Stochastic Optimization via Forward Slice

Optimization consists of maximizing or minimizing a real-valued objective function. In many problems, the objective function may not yield closed-form solutions. Over many decades, optimization methods, both deterministic and stochastic, have been developed to provide solutions to these problems. However, some common limitations of these methods are the sensitivity to the initial value and that often current methods only find a local (non-global) extremum. In this article, we propose an alternative stochastic optimization method, which we call Forward Slice , and assess its performance relative to available optimization methods

TINJAUAN HUKUM ACARA PERDATA TERHADAP PENGAMBILAN KETERANGAN SAKSI DI PENGADILAN AGAMA ( STUDI KASUS DI PA KABUPATEN MALANG )

AbstractThis writing is motivated after reviewing the divorce case trial process in the religious court. when the judge calls two witnesses as evidence in the case of divorce simultaneously, but there are some judges who do not approve the matter of calling two witnesses together. So from the findings the authors found there were differences between the positive law in force regarding the procedure for hearing or taking witness statements in religious courts, especially in Malang district religious courts.The method  in this research is field research. This study aims to study intensively about the background and is carried out by going directly to the field to explore the data needed. The results of this study explain the ability to collect witnesses' information simultaneously. In general, the Panel of Judges is bound by legal evidence that is regulated in the Act. The evidence in accordance with the provisions of the Indonesian Civil Procedure Code. Among others: (1) evidence of letters (2) evidence of witnesses (3) evidence of alleged or prejudice (4) evidence of oaths. The law in theory is generally different in practice. The law is no longer as understood, which is more in accordance with its scope.Keywords: witness, religious court.

Long-Term Effectiveness of Adalimumab in Patients with Rheumatoid Arthritis: An Observational Analysis from the Corrona Rheumatoid Arthritis Registry

INTRODUCTION: Current recommendations for the management of rheumatoid arthritis (RA) focus on a treat-to-target approach with the objective of maximizing long-term health-related quality-of-life in patients with RA. Published studies from randomized clinical trials have reported limited data regarding the long-term efficacy and safety of adalimumab in patients with RA. This study aims to evaluate the long-term (10+ years) persistency and effectiveness of adalimumab in patients with RA in a real-world setting. METHODS: Included in this study were biologic-naive adults with RA initiating adalimumab during follow-up enrolled in the Corrona RA registry. More than 10 years of data on persistency of adalimumab and rheumatologist-supplied reasons for discontinuation were examined. Among patients who persisted on adalimumab over the years, clinical [e.g., clinical disease activity index scores (CDAI), physician global assessment, tender joint count, and swollen joint count] and patient-reported outcomes (PRO), such as physical function, pain, fatigue, and morning stiffness, were examined. RESULTS: Of 1791 biologic-naive patients treated with adalimumab who had \u3e /=1 follow-up registry visit, 64.1% were still on therapy at 1 year and 10.2% were still on therapy by the end of year 12. Among patients who persisted on adalimumab for at least 1 year (77.1% female, mean age 53.9 years), 67.0% were in low disease activity (LDA)/remission (CDAI \u3c /=10) and had clinically meaningful improvements from baseline in all clinical assessments and PROs. Initial improvements in LDA/remission and in clinical and PRO assessments observed at year 1 were sustained in those patients who remained on adalimumab over 10 years of follow-up. Among patients who discontinued adalimumab, 61.6% were not in LDA/remission and 41.9% switched to another biologic within 12 months after discontinuing adalimumab. CONCLUSIONS: Real-world data demonstrate a sustained effectiveness of adalimumab in the treatment of RA for patients who remained on therapy for 10 years. FUNDING: Corrona, LLC and AbbVie

Consensus Statement on Bone Conduction Devices and Active Middle Ear Implants in Conductive and Mixed Hearing Loss

Nowadays, several options are available to treat patients with conductive or mixed hearing loss. Whenever surgical intervention is not possible or contra-indicated, and amplification by a conventional hearing device (e.g., behind-the-ear device) is not feasible, then implantable hearing devices are an indispensable next option. Implantable bone-conduction devices and middle-ear implants have advantages but also limitations concerning complexity/invasiveness of the surgery, medical complications, and effectiveness. To counsel the patient, the clinician should have a good overview of the options with regard to safety and reliability as well as unequivocal technical performance data. The present consensus document is the outcome of an extensive iterative process including ENT specialists, audiologists, health-policy scientists, and representatives/technicians of the main companies in this field. This document should provide a first framework for procedures and technical characterization to enhance effective communication between these stakeholders, improving health care

How cigarette smoking may increase the risk of anxiety symptoms and anxiety disorders : a critical review of biological pathways

Multiple studies have demonstrated an association between cigarette smoking and increased anxiety symptoms or disorders, with early life exposures potentially predisposing to enhanced anxiety responses in later life. Explanatory models support a potential role for neurotransmitter systems, inflammation, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophins and neurogenesis, and epigenetic effects, in anxiety pathogenesis. All of these pathways are affected by exposure to cigarette smoke components, including nicotine and free radicals. This review critically examines and summarizes the literature exploring the role of these systems in increased anxiety and how exposure to cigarette smoke may contribute to this pathology at a biological level. Further, this review explores the effects of cigarette smoke on normal neurodevelopment and anxiety control, suggesting how exposure in early life (prenatal, infancy, and adolescence) may predispose to higher anxiety in later life. A large heterogenous literature was reviewed that detailed the association between cigarette smoking and anxiety symptoms and disorders with structural brain changes, inflammation, and cell-mediated immune markers, markers of oxidative and nitrosative stress, mitochondrial function, neurotransmitter systems, neurotrophins and neurogenesis. Some preliminary data were found for potential epigenetic effects. The literature provides some support for a potential interaction between cigarette smoking, anxiety symptoms and disorders, and the above pathways; however, limitations exist particularly in delineating causative effects. The literature also provides insight into potential effects of cigarette smoke, in particular nicotine, on neurodevelopment. The potential treatment implications of these findings are discussed in regards to future therapeutic targets for anxiety. The aforementioned pathways may help mediate increased anxiety seen in people who smoke. Further research into the specific actions of nicotine and other cigarette components on these pathways, and how these pathways interact, may provide insights that lead to new treatment for anxiety and a greater understanding of anxiety pathogenesis

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Stochastic Optimization and Subgroup Selection

Thesis (Ph.D.)--University of Washington, 2015An important area in statistics is that of experimental or study design. The most typical problem is that of finding the required sample size that meets specific goals such as controlling type I and II error rates at given levels. In most experiments, additional constraints may be imposed from both practical and technical perspectives. From the practical perspective, it is expensive, both in monetary and time scales, or even impossible, to perform experiments over all possible values that the design variables can take. Some approaches have been developed to design an experiment to achieve maximum information given the restrictions in sample size, known as `optimal designs'. In an optimal design, the design points are selected to maximize a pre-selected optimality criterion, and it can be done using optimization methods. In this work, we propose a method for stochastic optimization called “forward slice” and evaluate its performance relative to other optimization methods. We also demonstrate the use of our method in design problems. Specifically, our simulation studies indicate that the “forward slice” selects the global optimum more often than other optimization methods. Further, when applying the “forward slice” to design problems, our method performs well when obtaining locally D-optimal design points and achieves a higher median overall D-optimality compared to the design points obtained using an alternative algorithm. In addition to experimental design, optimality considerations also arise post-design and post-experiment. One such example is in the problem of subgroup selection in a clinical trial. Most studies are designed to address only the primary inferential questions. However, in many studies, it is also of interest to assess differential associations in subpopulations. We propose a decision-theoretic approach to subgroup analysis consisting of two stages: model selection and subgroup reporting. We assess and compare the performance of our proposed method with some traditional approaches for subgroup selection under different scenarios. Our simulation studies show that the performance of the decision-theoretic method is similar to that of testing an interaction followed by stratified analyses based on the results of the interaction test. In the selection of the subgroups, the proposed method favors reporting subgroups that exhibit larger treatment effect, are larger, and are simpler (less complex). We also observe a trade-off where approaches that tend to have a larger power for detecting a subpopulation may perform more poorly when the effect is in fact homogeneous in the overall population. In addition, the proposed method allows for incorporation of prior information in both the model selection and subgroup reporting stages which may increase power while keeping the type-I error controlled

From Retrofitting to Renewables: Navigating Energy Transition Pathways for European Residential Space Heating

Transformative actions are crucial across all sectors emitting greenhouse gases. Nonetheless, energy transition research to date displays a notable imbalance, with a larger emphasis on the supply side than on the demand side. The present study addresses this inequity by focusing on residential sector space heating demand, a frequently overlooked energy service that currently contributes substantially to global greenhouse gas emissions. Our primary objective is to pinpoint effective climate policies and space heating strategies that align with the EU’s ambitious targets for emission reduction. We employ the recently developed TIMES-Europe model to conduct a comprehensive analysis of the residential sector’s policy frameworks, technological advancements, and associated costs. This analysis aims to determine the measures necessary to meet ambitious climate objectives within the European context. To achieve this, we formulate four distinct scenarios, each representing varying levels of ambition and collaboration among EU member states, thereby providing insight into the pathways toward achieving these targets. By implementing current intended EU policies on the renovation of dwellings, we project a substantial reduction of at most 850 PJ, or, i.e., a 19% decrease, in yearly energy demand for space heating between 2020 and 2050. In contrast, if the recent pace of dwelling renovation within the EU were to continue, space heating energy savings from renovation would only amount to less than 400 PJ/yr (i.e., a 9% reduction) in the same period. In our more ambitious climate scenarios, phasing out fossil fuels leads to widespread electrification of the European residential sector, and by 2050, electricity from heat pumps and electric boilers accounts for over 68% of the total residential sector space heating demand. The outcomes of our study underline the importance of implementing the currently planned EU policies. We also demonstrate the necessity for collaboration among EU member states in order to attain the common European climate targets under the most effective resource allocation