Search

BACKGROUND/OBJECTIVES: The phase 3 REGAIN study and its open-label extension demonstrated the efficacy of the complement C5 inhibitor eculizumab in patients with treatment-refractory, acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG). The aim of the ELEVATE study was to assess the effectiveness of eculizumab in clinical practice in adults with MG in the United States. METHODS: A retrospective chart review was conducted in adults with MG who initiated eculizumab treatment between October 23, 2017 and December 31, 2019. Outcomes assessed before and during eculizumab treatment using a pre- versus post-treatment study design included Myasthenia Gravis-Activities of Daily Living (MG-ADL) total scores; minimal symptom expression (MSE); physician impression of clinical change; minimal manifestation status (MMS); and concomitant medication use. RESULTS: In total, 119 patients were included in the study. A significant reduction was observed in mean MG-ADL total score, from 8.0 before eculizumab initiation to 5.4 at 3 months and to 4.7 at 24 months after eculizumab initiation (both p

AbstractIn this study, we consider 2- and 3-step estimators for censored quantile regression models with fixed effects. In the first step of these estimators, the informative subset is determined through the estimation of censoring probability. While previous studies often employ symmetric link functions for estimating the censoring probability, these may not accurately identify the best subset when the distribution of the censoring probability is skewed. Given the prevalence of asymmetrically censored data in empirical analyses, we propose using an asymmetric link function for more accurate subset determination. We conduct Monte Carlo simulations and empirical analysis to assess our proposed methods. Our Monte Carlo simulations and empirical analysis confirm that an asymmetric link function offers a better fit for asymmetrically censored data. For symmetrically censored data, the symmetric link function performs better in moderate and large samples, while the asymmetric link function performs slightly better in small samples. These findings underscore the importance of considering both the censoring probability distribution and sample size in panel quantile regression. [ABSTRACT FROM AUTHOR]

Background: Clinical efficacy of zilucoplan has been demonstrated in a 12-week, placebo-controlled, phase III study in patients with acetylcholine receptor autoantibody-positive generalised myasthenia gravis (gMG). However, placebo-controlled zilucoplan data past 12 weeks are not available. Objectives: Predict the treatment effect of zilucoplan versus control (placebo or standard of care) in patients with gMG up to 24 weeks. Design: A model-informed analysis (MIA) within a Bayesian framework. Methods: Part 1 of the MIA comprised a control meta-regression using aggregate data on control response over time from randomised studies and a national myasthenia gravis (MG) registry. In Part 2, a combined Bayesian analysis of individual patient-level data from the phase II (NCT03315130), RAISE (NCT04115293) and RAISE-XT (NCT04225871) studies of zilucoplan was conducted using posterior distributions from Part 1 as informative priors. Population mean treatment effect in the change from baseline (CFB) at week 24 in MG-Activities of Daily Living (MG-ADL) and quantitative MG (QMG) scores for zilucoplan versus control were assessed. Results: At week 24, the predicted mean CFB in MG-ADL score was −4.55 (95% credible interval: −6.04, −3.13) with zilucoplan versus −2.00 (−3.35, −0.64) with control (difference: −2.55 [−3.76, −1.40]). The probability of a favourable treatment effect as measured by MG-ADL score at week 24 with zilucoplan versus control was >99.9%. There was an 82.8% probability that the difference in the predicted mean CFB in MG-ADL score at week 24 was greater than the clinically meaningful threshold (⩾2.0-point improvement). Comparable results were observed with QMG. Conclusion: This MIA demonstrates the maintenance of efficacy with zilucoplan versus control up to 24 weeks. Through combining real-world evidence with data from randomised studies, this novel method to estimate long-term treatment efficacy facilitated reduced exposure to placebo in the phase III RAISE study. This methodology could be used to reduce the length of future placebo-controlled studies. [ABSTRACT FROM AUTHOR]

Using survey data from Australia, this paper examines whether the economic relationship, complements versus substitutes, between cannabis and tobacco varies over the life cycle. They are often consumed as a ‘bundle,’ but using a range of approaches, we find compelling evidence that these goods are complements at younger ages and change to substitutes at older ages. The importance of these findings is illustrated by considering the likely impacts of tobacco price changes on cannabis consumption rates over the age spectrum. [ABSTRACT FROM AUTHOR]

Pozelimab, a monoclonal antibody directed against C5, is the first and only treatment for adult and pediatric patients (≥ 1 year) with CD55-deficient protein-losing enteropathy (CHAPLE) disease. A target-mediated drug disposition (TMDD) population pharmacokinetic (PopPK) model was developed using pooled data from four phase 1–3 studies to characterize the pharmacokinetics (PK) of total pozelimab and total C5, and to simulate free pozelimab and free C5 to support the dose regimen in patients with CHAPLE disease. A TMDD PopPK model was developed using total pozelimab and total C5 concentration–time data from 106 participants (82 healthy volunteers; 24 patients with paroxysmal nocturnal hemoglobinuria [PNH]). This model was refined and updated to include PK data from 10 patients with CHAPLE disease from a phase 2/3 study. Stochastic simulations predicted concentration–time profiles for total pozelimab, free pozelimab, and free C5, to obtain pozelimab exposure metrics for patients with CHAPLE disease. A two-compartment TMDD model with two binding sites based on the quasi-equilibrium approximation adequately described the concentration–time profiles of total pozelimab and total C5. Body weight was identified as the most important source of pozelimab PK variability; therefore, the dose was adjusted based on body weight for the predominantly pediatric patients with CHAPLE disease. A robust TMDD PopPK model was developed to describe the PK of total pozelimab and total C5 following pozelimab administration. Reliable predictions for individual exposures of total pozelimab and free C5 were possible and supported the 10 mg/kg weight-based dose regimen in patients with CHAPLE disease. [ABSTRACT FROM AUTHOR]

We investigate the socioeconomic determinants of early childhood development (ECD) in Türkiye, focusing on maternal education and household wealth, using representative microdata from the 2018 Türkiye Demographic and Health Survey (TDHS), which collected data on the developmental status of young children aged 36–59 months for the first time. Using this data, we construct an ECD index based on four developmental domains (i.e., literacy-numeracy, physical development, learning readiness and socio-emotional). Our results suggest that 74 percent of children (70.3 percent of boys and 78 percent of girls) are developmentally on track. We find that while over 96 percent of children are developmentally on track in physical and learning readiness domains, only 14.5 percent and 73.6 percent are in the literacy-numeracy and socio-emotional development domains, respectively. The multivariate regression results suggest both maternal education and household wealth improve children's ECD outcomes but the latter has a stronger effect. In fact, we find that mother's schooling is only positively and statistically associated with ECD once mothers have at least a high school education. Kindergarten attendance, which stands at a meagre 11.3 percent, is only likely for children from well-to-do and educated households. As a result, we find large gaps in ECD and its components between children with low and high socioeconomic backgrounds. We conclude that leveling the playing field is only possible via a nationwide multisectoral initiative that can support and educate caregivers and children simultaneously. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to examine the price and income elasticities of short- and long-run industrial electricity demand in Brazil between 2003 and 2020. The research also examines the impacts of COVID-19 in Brazil's industrial electricity sector, including an analysis in states more and less industrialized. Design/methodology/approach: Dynamic adjustments models in panel data are used to present robust estimates and analyze the impact of different methodologies on reported elasticities. Findings: The short-run price elasticity is estimated at −0.448, while the long-run values are around −1.60. Regarding income elasticity, the value is 0.069 in the short-run and is concentrated in 0.25 in the long-run. The inelastic results of income show that the industrial demand for electric energy follows the trend of loss of competitiveness of the Brazilian industry in the past years. In addition, the price of natural gas, the level of employment, and, in specific cases, the level of imports also influence industrial electricity demand. Originality/value: The research is a pioneer in the investigation of the industrial behavior of electricity of the Brazilian industrial branch, using as control variables, the average temperature, and the level of rainfall, this one, so important for a country whose main source is hydroelectric. In addition, to the best of the authors' knowledge, it is the first study, which is prepared to analyze the effects of COVID-19 on electric consumption in the industrial sector, investigating these impacts, including in the states considered more and less industrialized. The estimates generated may help in the design of the Brazilian energy policy. [ABSTRACT FROM AUTHOR]

Purpose: India is not geographically close to either Russia or Ukraine. However, India's trade relations with them make it vulnerable to the consequences of the war between these countries. Thus, the present study aims to examine the impact of the Russia–Ukraine war on various sectoral indices of the Indian economy. Design/methodology/approach: Event study methodology has been used in this study for analysis. The date of the war announcement is the event day. The sample studied includes ten sectors of the Indian economy listed on the National Stock Exchange (NSE). Results correspond to the period of −167 days to +20 days of the announcement of the war, i.e. from June 25, 2021, to March 28, 2022. Findings: Almost all the sample sectors earned significantly positive abnormal returns in the post-event period. The metal industry has led this group by showcasing the highest abnormal returns. Though Indian sectors made overall positive returns, the market soon corrected itself and abnormal returns were wiped out. Practical implications: These results can benefit portfolio managers, analysts, investors and policymakers in hedging risks and selecting suitable investments during increased global uncertainty. The study's conclusions help policymakers establish an institutional and supervisory framework that will make it easier to spot systematic risks and reduce them by putting countercyclical measures in place. Originality/value: India has no geographical proximity or trade relations with Russia or Ukraine, as strong as any other European country. However, Russia has remained a strong ally to India in the trade of defense equipment. Similar is the case with Ukraine, a significant global partner for India. Thus, the impact of conflict between these two countries has not been limited to Europe only but has also engulfed related economies. Hence, the present study is one of the first attempts to examine the burns sustained by the Indian economy due to this war. [ABSTRACT FROM AUTHOR]

Econometrics is a branch of economics that uses mathematical and statistical methods to study quantitative and qualitative relationships within economic phenomena. The purpose of this article is to study the impact of the capital market (financial instruments) on economic growth in Kazakhstan and the CIS countries through an understanding of the concept of “econometrics”. The task of the study is to determine the dependence of gross domestic product as a resultant factor over the past 20 years. Methods. The article determines the assessment of the impact of financial factors on economic growth in the short term. An econometric model was used for this purpose. The resulting factor was the gross domestic product over the past 20 years. Results. The results indicate that the capital market influences economic growth in Kazakhstan and the CIS countries. This paper presents a model of the GDP function for the economy of Kazakhstan. In the course of the study, coefficients and variables of the model were estimated to predict the level and future changes in the country’s GDP. Thus, the size of the capital market (Y1) depends on the following variables tested in the model: the number of securities issuance transactions; the volume of securities issuance transactions; the number of transactions of non-residents with shares at the secondary auction of KASE; the rate of change of shares of leading issuers on KASE

Adequate enterprise financial risk management (EFRM) represents a leading competitive advantage of enterprises that determines market survival and business success in an uncertain global environment. Over time, EFRM has become a constituent part of integral business dealings of enterprises and one of the strategic functions of enterprise management. The main purpose of the paper is to explore the effects of the EFRM function/system on the financial performance of enterprises in Bosnia and Herzegovina (BiH). The basic source of data in the research was collected by means of a structured questionnaire. The target population in the research consists of large enterprises that have continuously operated in the territory of BiH (2013-2017). The selection of enterprises was made applying a random sampling method and contains 72 enterprises. Appropriate descriptive and inferential statistical methods were used in the data analysis and panel data analysis was used to assess effects of EFRM function on financial performance. The scientific contribution of the paper is reflected in the fact that the research is pioneering for Bosnia and Herzegovina with the analysis of effects of the EFRM function on enterprise financial performance (EFP). The results show that there are no systematic, statistically significant differences between large enterprises that engage in risk management (‘hedgers’) and enterprises that do not engage in risk management (‘non-hedgers’) in BiH.

With the introduction of therapies to treat geographic atrophy (GA), GA management in clinical practice is now possible. A living systematic review can provide access to timely and robust evidence synthesis. This review found that complement factor 3 and 5 (C3 and C5) inhibition compared to sham likely reduces change in square root GA area at 12 months and untransformed GA area at 24 months. There is likely little to no difference in the rate of systemic treatment-emergent adverse events compared to sham. C3 and C5 inhibition, however, likely does not improve best-corrected visual acuity (BCVA) at 12 months, and the evidence is uncertain regarding change in BCVA at 24 months. Higher rates of ocular treatment emergent adverse effects with complement inhibition occur at 12 months and likely at 24 months. Complement inhibition likely results in new onset neovascular age-related macular degeneration at 12 months. This living meta-analysis will continuously incorporate new evidence. [ABSTRACT FROM AUTHOR]

The human adenovirus (HAdV) is a common pathogen in children that can cause acute respiratory virus infection (ARVI). However, the molecular epidemiological and clinical information relating to HAdV among hospitalized children with ARVI is rarely reported in Russia. A 4-year longitudinal (2019–2022) study among hospitalized children (0–17 years old) with ARVI in Novosibirsk, Russia, was conducted to evaluate the epidemiological and molecular characteristics of HAdV. Statistically significant differences in the detection rates of epidemiological and virological data of all positive viral detections of HAdV were analyzed using a two-tailed Chi-square test. The incidence of HAdV and other respiratory viruses such as human influenza A and B viruses, respiratory syncytial virus, coronavirus, parainfluenza virus, metapneumovirus, rhinovirus, bocavirus, and SARS-CoV-2 was investigated among 3190 hospitalized children using real-time polymerase chain reaction. At least one of these respiratory viruses was detected in 74.4% of hospitalized cases, among which HAdV accounted for 4%. A total of 1.3% co-infections with HAdV were also registered. We obtained full-genome sequences of 12 HAdVs, which were isolated in cell cultures. Genetic analysis revealed the circulation of adenovirus of genotypes C1, C2, C5, C89, and 108 among hospitalized children in the period from 2019–2022. [ABSTRACT FROM AUTHOR]

Energy production plays a major role in the Saudi Arabian economy, but energy production can lead to an increase in environmental pollution.

Climate change and its impact on economic growth or vice versa is an important burning issue in the present world and therefore the present world and its population, especially in West Africa, are bound to face various calamities in recent times and the excessive emission of carbon (1.8 per cent of total carbon emission by the world’s emission) is one of the important reasons behind it. Therefore, it is very important to examine the relationship between carbon emissions and economic growth in the region and for this, the present article is focusing over some selected countries of Economic Community of West African States (ECOWAS) and therefore the 10 ECOWAS countries are selected randomly, out of 15 ECOWAS countries and 32 years of data from 1991-2022 are utilized which is sourced from World Development Indicators (WDI), World Bank and Central Bank of Nigeria (CBN) Bulletins. A panel data regression technique employed for the analysis of data. The Fixed Effect Model (FEM) estimates indicates that the out of eight explanatory variables four are negatively associated with Co2 emissions and one is statistically significant while other three are insignificant statistically. The Random Effect Model (REM) estimates pointed out that the out of eight independent variables three are having negative effects over the Co2 emission and five are having positive impact over the emissions. Therefore, the study perceived that emission of Co2, Gross Domestic Product (GDP) and industrial growth are not enough to lead the climate change in the region.

This study investigates the role of renewable and non-renewable energy sources in exports performance of 18 emerging economies from 2000 to 2020. This is done to better elucidate the potential implications of energy transition on the export performance of emerging economies. The estimated models also control for the influences of per capita income, population, and government effectiveness. The Westerlund cointegration confirms the presence of a significant long-run relationship between the variables under consideration. In this regard, two-step System Generalized Method of Moments (GMM) estimation demonstrates that non-renewable energy consumption promotes exports in emerging economies and renewable energy use hampers it in the long run. At the same time, increase in per-capita income and population size negatively influence the exports. On the other hand, though insignificant, government effectiveness contributes positively to the export performance. The Kernel Regularized Least Squares (KRLS) estimation also confirms the reliability of these baseline findings. Potential policy suggestions for the export promotion of emerging economies are also discussed. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a prevalent cause of vision impairment, affecting millions worldwide. This chronic condition encompasses two main forms: non-exudative (dry) AMD and exudative (wet) AMD. Dry AMD, characterized by the accumulation of drusen and alterations in the retinal pigment epithelium, can evolve into geographic atrophy (GA), culminating in irreversible vision impairment. Despite its considerable impact, therapeutic options for GA were historically constrained until recent advancements emerged. This comprehensive review underscores the pivotal role of the complement system in the pathogenesis of GA. Recent breakthroughs in AMD management have introduced innovative therapeutic modalities targeting complement factors, notably pegcetacoplan and avacincaptad pegol, both of which have garnered FDA approval. These agents have exhibited efficacy in decelerating the growth of GA lesions, offering a promising avenue for GA treatment. Additionally, we delve into past and ongoing clinical trials investigating supplementary complement inhibitors, including IONIS-FB-LRx, NGM621, ANX007, danicopan and AVD-104, highlighting their potential to shape future research endeavours and treatment paradigms. Challenges such as dosing frequency, the risk of neovascular conversion, and interindividual variability in treatment response underscore the imperative for ongoing research and the refinement of therapeutic strategies. While further investigations are warranted to delineate optimal treatment regimens and address extant challenges, the development of complement inhibitors represent a promising stride toward preserving vision and enhancing outcomes for individuals afflicted by this debilitating condition. [ABSTRACT FROM AUTHOR]

This paper estimated a monetary policy rule for Nigeria by augmenting the traditional Taylor rule model, using data spanning 2010Q1 to 2023Q2 in a Dynamic Ordinary Least Square regression. The results from competing models – the Taylor rule and extended Taylor rule (exchange rate augmented) – were subjected to forecast evaluation to ascertain their relative predictive power. Same models were estimated for South Africa for the purposes of comparison, and the results were consistent with Nigeria's. The findings indicate the predictors of the policy rate – monetary policy inertia, inflation, output gap and exchange rate – to be significant and with the expected signs. Forecast evaluation of the estimated extended Taylor rule model produced lower Root Mean Square Error (RMSE) and Theil statistics, compared with the traditional Taylor rule model, reflecting the higher predictive power of the former. The baseline and unequally-weighted two-quarter-ahead forecast of the extended model predicts a maximum inflation rate of 20.77 % and 21.04 % in 2023Q3 and 2023Q4, respectively, suggesting lower inflationary episode for Nigeria. The implication of the finding is that the extant monetary policy rule based on the traditional Taylor rule is inadequate in setting the nominal interest rate by the Central Bank of Nigeria, and recommends the adoption of the extended Taylor rule to enhance the effectiveness of monetary policy in Nigeria.

The main mechanism of innate immunity is the complement system. Its components include the protein products of the C1R and C5 genes, which are involved in the classical activation pathway as well as the inflammatory and cytolytic immune responses, respectively. The aim of this study was to determine the relationship between PCR-restriction fragment length polymorphism in C1R (726T > C) and C5 (1044A > C) genes, and the values of hematological and biochemical blood indices in suckling crossbred (Polish Large White × Polish Landrace × Duroc × Pietrain) piglets (n = 473), considering their age (younger, 21 ± 3 days, n = 274; older, 35 ± 3 days, n = 199) and health status. The frequencies of the C5 genotypes deviated from the Hardy–Weinberg expectations. Younger piglets, healthy piglets, piglets that deviated from physiological norms and older piglets with the C1R TT genotype all had lower white and red blood cell indices. In piglets with the C5 CC genotype, younger piglets, piglets that deviated from physiological norms and older piglets, a greater number and/or percentage of monocytes were recorded in the blood. Older piglets also showed an increase in the number of leukocytes and granulocytes, along with a tendency for a decrease in the percentage of lymphocytes in their blood. We concluded that a polymorphism in the C1R gene may exhibit a functional association or genetic linkage with other genes involved in the process of erythropoiesis. Furthermore the relationship between the C5 gene polymorphism and the number and/or percentage of monocytes in the blood may modify the body's defense abilities. Piglets with the CC genotype, having an increased number/proportion of these cells in their blood, probably display a weakened immune response to pathogens or a chronic stimulation of the immune system. [ABSTRACT FROM AUTHOR]

Employing a recently developed panel econometric technique, first, we show that accounting for spatial dependence and heterogeneity yields more accurate risk factor coefficients and abnormal housing returns. Rather than systematic risks, idiosyncratic risks explain the variations in residential housing excess returns. After controlling for asset-specific and systematic risk factors, the positive and significant impact of the unobservable common factors on the excess returns suggests that speculative market forces drive the housing excess returns. Second, we then analyze the risks and returns of houses in affordable and expensive submarkets allowing for spatial dependence and heterogeneity. We find that houses in the affordable submarkets perform better than houses in the expensive submarkets. Thus, the potential demand for houses in the affordable submarket may aggravate the housing affordability crisis. Our study's results, therefore, encourage policymakers and investors to view the housing market as a collection of regional units and submarkets, but not as a single national market. [ABSTRACT FROM AUTHOR]

Myasthenia gravis is a prototypic neuroimmune disorder with autoantibodies targeting the acetylcholine receptor complex at the neuromuscular junction. Patients present with mainly ocular muscle weakness and tend to have a generalized muscle weakness later in the clinical course. The weakness can be severe and fatal when bulbar muscles are heavily involved. Acetylcholine receptor antibodies are present in the majority of patients and are of IgG1 and IgG3 subtypes which can activate the complement system. The complement involvement plays a major role in the neuromuscular junction damage and the supporting evidence in the literature is described in this article. Complement therapies were initially studied and approved for paroxysmal nocturnal hemoglobinuria and in the past decade, those have also been studied in myasthenia gravis. The currently available randomized control trial and real-world data on the efficacy and safety of the approved and investigational complement therapies are summarized in this review. [ABSTRACT FROM AUTHOR]

Allergic conditions are associated with canonical and noncanonical activation of the complement system leading to the release of several bioactive mediators with inflammatory and immunoregulatory properties that regulate the immune response in response to allergens during the sensitization and/or the effector phase of allergic diseases. Further, immune sensors of complement and regulator proteins of the cascade impact on the development of allergies. These bioactive mediators comprise the small and large cleavage fragments of C3 and C5. Here, we provide an update on the multiple roles of immune sensors, regulators, and bioactive mediators of complement in allergic airway diseases, food allergies, and anaphylaxis. A particular emphasis is on the anaphylatoxins C3a and C5a and their receptors, which are expressed on many of the effector cells in allergy such as mast cells, eosinophils, basophils, macrophages, and neutrophils. Also, we will discuss the multiple pathways, by which the anaphylatoxins initiate and control the development of maladaptive type 2 immunity including their impact on innate lymphoid cell recruitment and activation. Finally, we briefly comment on the potential to therapeutically target the complement system in different allergic conditions. [ABSTRACT FROM AUTHOR]

The present study examines import determinants of Pakistan with the top 28 trade partners from 2002 to 2018. To achieve this objective, the augmented gravity model of trade has been applied by incorporating both time-variant and time-invariant variables. In addition, the analysis quantifies the impact of free trade agreements (FTA) signed by Pakistan with China and other trade partners. The results show that along with income and distance, FTA, common language, and common border plays an essential role in imports of Pakistan with its main trade partners. In addition to identifying trade determinants, the impact of adherence to a particular trade agreement was also examined. The results indicate that FTA signed by Pakistan with China and other trade partners has created trade opportunities for participating countries, highlighting the importance of trade liberalization for the long-run development of the country.