scholarly journals A computational approach to aid clinicians in selecting anti-viral drugs for COVID-19 trials

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aanchal Mongia ◽  
Sanjay Kr. Saha ◽  
Emilie Chouzenoux ◽  
Angshul Majumdar
Keyword(s):  
Computational Models ◽  
Genomic Structure ◽  
Matrix Completion ◽  
Ongoing Research ◽  
Long Run ◽  
Experimental Protocols ◽  
Standard Set ◽  
Tenofovir Alafenamide ◽  
The Right ◽  
Similarity Information

AbstractThe year 2020 witnessed a heavy death toll due to COVID-19, calling for a global emergency. The continuous ongoing research and clinical trials paved the way for vaccines. But, the vaccine efficacy in the long run is still questionable due to the mutating coronavirus, which makes drug re-positioning a reasonable alternative. COVID-19 has hence fast-paced drug re-positioning for the treatment of COVID-19 and its symptoms. This work builds computational models using matrix completion techniques to predict drug-virus association for drug re-positioning. The aim is to assist clinicians with a tool for selecting prospective antiviral treatments. Since the virus is known to mutate fast, the tool is likely to help clinicians in selecting the right set of antivirals for the mutated isolate. The main contribution of this work is a manually curated database publicly shared, comprising of existing associations between viruses and their corresponding antivirals. The database gathers similarity information using the chemical structure of drugs and the genomic structure of viruses. Along with this database, we make available a set of state-of-the-art computational drug re-positioning tools based on matrix completion. The tools are first analysed on a standard set of experimental protocols for drug target interactions. The best performing ones are applied for the task of re-positioning antivirals for COVID-19. These tools select six drugs out of which four are currently under various stages of trial, namely Remdesivir (as a cure), Ribavarin (in combination with others for cure), Umifenovir (as a prophylactic and cure) and Sofosbuvir (as a cure). Another unanimous prediction is Tenofovir alafenamide, which is a novel Tenofovir prodrug developed in order to improve renal safety when compared to its original counterpart (older version) Tenofovir disoproxil. Both are under trail, the former as a cure and the latter as a prophylactic. These results establish that the computational methods are in sync with the state-of-practice. We also demonstrate how the drugs to be used against the virus would vary as SARS-Cov-2 mutates over time by predicting the drugs for the mutated strains, suggesting the importance of such a tool in drug prediction. We believe this work would open up possibilities for applying machine learning models to clinical research for drug-virus association prediction and other similar biological problems.

Hypothesis testing with error correction models

2021 ◽  
pp. 1-9
Author(s):  
Patrick W. Kraft ◽  
Ellen M. Key ◽  
Matthew J. Lebo
Keyword(s):  
Hypothesis Testing ◽  
Error Correction ◽  
Null Hypothesis ◽  
Alternative Hypothesis ◽  
Correction Coefficient ◽  
Correction Model ◽  
Long Run ◽  
Independent Variable ◽  
The Right ◽  
General Error

Abstract Grant and Lebo (2016) and Keele et al. (2016) clarify the conditions under which the popular general error correction model (GECM) can be used and interpreted easily: In a bivariate GECM the data must be integrated in order to rely on the error correction coefficient, $\alpha _1^\ast$ , to test cointegration and measure the rate of error correction between a single exogenous x and a dependent variable, y. Here we demonstrate that even if the data are all integrated, the test on $\alpha _1^\ast$ is misunderstood when there is more than a single independent variable. The null hypothesis is that there is no cointegration between y and any x but the correct alternative hypothesis is that y is cointegrated with at least one—but not necessarily more than one—of the x's. A significant $\alpha _1^\ast$ can occur when some I(1) regressors are not cointegrated and the equation is not balanced. Thus, the correct limiting distributions of the right-hand-side long-run coefficients may be unknown. We use simulations to demonstrate the problem and then discuss implications for applied examples.

scholarly journals Actuarial deductions for early retirement

2021 ◽  
pp. 1-27
Author(s):  
Markus Knell
Keyword(s):  
Early Retirement ◽  
Pension System ◽  
Budget Constraint ◽  
Retirement Age ◽  
Single Individual ◽  
Internal Rate Of Return ◽  
Market Interest Rate ◽  
Long Run ◽  
Retirement Behavior ◽  
The Right

Abstract This paper studies how the rates of deduction for early retirement have to be determined in pay-as-you-go (PAYG) systems in order to keep their budget stable. The derivation of these deductions requires the use of a multiperiod intertemporal budget constraint that involves assumptions about the retirement behavior of past, present, and future cohorts. In general, it is not possible to calculate budget-neutral deductions from the budget constraint of a single individual who retires before the target retirement age—an approach that dominates the related literature. Only for specific cases one can use this second approach but then one has to adjust the discount rate to the assumption about collective retirement. If there is only one deviating individual, then the right choice is the market interest rate while for a stationary retirement distribution it is the internal rate of return of the PAYG system. In this case, the necessary deductions are lower than under the standard approach. This is also true for retirement ages that fluctuate randomly around a stationary distribution. Various long-run developments (e.g., increases in life expectancy or permanent changes in the average retirement age) might cause challenges for the sustainability of the pension system. These developments, however, can only be dealt with by adequate adjustments to the basic pension formulas and not by the use of deduction rates.

scholarly journals Designing Work with People Living with Dementia: Reflecting on a Decade of Research

2021 ◽  
Vol 18 (22) ◽  
pp. 11742
Author(s):  
Paul A. Rodgers
Keyword(s):  
Human Rights ◽  
United Nations ◽  
Cultural Development ◽  
General Assembly ◽  
International Human Rights Law ◽  
Ongoing Research ◽  
Right To Work ◽  
Health And Social Care ◽  
The United Nations ◽  
The Right

The United Nations Universal Declaration of Human Rights is widely acknowledged as a landmark document in the history of human rights. Drafted by representatives from all over the world, the declaration was proclaimed by the United Nations General Assembly in Paris on 10 December 1948 (General Assembly resolution 217 A) as a common standard for all peoples and all nations. The declaration sets out a series of articles that articulate a number of fundamental human rights to be universally protected. Article 23 of the declaration relates to the right to work and states that people have a human right to work, or engage in productive employment, and may not be prevented from doing so. The right to work is enshrined in international human rights law through its inclusion in the International Covenant on Economic, Social and Cultural Rights, where the right to work emphasizes economic, social and cultural development. This paper presents ongoing research that highlights how a disruptive co-design approach contributes to upholding UN Article 23 through the creation of a series of innovative working practices developed with people living with dementia. The research, undertaken in collaboration with several voluntary and third sector organizations in the UK, looks to break the cycle of prevailing opinions, traditional mindsets, and ways-of-doing that tend to remain uncontested in the health and social care of people living with dementia. As a result, this research has produced a series of innovative work opportunities for people living with dementia and their formal and informal carers that change the perception of dementia by showing that people living with dementia are capable of designing and making desirable products and offering much to UK society after diagnosis. In this ongoing research, the right to continue to work for people living with dementia post-diagnosis in creative and innovative ways has clearly helped to reconnect them to other people, helped build their self-esteem, identity and dignity and helped keep the person with dementia connected to their community, thus delaying the need for crisis interventions. This paper reports on a series of future work initiatives for people living with dementia where we have used design as a disruptive force for good to ensure that anyone diagnosed with dementia can exercise their right to work and engage in productive and rewarding employment.

scholarly journals ETMR-07. ETANTR: A RARE TUMOR IN A RESOURCE-LIMITED SETTING

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii324-iii324
Author(s):  
Julieta Hoveyan ◽  
Manushak Avagyan ◽  
Anna Avagyan ◽  
Ruzanna Papyan ◽  
Samvel Iskanyan ◽  
...  
Keyword(s):  
Survival Rates ◽  
Tumor Resection ◽  
Large Mass ◽  
Intrathecal Methotrexate ◽  
High Dose ◽  
Ongoing Research ◽  
Resource Limited ◽  
The Right ◽  
Immunohistochemical Analyses ◽  
Limited Setting

Abstract INTRODUCTION Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a rare aggressive brain tumor with low survival rates. There are about 80 cases reported in literature since 2000 when it was first described. There is no standard treatment scheme for ETANTR yet. CASE REPORT: A 2 years old boy presented with a month-long of headache and inability to hold his head. CT scan and MRI revealed a large mass in the right frontal lobe with midline shift. Subtotal tumor resection was done. Histological and immunohistochemical analyses was consistent with ETANTR in one laboratory and PNET in another. The second opinion suggested by the Center of Pediatric Oncology, Hematology and Immunology in Moscow the diagnosis ETANTR was confirmed. Taking into account certain similarities with medulloblastoma was decided to provide treatment according to HIT-2014 protocol. Control MRI done after 2 cycles of Block SKK Carboplatin/Etoposide found tumor progression and for that reason patient underwent second surgical resection. Considering the age of the child radiation therapy was not expedient and the decision was to continue treatment with HIT 2014 intensified regimen, which includes Cisplatin, Vincristine, Etoposide, Cyclophosphamide and intravenous High dose Methotrexate with intrathecal Methotrexate. Aiming to evaluate the effectiveness of treatment we are planning to perform MRI after this 2nd cycle of intensified regimen. DISCUSSION There are difficulties in diagnosis of rare types of cancers in Armenia. Since there is no approved treatment for ETANTR, there is a need for ongoing research to improve its prognosis.

Consumption, aggregate wealth and expected stock returns: a quantile cointegration approach

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ricardo Quineche
Keyword(s):  
Stock Returns ◽  
The United States ◽  
Labor Income ◽  
Left Tail ◽  
Long Run ◽  
Short Run ◽  
Excess Stock Returns ◽  
Aggregate Wealth ◽  
Risk Free Rate ◽  
The Right

Abstract This paper empirically examines the long-run relationship between consumption, asset wealth and labor income (i.e., cay) in the United States through the lens of a quantile cointegration approach. The advantage of using this approach is that it allows for a nonlinear relationship between these variables depending on the level of consumption. We estimate the coefficients using a Phillips–Hansen type fully modified quantile estimator to correct for the presence of endogeneity in the cointegrating relationship. To test for the null of cointegration at each quantile, we apply a quantile CUSUM test. Results show that: (i) consumption is more sensitive to changes in labor income than to changes in asset wealth for the entire distribution of consumption, (ii) the elasticity of consumption with respect to labor income (asset wealth) is larger at the right (left) tail of the consumption distribution than at the left (right) tail, (iii) the series are cointegrated around the median, but not in the tails of the distribution of consumption, (iv) using the estimated cay obtained for the right (left) tail of the distribution of consumption improves the long-run (short-run) forecast ability on real excess stock returns over a risk-free rate.

Who Ya Gonna Call? The Police as Problem-Busters

1987 ◽  
Vol 33 (1) ◽  
pp. 31-52 ◽  
Author(s):  
John E. Eck ◽  
William Spelman
Keyword(s):  
Community Policing ◽  
Crime Control ◽  
Police Departments ◽  
Public And Private ◽  
Long Run ◽  
Underlying Causes ◽  
Standard Set ◽  
Problem Oriented Policing ◽  
The City

Current police practice is dominated by two, competing strategies—“community policing” and “crime control policing.” Both are limited: they each apply a standard set of police tactics to a wide variety of differing circumstances; they focus on incidents, rather than the underlying problems which cause these incidents. Recently, two police departments have developed an alternative. Through “problem-oriented policing,” officers focus on these underlying causes. They collect information from numerous sources, and enlist the support of a wide variety of public and private agencies and individuals in their attempts to solve problems. Case studies in these departments show that use of the problem-oriented approach can substantially reduce crime and fear. In the long run, problem-oriented policing will require changes in management structure, the role of the police in the community and the city bureaucracy, and the limits of police authority.

Review of Cardiac Pacemaker Lead Designs for Computational Models in a VR Environment

2017 ◽  
Author(s):  
Bethany Tourek ◽  
Dan Orban ◽  
Lingyu Meng ◽  
Hakizumwami Birali Runesha ◽  
Dan Keefe ◽  
...  
Keyword(s):  
Computational Models ◽  
Cardiac Pacemaker ◽  
Model Complexity ◽  
Element Analysis ◽  
Parameterized Design ◽  
Pacemaker Leads ◽  
Computational Fluid Dynamics Cfd ◽  
The Right ◽  
Implantable Cardiac Pacemaker ◽  
Computational Resources

An implantable cardiac pacemaker is used to modify and treat irregular heartbeats [1] and invented in 1958 [2]. Devices have no fixation or fixed to the heart wall. No fixation leads lay in the bottom of heart cavities, while fixed leads have tines (passive) or a helix screw (active) to attach to the heart. Lead geometries and material properties vary between companies, with geometric sizing based primarily on the internal mechanics of the lead. Finite element analysis (FEA), computational fluid dynamics (CFD) and bench-top simulations are used to evaluate cardiac leads. These simulations analyze only one lead and struggle to compare and test variations in lead designs. Advanced computational resources can run many computer simulations of anatomical environments, however model complexity increases the time to run each simulation. To address this issue, we present a simplified parameterized design space for cardiac pacemaker leads in the right atrium. This information will be used to run multiple simulations of leads in blood flow, for visualization in a single virtual reality (VR) environment and allow the designer to iterate through many design variations (See Figure 1).

scholarly journals Behavioral and electrophysiological auditory processing measures in traumatic brain injury after acoustically controlled auditory training: a long-term study

2015 ◽  
Vol 13 (4) ◽  
pp. 535-540 ◽  
Author(s):  
Carolina Calsolari Figueiredo ◽  
Adriana Neves de Andrade ◽  
Andréa Tortosa Marangoni-Castan ◽  
Daniela Gil ◽  
Italo Capraro Suriano
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Auditory Processing ◽  
Behavioral Assessment ◽  
Auditory Training ◽  
Long Term Study ◽  
Long Run ◽  
One Year ◽  
The Right

ABSTRACT Objective To investigate the long-term efficacy of acoustically controlled auditory training in adults after tarumatic brain injury. Methods A total of six audioogically normal individuals aged between 20 and 37 years were studied. They suffered severe traumatic brain injury with diffuse axional lesion and underwent an acoustically controlled auditory training program approximately one year before. The results obtained in the behavioral and electrophysiological evaluation of auditory processing immediately after acoustically controlled auditory training were compared to reassessment findings, one year later. Results Quantitative analysis of auditory brainsteim response showed increased absolute latency of all waves and interpeak intervals, bilaterraly, when comparing both evaluations. Moreover, increased amplitude of all waves, and the wave V amplitude was statistically significant for the right ear, and wave III for the left ear. As to P3, decreased latency and increased amplitude were found for both ears in reassessment. The previous and current behavioral assessment showed similar results, except for the staggered spondaic words in the left ear and the amount of errors on the dichotic consonant-vowel test. Conclusion The acoustically controlled auditory training was effective in the long run, since better latency and amplitude results were observed in the electrophysiological evaluation, in addition to stability of behavioral measures after one-year training.

scholarly journals Improved Prediction of miRNA-Disease Associations Based on Matrix Completion with Network Regularization

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 881 ◽  
Author(s):  
Jihwan Ha ◽  
Chihyun Park ◽  
Chanyoung Park ◽  
Sanghyun Park
Keyword(s):  
Computational Models ◽  
Matrix Completion ◽  
Area Under The Curve ◽  
Excellent Performance ◽  
Novel Mirna ◽  
Lack Of Information ◽  
Disease Associations ◽  
Roc Area ◽  
Leave One Out ◽  
Global And Local

The identification of potential microRNA (miRNA)-disease associations enables the elucidation of the pathogenesis of complex human diseases owing to the crucial role of miRNAs in various biologic processes and it yields insights into novel prognostic markers. In the consideration of the time and costs involved in wet experiments, computational models for finding novel miRNA-disease associations would be a great alternative. However, computational models, to date, are biased towards known miRNA-disease associations; this is not suitable for rare miRNAs (i.e., miRNAs with a few known disease associations) and uncommon diseases (i.e., diseases with a few known miRNA associations). This leads to poor prediction accuracies. The most straightforward way of improving the performance is by increasing the number of known miRNA-disease associations. However, due to lack of information, increasing attention has been paid to developing computational models that can handle insufficient data via a technical approach. In this paper, we present a general framework—improved prediction of miRNA-disease associations (IMDN)—based on matrix completion with network regularization to discover potential disease-related miRNAs. The success of adopting matrix factorization is demonstrated by its excellent performance in recommender systems. This approach considers a miRNA network as additional implicit feedback and makes predictions for disease associations relevant to a given miRNA based on its direct neighbors. Our experimental results demonstrate that IMDN achieved excellent performance with reliable area under the receiver operating characteristic (ROC) area under the curve (AUC) values of 0.9162 and 0.8965 in the frameworks of global and local leave-one-out cross-validations (LOOCV), respectively. Further, case studies demonstrated that our method can not only validate true miRNA-disease associations but also suggest novel disease-related miRNA candidates.

scholarly journals The wrong track also leads someplace: Milton Friedman's presidential address at 50

2018 ◽  
Vol 6 (4) ◽  
pp. 517-532 ◽  
Author(s):  
Servaas Storm
Keyword(s):  
Phillips Curve ◽  
Presidential Address ◽  
Aggregate Demand ◽  
Financial Fragility ◽  
American Economic Association ◽  
Structural Forces ◽  
Long Run ◽  
Economic Association ◽  
The Right ◽  
Do So

Milton Friedman's presidential address to the American Economic Association holds a mythical status as the harbinger of the supply-side counter-revolution in macroeconomics – centred on the rejection of the long-run Phillips-curve inflation–unemployment trade-off. Friedman (seconded by Edmund Phelps) argued that the long run is determined by ‘structural’ forces, not demand, and his view swept the profession and dominated academic economics and macro policymaking for four decades. Friedman, tragically, put macroeconomics on the wrong track which led to disaster: secular stagnation, rising inequality, mounting indebtedness, financial fragility, a banking catastrophe and recession – and no free lunches. This is Friedman's legacy. We have to unlearn the wrong lessons and return macroeconomics to the right track. To do so, this paper shows that Friedman's (and Phelps's) conclusions break down in a general model of the long run in which productivity growth is endogenous – aggregate demand is driving everything again, short and long.

Sign in / Sign up

Export Citation Format

Share Document