at many hundreds of RTD sensors with modest space and price requirements. For humidity monitoring, we have identified a potential sensing element and designed, built and tested the conditioning electronics capable of nullifying the capacitance of the long cables.

BackgroundA learning health system (LHS) is a health system in which patients and clinicians work together to choose care on the basis of best evidence and to drive discovery as a natural outgrowth of every clinical encounter to ensure the right care at the right time. An LHS for dentistry is now feasible, as an increased number of oral health care encounters are captured in electronic health records (EHRs).MethodsThe authors used EHRs data to track periodontal health outcomes at 3 large dental institutions. The 2 outcomes of interest were a new periodontitis case (for patients who had not received a diagnosis of periodontitis previously) and tooth loss due to progression of periodontal disease.ResultsThe authors assessed a total of 494,272 examinations (new periodontitis outcome: n= 168,442; new tooth loss outcome: n= 325,830), representing a total of 194,984 patients. Dynamic dashboards displaying performance on both measures over time allow users to compare demographic and risk factors for patients. The incidence of new periodontitis and tooth loss was 4.3% and 1.2%, respectively.ConclusionsPeriodontal disease, diagnosis, prevention, and treatment are particularly well suited for an LHS model. The results showed the feasibility of automated extraction and interpretation of critical data elements from the EHRs. The 2 outcome measures are being implemented as part of a dental LHS. The authors are using this knowledge to target the main drivers of poorer periodontal outcomes in a specific patient population, and they continue to use clinical health data for the purpose of learning and improvement.Practical implicationsDental institutions of any size can conduct contemporaneous self-evaluation and immediately implement targeted strategies to improve oral health outcomes.

Traditional ecological knowledge enables pastoralists to cope with social-ecological changes, thereby increasing thesustainability of their practices and fostering social-ecological resilience. Yet, there is a significant knowledge gap concerning the extentto which pastoral traditional ecological knowledge has changed over time at the global level. We aim to fill this gap through a systematicliterature review of 288 scientific studies on pastoral traditional ecological knowledge. We reviewed 152 papers in detail (selectedrandomly from the 288) for their content, and focused specifically on 61 papers that explicitly mentioned one of the four types ofknowledge transition (i.e., retention, erosion, adaptation, or hybridization). Studies on pastoral traditional knowledge represent lessthan 3% of all the scholarly literature on traditional ecological knowledge. Geographical distribution of the 288 case studies was largelybiased. Knowledge domains of pastoral knowledge such as herd and livestock management, forage and medicinal plants, and landscapeand wildlife were relatively equally covered; however, climate-related knowledge was less often studied. Of the 63 papers that explicitlymentioned transition of pastoral traditional ecological knowledge, 52 reported erosion, and only 11 studies documented explicitlyknowledge retention, adaptation, or hybridization of traditional knowledge. Thus, adaptation and hybridization was understudied,although some case studies showed that adaptation and hybridization of knowledge can efficiently help pastoralists navigate amongsocial-ecological changes. Based on the review, we found 13 drivers which were mentioned as the main reasons for knowledge transitionamong which social-cultural changes, formal schooling, abandonment of pastoral activities, and transition to a market economy weremost often reported. We conclude that future research should focus more on the diverse dynamics of pastoral traditional knowledge,be more careful in distinguishing the four knowledge transition types, and analyze how changes in knowledge impact change in pastoralpractices and lifestyles. Understanding these phenomena could help pastoralists' adaptations and support their stewardship of theirrangeland ecosystems and biocultural diversity.

This virtual workshop was convened by the National Heart, Lung, and Blood Institute, in partnership with the Office of Strategic Coordination of the Office of the National Institutes of Health Director, and held September 2 to 3, 2020. The intent was to assemble a multidisciplinary group of experts in basic, translational, and clinical research in neuroscience and cardiopulmonary disorders to identify knowledge gaps, guide future research efforts, and foster multidisciplinary collaborations pertaining to autonomic neural mechanisms of cardiopulmonary regulation. The group critically evaluated the current state of knowledge of the roles that the autonomic nervous system plays in regulation of cardiopulmonary function in health and in pathophysiology of arrhythmias, heart failure, sleep and circadian dysfunction, and breathing disorders. Opportunities to leverage the Common Fund's SPARC (Stimulating Peripheral Activity to Relieve Conditions) program were characterized as related to nonpharmacologic neuromodulation and device-based therapies. Common themes discussed include knowledge gaps, research priorities, and approaches to develop novel predictive markers of autonomic dysfunction. Approaches to precisely target neural pathophysiological mechanisms to herald new therapies for arrhythmias, heart failure, sleep and circadian rhythm physiology, and breathing disorders were also detailed.

For several decades, surface grafted polyethylene glycol (PEG) has been a go-to strategy for preserving the synthetic identity of liposomes in physiological milieu and preventing clearance by immune cells. However, the limited clinical translation of PEGylated liposomes is mainly due to the protein corona formation and the subsequent modification of liposomes’ synthetic identity, which affects their interactions with immune cells and blood residency. Here we exploit the electric charge of DNA to generate unPEGylated liposome/DNA complexes that, upon exposure to human plasma, gets covered with an opsonin-deficient protein corona. The final product of the synthetic process is a biomimetic nanoparticle type covered by a proteonucleotidic corona, or “proteoDNAsome”, which maintains its synthetic identity in vivo and is able to slip past the immune system more efficiently than PEGylated liposomes. Accumulation of proteoDNAsomes in the spleen and the liver was lower than that of PEGylated systems. Our work highlights the importance of generating stable biomolecular coronas in the development of stealth unPEGylated particles, thus providing a connection between the biological behavior of particles in vivo and their synthetic identity.

Bacteria are efficient colonizers of a wide range of secluded microhabitats, such as soil pores, skin follicles, or intestinal crypts. How the structural diversity of these habitats modulates microbial self-organization remains poorly understood, in part because of the difficulty to precisely manipulate the physical structure of microbial environments. Using a microfluidic device to grow bacteria in crypt-like incubation chambers of systematically varied lengths, we show that small variations in the physical structure of the microhabitat can drastically alter bacterial colonization success and resistance against invaders. Small crypts are uncolonizable; intermediately sized crypts can stably support dilute populations, while beyond a second critical length scale, populations phase separate into a dilute region and a jammed region. The jammed state is characterized by extreme colonization resistance, even if the resident strain is suppressed by an antibiotic. Combined with a flexible biophysical model, we demonstrate that colonization resistance and associated priority effects can be explained by a crowding-induced phase transition, which results from a competition between proliferation and density-dependent cell leakage. The emerging sensitivity to scale underscores the need to control for scale in microbial ecology experiments. Systematic flow-adjustable length-scale variations may serve as a promising strategy to elucidate further scale-sensitive tipping points and to rationally modulate the stability and resilience of microbial colonizers.

Assessing the quality of parameter estimates for models describing the motion of single molecules in cellular environments is an important problem in fluorescence microscopy. In this work, we consider the fundamental data model, where molecules emit photons at random time instances and these photons arrive at random locations on the detector ac- cording to complex point spread functions (PSFs). The randomness and non-Gaussian PSF of the detection process, and the random trajectory of the molecule, makes inference challenging. Moreover, the presence of other closely spaced molecules causes further un- certainty in the origin of the measurements, which impacts the statistical precision of the estimates. We quantify the limits of accuracy of model parameter estimates and separation distance between closely spaced molecules (known as the resolution problem) by computing the Cram ́er-Rao lower bound (CRLB), or equivalently the inverse of the Fisher informa- tion matrix (FIM), for the variance of estimates. Results on the CRLB obtained from the fundamental model are crucial, in that they provide a lower bound for more practical scenar- ios. While analytic expressions for the FIM can be derived for static and deterministically moving molecules, the analytical tools to evaluate the FIM for molecules whose trajecto- ries follow stochastic differential equations (SDEs) are still for the most part missing. We address this by presenting a general sequential Monte Carlo (SMC) based methodology for both parameter inference and computing the desired accuracy limits for non-static molecules and a non-Gaussian fundamental detection model. For the first time, we are able to estimate the FIM for stochastically moving molecules observed through the Airy and Born and Wolf detection models. This is achieved by estimating the score and observed information matrix via SMC. We summarise the outcome of our numerical work by delineating the qualitative behaviours for the accuracy limits as functions of various experimental settings like collected photon count, molecule diffusion, etc. We also verify that we can recover known results from the static molecule case.

Purpose: This study aims to examine the effect of ileal transposition (IT) on plasma levels of the total antioxidant status (TAS), total oxidant status (TOS), Oxidative Stress Index (OSI), Superoxide dismutase (SOD), Nicotinamide adenine dinucleotide phosphate oxidase (NOX), Catalase (CAT), Reduced Glutathione (GSH) in both rats with Metabolic syndrome (MetS) and healthy controls. Materials and Methods: In the MetS model, newborn male Wistar albino rats were given MSG (4 g/mg) on days 0, 2, 4, 6, 8, and 10. The control group was injected only saline. In the 5th month, sham and IT animals underwent selected surgery. 2 months after surgery TOS, TAS, OSI, SOD, NOX, CAT, and GSH levels were assessed in the plasma. Results: IT procedure significantly increased SOD and CAT levels in MetS + IT group when compared to the MetS group (SOD; MetS 1.75 +/- 0.04, MetS+IT 2.1 +/- 0.15, CAT; MetS 32.02 +/- 1.73, MetS+IT 41.64 +/- 1.18,). As expected, while GSH levels was increased in MetS+IT rats compared to MetS rats, but the difference was not significant (MetS 243.31 +/- 6.36, MetS+IT 269.76 +/- 9.17). The NOX activity was significantly lower in MetS+IT group than MetS and MetS+S groups (MetS 610.35 +/- 26.25, MetS+IT 348.86 +/- 14.12). Conclusion: These data revealed the healing effect of IT surgery against oxidative stress associated with MetS. The available data endorses IT surgery as an effective strategy to reduce oxidative damage in rats with MetS by modulating systemic oxidant and antioxidant responses.

In this study, biobased gel polymer electrolyte (GPE) membranes were developed via the esterification reaction of a cardanol-based epoxy resin with glutaric anhydride, succinic anhydride, and hexahydro-4-methylphthalic anhydride. Nonisothermal differential scanning calorimetry was used to assess the optimal curing time and temperature of the formulations, evidencing a process activation energy of ∼65-70 kJ mol

Several geopolymer-based materials were produced and characterized by mixing metakaolin, a commercial sodium silicate solution, a sodium hydroxide solution, and a loose waste olivine sand deriving from a metallurgical process devoted to the production of a high manganese steel. Olivine sand was added either in the as-received form or after a thermal treatment at 900 °C. Hardened materials containing different amounts of olivine sand were characterized and their behavior was compared to that of a blank geopolymeric matrix. Materials were examined by X-ray diffraction, Fourier Transform Infrared Radiation, and optical and scanning electron microscope investigation; mechanical compressive strength was discussed taking into account water absorption and microstructure. It has been observed that all compositions containing the as-received olivine sands badly perform, whereas those prepared using thermally treated olivine have higher compressive strength than the reference blank composition. In particular, samples with composition containing 100 g of metakaolin and 75 g of olivine displayed the best overall behavior. Graphical Abstract

OBJECTIVE Sporadic brain arteriovenous malformation (BAVM) is a tangled vascular lesion characterized by direct artery-to-vein connections that can cause life-threatening intracerebral hemorrhage (ICH). Recently, somatic mutations in KRAS have been reported in sporadic BAVM, and mutations in other mitogen-activated protein kinase (MAPK) signaling pathway genes have been identified in other vascular malformations. The objectives of this study were to systematically evaluate somatic mutations in MAPK pathway genes in patients with sporadic BAVM lesions and to evaluate the association of somatic mutations with phenotypes of sporadic BAVM severity. METHODS The authors performed whole-exome sequencing on paired lesion and blood DNA samples from 14 patients with sporadic BAVM, and 295 genes in the MAPK signaling pathway were evaluated to identify genes with somatic mutations in multiple patients with BAVM. Digital droplet polymerase chain reaction was used to validate KRAS G12V and G12D mutations and to assay an additional 56 BAVM samples. RESULTS The authors identified a total of 24 candidate BAVM-associated somatic variants in 11 MAPK pathway genes. The previously identified KRAS G12V and G12D mutations were the only recurrent mutations. Overall, somatic KRAS G12V was present in 14.5% of BAVM lesions and G12D was present in 31.9%. The authors did not detect a significant association between the presence or allelic burden of KRAS mutation and three BAVM phenotypes: lesion size (maximum diameter), age at diagnosis, and age at ICH. CONCLUSIONS The authors confirmed the high prevalence of somatic KRAS mutations in sporadic BAVM lesions and identified several candidate somatic variants in other MAPK pathway genes. These somatic variants may contribute to understanding of the etiology of sporadic BAVM and the clinical characteristics of patients with this condition.

The massive use of social media causes rapid information dissemination that amplifies harmful messages such as fake news. Fake-news is misleading information presented as factual news that is generally used to manipulate public opinion. In particular, fake news related to COVID-19 is defined as 'infodemic' by World Health Organization. An infodemic is a misleading information that causes confusion which may harm health. There is a high volume of misinformation about COVID-19 that causes panic and high stress. Therefore, the importance of development of COVID-19 related fake news identification model is clear and it is particularly important for Turkish language from COVID-19 fake news identification point of view. In this article, we propose an advanced deep language transformer model to identify the truth of Turkish COVID-19 news from social media. For this aim, we first generated Turkish COVID-19 news from various sources as a benchmark dataset. Then we utilized five conventional machine learning algorithms (i.e. Naive Bayes, Random Forest, K-Nearest Neighbor, Support Vector Machine, Logistic Regression) on top of several language preprocessing tasks. As a next step, we used novel deep learning algorithms such as Long Short -Term Memory, Bi-directional Long-Short-Term-Memory, Convolutional Neural Networks, Gated Recurrent Unit and Bi-directional Gated Recurrent Unit. For further evaluation, we made use of deep learning based language transformers, i.e. Bi-directional Encoder Representations from Transformers and its variations, to improve efficiency of the proposed approach. From the obtained results, we observed that neural transformers, in particular Turkish dedicated transformer BerTURK, is able to identify COVID-19 fake news in 98.5% accuracy.

Stabilized Runge-Kutta methods are especially efficient for the numerical solution of large systems of stiff nonlinear differential equations because they are fully explicit. For semi-discrete parabolic problems, for instance, stabilized Runge-Kutta methods overcome the stringent stability condition of standard methods without sacrificing explicitness. However, when stiffness is only induced by a few components, as in the presence of spatially local mesh refinement, their efficiency deteriorates. To remove the crippling effect of a few severely stiff components on the entire system of differential equations, we derive a modified equation, whose stiffness solely depend on the remaining mildly stiff components. By applying stabilized Runge-Kutta methods to this modified equation, we then devise an explicit multirate Runge-Kutta-Chebyshev (mRKC) method whose stability conditions are independent of a few severely stiff components. Stability of the mRKC method is proved for a model problem, whereas its efficiency and usefulness are demonstrated through a series of numerical experiments., Comment: With respect to the previous version: Added a new numerical experiment where the mRKC method (first-order) is compared against a second-order RKC method and implicit Euler method on a nonlinear problem

Intestinal ischemia–reperfusion (IR) injury is a severe clinical condition, and unraveling its pathophysiology is crucial to improve therapeutic strategies and reduce the high morbidity and mortality rates. Here, we studied the dynamic proteome and phosphoproteome in the human intestine during ischemia and reperfusion, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to gain quantitative information of thousands of proteins and phosphorylation sites, as well as mass spectrometry imaging (MSI) to obtain spatial information. We identified a significant decrease in abundance of proteins related to intestinal absorption, microvillus, and cell junction, whereas proteins involved in innate immunity, in particular the complement cascade, and extracellular matrix organization increased in abundance after IR. Differentially phosphorylated proteins were involved in RNA splicing events and cytoskeletal and cell junction organization. In addition, our analysis points to mitogen-activated protein kinase (MAPK) and cyclin-dependent kinase (CDK) families to be active kinases during IR. Finally, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) MSI presented peptide alterations in abundance and distribution, which resulted, in combination with Fourier-transform ion cyclotron resonance (FTICR) MSI and LC-MS/MS, in the annotation of proteins related to RNA splicing, the complement cascade, and extracellular matrix organization. This study expanded our understanding of the molecular changes that occur during IR in the human intestine and highlights the value of the complementary use of different MS-based methodologies.

Sodium-glucose cotransporter-2 inhibitor therapy is well suited for initiation during the heart failure hospitalization, owing to clinical benefits that accrue rapidly within days to weeks, a strong safety and tolerability profile, minimal to no effects on blood pressure, and no excess risk of adverse kidney events. There is no evidence to suggest that deferring initiation to theoutpatient setting accomplishes anything beneficial. Instead, there is compelling evidence that deferring in-hospital initiation exposes patients to excess risk of early postdischarge clinical worsening and death. Lessons from other heart failure with reduced ejection fraction therapies highlight that deferring initiation of guideline-recommended medications tothe U.S. outpatient setting carries a >75% chance they will not be initiated within the next year. Recognizing that 1 in 4patients hospitalized for worsening heart failure die or are readmitted within 30days, clinicians should embrace the in-hospital period as an optimal time to initiate sodium-glucose cotransporter-2 inhibitor therapy and treat this populationwith the urgency it deserves.

Background There are currently no recommendations guiding when best to perform coronary artery calcium (CAC) scanning among young adults to identify those susceptible for developing premature atherosclerosis. Objectives The purpose of this study was to determine the ideal age at which a first CAC scan has the highest utility according to atherosclerotic cardiovascular disease (ASCVD) risk factor profile. Methods We included 22,346 CAC Consortium participants aged 30-50 years who underwent noncontrast computed tomography. Sex-specific equations were derived from multivariable logistic modeling to estimate the expected probability of CAC >0 according to age and the presence of ASCVD risk factors. Results Participants were on average 43.5 years of age, 25% were women, and 34% had CAC >0, in whom the median CAC score was 20. Compared with individuals without risk factors, those with diabetes developed CAC 6.4 years earlier on average, whereas smoking, hypertension, dyslipidemia, and a family history of coronary heart disease were individually associated with developing CAC 3.3-4.3 years earlier. Using a testing yield of 25% for detecting CAC >0, the optimal age for a potential first scan would be at 36.8 years (95% CI: 35.5-38.4 years) in men and 50.3 years (95% CI: 48.7-52.1 years) in women with diabetes, and 42.3 years (95% CI: 41.0-43.9 years) in men and 57.6 years (95% CI: 56.0-59.5 years) in women without risk factors. Conclusions Our derived risk equations among health-seeking young adults enriched in ASCVD risk factors inform the expected prevalence of CAC >0 and can be used to determine an appropriate age to initiate clinical CAC testing to identify individuals most susceptible for early/premature atherosclerosis.

Publisher Copyright: © 2021 The Authors. Although the children of first-generation immigrants tend to have better health than the native population, the health advantage of the children of immigrant families deteriorates over generations. It is, however, poorly understood where on the generational health assimilation spectrum children with one immigrant and one native parent (i.e., exogamous families) lie, to what extent family resources explain health assimilation, and whether the process of assimilation varies across health conditions. We seek to extend our understanding of the process of health assimilation by analyzing the physical and mental health of immigrant generations, assessing the role of exoga-mous family arrangements, and testing the contributions of family material and social resources to children’s outcomes. We use register-based longitudinal data on all children residing in Finland, born in 1986–2000, and alive in 2000; these data are free of report-ing bias and loss to follow-up. We estimate the risk of receiving inpatient and outpatient care for somatic conditions, psychopathological disorders, and injuries by immigrant generation status. Our results show evidence of a negative health assimilation process, with both first-and second-generation immigrant children having a higher prevalence of physical problems and particularly mental health problems than native children that is only partially explained by family resources. We find that the children of exogamous families are at especially high risk of developing psychopathological disorders. These results provide strong support for the hypothesis that children of exogamous families constitute a specific health risk group and that the impact on children’s health of family social and material resources seems to be secondary to other unobserved factors.

Jessica R Lunsford-Avery,1 Jack D Edinger,1,2 Andrew D Krystal1,3 1Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, 27710, USA; 2Department of Medicine, National Jewish Health, Denver, CO, 80206, USA; 3Departments of Psychiatry and Neurology, University of California San Francisco School of Medicine, San Francisco, CA, 94143, USACorrespondence: Jessica R Lunsford-Avery, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, 2608 Erwin Road Suite 300, Durham, NC, 27710, USA, Tel +1 919-681-0035, Fax +1 919-681-0016, Email jessica.r.avery@duke.eduPurpose: Sleep is vital to cognition, yet underlying mechanisms remain unclear. Although sleep duration and continuity are two well-established contributors, additional factors—including homeostatic sleep drive processes—may also underlie cognition-related sleep restoration. This study investigates the relative contributions of sleep EEG factors to psychomotor functioning in adults with insomnia and healthy controls (HC) to identify the most significant sleep factors supporting psychomotor functioning.Materials and Methods: Adults with insomnia (n = 37) and HC (n = 39) completed 3 nights of polysomnography and a complex psychomotor task (switching attention task; SAT). Univariate correlations identified the most significant predictors (traditional PSG, spectral EEG, initial delta peak, and overnight delta decline) of SAT performance, which were then entered into multivariable linear regressions examining whether predictors remained significant after accounting for shortened/fragmented sleep and whether relationships differed across groups.Results: In addition to greater wake after sleep onset (WASO; r = 0.33), a slower overnight delta decline (r = 0.50) and a lower initial delta peak (r = − 0.38) were the most significant predictors of poorer SAT performance. Both overnight delta decline (F(7, 68) = 12.52, p < 0.001) and initial delta peak (F(7, 68) = 7.85, p = 0.007) remained significant predictors after controlling for demographics, total sleep time, and WASO. Relationships were analogous across subject groups.Conclusion: Findings suggest that, in addition to sleep duration and continuity, processes related to recovery from and dissipation of homeostatic sleep drive may support psychomotor performance and broadly support daytime functioning in individuals with and without insomnia. Future research may examine overnight delta dynamics as transdiagnostic processes supporting cognition-related sleep restoration across a range of clinical populations.Keywords: insomnia, EEG, homeostatic sleep drive, delta power, cognition, reaction time