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Costos de la Atención en Salud , Neoplasias , Humanos , Neoplasias/economía , Neoplasias/terapia , AustraliaRESUMEN
INTRODUCTION: There are significant challenges and a lack of data related to culturally and linguistically diverse (CALD) cancer patients. We compared patient characteristics, treatment patterns, and outcomes of patients with advanced pancreatic cancer that required an interpreter. METHODS: Registry data was extracted for advanced pancreatic cancer patients from a single health institution with a comprehensive Transcultural and Language Service (TALS). Demographic and clinicopathologic characteristics were compared. Kaplan-Meier survival estimates with log-rank testing, and univariate and multivariable regression analysis were performed to compare the group with limited English proficiency (LEP) to the English proficient (EP) group. RESULTS: Of 155 patients, 32.9% (n = 51) required the TALS. The LEP group had a higher mean age (71.2 vs. 76.8 years; p = 0.005) and received less chemotherapy (42.3% vs. 31.4%, p = 0.220). Univariate analysis revealed a shorter median overall survival (OS) in the LEP group (3.6 vs. 5.0 months), with a hazard ratio [HR] of 1.51 (95% confidence interval [CI]: 1.03-2.21, p = 0.033). Upon multivariable analysis, adjusting for Eastern Cooperative Oncology Group (ECOG) performance scale, the number of sites of metastatic disease and chemotherapy use, the strength of association between LEP and OS reduced marginally (HR 1.42, 95% CI: 0.93-2.16), and was no longer statistically significant (p = 0.103). CONCLUSIONS: In patients with advanced pancreatic cancer utilizing a comprehensive TALS, there was a trend to poorer survival with limited English proficiency, although this association was not statistically significant. An ongoing research commitment to the CALD experience is necessary to build a granular understanding of this population and ensure equitable outcomes.
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Disparidades en Atención de Salud , Dominio Limitado del Inglés , Neoplasias Pancreáticas , Humanos , Femenino , Masculino , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Anciano , Disparidades en Atención de Salud/estadística & datos numéricos , Persona de Mediana Edad , Anciano de 80 o más AñosRESUMEN
INTRODUCTION: Patients undergoing vascular procedures are prone to developing postoperative complications affecting their shortterm mortality. Prospective reports describing the incidence of longterm complications after vascular surgery are lacking. OBJECTIVES: We aimed to describe the incidence of complications 1 year after vascular surgery and to evaluate an association between myocardial injury after noncardiac surgery (MINS) and 1year mortality. PATIENTS AND METHODS: This is a substudy of a large prospective cohort study Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION). Recruitment took place in 28 centers across 14 countries from August 2007 to November 2013. We enrolled patients aged 45 years or older undergoing vascular surgery, receiving general or regional anesthesia, and hospitalized for at least 1 night postoperatively. Plasma cardiac troponin T concentration was measured before the surgery and on the first, second, and third postoperative day. The patients or their relatives were contacted 1 year after the procedure to assess the incidence of major postoperative complications. RESULTS: We enrolled 2641 patients who underwent vascular surgery, 2534 (95.9%) of whom completed 1year followup. Their mean (SD) age was 68.2 (9.8) years, and the cohort was predominantly male (77.5%). The most frequent 1year complications were myocardial infarction (224/2534, 8.8%), amputation (187/2534, 7.4%), and congestive heart failure (67/2534, 2.6%). The 1year mortality rate was 8.8% (223/2534). MINS occurred in 633 patients (24%) and was associated with an increased 1year mortality (hazard ratio, 2.82; 95% CI, 2.14-3.72; P <0.001). CONCLUSIONS: The incidence of major postoperative complications after vascular surgery is high. The occurrence of MINS is associated with a nearly 3fold increase in 1year mortality.
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Lesiones Cardíacas , Infarto del Miocardio , Humanos , Masculino , Femenino , Estudios Prospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Infarto del Miocardio/etiología , Procedimientos Quirúrgicos Vasculares/efectos adversos , Troponina TRESUMEN
BACKGROUND: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery. METHODS: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis. RESULTS: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr). CONCLUSIONS: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge.
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Alta del Paciente , Sepsis , Humanos , Estudios Prospectivos , Cuidados Posteriores , Hemorragia , Complicaciones Posoperatorias/epidemiología , Factores de RiesgoRESUMEN
Developmental exposure to ethanol is a leading cause of cognitive, emotional and behavioral problems, with fetal alcohol spectrum disorder (FASD) affecting more than 1:100 children. Recently, comorbid sleep deficits have been highlighted in these disorders, with sleep repair a potential therapeutic target. Animal models of FASD have shown non-REM (NREM) sleep fragmentation and slow-wave oscillation impairments that predict cognitive performance. Here we use a mouse model of perinatal ethanol exposure to explore whether reduced sleep pressure may contribute to impaired NREM sleep, and compare the function of a brain network reported to be impacted by insomnia-the Salience network-in developmental ethanol-exposed mice with sleep-deprived, saline controls. Mice were exposed to ethanol or saline on postnatal day 7 (P7) and allowed to mature to adulthood for testing. At P90, telemetered cortical recordings were made for assessment of NREM sleep in home cage before and after 4 h of sleep deprivation to assess basal NREM sleep and homeostatic NREM sleep response. To assess Salience network functional connectivity, mice were exposed to the 4 h sleep deprivation period or left alone, then immediately sacrificed for immunohistochemical analysis of c-Fos expression. The results show that developmental ethanol severely impairs both normal rebound NREM sleep and sleep deprivation induced increases in slow-wave activity, consistent with reduced sleep pressure. Furthermore, the Salience network connectome in rested, ethanol-exposed mice was most similar to that of sleep-deprived, saline control mice, suggesting a sleep deprivation-like state of Salience network function after developmental ethanol even without sleep deprivation.
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BT75, a boron-containing retinoid, is a novel retinoic acid receptor (RAR)α agonist synthesized by our group. Previous studies indicated that activation of retinoic acid (RA) signaling may attenuate progression of Alzheimer's disease (AD). Presently, we aimed to examine the anti-inflammatory effect of BT75 and explore the possible mechanism using cultured cells and an AD mouse model. Pretreatment with BT75 (1-25 µM) suppressed the release of nitric oxide (NO) and IL-1ß in the culture medium of mouse microglial SIM-A9 cells activated by LPS. BMS195614, an RARα antagonist, partially blocked the inhibition of NO production by BT75. Moreover, BT75 attenuated phospho-Akt and phospho-NF-κB p65 expression augmented by LPS. In addition, BT75 elevated arginase 1, IL-10, and CD206, and inhibited inducible nitric oxide synthase (iNOS) and IL-6 formation in LPS-treated SIM-A9 cells, suggesting the promotion of M1-M2 microglial phenotypic polarization. C57BL/6 mice were injected intracerebroventricularly (icv) with streptozotocin (STZ) (3 mg/kg) to provide an AD-like mouse model. BT75 (5 mg/kg) or the vehicle was intraperitoneally (ip) injected to icv-STZ mice once a day for 3 weeks. Immunohistochemical analyses indicated that GFAP-positive cells and rod or amoeboid-like Iba1-positive cells, which increased in the hippocampal fimbria of icv-STZ mice, were reduced by BT75 treatment. Western blot results showed that BT75 decreased levels of neuronal nitric oxide synthase (nNOS), GFAP, and phosphorylated Tau, and increased levels of synaptophysin in the hippocampus of icv-STZ mice. BT75 may attenuate neuroinflammation by affecting the Akt/NF-κB pathway and microglial M1-M2 polarization in LPS-stimulated SIM-A9 cells. BT75 also reduced AD-like pathology including glial activation in the icv-STZ mice. Thus, BT75 may be a promising anti-inflammatory and neuroprotective agent worthy of further AD studies.
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Enfermedad de Alzheimer , Microglía , Ratones , Animales , Microglía/metabolismo , FN-kappa B/metabolismo , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Lipopolisacáridos/toxicidad , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones Endogámicos C57BL , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéuticoRESUMEN
The aim of this paper is to evaluate the extent of the practice of using informal payments for accessing the services of public clinics or hospitals across Europe and to explain the prevalence of this corrupt practice using the framework of institutional theory. To achieve this, a multi-level mixed-effect logistic regression on 25,744 interviews undertaken in 2020 with patients across 27 European Union countries is conducted. The finding is that the practice of making informal payments remains a prevalent practice, although there are large disparities in the usage of this practice in different European countries. However, informal payments by patients are more likely when there is a lower institutional trust and a higher degree of asymmetry between formal and informal institutions. The resultant proposal is that policy makers need to address the institutional environment to tackle such informal payments. How this can be achieved is outlined.
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Objectives: The objective of this paper is to evaluate the use of informal payments and personal connections to gain preferential access to public health services during the COVID-19 pandemic and to propose effective policy measures for tackling this phenomenon. Methods: Using data from 25,744 patients in the European Union, six different scenarios are analyzed in relation to making informal payments and/or relying on personal connections to access public healthcare services. To evaluate the propensity to engage in informal practices in healthcare, probit regressions with sample selection and predicted probabilities are used. Robustness checks are also performed to test the reliability of the findings. Results: For each scenario, a statistically significant association is revealed between the propensity to make informal payments and/or rely on personal connections and the asymmetry between the formal rules and the patients' personal norms and trust in public authorities. Conclusion: To tackle informal practices in healthcare, policy measures are required to reduce the asymmetry between the formal rules and personal norms by raising trust in public authorities.
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COVID-19 , Financiación Personal , Humanos , Unión Europea , Pandemias , COVID-19/epidemiología , Reproducibilidad de los Resultados , Atención a la Salud , Gastos en SaludRESUMEN
This paper evaluates whether different labor market policy interventions taken in response to the COVID-19 pandemic have been effective in reducing its adverse impacts. We construct a database covering 165 countries and 39 labor market interventions grouped into four pillars: stimulating the economy and jobs (pillar 1); supporting enterprises, employment, and incomes (pillar 2); protecting workers (pillar 3); and social dialogue (pillar 4). The results revealed that measures taken under pillars 1, 2, and 3 have reduced the impacts of the pandemic on economic growth; measures under pillar 4 were significantly associated with reducing its impacts on employment and those under pillar 2 with reducing its impacts on working hours.
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In recent decades scholars have acknowledged that transactions in the informal economy have not vanished with modernization and industrialization as expected but rather remain an important contemporary aspect of overall production and consumption across the world, in both developing and developed countries. Yet little is known about the profile of the consumers in this realm or what drives them to purchase from the informal economy. A systematic review of the literature investigating consumption in the informal economy reveals a severely underdeveloped area of consumer studies with significant gaps in terms of its theoretical approaches, methods and regional coverage. The findings of the existing literature is that multiple motives are used by consumers for justifying their purchases in the informal economy beyond the dominant simplistic view that they do simply for financial gain or for a lower price (namely, it identifies social ends and failures in formal market provision in terms of availability, speed of provision and quality). The outcome is a recognition that responsibility to reducing this phenomenon with negative effects on governments, businesses, workers and consumers lies not just with public authorities but also practitioners who need to correct the failures in formal market provision. The significant gaps identified in the literature are then used to highlight a comprehensive future research agenda, which includes the need for the development of an institutionalist theoretical perspective when explaining consumers' participation in the informal economy and social marketing interventions.
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In this paper, we use a novel cross-country dataset to investigate the relationship between the prevalence of the shadow economy and fiscal policy responses to the economic crisis induced by the pandemic. The finding is that countries with a relatively larger shadow economy before the pandemic have adopted a smaller fiscal policy package. The results are robust to different econometric specifications, including an instrumental variable estimation. This reinforces the wider literature that countries (especially those with larger shadow economies) generally follow a procyclical policy as opposed to the optimal and countercyclical one.
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Conventional cytogenetic analysis of products of conception (POC) is of limited utility because of failed cultures, as well as microbial and maternal cell contamination (MCC). Optical genome mapping (OGM) is an emerging technology that has the potential to replace conventional cytogenetic methods. The use of OGM precludes the requirement for culturing (and related microbial contamination). However, a high percentage of MCC impedes a definitive diagnosis, which can be addressed by an additional pre-analytical quality control step that includes histological assessment of H&E stained slides from formalin-fixed paraffin embedded (FFPE) tissue with macro-dissection for chorionic villi to enrich fetal tissue component for single nucleotide polymorphism microarray (SNPM) analysis. To improve the diagnostic yield, an integrated workflow was devised that included MCC characterization of POC tissue, followed by OGM for MCC-negative cases or SNPM with histological assessment for MCC-positive cases. A result was obtained in 93% (29/31) of cases with a diagnostic yield of 45.1% (14/31) with the proposed workflow, compared to 9.6% (3/31) and 6.4% (2/31) with routine workflow, respectively. The integrated workflow with these technologies demonstrates the clinical utility and higher diagnostic yield in evaluating POC specimens.
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Fertilización , Polimorfismo de Nucleótido Simple , Mapeo Cromosómico/métodos , Análisis Citogenético/métodos , Análisis por Micromatrices/métodosRESUMEN
Healthcare accessibility and equity remain important issues, as corruption in the form of informal payments is still prevalent in many countries across the world. This study employs a panel data analysis over the 2006-2013 period to explore the role of different institutional factors in explaining the prevalence of informal payments. Covering 117 countries, our findings confirm the significant role of both formal and informal institutions. Good governance, a higher trust among individuals, and a higher commitment to tackling corruption are associated with diminishing informal payments. In addition, higher shares of private finance, such as out-of-pocket and domestic private health expenditure, are also correlated with a lower prevalence of informal payments. In policy terms, this displays how correcting institutional imperfections may be among the most efficient ways to tackle informal payments in healthcare.
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Financiación Personal , Servicios de Salud , Atención a la Salud , Gastos en Salud , Accesibilidad a los Servicios de Salud , HumanosRESUMEN
Although major advances have been made in relation to explaining the supply side of the informal economy, this is not the case for the demand-side of the informal economy. This study analyses for the first time the purchasers of undeclared goods and services in the healthcare sector. To evaluate the purchase of undeclared healthcare goods and services, logistic regression analysis and robustness tests are used on 3048 interviews in Cyprus, Greece, Italy and Malta. The finding is that an important share of the purchasers make this type of purchase unknowingly. However, no difference in terms of socio-economics characteristics of those who knowingly and those who unknowingly made purchases of undeclared healthcare goods and services was identified. Meanwhile a significant influence of trust (in government and in other citizens) has been identified in relation to those who made these purchases knowingly. As such, policy measures aimed at decreasing unknowing purchases and at nurturing trust are discussed in the concluding section.
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Comportamiento del Consumidor , Confianza , Atención a la Salud , Grecia , ItaliaRESUMEN
Confronted with a global pandemic, public healthcare systems are under pressure, making access to healthcare services difficult for patients. This provides fertile ground for using illegal practices such as informal payments to gain access. This paper aims to evaluate the use of informal payments by patients during the COVID-19 pandemic and the institutions that affect the prevalence of this practice. Various measurements of formal and informal institutions are here investigated, namely the acceptability of corruption, the level of trust, transparency, and performance of the healthcare system. To do so, a logistic regression of 10,859 interviews with patients conducted across 11 Central and Eastern Europe countries in October-December 2020 is employed. The finding is that there are large disparities between countries in the prevalence of informal payments, and that the practice is more likely to occur where there are poorer formal and informal institutions, namely higher acceptability of corruption, lower trust in authorities, lower perceived transparency in handling the COVID-19 pandemic, difficult access to, and poor quality of, healthcare services, and higher mortality rates due to the COVID-19 pandemic. These findings suggest that policy measures for tackling informal payments need to address the current state of the institutional environment.
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COVID-19 , Pandemias , Europa Oriental , Financiación Personal , Gastos en Salud , Humanos , SARS-CoV-2RESUMEN
Two serious public health challenges have emerged in the current COVID-19 pandemic namely, deficits in SARS-CoV-2 variant monitoring and neglect of other co-circulating respiratory viruses. Additionally, accurate assessment of the evolution, extent, and dynamics of the outbreak is required to understand the transmission of the virus. To address these challenges, we evaluated 533 samples using a high-throughput next-generation sequencing (NGS) respiratory viral panel (RVP) that includes 40 viral pathogens. The performance metrics revealed a PPA, NPA, and accuracy of 95.98%, 85.96%, and 94.4%, respectively. The clade for pangolin lineage B that contains certain distant variants, including P4715L in ORF1ab, Q57H in ORF3a, and S84L in ORF8 covarying with the D614G spike protein mutation, were the most prevalent early in the pandemic in Georgia, USA. The isolates from the same county formed paraphyletic groups, indicating virus transmission between counties. The study demonstrates the clinical and public health utility of the NGS-RVP to identify novel variants that can provide actionable information to prevent or mitigate emerging viral threats and models that provide insights into viral transmission patterns and predict transmission/resurgence of regional outbreaks as well as providing critical information on co-circulating respiratory viruses that might be independent factors contributing to the global disease burden.
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COVID-19/epidemiología , Genoma Viral/genética , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/virología , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/transmisión , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Límite de Detección , Filogenia , SARS-CoV-2/aislamiento & purificación , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
Usually, studies on the informal economy focus mainly upon those working in the informal economy (supply side). However, many exchanges in the informal economy are initiated by purchasers asking how much a good or service costs if paid cash in hand. Therefore, the aim of this paper is to advance understanding of who make purchases in the informal economy and the reasons of the consumers making these purchases (demand side). Two potential explanations are evaluated. Firstly, consumers are explained as rational economic actors seeking a more convenient deal or profit maximisation (i.e., lower price or better value for money), making purchases from the informal economy due to the lack of availability of the product or service they need on the formal market, or they make such purchases involuntarily, due to the lack of perfect information necessary to make a fully rational economic decision when purchasing. Secondly, the consumers are portrayed as social actors pursuing community help. Using a multilevel mixed-effects logistic regression analysis on a 2019 Eurobarometer interviews in 27 EU member states and the UK reveal how the prevalence of these motives significantly varies across populations and regions. The theoretical and policy implications of the findings are discussed in the concluding section.
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Comercio/economía , Comportamiento del Consumidor/economía , Sector Informal , Unión Europea , Humanos , Modelos Logísticos , Motivación , Análisis Multinivel , Reino UnidoRESUMEN
This review discusses the current testing methodologies for COVID-19 diagnosis and explores next-generation sequencing (NGS) technology for the detection of SARS-CoV-2 and monitoring phylogenetic evolution in the current COVID-19 pandemic. The review addresses the development, fundamentals, assay quality control and bioinformatics processing of the NGS data. This article provides a comprehensive review of the obstacles and opportunities facing the application of NGS technologies for the diagnosis, surveillance, and study of SARS-CoV-2 and other infectious diseases. Further, we have contemplated the opportunities and challenges inherent in the adoption of NGS technology as a diagnostic test with real-world examples of its utility in the fight against COVID-19.
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COVID-19/virología , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/genética , Biología Computacional/métodos , Humanos , Epidemiología Molecular/métodos , Pandemias , Filogenia , SARS-CoV-2/aislamiento & purificaciónRESUMEN
The calcium-activated chloride channel (CaCC) TMEM16A enables chloride secretion across several transporting epithelia, including in the airways. Additional roles for TMEM16A have been proposed, which include regulating mucus production and secretion and stimulating smooth muscle contraction. The aim of the present study was to test whether the pharmacological regulation of TMEM16A channel function, could affect any of these proposed biological roles in the airways. In vitro, neither a potent and selective TMEM16A potentiator (ETX001) nor the potent TMEM16A inhibitor (Ani9) influenced either baseline mucin release or goblet cell numbers in well-differentiated primary human bronchial epithelial (HBE) cells. In vivo, a TMEM16A potentiator was without effect on goblet cell emptying in an IL-13 stimulated goblet cell metaplasia model. Using freshly isolated human bronchi and pulmonary arteries, neither ETX001 or Ani9 had any effect on the contractile or relaxant responses of the tissues. In vivo, ETX001 also failed to influence either lung or cardiovascular function when delivered directly into the airways of telemetered rats. Together, these studies do not support a role for TMEM16A in the regulation of goblet cell numbers or baseline mucin release, or on the regulation of airway or pulmonary artery smooth muscle contraction.
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BACKGROUND: Among adults undergoing contemporary noncardiac surgery, little is known about the frequency and timing of death and the associations between perioperative complications and mortality. We aimed to establish the frequency and timing of death and its association with perioperative complications. METHODS: We conducted a prospective cohort study of patients aged 45 years and older who underwent inpatient noncardiac surgery at 28 centres in 14 countries. We monitored patients for complications until 30 days after surgery and determined the relation between these complications and 30-day mortality using a Cox proportional hazards model. RESULTS: We included 40 004 patients. Of those, 715 patients (1.8%) died within 30 days of surgery. Five deaths (0.7%) occurred in the operating room, 500 deaths (69.9%) occurred after surgery during the index admission to hospital and 210 deaths (29.4%) occurred after discharge from the hospital. Eight complications were independently associated with 30-day mortality. The 3 complications with the largest attributable fractions (AF; i.e., potential proportion of deaths attributable to these complications) were major bleeding (6238 patients, 15.6%; adjusted hazard ratio [HR] 2.6, 95% confidence interval [CI] 2.2-3.1; AF 17.0%); myocardial injury after noncardiac surgery [MINS] (5191 patients, 13.0%; adjusted HR 2.2, 95% CI 1.9-2.6; AF 15.9%); and sepsis (1783 patients, 4.5%; adjusted HR 5.6, 95% CI 4.6-6.8; AF 12.0%). INTERPRETATION: Among adults undergoing noncardiac surgery, 99.3% of deaths occurred after the procedure and 44.9% of deaths were associated with 3 complications: major bleeding, MINS and sepsis. Given these findings, focusing on the prevention, early identification and management of these 3 complications holds promise for reducing perioperative mortality. Study registration: ClinicalTrials.gov, no. NCT00512109.