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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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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

CRISPR-based targeted modification of epigenetic marks such as DNA cytosine methylation is an important strategy to regulate the expression of genes and their associated phenotypes. Although plants have DNA methylation in all sequence contexts (CG, CHG, CHH, where H = A, T, C), methylation in the symmetric CG context is particularly important for gene silencing and is very efficiently maintained through mitotic and meiotic cell divisions. Tools that can directly add CG methylation to specific loci are therefore highly desirable but are currently lacking in plants. Here we have developed two CRISPR-based CG-specific targeted DNA methylation systems for plants using a variant of the bacterial CG-specific DNA methyltransferase MQ1 with reduced activity but high specificity. We demonstrate that the methylation added by MQ1 is highly target specific and can be heritably maintained in the absence of the effector. These tools should be valuable both in crop engineering and in plant genetic research.

Organic-inorganic layered perovskites are two-dimensional quantum wells with layers of lead-halide octahedra stacked between organic ligand barriers. The combination of their dielectric confinement and ionic sublattice results in excitonic excitations with substantial binding energies that are strongly coupled to the surrounding soft, polar lattice. However, the ligand environment in layered perovskites can significantly alter their optical properties due to the complex dynamic disorder of soft perovskite lattice. Here, we observe the dynamic disorder through phonon dephasing lifetimes initiated by ultrafast photoexcitation employing high-resolution resonant impulsive stimulated Raman spectroscopy of a variety of ligand substitutions. We demonstrate that vibrational relaxation in layered perovskite formed from flexible alkyl-amines as organic barriers is fast and relatively independent of the lattice temperature. Relaxation in aromatic amine based layered perovskite is slower, though still fast relative to pure inorganic lead bromide lattices, with a rate that is temperature dependent. Using molecular dynamics simulations, we explain the fast rates of relaxation by quantifying the large anharmonic coupling of the optical modes with the ligand layers and rationalize the temperature independence due to their amorphous packing. This work provides a molecular and time-domain depiction of the relaxation of nascent optical excitations and opens opportunities to understand how they couple to the complex layered perovskite lattice, elucidating design principles for optoelectronic devices., 7 pages, 4 figures, SI

Systemic sclerosis (SSc) is a rare, systemic autoimmune disease of unknown etiology. Among the systemic rheumatic diseases, SSc carries the highest mortality, in part due to the historical lack of disease modifying therapies. Recently, landmark randomized controlled trials (RCTs) have been conducted that have illustrated the heterogeneous nature of SSc and furthered our understanding of the key inflammatory and fibrotic pathways involved in SSc pathogenesis. Although SSc affects various organ systems, RCTs have focused on investigating treatments for diffuse cutaneous sclerosis (dcSSc) and interstitial lung disease (ILD). While recent RCTs for dcSSc have failed to demonstrate a treatment benefit, the outcomes of two RCTs led to the approval of two novel therapies for SSc-ILD: nintedanib and tocilizumab. This review summarizes the salient outcome data from recent SSc trials within a practical clinical framework and points out gaps in knowledge that may help inform the design of future SSc studies.

Numerical continuation in the context of optimization can be used to mitigate convergence issues due to a poor initial guess. In this work, we extend this idea to Riemannian optimization problems, that is, the minimization of a target function on a Riemannian manifold. For this purpose, a suitable homotopy is constructed between the original problem and a problem that admits an easy solution. We develop and analyze a path-following numerical continuation algorithm on manifolds for solving the resulting parameter-dependent equation. To illustrate our developments, we consider two typical classical applications of Riemannian optimization: the computation of the Karcher mean and low-rank matrix completion. We demonstrate that numerical continuation can yield improvements for challenging instances of both problems.

OBJECTIVES This study sought to describe worldwide variations in the use of myocardial perfusion imaging hardware, software, and imaging protocols and their impact on radiation effective dose (ED). BACKGROUND Concerns about long-term effects of ionizing radiation have prompted efforts to identify strategies for dose optimization in myocardial perfusion scintigraphy. Studies have increasingly shown opportunities for dose reduction using newer technologies and optimized protocols. METHODS Data were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study) registry, a multinational, cross-sectional study comprising 7,911 imaging studies from 308 labs in 65 countries. The study compared regional use of camera technologies, advanced post-processing software, and protocol characteristics and analyzed the influence of each factor on ED. RESULTS Cadmium-zinc-telluride and positron emission tomography (PET) cameras were used in 10% (regional range 0% to 26%) and 6% (regional range 0% to 17%) of studies worldwide. Attenuation correction was used in 26% of cases (range 10% to 57%), and advanced post-processing software was used in 38% of cases (range 26% to 64%). Stress-first single-photon emission computed tomography (SPECT) imaging comprised nearly 20% of cases from all world regions, except North America, where it was used in just 7% of cases. Factors associated with lower ED and odds ratio for achieving radiation dose

Approximately 50% of colorectal cancer (CRC) patients still die from recurrence and metastatic disease, highlighting the need for novel therapeutic strategies. Drug repurposing is attracting increasing attention because, compared to traditional de novo drug discovery processes, it may reduce drug development periods and costs. Epidemiological and preclinical evidence support the antitumor activity of antipsychotic drugs. Herein, we dissect the mechanism of action of the typical antipsychotic spiperone in CRC. Spiperone can reduce the clonogenic potential of stem-like CRC cells (CRC-SCs) and induce cell cycle arrest and apoptosis, in both differentiated and CRC-SCs, at clinically relevant concentrations whose toxicity is negligible for non-neoplastic cells. Analysis of intracellular Ca2+ kinetics upon spiperone treatment revealed a massive phospholipase C (PLC)-dependent endoplasmic reticulum (ER) Ca2+ release, resulting in ER Ca2+ homeostasis disruption. RNA sequencing revealed unfolded protein response (UPR) activation, ER stress, and induction of apoptosis, along with IRE1-dependent decay of mRNA (RIDD) activation. Lipidomic analysis showed a significant alteration of lipid profile and, in particular, of sphingolipids. Damage to the Golgi apparatus was also observed. Our data suggest that spiperone can represent an effective drug in the treatment of CRC, and that ER stress induction, along with lipid metabolism alteration, represents effective druggable pathways in CRC.

Mixed vaginitis is defined as the simultaneous presence of at least two different vaginal pathogens, both contributing to an abnormal vaginal milieu leading to signs and symptoms. Pathogen coinfection occurs frequently in women with vaginitis, and both coinfection and mixed vaginitis have relevant clinical and therapeutic implications. Fenticonazole, an imidazole derivative with a broad spectrum of antimycotic and antimicrobial activity, appears at least as effective as other topical antifungals in the treatment of vulvovaginal candidiasis and can also have a major role in the treatment of mixed infections or coinfections of the lower genital tract. This paper will address the current role of topical fenticonazole as an empiric treatment of vulvovaginal infections, with a focus on the effectiveness in the treatment of mixed vaginitis and the possible implications of this.

This manuexamines whether the effect of anchoring bias is greater when citizens evaluate the quality of a publicservice after receiving negative initial information about service performance than after receiving positive information.It also tests whether there are differences in this anchoring bias by comparing formal (report) vs. informal (rumor)communication. Two field experiments were conducted with the participation of passengers of a commuter public traintransportation organization (Experiment 1, N = 105) and users of a public university administrative service (Experiment 2,N = 172). The first experiment confirmed the bias produced by the negative initial information, whereas this bias does notexist for the positive information. The second experiment showed that the bias produced by the initial information hasthe same magnitude for both formal and informal communication. This paper concludes with a discussion of theoreticaland practical implications for managing reputation in public services. Este manuscrito examina si el efecto del sesgo de anclaje es mayor cuando los ciudadanos evalúan la calidad de un serviciopúblico después de recibir información inicial negativa sobre la calidad del servicio, que después de recibir informaciónpositiva. También pone a prueba si hay diferencias en este sesgo de anclaje al comparar la comunicación formal (informe)con la comunicación informal (rumor). Se realizaron dos experimentos de campo con la participación de pasajerosde una compañía pública de trenes de cercanías (experimento 1, N = 105) y usuarios del servicio administrativo de unauniversidad pública (experimento 2, N = 172). El primer experimento confirmó el sesgo producido por la informacióninicial negativa, mientras que este sesgo no existe para la información positiva. El segundo experimento mostró que elsesgo producido por la información inicial tiene la misma magnitud tanto para la comunicación formal como para lainformal. El trabajo concluye con una discusión de las implicaciones teóricas y prácticas para la gestión de la reputaciónde los servicios públicos.

Employees’ workplace deviant behaviors have a harmful potential for organizations in many respects. Past research hasindicated that individual variables may ac for personal differences in work deviance. One of the prevalent findingsis that men display direct aggression more frequently than women. Yet, most of the past studies have reported resultsproviding information on the magnitude of a general behavioral tendency of each gender, leading to rough distinctions.Unlike the previous studies, we focused on examining profiles of the role of gender in interpersonal and organizationaldeviance, utilizing Profile Analysis via Multidimensional Scaling that allowed us to compare specific deviance behaviorindicators between males and females d in the profiles. The current exploratory study reveals that gender differencesin aggressive workplace behavior are not only those apparent in inter-personal relations but also when directed towardsthe organization. Moreover, the reported results point to specific behavioral profiles of men and women that could not berevealed using the mean difference analyses. Las conductas inapropiadas de los empleados en el lugar de trabajo tienen un potencial perjudicial para las organizacionesen muchos aspectos. Investigaciones anteriores indican que las variables individuales pueden explicar las diferenciaspersonales en el comportamiento laboral inadecuado. Uno de los hallazgos prevalentes es que los hombres muestranagresión directa con más frecuencia que las mujeres. Sin embargo, la mayoría de los estudios presentan resultados coninformación sobre la magnitud de una tendencia de comportamiento general de cada género, lo que lleva a distincionesmuy generales. A diferencia de los estudios anteriores, nos centramos en examinar el papel del género en la inadecuacióninterpersonal y organizacional utilizando el Análisis de Perfil por Escalamiento Multidimensional, que permite compararlos indicadores específicos de comportamiento inadecuado entre hombres y mujeres incluidos en los perfiles. El estudioactual revela que las diferencias de género en el comportamiento agresivo en el lugar de trabajo no sólo son evidentes enlas relaciones interpersonales, sino también cuando se dirigen hacia la organización. Además, los resultados apuntan aperfiles de conducta específicos de hombres y mujeres que no aparecían en los análisis de diferencia de medias.

Obesity, defined as excess fat mass, increases risks for multiple chronic diseases, such as type 2 diabetes, cardiovascular disease, and several types of cancer. Beyond adiposity per se, the pattern of fat distribution, android or truncal as compared to gynoid or peripheral, has a profound influence on systemic metabolism and hence risk for obesity complications. Not only factors as genetics, environment, gender, and age account for the apparent compartmentalization of white adipose tissue (WAT) in the body. Indeed, the heterogeneity among different anatomical depots also appears to stem from their intrinsic diversity, including cellular developmental origin, proliferative capacity, glucose and lipid metabolism, insulin sensitivity, cytokine pattern, thermogenic ability, and vascularization. Under the obese condition, these depot-specific differences translate into specific WAT distribution patterns, giving rise to different cardiometabolic consequences. This review summarizes the clinical and mechanistic evidence for the depot-specific differences and the phenotypic characteristics of different WAT depots that link their depot-specific biology to obesity-specific complications.

We classify finite-dimensional real nilpotent Lie algebras with 2-dimensional central commutator ideals admitting a Lie group of automorphisms isomorphic to SO 2 ⁢ ( ℝ ) ${{\mathrm{SO}}_{2}(\mathbb{R})}$ . This is the first step to extend the class of nilpotent Lie algebras 𝔥 ${{\mathfrak{h}}}$ of type { n , 2 } ${\{n,2\}}$ to solvable Lie algebras in which 𝔥 ${{\mathfrak{h}}}$ has codimension one.

Blood blister-like aneurysms (BBA) were described for the first time in the 1990s, as small hemispherical bulges arising from a very fragile arterial wall. Until 2008, it was thought that this type of aneurysm almost exclusively affected the internal carotid artery, in particular, its dorsal portion. Subsequently, it was discovered that a BBA may also be present on the anterior communicating artery and on the vessels of the posterior cranial fossa. However, we found no reports in English-language literature of BBA arising from the middle cerebral artery (MCA). In this article, we present three cases of MCA BBA and discuss the unique diagnostic and therapeutic aspects of this vascular lesion. In our retrospective, multicenter review of 1330 patients with non-traumatic subarachnoid hemorrhage admitted to our services from 2000 to 2013, we found three cases (all in men) of MCA BBA. The patients' outcome was assessed using the modified Rankin scale. All three patients underwent angio-computed tomography, which did not reveal any aneurysms. Digital subtraction angiography performed within 24-48 h after admission, in all cases, demonstrated a very small aneurysm (

ARACHNIDA Acari, Hydrachnidia Hydryphantidae Wandesia (Pseudowandesia) minuta sp. nov. Smit : Australia, Victoria, Moleside Creek, Lower Glenelg NP, Momoniidae Partidomomonia elongata sp. nov. Smit : Australia, Tasmania, Franklin River, Franklin-Gordon Wild Rivers NP. Athienemanniidae Mellamunda tasmanica sp. nov. Smit: Australia, Tasmania, Franklin River, Franklin-Gordon Wild Rivers NP CRUSTACEA Isopoda, Microparasellidae Microcharon boulanouari sp. nov. Coineau, Boutin, Artheau : France, Corbieres, Aude River. Microcharon ariegensis sp. nov. Coineau, Boutin, Artheau : France, Central Pyrenees, Lachein River.

In the present study, a complex of compounds (red orange complex, ROC), obtained from three red orange varieties (Citrus sinensis varieties: Moro, Tarocco and Sanguinello), containing cyanidin glycosides, hydroxycinnamic acids, flavanone glycosides and ascorbic acid, was screened to discover new lead compounds in the suppression of the production of key molecules released during inflammatory events in interleukin-1beta (IL-beta) stimulated human primary chondrocytes. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX)-2 and intercellular adhesion molecule-1 (ICAM-1), and the release of nitric oxide, prostaglandin (PG)E(2) and interleukin-8 (IL-8) were determined. Indomethacin was used as an anti-inflammatory drug reference. ROC acts as a potent inhibitor of iNOS and COX-2 gene expression while also suppressing the production of PGE(2) and nitrite in human chondrocytes. In addition, ROC induces a significant decrease in ICAM expression and IL-8 release. These findings suggest that ROC exerts anti-inflammatory effects probably through the suppression of COX-2 and iNOS expression.

Summary Objective: The aim of this study was to evaluate the efficacy and the effect of sulphurous thermal water inhalations in the treatment of the recurrent upper respiratory tract (RURT) infections in children. Methods: A total of 100 children with RURT infections were included. All children underwent a 12-day course warm vapour inhalations. For the inhalations, we used sulphurous thermal water in the group A, while physiological solution in the group B. At the beginning, at the end and 3 months after start, all children underwent medical history, ENTexamination, plasma levels of immunoglobulins class E, G, A, M (IgE, IgG, IgA, IgM), subjective assessment of symptoms (VAS), nasal mucociliar transport time (NMTT) determination, and evaluation of frequency, duration, severity and social impact of RURT episodes. Results: Compared with group B, after the treatment and at the end of the study, in children treated with sulphurous thermal water, the serum concentration of IgE was significantly (p < 0.05) lower (75.13 27.1 mg/dl vs 96.87 41.3 mg/dl; 74.23 26.2 mg/dl vs 98.24 42.7 mg/dl), IgA titers were higher (238.14 122.1 mg/dl vs 218.62 115.8 mg/dl;239.72 119.7 mg/dlvs210.46 107.3 mg/dl),serumconcentrations of IgG and IgM unchanged, VAS scores presented a significant (p < 0.05) improvement (1.8 0.19 vs 6.8 0.54; 1.9 0.21 vs 6.9 0.61), NMTT was normal (11.15 1.59 min vs 17.63 2.17; 11.25 2.10 min vs 17.77 2.19 min) and frequency, duration, severity and social impact of RURT episodes were significantly (p < 0.05) lower. Conclusions: Our findings indicate that, in addition to their known effects, the sulphurous water also have an immunomodulant activity that contributes to their therapeutic effects. # 2008 Elsevier Ireland Ltd. All rights reserved.

We prove that under certain mild moment and continuity assumptions, the d-dimensional continuum Gaussian free field is the only stochastic process satisfying the usual domain Markov property and a scaling assumption. Our proof is based on a decomposition of the underlying functional space in terms of radial processes and spherical harmonics.

We demonstrate a nonlinear plasmonic metasurface that exhibits strongly asymmetric second-harmonic generation: nonlinear scattering is efficient upon excitation in one direction and it is substantially suppressed when the excitation direction is reversed, thus enabling a diode-like functionality. A significant (approximately 10 dB) extinction ratio of SHG upon opposite excitations is measured experimentally and those findings are substantiated with full-wave simulations. The combination of two commonly used metals - aluminium and silver - produces a material composition asymmetry that results into a bianisotropic response of the system, as confirmed by performing homogenization analysis and extracting an effective susceptibility tensor. Finally, we discuss the implications of our results from the more fundamental perspectives of reciprocity and time-reversal asymmetry., 7 pages, 4 figures in the main text; 4 pages and 6 figures in the supporting information