Maximizing in vivo target clearance by design of pH-dependent target binding antibodies with altered affinity to FcRn.

PubMed

Yang, Danlin; Giragossian, Craig; Castellano, Steven; Lasaro, Marcio; Xiao, Haiguang; Saraf, Himanshu; Hess Kenny, Cynthia; Rybina, Irina; Huang, Zhong-Fu; Ahlberg, Jennifer; Bigwarfe, Tammy; Myzithras, Maria; Waltz, Erica; Roberts, Simon; Kroe-Barrett, Rachel; Singh, Sanjaya

2017-10-01

Antibodies with pH-dependent binding to both target antigens and neonatal Fc receptor (FcRn) provide an alternative tool to conventional neutralizing antibodies, particularly for therapies where reduction in antigen level is challenging due to high target burden. However, the requirements for optimal binding kinetic framework and extent of pH dependence for these antibodies to maximize target clearance from circulation are not well understood. We have identified a series of naturally-occurring high affinity antibodies with pH-dependent target binding properties. By in vivo studies in cynomolgus monkeys, we show that pH-dependent binding to the target alone is not sufficient for effective target removal from circulation, but requires Fc mutations that increase antibody binding to FcRn. Affinity-enhanced pH-dependent FcRn binding that is double-digit nM at pH 7.4 and single-digit nM at pH 6 achieved maximal target reduction when combined with similar target binding affinities in reverse pH directions. Sustained target clearance below the baseline level was achieved 3 weeks after single-dose administration at 1.5 mg/kg. Using the experimentally derived mechanistic model, we demonstrate the essential kinetic interplay between target turnover and antibody pH-dependent binding during the FcRn recycling, and identify the key components for achieving maximal target clearance. These results bridge the demand for improved patient dosing convenience with the "know-how" of therapeutic modality by design.

Maximizing Student Achievement: Using Student-Centered Learning

ERIC Educational Resources Information Center

Johnson, William L.; Johnson, Annabel M.; Johnson, Jared W.

2017-01-01

The document is from a featured presentation at the 2017 annual conference of the Science Teachers Association of Texas (STAT) in Houston, Texas, November 9-11, 2017. When educators discuss student achievement, it is rare not to hear names like Robert Marzano and John Hattie. Both have clear, specific, and concrete strategies teachers can use to…

The Achievement of Therapeutic Objectives Scale: Interrater Reliability and Sensitivity to Change in Short-Term Dynamic Psychotherapy and Cognitive Therapy

ERIC Educational Resources Information Center

Valen, Jakob; Ryum, Truls; Svartberg, Martin; Stiles, Tore C.; McCullough, Leigh

2011-01-01

This study examined interrater reliability and sensitivity to change of the Achievement of Therapeutic Objectives Scale (ATOS; McCullough, Larsen, et al., 2003) in short-term dynamic psychotherapy (STDP) and cognitive therapy (CT). The ATOS is a process scale originally developed to assess patients' achievements of treatment objectives in STDP,…

Maximal coherence and the resource theory of purity

NASA Astrophysics Data System (ADS)

Streltsov, Alexander; Kampermann, Hermann; Wölk, Sabine; Gessner, Manuel; Bruß, Dagmar

2018-05-01

The resource theory of quantum coherence studies the off-diagonal elements of a density matrix in a distinguished basis, whereas the resource theory of purity studies all deviations from the maximally mixed state. We establish a direct connection between the two resource theories, by identifying purity as the maximal coherence which is achievable by unitary operations. The states that saturate this maximum identify a universal family of maximally coherent mixed states. These states are optimal resources under maximally incoherent operations, and thus independent of the way coherence is quantified. For all distance-based coherence quantifiers the maximal coherence can be evaluated exactly, and is shown to coincide with the corresponding distance-based purity quantifier. We further show that purity bounds the maximal amount of entanglement and discord that can be generated by unitary operations, thus demonstrating that purity is the most elementary resource for quantum information processing.

Formation Control for the Maxim Mission.

NASA Technical Reports Server (NTRS)

Luquette, Richard J.; Leitner, Jesse; Gendreau, Keith; Sanner, Robert M.

2004-01-01

Over the next twenty years, a wave of change is occurring in the spacebased scientific remote sensing community. While the fundamental limits in the spatial and angular resolution achievable in spacecraft have been reached, based on today's technology, an expansive new technology base has appeared over the past decade in the area of Distributed Space Systems (DSS). A key subset of the DSS technology area is that which covers precision formation flying of space vehicles. Through precision formation flying, the baselines, previously defined by the largest monolithic structure which could fit in the largest launch vehicle fairing, are now virtually unlimited. Several missions including the Micro-Arcsecond X-ray Imaging Mission (MAXIM), and the Stellar Imager will drive the formation flying challenges to achieve unprecedented baselines for high resolution, extended-scene, interferometry in the ultraviolet and X-ray regimes. This paper focuses on establishing the feasibility for the formation control of the MAXIM mission. The Stellar Imager mission requirements are on the same order of those for MAXIM. This paper specifically addresses: (1) high-level science requirements for these missions and how they evolve into engineering requirements; (2) the formation control architecture devised for such missions; (3) the design of the formation control laws to maintain very high precision relative positions; and (4) the levels of fuel usage required in the duration of these missions. Specific preliminary results are presented for two spacecraft within the MAXIM mission.

Therapeutic effects of maximal strength training on walking efficiency in patients with schizophrenia - a pilot study.

PubMed

Heggelund, Jørn; Morken, Gunnar; Helgerud, Jan; Nilsberg, Geir E; Hoff, Jan

2012-07-03

Patients with schizophrenia frequently have disabling gait deficits. The net mechanical efficiency of walking (ϵnet) is an accurate measure often used to evaluate walking performance. Patients with gait deficits have a reduced ϵnet with excessive energy expenditure during sub-maximal walking. Maximal strength training (MST) improves ϵnet in healthy individuals and is associated with reduced risk of mortality. The aim of this study was to investigate whether MST improves ϵnet in patients with schizophrenia. Patients (ICD-10 schizophrenia, schizotypal or delusional disorders (F20-F29)) were included in a non-randomized trial. Patients were assigned to one of two groups: 1) MST consisting of 4x4 repetitions at 85-90% one repetition maximum (1RM) performed in a leg press apparatus or 2) playing computer games (CG). Both groups carried out their activity three days per week for eight weeks. 1RM, ϵnet at 60 watt walking, peak oxygen uptake (VO2peak), the Positive and Negative Syndrome Scale (PANSS) and the 36-items short form (SF-36) were measured pre and post intervention. The baseline ϵnet was 17.3 ± 1.2% and 19.4 ± 3.0% in the MST (n = 6) and CG groups (n = 7), respectively, which is categorized as mechanical inefficiency. The MST group improved 1RM by 79 kg (p = 0.006) and ϵnet by 3.4% (p = 0.046) more than the CG group. The MST group improved 1RM and ϵnet, by a mean of 83 kg (p = 0.028) and 3.4% (p = 0.028), respectively. VO2peak at baseline was 34.2 ± 10.2 and 38.3 ± 9.8 ml·kg-1·min-1 in the MST and CG groups, respectively, and did not change (p > 0.05). No change was observed in PANSS or SF-36 (p > 0.05). MST improves 1RM and ϵnet in patients with schizophrenia. MST could be used as a therapeutic intervention for patients with schizophrenia to normalize their reduced ϵnet.

A Note on Maximized Posttest Contrasts.

ERIC Educational Resources Information Center

Williams, John D.

1979-01-01

Hollingsworth recently showed a posttest contrast for analysis of variance situations that, for equal sample sizes, had several favorable qualities. However, for unequal sample sizes, the contrast fails to achieve status as a maximized contrast; thus, separate testing of the contrast is required. (Author/GSK)

Intracavitary Therapeutics for Pleural Malignancies.

PubMed

Murthy, Vivek; Mangalick, Keshav; Sterman, Daniel H

2018-03-01

Pleural malignancies remain a serious therapeutic challenge, and are frequently refractory to standard treatment; however, they have the advantage of occurring in an enclosed cavity readily accessible for examination, biopsy, and serial sampling. Novel therapeutics can be administered via intracavitary delivery to maximize efficacy by targeting the site of involvement and potentially mitigating the adverse effects of systemic therapies. The easy accessibility of the pleural space lends itself well to repeated sampling and analysis to determine efficacy and toxicity of a given treatment paradigm. These factors support the rationale for delivery of novel therapeutics directly into the pleural space. Copyright © 2017 Elsevier Inc. All rights reserved.

Formation Control for the MAXIM Mission

NASA Technical Reports Server (NTRS)

Luquette, Richard J.; Leitner, Jesse; Gendreau, Keith; Sanner, Robert M.

2004-01-01

Over the next twenty years, a wave of change is occurring in the space-based scientific remote sensing community. While the fundamental limits in the spatial and angular resolution achievable in spacecraft have been reached, based on today s technology, an expansive new technology base has appeared over the past decade in the area of Distributed Space Systems (DSS). A key subset of the DSS technology area is that which covers precision formation flying of space vehicles. Through precision formation flying, the baselines, previously defined by the largest monolithic structure which could fit in the largest launch vehicle fairing, are now virtually unlimited. Several missions including the Micro-Arcsecond X-ray Imaging Mission (MAXIM), and the Stellar Imager will drive the formation flying challenges to achieve unprecedented baselines for high resolution, extended-scene, interferometry in the ultraviolet and X-ray regimes. This paper focuses on establishing the feasibility for the formation control of the MAXIM mission. MAXIM formation flying requirements are on the order of microns, while Stellar Imager mission requirements are on the order of nanometers. This paper specifically addresses: (1) high-level science requirements for these missions and how they evolve into engineering requirements; and (2) the development of linearized equations of relative motion for a formation operating in an n-body gravitational field. Linearized equations of motion provide the ground work for linear formation control designs.

Ehrenfest's Lottery--Time and Entropy Maximization

ERIC Educational Resources Information Center

Ashbaugh, Henry S.

2010-01-01

Successful teaching of the Second Law of Thermodynamics suffers from limited simple examples linking equilibrium to entropy maximization. I describe a thought experiment connecting entropy to a lottery that mixes marbles amongst a collection of urns. This mixing obeys diffusion-like dynamics. Equilibrium is achieved when the marble distribution is…

Marketing therapeutic recreation services.

PubMed

Thorn, B E

1984-01-01

The use of marketing strategies can enhance the delivery of therapeutic recreation services. This article discusses how agencies can adapt marketing techniques and use them to identify potential markets, improve image, evaluate external pressures, and maximize internal strengths. Four variables that can be controlled and manipulated in a proposed marketing plan are product, price, place and promotion.

Effects of Gender, Mathematics Anxiety and Achievement Motivation on College Students' Achievement in Mathematics

ERIC Educational Resources Information Center

Ajogbeje, Oke James; Borisade, Fidelis Tunde; Aladesaye, Charles Ademuyiwa; Ayodele, Oludolapo Bolanle

2013-01-01

The urge to excel or perform maximally in mathematics varies from individual to individual because achievement motivation is often developed or learnt during socialization and learning experiences. The study examined the relationship between College of Education students' achievement motivation and mathematics achievement, correlation coefficient…

Maximal temperature in a simple thermodynamical system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dai, De-Chang; Stojkovic, Dejan, E-mail: diedachung@gmail.com, E-mail: ds77@buffalo.edu

Temperature in a simple thermodynamical system is not limited from above. It is also widely believed that it does not make sense talking about temperatures higher than the Planck temperature in the absence of the full theory of quantum gravity. Here, we demonstrate that there exist a maximal achievable temperature in a system where particles obey the laws of quantum mechanics and classical gravity before we reach the realm of quantum gravity. Namely, if two particles with a given center of mass energy come at the distance shorter than the Schwarzschild diameter apart, according to classical gravity they will formmore » a black hole. It is possible to calculate that a simple thermodynamical system will be dominated by black holes at a critical temperature which is about three times lower than the Planck temperature. That represents the maximal achievable temperature in a simple thermodynamical system.« less

Subthalamic nucleus activity optimizes maximal effort motor responses in Parkinson's disease.

PubMed

Anzak, Anam; Tan, Huiling; Pogosyan, Alek; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Ashkan, Keyoumars; Bogdanovic, Marko; Green, Alexander L; Aziz, Tipu; Brown, Peter

2012-09-01

The neural substrates that enable individuals to achieve their fastest and strongest motor responses have long been enigmatic. Importantly, characterization of such activities may inform novel therapeutic strategies for patients with hypokinetic disorders, such as Parkinson's disease. Here, we ask whether the basal ganglia may play an important role, not only in the attainment of maximal motor responses under standard conditions but also in the setting of the performance enhancements known to be engendered by delivery of intense stimuli. To this end, we recorded local field potentials from deep brain stimulation electrodes implanted bilaterally in the subthalamic nuclei of 10 patients with Parkinson's disease, as they executed their fastest and strongest handgrips in response to a visual cue, which was accompanied by a brief 96-dB auditory tone on random trials. We identified a striking correlation between both theta/alpha (5-12 Hz) and high-gamma/high-frequency (55-375 Hz) subthalamic nucleus activity and force measures, which explained close to 70% of interindividual variance in maximal motor responses to the visual cue alone, when patients were ON their usual dopaminergic medication. Loud auditory stimuli were found to enhance reaction time and peak rate of development of force still further, independent of whether patients were ON or OFF l-DOPA, and were associated with increases in subthalamic nucleus power over a broad gamma range. However, the contribution of this broad gamma activity to the performance enhancements observed was only modest (≤13%). The results implicate frequency-specific subthalamic nucleus activities as substantial factors in optimizing an individual's peak motor responses at maximal effort of will, but much less so in the performance increments engendered by intense auditory stimuli.

Treatment-naïve Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4years in phase 3 trials.

PubMed

Zimran, Ari; Elstein, Deborah; Gonzalez, Derlis E; Lukina, Elena A; Qin, Yulin; Dinh, Quinn; Turkia, Hadhami Ben

2018-02-01

Gaucher disease is an inherited metabolic disease characterized by β-glucocerebrosidase deficiency and commonly treated with enzyme replacement therapy (ERT). The efficacy of ERT with velaglucerase alfa was assessed based on the achievement of published therapeutic goals and the normalization of disease parameters in 39 treatment-naïve patients with type 1 Gaucher disease, 6 to 62years of age, enrolled in phase 3 clinical trials. After 4years of ERT, therapeutic goals for thrombocytopenia and splenomegaly had been achieved in 100% of patients; goals for anemia and hepatomegaly had been achieved in 95% and 94% of patients, respectively. Consistent with the goal for bone mineral density, lumbar spine bone density improved in 87% of patients ≥18years of age. At year 4, compared with clinical ranges for healthy individuals, 86% of patients with a low baseline hemoglobin concentration had normalized, 60% with a low baseline platelet count had normalized, 67% with baseline splenomegaly had normalized, 58% with hepatomegaly had normalized, and lumbar spine bone density had normalized in 53% of adults. The decade-old therapeutic goals do not reflect the potential for normalization of clinical parameters in ERT-treated patients. Goals consistent with normalization or near-normalization should be considered. ClinicalTrials.gov identifiers: NCT00430625, NCT00553631, NCT00635427. Copyright © 2016 Shire Human Genetic Therapies, Inc. Published by Elsevier Inc. All rights reserved.

Maximizing the Effective Use of Formative Assessments

ERIC Educational Resources Information Center

Riddell, Nancy B.

2016-01-01

In the current age of accountability, teachers must be able to produce tangible evidence of students' concept mastery. This article focuses on implementation of formative assessments before, during, and after instruction in order to maximize teachers' ability to effectively monitor student achievement. Suggested strategies are included to help…

Comparison of therapeutic lipid target achievements among high-risk patients in Oman.

PubMed

Al-Waili, Khalid; Al-Zakwani, Ibrahim; Al-Dughaishi, Tamima; Baneerje, Yajnavalka; Al-Sabti, Hilal; Al-Hashmi, Khamis; Farhan, Hatem; Habsi, Khadija Al; Al-Hinai, Ali T; Al-Rasadi, Khalid

2014-05-01

We compared therapeutic lipid target achievements among patients with diabetes or coronary heart disease (CHD) in Oman. A retrospective chart review of 94 patients was conducted at an outpatient clinic in Sultan Qaboos University Hospital, Muscat, Oman. The variables included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (apo B). The overall mean age of the cohort was 59 ± 12 years, 54% were male, 66% were diabetic, 48% hypertensive, 45% had CHD, 94% were on simvastatin, 4% were on fenofibrate, and 2% were on both simvastatin and fenofibrate. Lipid goal attainments of calculated LDL-C (<2.6 mmol/L), apo B (<0.9 g/L), and non-HDL-C (<3.36 mmol/L) were reached in 52%, 39%, and 53% of the patients, respectively. A significant proportion of high-risk patients treated with lipid-lowering agents reach LDL-C but not the apo B treatment targets, suggesting that the use of apo B target values should also be considered.

Disk Density Tuning of a Maximal Random Packing

PubMed Central

Ebeida, Mohamed S.; Rushdi, Ahmad A.; Awad, Muhammad A.; Mahmoud, Ahmed H.; Yan, Dong-Ming; English, Shawn A.; Owens, John D.; Bajaj, Chandrajit L.; Mitchell, Scott A.

2016-01-01

We introduce an algorithmic framework for tuning the spatial density of disks in a maximal random packing, without changing the sizing function or radii of disks. Starting from any maximal random packing such as a Maximal Poisson-disk Sampling (MPS), we iteratively relocate, inject (add), or eject (remove) disks, using a set of three successively more-aggressive local operations. We may achieve a user-defined density, either more dense or more sparse, almost up to the theoretical structured limits. The tuned samples are conflict-free, retain coverage maximality, and, except in the extremes, retain the blue noise randomness properties of the input. We change the density of the packing one disk at a time, maintaining the minimum disk separation distance and the maximum domain coverage distance required of any maximal packing. These properties are local, and we can handle spatially-varying sizing functions. Using fewer points to satisfy a sizing function improves the efficiency of some applications. We apply the framework to improve the quality of meshes, removing non-obtuse angles; and to more accurately model fiber reinforced polymers for elastic and failure simulations. PMID:27563162

Disk Density Tuning of a Maximal Random Packing.

PubMed

Ebeida, Mohamed S; Rushdi, Ahmad A; Awad, Muhammad A; Mahmoud, Ahmed H; Yan, Dong-Ming; English, Shawn A; Owens, John D; Bajaj, Chandrajit L; Mitchell, Scott A

2016-08-01

We introduce an algorithmic framework for tuning the spatial density of disks in a maximal random packing, without changing the sizing function or radii of disks. Starting from any maximal random packing such as a Maximal Poisson-disk Sampling (MPS), we iteratively relocate, inject (add), or eject (remove) disks, using a set of three successively more-aggressive local operations. We may achieve a user-defined density, either more dense or more sparse, almost up to the theoretical structured limits. The tuned samples are conflict-free, retain coverage maximality, and, except in the extremes, retain the blue noise randomness properties of the input. We change the density of the packing one disk at a time, maintaining the minimum disk separation distance and the maximum domain coverage distance required of any maximal packing. These properties are local, and we can handle spatially-varying sizing functions. Using fewer points to satisfy a sizing function improves the efficiency of some applications. We apply the framework to improve the quality of meshes, removing non-obtuse angles; and to more accurately model fiber reinforced polymers for elastic and failure simulations.

Combination therapeutics in complex diseases.

PubMed

He, Bing; Lu, Cheng; Zheng, Guang; He, Xiaojuan; Wang, Maolin; Chen, Gao; Zhang, Ge; Lu, Aiping

2016-12-01

The biological redundancies in molecular networks of complex diseases limit the efficacy of many single drug therapies. Combination therapeutics, as a common therapeutic method, involve pharmacological intervention using several drugs that interact with multiple targets in the molecular networks of diseases and may achieve better efficacy and/or less toxicity than monotherapy in practice. The development of combination therapeutics is complicated by several critical issues, including identifying multiple targets, targeting strategies and the drug combination. This review summarizes the current achievements in combination therapeutics, with a particular emphasis on the efforts to develop combination therapeutics for complex diseases. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Phenomenology of maximal and near-maximal lepton mixing

NASA Astrophysics Data System (ADS)

Gonzalez-Garcia, M. C.; Peña-Garay, Carlos; Nir, Yosef; Smirnov, Alexei Yu.

2001-01-01

The possible existence of maximal or near-maximal lepton mixing constitutes an intriguing challenge for fundamental theories of flavor. We study the phenomenological consequences of maximal and near-maximal mixing of the electron neutrino with other (x=tau and/or muon) neutrinos. We describe the deviations from maximal mixing in terms of a parameter ɛ≡1-2 sin2 θex and quantify the present experimental status for \\|ɛ\\|<0.3. We show that both probabilities and observables depend on ɛ quadratically when effects are due to vacuum oscillations and they depend on ɛ linearly if matter effects dominate. The most important information on νe mixing comes from solar neutrino experiments. We find that the global analysis of solar neutrino data allows maximal mixing with confidence level better than 99% for 10-8 eV2<~Δm2<~2×10-7 eV2. In the mass ranges Δm2>~1.5×10-5 eV2 and 4×10-10 eV2<~Δm2<~2×10-7 eV2 the full interval \\|ɛ\\|<0.3 is allowed within ~4σ (99.995% CL) We suggest ways to measure ɛ in future experiments. The observable that is most sensitive to ɛ is the rate [NC]/[CC] in combination with the day-night asymmetry in the SNO detector. With theoretical and statistical uncertainties, the expected accuracy after 5 years is Δɛ~0.07. We also discuss the effects of maximal and near-maximal νe mixing in atmospheric neutrinos, supernova neutrinos, and neutrinoless double beta decay.

HDAC4 as a potential therapeutic target in neurodegenerative diseases: a summary of recent achievements

PubMed Central

Mielcarek, Michal; Zielonka, Daniel; Carnemolla, Alisia; Marcinkowski, Jerzy T.; Guidez, Fabien

2015-01-01

For the past decade protein acetylation has been shown to be a crucial post-transcriptional modification involved in the regulation of protein functions. Histone acetyltransferases (HATs) mediate acetylation of histones which results in the nucleosomal relaxation associated with gene expression. The reverse reaction, histone deacetylation, is mediated by histone deacetylases (HDACs) leading to chromatin condensation followed by transcriptional repression. HDACs are divided into distinct classes: I, IIa, IIb, III, and IV, on the basis of size and sequence homology, as well as formation of distinct repressor complexes. Implications of HDACs in many diseases, such as cancer, heart failure, and neurodegeneration, have identified these molecules as unique and attractive therapeutic targets. The emergence of HDAC4 among the members of class IIa family as a major player in synaptic plasticity raises important questions about its functions in the brain. The characterization of HDAC4 specific substrates and molecular partners in the brain will not only provide a better understanding of HDAC4 biological functions but also might help to develop new therapeutic strategies to target numerous malignancies. In this review we highlight and summarize recent achievements in understanding the biological role of HDAC4 in neurodegenerative processes. PMID:25759639

Carnot cycle at finite power: attainability of maximal efficiency.

PubMed

Allahverdyan, Armen E; Hovhannisyan, Karen V; Melkikh, Alexey V; Gevorkian, Sasun G

2013-08-02

We want to understand whether and to what extent the maximal (Carnot) efficiency for heat engines can be reached at a finite power. To this end we generalize the Carnot cycle so that it is not restricted to slow processes. We show that for realistic (i.e., not purposefully designed) engine-bath interactions, the work-optimal engine performing the generalized cycle close to the maximal efficiency has a long cycle time and hence vanishing power. This aspect is shown to relate to the theory of computational complexity. A physical manifestation of the same effect is Levinthal's paradox in the protein folding problem. The resolution of this paradox for realistic proteins allows to construct engines that can extract at a finite power 40% of the maximally possible work reaching 90% of the maximal efficiency. For purposefully designed engine-bath interactions, the Carnot efficiency is achievable at a large power.

MAXIM: The Blackhole Imager

NASA Technical Reports Server (NTRS)

Gendreau, Keith; Cash, Webster; Gorenstein, Paul; Windt, David; Kaaret, Phil; Reynolds, Chris

2004-01-01

The Beyond Einstein Program in NASA's Office of Space Science Structure and Evolution of the Universe theme spells out the top level scientific requirements for a Black Hole Imager in its strategic plan. The MAXIM mission will provide better than one tenth of a microarcsecond imaging in the X-ray band in order to satisfy these requirements. We will overview the driving requirements to achieve these goals and ultimately resolve the event horizon of a supermassive black hole. We will present the current status of this effort that includes a study of a baseline design as well as two alternative approaches.

Maximal Oxygen Intake and Maximal Work Performance of Active College Women.

ERIC Educational Resources Information Center

Higgs, Susanne L.

Maximal oxygen intake and associated physiological variables were measured during strenuous exercise on women subjects (N=20 physical education majors). Following assessment of maximal oxygen intake, all subjects underwent a performance test at the work level which had elicited their maximal oxygen intake. Mean maximal oxygen intake was 41.32…

Therapeutic patient education and disclosure of status of HIV infected children in Yaounde, Cameroon Achievements and competence.

PubMed

Njom Nlend, A E; Lyeb, A S; Moyo, S; Nsangou, D

2016-08-01

Psychosocial support and therapeutic patient education are recommended practices that are poorly reported. Our objective was to describe the main achievements after a patient therapeutic education program conducted for pre-adolescents and adolescents with HIV infection. This qualitative study of 37 children with a mean age of 11 years assessed the outcome of an educational program of 8 sessions that ended by the disclosure of their HIV status. Semistructured interviews that took place 8 weeks after the last session and lasted 20 minutes evaluated the following areas: knowledge of the disease, its treatment, its prevention, and their skills in managing their treatment and the secret. The level of knowledge was acceptable except about HIV transmission, and specifically, how they had acquired the disease. In all, 33/37 (89%) of the children were able to cite or write the name of their disease; 29/37 (78%) had acquired knowledge of their treatment (name of the drugs, objective, and daily treatment times); they were able to manage treatment intake away from home; and secrecy was the standard for all. However, many were unable to explain how they had acquired the virus. Therapeutic patient education for HIV status disclosure enables adolescents to acquire knowledge about their disease and the ability to manage it. The poor results observed for knowledge of transmission needs to be improved after disclosure in support groups.

Achievement of Target Blood Pressure Levels among Japanese Workers with Hypertension and Healthy Lifestyle Characteristics Associated with Therapeutic Failure.

PubMed

Kudo, Nagako; Yokokawa, Hirohide; Fukuda, Hiroshi; Sanada, Hironobu; Miwa, Yuichi; Hisaoka, Teruhiko; Isonuma, Hiroshi

2015-01-01

Few studies have examined Japanese with regard to the achievement rates for target blood pressure levels, or the relationship between these rates and healthy lifestyle characteristics in patients with hypertension as defined by the newly established hypertension management guidelines (JSH2014). The aim of this study was to elucidate achievement rates and examine healthy lifestyle characteristics associated with achievement status among Japanese. This cross-sectional study, conducted in January-December 2012, examined blood pressure control and healthy lifestyle characteristics in 8,001 Japanese workers with hypertension (mean age, 57.0 years; 78.8% were men) who participated in a workplace health checkup. Data were collected from workplace medical checkup records and participants' self-administered questionnaires. We divided into 5 groups [G1; young, middle-aged, and early-phase elderly patients (65-74 years old) without diabetes mellitus or chronic kidney disease (CKD) (<140/90 mmHg), G2; late-phase elderly patients (≥75 years old) without diabetes mellitus or CKD (<150/90 mmHg), G3; diabetic patients (<130/80 mmHg), G4; patients with CKD (<130/80 mmHg), and G5; patients with cerebrovascular and/or coronary artery diseases (<140/90 mmHg)] according to JSH2014. And then, achievement rates were calculated in each group. Multivariate analysis identified healthy lifestyle characteristics associated with "therapeutic failure" of target blood pressure. Target blood pressures were achieved by 60.2% of young, middle-aged, and early-phase elderly patients (G1), 71.4% of late-phase elderly patients (G2), 30.5% of diabetic patients (G3), 33.4% of those with chronic kidney disease (G4), and 66.0% of those with cerebrovascular and/or coronary artery diseases (G5). A body mass index of 18.5-24.9 and non-daily alcohol consumption were protective factors, and adequate sleep was found to contribute to therapeutic success. We found low achievement rates for treatment goals among

Dual Competing Photovoltaic Supply Chains: A Social Welfare Maximization Perspective

PubMed Central

Su, Shong-Iee Ivan

2017-01-01

In the past decades, the inappropriate subsidy policies in many nations have caused problems such as serious oversupply, fierce competition and subpar social welfare in the photovoltaic (PV) industry in many nations. There is a clear shortage in the PV industry literature regarding how dual supply chains compete and the key decision issues regarding the competition between dual PV supply chains. It is critical to develop effective subsidy policies for the competing PV supply chains to achieve social welfare maximization. This study has explored the dual PV supply chain competition under the Bertrand competition assumption by three game-theoretical modeling scenarios (or supply chain strategies) considering either the public subsidy or no subsidy from a social welfare maximization perspective. A numerical analysis complemented by two sensitivity analyses provides a better understanding of the pricing and quantity decision dynamics in the dual supply chains under three different supply chain strategies and the corresponding outcomes regarding the total supply chain profits, the social welfare and the required total subsidies. The key findings disclose that if there are public subsidies, the dual PV supply chains have the strongest intention to pursue the decentralized strategy to achieve their maximal returns rather than the centralized strategy that would achieve the maximal social welfare; however, the government would need to pay for the maximal subsidy budget. Thus, the best option for the government would be to encourage the dual PV supply chains to adopt a centralized strategy since this will not only maximize the social welfare but also, at the same time, minimize the public subsidy. With a smart subsidy policy, the PV industry can make the best use of the subsidy budget and grow in a sustainable way to support the highly demanded solar power generation in many countries trying very hard to increase the proportion of their clean energy to combat the global

Dual Competing Photovoltaic Supply Chains: A Social Welfare Maximization Perspective.

PubMed

Chen, Zhisong; Su, Shong-Iee Ivan

2017-11-20

In the past decades, the inappropriate subsidy policies in many nations have caused problems such as serious oversupply, fierce competition and subpar social welfare in the photovoltaic (PV) industry in many nations. There is a clear shortage in the PV industry literature regarding how dual supply chains compete and the key decision issues regarding the competition between dual PV supply chains. It is critical to develop effective subsidy policies for the competing PV supply chains to achieve social welfare maximization. This study has explored the dual PV supply chain competition under the Bertrand competition assumption by three game-theoretical modeling scenarios (or supply chain strategies) considering either the public subsidy or no subsidy from a social welfare maximization perspective. A numerical analysis complemented by two sensitivity analyses provides a better understanding of the pricing and quantity decision dynamics in the dual supply chains under three different supply chain strategies and the corresponding outcomes regarding the total supply chain profits, the social welfare and the required total subsidies. The key findings disclose that if there are public subsidies, the dual PV supply chains have the strongest intention to pursue the decentralized strategy to achieve their maximal returns rather than the centralized strategy that would achieve the maximal social welfare; however, the government would need to pay for the maximal subsidy budget. Thus, the best option for the government would be to encourage the dual PV supply chains to adopt a centralized strategy since this will not only maximize the social welfare but also, at the same time, minimize the public subsidy. With a smart subsidy policy, the PV industry can make the best use of the subsidy budget and grow in a sustainable way to support the highly demanded solar power generation in many countries trying very hard to increase the proportion of their clean energy to combat the global

Matching Pupils and Teachers to Maximize Expected Outcomes.

ERIC Educational Resources Information Center

Ward, Joe H., Jr.; And Others

To achieve a good teacher-pupil match, it is necessary (1) to predict the learning outcomes that will result when each student is instructed by each teacher, (2) to use the predicted performance to compute an Optimality Index for each teacher-pupil combination to indicate the quality of each combination toward maximizing learning for all students,…

Time to clinical response and remission for therapeutics in inflammatory bowel diseases: What should the clinician expect, what should patients be told?

PubMed Central

Vasudevan, Abhinav; Gibson, Peter R; van Langenberg, Daniel R

2017-01-01

An awareness of the expected time for therapies to induce symptomatic improvement and remission is necessary for determining the timing of follow-up, disease (re)assessment, and the duration to persist with therapies, yet this is seldom reported as an outcome in clinical trials. In this review, we explore the time to clinical response and remission of current therapies for inflammatory bowel disease (IBD) as well as medication, patient and disease related factors that may influence the time to clinical response. It appears that the time to therapeutic response varies depending on the indication for therapy (Crohn’s disease or ulcerative colitis). Agents with the most rapid time to clinical response included corticosteroids, calcineurin inhibitors, exclusive enteral nutrition, aminosalicylates and anti-tumor necrosis factor therapy which will work in most patients within the first 2 mo. Vedolizumab, methotrexate and thiopurines had a longer time to clinical response and can take several months to achieve maximal efficacy. Factors affecting the time to clinical response of therapies included use of concomitant therapy, disease duration, smoking status, disease phenotype and advanced age. There appears to be marked variation in time to clinical response for therapies used in IBD which is further influenced by disease and patient related factors. Understanding the expected time to therapeutic response is integral to inform further decision making, maintain a patient-centered approach and ensure treatment is given an appropriate timeframe to achieve maximal benefit prior to cessation. PMID:29085188

Time to clinical response and remission for therapeutics in inflammatory bowel diseases: What should the clinician expect, what should patients be told?

PubMed

Vasudevan, Abhinav; Gibson, Peter R; van Langenberg, Daniel R

2017-09-21

An awareness of the expected time for therapies to induce symptomatic improvement and remission is necessary for determining the timing of follow-up, disease (re)assessment, and the duration to persist with therapies, yet this is seldom reported as an outcome in clinical trials. In this review, we explore the time to clinical response and remission of current therapies for inflammatory bowel disease (IBD) as well as medication, patient and disease related factors that may influence the time to clinical response. It appears that the time to therapeutic response varies depending on the indication for therapy (Crohn's disease or ulcerative colitis). Agents with the most rapid time to clinical response included corticosteroids, calcineurin inhibitors, exclusive enteral nutrition, aminosalicylates and anti-tumor necrosis factor therapy which will work in most patients within the first 2 mo. Vedolizumab, methotrexate and thiopurines had a longer time to clinical response and can take several months to achieve maximal efficacy. Factors affecting the time to clinical response of therapies included use of concomitant therapy, disease duration, smoking status, disease phenotype and advanced age. There appears to be marked variation in time to clinical response for therapies used in IBD which is further influenced by disease and patient related factors. Understanding the expected time to therapeutic response is integral to inform further decision making, maintain a patient-centered approach and ensure treatment is given an appropriate timeframe to achieve maximal benefit prior to cessation.

Maximal and submaximal endurance performance in adults with severe haemophilia.

PubMed

Herbsleb, M; Hilberg, T

2009-01-01

Maximal exercise testing, including the determination of maximal performance and maximal oxygen uptake (VO(2max)), is considered the gold standard for assessing maximal endurance performance. The effectiveness of such testing is often reduced in haemophilic adults owing to musculoskeletal impairments or pain rather than because of cardiac exertion. The measurement of submaximal performance parameters overcomes many limitations of maximal exercise testing but a testing standard is still lacking. The aim of this study was to investigate maximal and particularly submaximal endurance performance of adult patients with severe haemophilia A and B. Eleven patients and 11 matched healthy controls were tested by spiroergometry with a specific treadmill test and the power was calculated in Watts. The haemophilic group achieved lower absolute (210 +/- 63 W) and weight-related (2.94 +/- 0.98 W kg(-1)) maximal endurance performance compared with the control group (287 +/- 50 W resp. 3.82 +/- 0.53 W kg(-1); P maximal and submaximal endurance performance, which can be easily measured by the described test procedure.

Maximizing RNA folding rates: a balancing act.

PubMed Central

Thirumalai, D; Woodson, S A

2000-01-01

Large ribozymes typically require very long times to refold into their active conformation in vitro, because the RNA is easily trapped in metastable misfolded structures. Theoretical models show that the probability of misfolding is reduced when local and long-range interactions in the RNA are balanced. Using the folding kinetics of the Tetrahymena ribozyme as an example, we propose that folding rates are maximized when the free energies of forming independent domains are similar to each other. A prediction is that the folding pathway of the ribozyme can be reversed by inverting the relative stability of the tertiary domains. This result suggests strategies for optimizing ribozyme sequences for therapeutics and structural studies. PMID:10864039

Therapeutic jurisprudence and sex offenders: a psycho-legal approach to protection.

PubMed

Birgden, Astrid

2004-10-01

Societal response to sex offenders is marked by uncertainty about whether punishment or treatment should occur. The distinction between punishment, prevention, and protection is useful to determine how best to assess, treat, and manage sex offenders within the criminal justice system. Once convicted, both law and psychology are concerned with sex offenders changing their behavior in order to protect the community. Therapeutic jurisprudence is a legal theory that aims to maximize therapeutic effects of the law and minimize anti-therapeutic consequences of the law. Therapeutic jurisprudence provides a framework to combine legal and psychological processes to balance prevention and protection. Legal and correctional practitioners can work together to address both community protection and offender protection concerns.

Therapeutic Applications Of Argon Laser

NASA Astrophysics Data System (ADS)

Brunetaud, J. M.; Mosquet, L.; Mordon, S.; Rotteleur, G.

1984-03-01

Argon laser has a C.W. emission and emits several lines between 487 and 544 nm. This radiation is well absorbed by living tissue and especially where there are red pigments (hemoglobin, myoglobin) or black pigments (melanine). Therapeutic applications mainly use thermal effects. By varying the parameters, (optic power, size of exposed area, exposure time) ; one can obtain a coagulation (maximal tissular temperature 60° - 80°) or a vaporization (temperature over 100°). Section occures when the vaporized area is very thin (below 0.5 mm).

Spiders Tune Glue Viscosity to Maximize Adhesion.

PubMed

Amarpuri, Gaurav; Zhang, Ci; Diaz, Candido; Opell, Brent D; Blackledge, Todd A; Dhinojwala, Ali

2015-11-24

Adhesion in humid conditions is a fundamental challenge to both natural and synthetic adhesives. Yet, glue from most spider species becomes stickier as humidity increases. We find the adhesion of spider glue, from five diverse spider species, maximizes at very different humidities that matches their foraging habitats. By using high-speed imaging and spreading power law, we find that the glue viscosity varies over 5 orders of magnitude with humidity for each species, yet the viscosity at maximal adhesion for each species is nearly identical, 10(5)-10(6) cP. Many natural systems take advantage of viscosity to improve functional response, but spider glue's humidity responsiveness is a novel adaptation that makes the glue stickiest in each species' preferred habitat. This tuning is achieved by a combination of proteins and hygroscopic organic salts that determines water uptake in the glue. We therefore anticipate that manipulation of polymer-salts interaction to control viscosity can provide a simple mechanism to design humidity responsive smart adhesives.

Mentoring as Professional Development for Novice Entrepreneurs: Maximizing the Learning

ERIC Educational Resources Information Center

St-Jean, Etienne

2012-01-01

Mentoring can be seen as relevant if not essential in the continuing professional development of entrepreneurs. In the present study, we seek to understand how to maximize the learning that occurs through the mentoring process. To achieve this, we consider various elements that the literature suggested are associated with successful mentoring and…

Ischemic preconditioning of the muscle improves maximal exercise performance but not maximal oxygen uptake in humans.

PubMed

Crisafulli, Antonio; Tangianu, Flavio; Tocco, Filippo; Concu, Alberto; Mameli, Ombretta; Mulliri, Gabriele; Caria, Marcello A

2011-08-01

Brief episodes of nonlethal ischemia, commonly known as "ischemic preconditioning" (IP), are protective against cell injury induced by infarction. Moreover, muscle IP has been found capable of improving exercise performance. The aim of the study was the comparison of standard exercise performances carried out in normal conditions with those carried out following IP, achieved by brief muscle ischemia at rest (RIP) and after exercise (EIP). Seventeen physically active, healthy male subjects performed three incremental, randomly assigned maximal exercise tests on a cycle ergometer up to exhaustion. One was the reference (REF) test, whereas the others were performed after the RIP and EIP sessions. Total exercise time (TET), total work (TW), and maximal power output (W(max)), oxygen uptake (VO(2max)), and pulmonary ventilation (VE(max)) were assessed. Furthermore, impedance cardiography was used to measure maximal heart rate (HR(max)), stroke volume (SV(max)), and cardiac output (CO(max)). A subgroup of volunteers (n = 10) performed all-out tests to assess their anaerobic capacity. We found that both RIP and EIP protocols increased in a similar fashion TET, TW, W(max), VE(max), and HR(max) with respect to the REF test. In particular, W(max) increased by ∼ 4% in both preconditioning procedures. However, preconditioning sessions failed to increase traditionally measured variables such as VO(2max), SV(max,) CO(max), and anaerobic capacity(.) It was concluded that muscle IP improves performance without any difference between RIP and EIP procedures. The mechanism of this effect could be related to changes in fatigue perception.

Compressed Secret Key Agreement:Maximizing Multivariate Mutual Information per Bit

NASA Astrophysics Data System (ADS)

Chan, Chung

2017-10-01

The multiterminal secret key agreement problem by public discussion is formulated with an additional source compression step where, prior to the public discussion phase, users independently compress their private sources to filter out strongly correlated components for generating a common secret key. The objective is to maximize the achievable key rate as a function of the joint entropy of the compressed sources. Since the maximum achievable key rate captures the total amount of information mutual to the compressed sources, an optimal compression scheme essentially maximizes the multivariate mutual information per bit of randomness of the private sources, and can therefore be viewed more generally as a dimension reduction technique. Single-letter lower and upper bounds on the maximum achievable key rate are derived for the general source model, and an explicit polynomial-time computable formula is obtained for the pairwise independent network model. In particular, the converse results and the upper bounds are obtained from those of the related secret key agreement problem with rate-limited discussion. A precise duality is shown for the two-user case with one-way discussion, and such duality is extended to obtain the desired converse results in the multi-user case. In addition to posing new challenges in information processing and dimension reduction, the compressed secret key agreement problem helps shed new light on resolving the difficult problem of secret key agreement with rate-limited discussion, by offering a more structured achieving scheme and some simpler conjectures to prove.

Postactivation potentiation biases maximal isometric strength assessment.

PubMed

Lima, Leonardo Coelho Rabello; Oliveira, Felipe Bruno Dias; Oliveira, Thiago Pires; Assumpção, Claudio de Oliveira; Greco, Camila Coelho; Cardozo, Adalgiso Croscato; Denadai, Benedito Sérgio

2014-01-01

Postactivation potentiation (PAP) is known to enhance force production. Maximal isometric strength assessment protocols usually consist of two or more maximal voluntary isometric contractions (MVCs). The objective of this study was to determine if PAP would influence isometric strength assessment. Healthy male volunteers (n = 23) performed two five-second MVCs separated by a 180-seconds interval. Changes in isometric peak torque (IPT), time to achieve it (tPTI), contractile impulse (CI), root mean square of the electromyographic signal during PTI (RMS), and rate of torque development (RTD), in different intervals, were measured. Significant increases in IPT (240.6 ± 55.7 N·m versus 248.9 ± 55.1 N·m), RTD (746 ± 152 N·m·s(-1) versus 727 ± 158 N·m·s(-1)), and RMS (59.1 ± 12.2% RMSMAX  versus 54.8 ± 9.4% RMSMAX) were found on the second MVC. tPTI decreased significantly on the second MVC (2373 ± 1200 ms versus 2784 ± 1226 ms). We conclude that a first MVC leads to PAP that elicits significant enhancements in strength-related variables of a second MVC performed 180 seconds later. If disconsidered, this phenomenon might bias maximal isometric strength assessment, overestimating some of these variables.

Managing the innovation supply chain to maximize personalized medicine.

PubMed

Waldman, S A; Terzic, A

2014-02-01

Personalized medicine epitomizes an evolving model of care tailored to the individual patient. This emerging paradigm harnesses radical technological advances to define each patient's molecular characteristics and decipher his or her unique pathophysiological processes. Translated into individualized algorithms, personalized medicine aims to predict, prevent, and cure disease without producing therapeutic adverse events. Although the transformative power of personalized medicine is generally recognized by physicians, patients, and payers, the complexity of translating discoveries into new modalities that transform health care is less appreciated. We often consider the flow of innovation and technology along a continuum of discovery, development, regulation, and application bridging the bench with the bedside. However, this process also can be viewed through a complementary prism, as a necessary supply chain of services and providers, each making essential contributions to the development of the final product to maximize value to consumers. Considering personalized medicine in this context of supply chain management highlights essential points of vulnerability and/or scalability that can ultimately constrain translation of the biological revolution or potentiate it into individualized diagnostics and therapeutics for optimized value creation and delivery.

Therapeutic applications of hydrogels in oral drug delivery

PubMed Central

Sharpe, Lindsey A; Daily, Adam M; Horava, Sarena D; Peppas, Nicholas A

2015-01-01

Introduction Oral delivery of therapeutics, particularly protein-based pharmaceutics, is of great interest for safe and controlled drug delivery for patients. Hydrogels offer excellent potential as oral therapeutic systems due to inherent biocompatibility, diversity of both natural and synthetic material options and tunable properties. In particular, stimuli-responsive hydrogels exploit physiological changes along the intestinal tract to achieve site-specific, controlled release of protein, peptide and chemotherapeutic molecules for both local and systemic treatment applications. Areas covered This review provides a wide perspective on the therapeutic use of hydrogels in oral delivery systems. General features and advantages of hydrogels are addressed, with more considerable focus on stimuli-responsive systems that respond to pH or enzymatic changes in the gastrointestinal environment to achieve controlled drug release. Specific examples of therapeutics are given. Last, in vitro and in vivo methods to evaluate hydrogel performance are discussed. Expert opinion Hydrogels are excellent candidates for oral drug delivery, due to the number of adaptable parameters that enable controlled delivery of diverse therapeutic molecules. However, further work is required to more accurately simulate physiological conditions and enhance performance, which is important to achieve improved bioavailability and increase commercial interest. PMID:24848309

An automated system for reduction of the firm's employees under maximal overall efficiency

NASA Astrophysics Data System (ADS)

Yonchev, Yoncho; Nikolov, Simeon; Baeva, Silvia

2012-11-01

Achieving maximal overall efficiency is a priority in all companies. This problem is formulated as a knap-sack problem and afterwards as a linear assignment problem. An automated system is created for solving of this problem.

Non-coding RNAs: Therapeutic Strategies and Delivery Systems.

PubMed

Ling, Hui

The vast majority of the human genome is transcribed into RNA molecules that do not code for proteins, which could be small ones approximately 20 nucleotide in length, known as microRNAs, or transcripts longer than 200 bp, defined as long noncoding RNAs. The prevalent deregulation of microRNAs in human cancers prompted immediate interest on the therapeutic value of microRNAs as drugs and drug targets. Many features of microRNAs such as well-defined mechanisms, and straightforward oligonucleotide design further make them attractive candidates for therapeutic development. The intensive efforts of exploring microRNA therapeutics are reflected by the large body of preclinical studies using oligonucleotide-based mimicking and blocking, culminated by the recent entry of microRNA therapeutics in clinical trial for several human diseases including cancer. Meanwhile, microRNA therapeutics faces the challenge of effective and safe delivery of nucleic acid therapeutics into the target site. Various chemical modifications of nucleic acids and delivery systems have been developed to increase targeting specificity and efficacy, and reduce the associated side effects including activation of immune response. Recently, long noncoding RNAs become attractive targets for therapeutic intervention because of their association with complex and delicate phenotypes, and their unconventional pharmaceutical activities such as capacity of increasing output of proteins. Here I discuss the general therapeutic strategies targeting noncoding RNAs, review delivery systems developed to maximize noncoding RNA therapeutic efficacy, and offer perspectives on the future development of noncoding RNA targeting agents for colorectal cancer.

Polarity related influence maximization in signed social networks.

PubMed

Li, Dong; Xu, Zhi-Ming; Chakraborty, Nilanjan; Gupta, Anika; Sycara, Katia; Li, Sheng

2014-01-01

Influence maximization in social networks has been widely studied motivated by applications like spread of ideas or innovations in a network and viral marketing of products. Current studies focus almost exclusively on unsigned social networks containing only positive relationships (e.g. friend or trust) between users. Influence maximization in signed social networks containing both positive relationships and negative relationships (e.g. foe or distrust) between users is still a challenging problem that has not been studied. Thus, in this paper, we propose the polarity-related influence maximization (PRIM) problem which aims to find the seed node set with maximum positive influence or maximum negative influence in signed social networks. To address the PRIM problem, we first extend the standard Independent Cascade (IC) model to the signed social networks and propose a Polarity-related Independent Cascade (named IC-P) diffusion model. We prove that the influence function of the PRIM problem under the IC-P model is monotonic and submodular Thus, a greedy algorithm can be used to achieve an approximation ratio of 1-1/e for solving the PRIM problem in signed social networks. Experimental results on two signed social network datasets, Epinions and Slashdot, validate that our approximation algorithm for solving the PRIM problem outperforms state-of-the-art methods.

Polarity Related Influence Maximization in Signed Social Networks

PubMed Central

Li, Dong; Xu, Zhi-Ming; Chakraborty, Nilanjan; Gupta, Anika; Sycara, Katia; Li, Sheng

2014-01-01

Influence maximization in social networks has been widely studied motivated by applications like spread of ideas or innovations in a network and viral marketing of products. Current studies focus almost exclusively on unsigned social networks containing only positive relationships (e.g. friend or trust) between users. Influence maximization in signed social networks containing both positive relationships and negative relationships (e.g. foe or distrust) between users is still a challenging problem that has not been studied. Thus, in this paper, we propose the polarity-related influence maximization (PRIM) problem which aims to find the seed node set with maximum positive influence or maximum negative influence in signed social networks. To address the PRIM problem, we first extend the standard Independent Cascade (IC) model to the signed social networks and propose a Polarity-related Independent Cascade (named IC-P) diffusion model. We prove that the influence function of the PRIM problem under the IC-P model is monotonic and submodular Thus, a greedy algorithm can be used to achieve an approximation ratio of 1-1/e for solving the PRIM problem in signed social networks. Experimental results on two signed social network datasets, Epinions and Slashdot, validate that our approximation algorithm for solving the PRIM problem outperforms state-of-the-art methods. PMID:25061986

A Brief Review of Effective Teaching Practices That Maximize Student Engagement

ERIC Educational Resources Information Center

Harbour, Kristin E.; Evanovich, Lauren L.; Sweigart, Chris A.; Hughes, Lindsay E.

2015-01-01

What teachers do and how students perform intersect, making teachers a critical factor for determining student success. When teachers use effective practices, they maximize the probability that students will be actively engaged in instruction. Student engagement is one of the most well-established predictors of achievement; when students are more…

Maximizing Lumen Gain With Directional Atherectomy.

PubMed

Stanley, Gregory A; Winscott, John G

2016-08-01

To describe the use of a low-pressure balloon inflation (LPBI) technique to delineate intraluminal plaque and guide directional atherectomy in order to maximize lumen gain and achieve procedure success. The technique is illustrated in a 77-year-old man with claudication who underwent superficial femoral artery revascularization using a HawkOne directional atherectomy catheter. A standard angioplasty balloon was inflated to 1 to 2 atm during live fluoroscopy to create a 3-dimensional "lumenogram" of the target lesion. Directional atherectomy was performed only where plaque impinged on the balloon at a specific fluoroscopic orientation. The results of the LPBI technique were corroborated with multimodality diagnostic imaging, including digital subtraction angiography, intravascular ultrasound, and intra-arterial pressure measurements. With the LPBI technique, directional atherectomy can routinely achieve <10% residual stenosis, as illustrated in this case, thereby broadly supporting a no-stent approach to lower extremity endovascular revascularization. © The Author(s) 2016.

Holistic Admissions after Affirmative Action: Does "Maximizing" the High School Curriculum Matter?

ERIC Educational Resources Information Center

Bastedo, Michael N.; Howard, Joseph E.; Flaster, Allyson

2016-01-01

Selective colleges and universities purport to consider students' achievement in the context of the academic opportunities available in their high schools. Thus, students who "maximize" their curricular opportunities should be more likely to gain admission. Using nationally representative data, we examine the effect of "maximizing…

Student Achievement: Improving Our Focus.

ERIC Educational Resources Information Center

Hawkins, Amber

An efficient way to help students achieve academically is to maximize the consistent attendance of permanent teachers in the classroom. Students nationwide are spending increased amounts of time with instructors other than their permanent teachers. A large contributor to the problem of teacher absenteeism is mandatory leave for professional…

Identification of the State of Maximal Hyperemia in the Assessment of Coronary Fractional Flow Reserve Using Non-Invasive Electrical Velocimetry.

PubMed

Murasawa, Takahide; Takahashi, Masao; Myojo, Masahiro; Kiyosue, Arihiro; Oguri, Atsushi; Ando, Jiro; Komuro, Issei

2017-05-31

Previous research revealed that, in patients with coronary pressure-derived fractional flow reserve (FFR) in the 'grey zone' (0.75-0.85), repeated FFR assessments sometimes yield conflicting results. One of the causes of the fluctuations in FFR values around the grey zone may be imprecise identification of the point where maximal hyperemia is achieved. Identification of the state of maximal hyperemia during assessment of FFR can be challenging. This study aimed to determine whether non-invasive electrical velocimetry (EV) can be used to identify the state of maximal hyperemia.Stroke volume (SV), SV variation (SVV), and systemic vascular resistance index (SVRI) were determined by EV in 15 patients who underwent FFR assessment. Time intervals from initiation of adenosine infusion to achieving maximal hyperemia (time mFRR ), as well as to achieving maximal cardiac output (CO), SV, SVV, and SVRI (time mCO , time mSV , time mSVV , and time mSVRI , respectively), were determined. Time mCO and time mSVV were closer to time mFRR than other values (time mSVV /time mFRR versus time mSVRI /time mFRR = 1.03 ± 0.2 versus 1.36 ± 0.4, P < 0.05). The maximum of SV was difficult to determine owing to considerable variations, but the maximum of SVV was clearly recognized. Time mCO and time mSVV were significantly correlated with time mFFR , with time mSVV showing a stronger correlation than time mSV (time mSVV : r = 0.92, P < 0.01; time mCO : r = 0.80, P < 0.01).Maximal SVV is reached close to maximal hyperemia. Monitoring of SVV with non-invasive EV during FFR assessment can help identify the state of maximal hyperemia.

Imaging a Black Hole - Maxim

NASA Astrophysics Data System (ADS)

Cash, W.

With the general acceptance of black holes as real entities the astrophysics community has turned its attention to studying their behavior and properties. Because of the great distance and compact size of the central engine, astronomers are currently limited to spectroscopic analysis. But to take a picture, or better yet a movie, of the black hole in silhouette against its accretion disk would be a triumph of exploration and scientific inquiry. Probing to the event horizon is best accomplished in the x-ray band, where material primarily radiates in the last orbits before its final plunge. Not only will the signal be bright and minimally confused in the x-ray, but the size of the required interferometer drops dramatically. We describe MAXIM, the Micro-Arcsecond X-ray Imaging Mission, which is now being studied and developed by NASA. We will explain the preliminary mission concept which will use currently existing technology to achieve spatial resolution one million times higher than that of the Hubble Space Telescope and capture the image of an event horizon in a nearby Active Galactic Nucleus. We will also describe the Maxim Pathfinder. Designed as a stepping stone at resolution of 100 microarcseconds, it will demonstrate the techniques of x-ray interferometry and perform groundbreaking science like resolving the coronae of the nearby stars.

Imaging a black hole - Maxim

NASA Astrophysics Data System (ADS)

Cash, W.

With the general acceptance of black holes as real entities the astrophysics community has turned its attention to studying their behavior and properties. Because of the great distance and compact size of the central engine, astronomers are currently limited to spectroscopic analysis. But to take a picture, or better yet a movie, of the black hole in silhouette against its accretion disk would be a triumph of exploration and scientific inquiry. Probing to the event horizon is best accomplished in the x-ray band, where material primarily radiates in the last orbits before its final plunge. Not only will the signal be bright and minimally confused in the x-ray, but the size of the required interferometer drops dramatically. We describe MAXIM, the Micro-Arcsecond X-ray Imaging Mission, which is now being studied and developed by NASA. We will explain the preliminary mission concept which will use currently existing technology to achieve spatial resolution one million times higher than that of the Hubble Space Telescope and capture the image of an event horizon in a nearby Active Galactic Nucleus. We will also describe the Maxim Pathfinder. Designed as a stepping stone at resolution of 100 microarcseconds, it will demonstrate the techniques of xray- interferometry and perform groundbreaking science like resolving the coronae of the nearby stars.

Imaging a black hole: MAXIM

NASA Astrophysics Data System (ADS)

Cash, W.

With the general acceptance of black holes as real entities the astrophysics community has turned its attention to studying their behavior and properties. Because of the great distance and compact size of the central engine, astronomers are limited to spectroscopic analysis. But to take a picture, or better yet a movie, of the black hole in silhouette against its accretion disk would be a triumph of exploration and scientific inquiry. Probing to the event horizon is best accomplished in the X-ray band, where material primarily radiates in the last orbits before its final plunge. Not only will the signal be bright and minimally confused in the X-ray, but the size of the required interferometer drops dramatically. We describe MAXIM, the Micro-Arcsecond X-ray Imaging Mission, which is now being studied and developed by NASA. We will explain the preliminary mission concept which will use currently existing technology to achieve spatial resolution one million times higher than that of the Hubble Space Telescope and capture the image of an event horizon in a nearby Active Galactic Nucleus. We will also describe the MAXIM Pathfinder. Designed as a stepping stone at resolution of 100 micro-arcseconds, it will demonstrate the techniques of X-ray interferometry and perform groundbreaking science like resolving the coronae of the nearby stars.

Causes of failure to achieve the low density lipoprotein cholesterol therapeutic target in patients with high and very high vascular risk controlled in Lipid and Vascular Risk Units. EROMOT study.

PubMed

Morales, Clotilde; Plana, Núria; Arnau, Anna; Matas, Laia; Mauri, Marta; Vila, Àlex; Vila, Lluís; Soler, Cristina; Montesinos, Jesús; Masana, Lluís; Pedro-Botet, Juan

Determination of the level of achievement of the low density lipoprotein cholesterol (LDL-C) therapeutic target in patients with high and very high vascular risk treated in Lipid Units, as well as the causes of non-achievement. Multicentre retrospective observational study that included patients over 18 years with high and very high vascular risk, according to the criteria of the 2012 European Guidelines on Cardiovascular Disease Prevention, referred consecutively to Lipid Units between January and June 2012 and with follow-up two years after the first visit. The study included a total of 243 patients from 16 lipid units. The mean age was 52.2 years (SD 13.7), of whom 62.6% were males, and 40.3% of them were very high risk. At the first visit, 86.8% (25.1% in combination) and 95.0% (47.3% in combination) in the second visit (P<.001) were treated with lipid-lowering treatment. The therapeutic target was achieved by 28% (95 CI: 22.4-34.1). As regards the causes of non-achievement, 24.6% were related to the medication (10.3% maximum tolerated dose and 10.9% due to the appearance of adverse effects), 43.4% due to the physician (19.4% by inertia, 13.7% considering that target already reached), and 46.9% due to the patient, highlighting the therapeutic non-compliance (31,4%). LDL-C targets were achieved in about one-third of patients. The low adherence of the patient, followed by medical inertia are the most frequent causes that can explain these results. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

From entropy-maximization to equality-maximization: Gauss, Laplace, Pareto, and Subbotin

NASA Astrophysics Data System (ADS)

Eliazar, Iddo

2014-12-01

The entropy-maximization paradigm of statistical physics is well known to generate the omnipresent Gauss law. In this paper we establish an analogous socioeconomic model which maximizes social equality, rather than physical disorder, in the context of the distributions of income and wealth in human societies. We show that-on a logarithmic scale-the Laplace law is the socioeconomic equality-maximizing counterpart of the physical entropy-maximizing Gauss law, and that this law manifests an optimized balance between two opposing forces: (i) the rich and powerful, striving to amass ever more wealth, and thus to increase social inequality; and (ii) the masses, struggling to form more egalitarian societies, and thus to increase social equality. Our results lead from log-Gauss statistics to log-Laplace statistics, yield Paretian power-law tails of income and wealth distributions, and show how the emergence of a middle-class depends on the underlying levels of socioeconomic inequality and variability. Also, in the context of asset-prices with Laplace-distributed returns, our results imply that financial markets generate an optimized balance between risk and predictability.

A Lyapunov based approach to energy maximization in renewable energy technologies

NASA Astrophysics Data System (ADS)

Iyasere, Erhun

This dissertation describes the design and implementation of Lyapunov-based control strategies for the maximization of the power captured by renewable energy harnessing technologies such as (i) a variable speed, variable pitch wind turbine, (ii) a variable speed wind turbine coupled to a doubly fed induction generator, and (iii) a solar power generating system charging a constant voltage battery. First, a torque control strategy is presented to maximize wind energy captured in variable speed, variable pitch wind turbines at low to medium wind speeds. The proposed strategy applies control torque to the wind turbine pitch and rotor subsystems to simultaneously control the blade pitch and tip speed ratio, via the rotor angular speed, to an optimum point at which the capture efficiency is maximum. The control method allows for aerodynamic rotor power maximization without exact knowledge of the wind turbine model. A series of numerical results show that the wind turbine can be controlled to achieve maximum energy capture. Next, a control strategy is proposed to maximize the wind energy captured in a variable speed wind turbine, with an internal induction generator, at low to medium wind speeds. The proposed strategy controls the tip speed ratio, via the rotor angular speed, to an optimum point at which the efficiency constant (or power coefficient) is maximal for a particular blade pitch angle and wind speed by using the generator rotor voltage as a control input. This control method allows for aerodynamic rotor power maximization without exact wind turbine model knowledge. Representative numerical results demonstrate that the wind turbine can be controlled to achieve near maximum energy capture. Finally, a power system consisting of a photovoltaic (PV) array panel, dc-to-dc switching converter, charging a battery is considered wherein the environmental conditions are time-varying. A backstepping PWM controller is developed to maximize the power of the solar generating

Dietary 2-oxoglutarate prevents bone loss caused by neonatal treatment with maximal dexamethasone dose

PubMed Central

Tomaszewska, Ewa; Muszyński, Siemowit; Blicharski, Tomasz; Pierzynowski, Stefan G

2017-01-01

Synthetic glucocorticoids (GCs) are widely used in the variety of dosages for treatment of premature infants with chronic lung disease, respiratory distress syndrome, allergies, asthma, and other inflammatory and autoimmune conditions. Yet, adverse effects such as glucocorticoid-induced osteoporosis and growth retardation are recognized. Conversely, 2-oxoglutarate (2-Ox), a precursor of glutamine, glutamate, and collagen amino acids, exerts protective effects on bone development. Our aim was to elucidate the effect of dietary administered 2-Ox on bone loss caused by neonatal treatment with clinically relevant maximal therapeutic dexamethasone (Dex) dose. Long bones of neonatal female piglets receiving Dex, Dex+2-Ox, or untreated were examined through measurements of mechanical properties, density, mineralization, geometry, histomorphometry, and histology. Selected hormones, bone turnover, and growth markers were also analyzed. Neonatal administration of clinically relevant maximal dose of Dex alone led to over 30% decrease in bone mass and the ultimate strength (P < 0.001 for all). The length (13 and 7% for femur and humerus, respectively) and other geometrical parameters (13–45%) decreased compared to the control (P < 0.001 for all). Dex impaired bone growth and caused hormonal imbalance. Dietary 2-Ox prevented Dex influence and vast majority of assessed bone parameters were restored almost to the control level. Piglets receiving 2-Ox had heavier, denser, and stronger bones; higher levels of growth hormone and osteocalcin concentration; and preserved microarchitecture of trabecular bone compared to the Dex group. 2-Ox administered postnatally had a potential to maintain bone structure of animals simultaneously treated with maximal therapeutic doses of Dex, which, in our opinion, may open up a new opportunity in developing combined treatment for children treated with GCs. Impact statement The present study has showed, for the first time, that dietary 2

Ethics Audit of a Therapeutic Recreation Course

ERIC Educational Resources Information Center

Nisbett, Nancy; Hinton, Jennifer

2008-01-01

The purpose of this study was to enhance awareness of the presence of ethics education within the allied health discipline of therapeutic recreation. To achieve this end, a curriculum audit was conducted in a therapeutic recreation course to determine the existence of ethics education within the course. Included topics, methods of delivery, and…

On the Relationship between Maximal Reliability and Maximal Validity of Linear Composites

ERIC Educational Resources Information Center

Penev, Spiridon; Raykov, Tenko

2006-01-01

A linear combination of a set of measures is often sought as an overall score summarizing subject performance. The weights in this composite can be selected to maximize its reliability or to maximize its validity, and the optimal choice of weights is in general not the same for these two optimality criteria. We explore several relationships…

Neurotrophic factors as a therapeutic target for Parkinson's disease.

PubMed

Evans, Jonathan R; Barker, Roger A

2008-04-01

The search for therapeutic agents that might alter the disease course in Parkinson's disease (PD) is ongoing. One area of particular interest involves neurotrophic factors (NTFs), with those of the glial cell line-derived neurotrophic factor (GDNF) family showing greatest promise. The safety and efficacy of these therapies has recently come into question. Furthermore, many of the key questions pertaining to such therapies, such as the optimal method of delivery, timing of treatment and selection of patients most likely to benefit, remain unanswered. In this review we sought to evaluate the therapeutic potential of NTFs in the treatment of PD. We appraised the evidence provided by both in vitro and in vivo work before proceeding to a critical assessment of the relevant clinical trial data. Relevant literature was identified using a PubMed search of articles published up to October 2007. Search terms included: 'Parkinson's disease', 'Neurotrophic factors', 'BDNF' (Brain-derived neurotrophic factor), 'GDNF' and 'Neurturin'. Original articles were reviewed, and relevant citations from these articles were also appraised. NTF therapy has potential in the treatment of nigrostriatal dysfunction in PD but numerous methodological and safety issues will need to be addressed before this approach can be widely adopted. Furthermore PD is now recognized as being more than a pure motor disorder, and one in which neuronal loss is not just confined to the dopaminergic nigrostriatal system. Non-motor symptomatology in PD is unlikely to benefit from therapies that target only the nigrostriatal system, and this must inform our thinking as to the maximal achievable benefit that NTFs are ever likely to provide.

Stanol esters as a component of maximal dietary therapy in the National Cholesterol Education Program Adult Treatment Panel III report.

PubMed

Grundy, Scott M

2005-07-04

Use of plant stanols/sterols in forms that are sufficiently bioavailable for therapeutic effect should be a key element of maximal dietary therapy. This principle was recognized by National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) and has been amply confirmed by experimental studies in humans. Since the introduction of statins, dietary therapy for control of elevated low-density lipoprotein (LDL) cholesterol levels has received less attention. The time has come, however, to reassert the importance of maximal dietary therapy as a cost-effective means for treatment of elevated LDL concentrations and for lifetime prevention of coronary heart disease.

New therapeutic principles in dyslipidaemia: focus on LDL and Lp(a) lowering drugs

PubMed Central

Norata, Giuseppe Danilo; Ballantyne, Christie M.; Catapano, Alberico Luigi

2013-01-01

Dyslipidaemias play a key role in determining cardiovascular risk; the discovery of statins has contributed a very effective approach. However, many patients do not achieve, at the maximal tolerated dose, the recommended goals for low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol, and apolipoprotein B (apoB). Available agents combined with statins can provide additional LDL-C reduction, and agents in development will increase therapeutic options impacting also other atherogenic lipoprotein classes. In fact, genetic insights into mechanisms underlying regulation of LDL-C levels has expanded potential targets of drug therapy and led to the development of novel agents. Among them are modulators of apoB containing lipoproteins production and proprotein convertase subtilisin/kexin type-9 inhibitors. Alternative targets such as lipoprotein(a) also require attention; however, until we have a better understanding of these issues, further LDL-C lowering in high and very high-risk patients will represent the most sound clinical approach. PMID:23509227

Sub-therapeutic doses of fluvastatin and valsartan are more effective than therapeutic doses in providing beneficial cardiovascular pleiotropic effects in rats: A proof of concept study.

PubMed

Janić, Miodrag; Lunder, Mojca; France Štiglic, Alenka; Jerin, Aleš; Skitek, Milan; Černe, Darko; Marc, Janja; Drevenšek, Gorazd; Šabovič, Mišo

2017-12-01

Statins and sartans can, in therapeutic doses, induce pleiotropic cardiovascular effects. Similar has recently been shown also for sub-therapeutic doses. We thus explored and compared the cardiovascular pleiotropic efficacy of sub-therapeutic vs. therapeutic doses. Wistar rats were randomly divided into 7 groups receiving fluvastatin, valsartan and their combination in sub-therapeutic and therapeutic doses, or saline. After 6weeks, the animals were euthanised, their hearts and thoracic aortas isolated, and blood samples taken. Endothelium-dependent relaxation of the thoracic aortae and ischaemic-reperfusion injury of the isolated hearts were assessed along with the related serum parameters and genes expression. Fluvastatin and valsartan alone or in combination were significantly more effective in sub-therapeutic than therapeutic doses. The sub-therapeutic combination greatly increased thoracic aorta endothelium-dependent relaxation and maximally protected the isolated hearts against ischaemia-reperfusion injury and was thus most effective. Beneficial effects were accompanied by increased levels of nitric oxide (NO) and decreased levels of asymmetric dimethylarginine (ADMA) in the serum (again prominently induced by the sub-therapeutic combination). Furthermore, nitric oxide synthase 3 (NOS3) and endothelin receptor type A (EDNRA) genes expression increased, but only in both combination groups and without significant differences between them. In the therapeutic dose groups, fluvastatin and valsartan decreased cholesterol values and systolic blood pressure. Sub-therapeutic doses of fluvastatin and valsartan are more effective in expressing cardiovascular pleiotropic effects than therapeutic doses of fluvastatin and/or valsartan. These results could be of significant clinical relevance. Copyright © 2017 Elsevier Inc. All rights reserved.

Maximizing the Performance and Job-Related Behaviors of Contract and Permanent IT Workers

ERIC Educational Resources Information Center

Pai, Tanusree

2010-01-01

As the use of contracting for Information Technology (IT) services steadily increases, IT managers are challenged with reconciling the need for flexibility achieved through the use of contract workers, with the need to understand the factors that maximize the performance and behaviors of contract and permanent IT workers. While several research…

Physical dose of therapeutic exercises in institutional neck rehabilitation.

PubMed

Wasenius, Niko; Karapalo, Teppo; Sjögren, Tuulikki; Pekkonen, Mika; Mälkiä, Esko

2013-03-01

To determine the intensity and volume of therapeutic exercises during a standard 13-day inpatient neck rehabilitation course in relation to overall physical activity in rehabilitation and everyday life. Cross-sectional study. Subjects (n = 19; 16 women and 3 men; mean age 48.6 years, standard deviation (SD) 6.6) with chronic non-specific neck pain were recruited from two inpatient neck rehabilitation courses. Intensity and volume of therapeutic exercises and physical activity were measured in metabolic equivalents (METs) with an objective measurement device and all-time recall questionnaire. Maximum oxygen uptake was determined in METs (METc) by direct maximal cycle ergometer. Subjects' mean METc was 7.2 METs (SD 1.4) or 25.3 ml/kg/min (SD 4.8). Intensity of all therapeutic exercises was 1.9 METs or 27 %METc (SD 5.1) and volume 7.7 MET-hours/week. Intensity of specific neck and shoulder exercises was 2.0 METs or 28 %METc (SD 5.4) and volume 2.5 MET-hours/week. In addition, subjects were more active in everyday life than in inpatient rehabilitation. The therapeutic exercise dose failed to reach previously reported target values for pain relief. The dose of therapeutic exercises and confounding physical activity should be carefully controlled in pain rehabilitation programmes.

2×2 dominant achievement goal profiles in high-level swimmers.

PubMed

Fernandez-Rio, Javier; Cecchini Estrada, Jose A; Mendez-Giménez, Antonio; Fernández-Garcia, Benjamín; Saavedra, Pablo

2014-01-01

The goal of this study was to assess achievement goal dominance, self-determined situational motivation and competence in high-level swimmers before and after three training sessions set at different working intensities (medium, sub-maximal and maximal). Nineteen athletes (males, n=9, 18.00±2.32 years; females, n=10, 16.30±2.01 years, range = 14-18) agreed to participate. They completed a questionnaire that included the Dominant Achievement Goal assessment instrument, the 2×2 Achievement Goals Questionnaire for Sport (AGQ-S), The Situational Motivation Scale (SIMS) and the Competence subscale of the Basic Psychological Needs in Exercise questionnaire (BPNES). Results indicated that participants overwhelmingly showed mastery-approach achievement goal dominance, and it remained stable at the conclusion of the different training sessions under all intensity levels. This profile was positively correlated to self-determined situational motivation and competence. However, swimmers' feelings of competence increased only after the medium intensity level training session. After the completion of the maximal intensity training session, swimmers' self-determined motivation was significantly lower compared to the other two training sessions, which could be caused by a temporary period of burnout. Results indicated that high-level swimmers had a distinct mastery-approach dominant achievement goal profile that was not affected by the workload of the different training sessions. They also showed high levels of self-determined situational motivation and competence. However, heavy workloads should be controlled because they can cause transitory burnout.

Maximally multipartite entangled states

NASA Astrophysics Data System (ADS)

Facchi, Paolo; Florio, Giuseppe; Parisi, Giorgio; Pascazio, Saverio

2008-06-01

We introduce the notion of maximally multipartite entangled states of n qubits as a generalization of the bipartite case. These pure states have a bipartite entanglement that does not depend on the bipartition and is maximal for all possible bipartitions. They are solutions of a minimization problem. Examples for small n are investigated, both analytically and numerically.

Maximally Symmetric Composite Higgs Models.

PubMed

Csáki, Csaba; Ma, Teng; Shu, Jing

2017-09-29

Maximal symmetry is a novel tool for composite pseudo Goldstone boson Higgs models: it is a remnant of an enhanced global symmetry of the composite fermion sector involving a twisting with the Higgs field. Maximal symmetry has far-reaching consequences: it ensures that the Higgs potential is finite and fully calculable, and also minimizes the tuning. We present a detailed analysis of the maximally symmetric SO(5)/SO(4) model and comment on its observational consequences.

UNUSUAL WARFARIN DOSE TO ACHIEVE THERAPEUTIC INR IN A 4-MONTH OLD CHILD: NON-GENETICS RISK FACTORS ARE STILL A CHALLENGE.

PubMed

Okumura, Lucas Miyake; Negretto, Giovanna Webster; Carvalho, Clarissa Gutiérrez

2017-01-01

To report a case of a 4-month old girl that required 0.7 mg/kg/day (5 mg) of warfarin and discuss relevant risk factors for requiring higher doses. In November 2015, a 5 kg female infant (36-week preterm) was admitted to the hospital due to status epilepticus and fever. Diazepam, phenytoin and ceftriaxone were prescribed. Cerebrospinal fluid contained 7 leukocytes, 150 mg/dL proteins, 1 mg/dL glucose and gram positive cocci were observed. Cranial tomography suggested hypodense signs in the cerebellum, right temporal lobe and left basal nuclei, which was consistent with pneumococcal meningitis-induced infectious vasculitis. She required low molecular weight heparin and warfarin for post-encephalitis thrombosis. About 10 days were required to achieve therapeutic INR, and warfarin was adjusted five times since the initial prescription. The risk factors for higher warfarin doses were age and enteral tube feeding. Phenobarbital and prednisone might also have contributed with one of the highest warfarin dose ever reported. Despite current importance given to genetics testing, clinicians should attempt to identify common contributing factors for prolonged non-therapeutic INR, to minimize the risk of coagulation, and to reduce costs of hospital stay and laboratory exams.

Comparison of Maximal Wall Thickness in Hypertrophic Cardiomyopathy Differs Between Magnetic Resonance Imaging and Transthoracic Echocardiography.

PubMed

Bois, John P; Geske, Jeffrey B; Foley, Thomas A; Ommen, Steve R; Pellikka, Patricia A

2017-02-15

Left ventricular (LV) wall thickness is a prognostic marker in hypertrophic cardiomyopathy (HC). LV wall thickness ≥30 mm (massive hypertrophy) is independently associated with sudden cardiac death. Presence of massive hypertrophy is used to guide decision making for cardiac defibrillator implantation. We sought to determine whether measurements of maximal LV wall thickness differ between cardiac magnetic resonance imaging (MRI) and transthoracic echocardiography (TTE). Consecutive patients were studied who had HC without previous septal ablation or myectomy and underwent both cardiac MRI and TTE at a single tertiary referral center. Reported maximal LV wall thickness was compared between the imaging techniques. Patients with ≥1 technique reporting massive hypertrophy received subset analysis. In total, 618 patients were evaluated from January 1, 2003, to December 21, 2012 (mean [SD] age, 53 [15] years; 381 men [62%]). In 75 patients (12%), reported maximal LV wall thickness was identical between MRI and TTE. Median difference in reported maximal LV wall thickness between the techniques was 3 mm (maximum difference, 17 mm). Of the 63 patients with ≥1 technique measuring maximal LV wall thickness ≥30 mm, 44 patients (70%) had discrepant classification regarding massive hypertrophy. MRI identified 52 patients (83%) with massive hypertrophy; TTE, 30 patients (48%). Although guidelines recommend MRI or TTE imaging to assess cardiac anatomy in HC, this study shows discrepancy between the techniques for maximal reported LV wall thickness assessment. In conclusion, because this measure clinically affects prognosis and therapeutic decision making, efforts to resolve these discrepancies are critical. Copyright © 2016 Elsevier Inc. All rights reserved.

Potential Therapeutics for Vascular Cognitive Impairment and Dementia.

PubMed

Sun, Miao-Kun

2017-10-16

As the human lifespan increases, the number of people affected by age-related dementia is growing at an epidemic pace. Vascular pathology dramatically affects cognitive profiles, resulting in dementia and cognitive impairment. While vascular dementia itself constitutes a medical challenge, hypoperfusion/vascular risk factors enhance amyloid toxicity and other memory-damaging factors and hasten Alzheimer's disease (AD) and other memory disorders' progression, as well as negatively affect treatment outcome. Few therapeutic options are, however, currently available to improve the prognosis of patients with vascular dementia and cognitive impairment, mixed AD dementia with vascular pathology, or other memory disorders. Emerging evidence, however, indicates that, like AD and other memory disorders, synaptic impairment underlies much of the memory impairment in the cognitive decline of vascular cognitive impairment and vascular dementia. Effective rescues of the memory functions might be achieved through synaptic and memory therapeutics, targeting distinct molecular signaling pathways that support the formation of new synapses and maintaining their connections. Potential therapeutic agents include: 1) memory therapeutic agents that rescue synaptic and memory functions after the brain insults; 2) anti-pathologic therapeutics and an effective management of vascular risk factors; and 3) preventative therapeutic agents that achieve memory therapy through functional enhancement. Their development and potential as clinically effective memory therapeutics for vascular cognitive impairment and dementia are discussed in this review. These therapeutic agents are also likely to benefit patients with AD and/or other types of memory disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Formation Control of the MAXIM L2 Libration Orbit Mission

NASA Technical Reports Server (NTRS)

Folta, David; Hartman, Kate; Howell, Kathleen; Marchand, Belinda

2004-01-01

The Micro-Arcsecond Imaging Mission (MAXIM), a proposed concept for the Structure and Evolution of the Universe (SEU) Black Hole Imaging mission, is designed to make a ten million-fold improvement in X-ray image clarity of celestial objects by providing better than 0.1 microarcsecond imaging. To achieve mission requirements, MAXIM will have to improve on pointing by orders of magnitude. This pointing requirement impacts the control and design of the formation. Currently the architecture is comprised of 25 spacecraft, which will form the sparse apertures of a grazing incidence X-ray interferometer covering the 0.3-10 keV bandpass. This configuration will deploy 24 spacecraft as optics modules and one as the detector. The formation must allow for long duration continuous science observations and also for reconfiguration that permits re-pointing of the formation. In this paper, we provide analysis and trades of several control efforts that are dependent upon the pointing requirements and the configuration and dimensions of the MAXIM formation. We emphasize the utilization of natural motions in the Lagrangian regions that minimize the control efforts and we address both continuous and discrete control via LQR and feedback linearization. Results provide control cost, configuration options, and capabilities as guidelines for the development of this complex mission.

Maximally reliable spatial filtering of steady state visual evoked potentials.

PubMed

Dmochowski, Jacek P; Greaves, Alex S; Norcia, Anthony M

2015-04-01

Due to their high signal-to-noise ratio (SNR) and robustness to artifacts, steady state visual evoked potentials (SSVEPs) are a popular technique for studying neural processing in the human visual system. SSVEPs are conventionally analyzed at individual electrodes or linear combinations of electrodes which maximize some variant of the SNR. Here we exploit the fundamental assumption of evoked responses--reproducibility across trials--to develop a technique that extracts a small number of high SNR, maximally reliable SSVEP components. This novel spatial filtering method operates on an array of Fourier coefficients and projects the data into a low-dimensional space in which the trial-to-trial spectral covariance is maximized. When applied to two sample data sets, the resulting technique recovers physiologically plausible components (i.e., the recovered topographies match the lead fields of the underlying sources) while drastically reducing the dimensionality of the data (i.e., more than 90% of the trial-to-trial reliability is captured in the first four components). Moreover, the proposed technique achieves a higher SNR than that of the single-best electrode or the Principal Components. We provide a freely-available MATLAB implementation of the proposed technique, herein termed "Reliable Components Analysis". Copyright © 2015 Elsevier Inc. All rights reserved.

Matching achievement contexts with implicit theories to maximize motivation after failure: a congruence model.

PubMed

El-Alayli, Amani

2006-12-01

Previous research has shown that matching person variables with achievement contexts can produce the best motivational outcomes. The current study examines whether this is also true when matching entity and incremental beliefs with the appropriate motivational climate. Participants were led to believe that a personal attribute was fixed (entity belief) or malleable (incremental belief). After thinking that they failed a test that assessed the attribute, participants performed a second (related) task in a context that facilitated the pursuit of either performance or learning goals. Participants were expected to exhibit greater effort on the second task in the congruent conditions (entity belief plus performance goal climate and incremental belief plus learning goal climate) than in the incongruent conditions. These results were obtained, but only for participants who either valued competence on the attribute or had high achievement motivation. Results are discussed in terms of developing strategies for optimizing motivation in achievement settings.

Using therapeutic cloning to fight human disease: a conundrum or reality?

PubMed

Hall, Vanessa J; Stojkovic, Petra; Stojkovic, Miodrag

2006-07-01

The development and transplantation of autologous cells derived from nuclear transfer embryonic stem cell (NT-ESC) lines to treat patients suffering from disease has been termed therapeutic cloning. Human NT is still a developing field, with further research required to improve somatic cell NT and human embryonic stem cell differentiation to deliver safe and effective cell replacement therapies. Furthermore, the implications of transferring mitochondrial heteroplasmic cells, which may harbor aberrant epigenetic gene expression profiles, are of concern. The production of human NT-ESC lines also remains plagued by ethical dilemmas, societal concerns, and controversies. Recently, a number of alternate therapeutic strategies have been proposed to circumvent the moral implications surrounding human nuclear transfer. It will be critical to overcome these biological, legislative, and moral restraints to maximize the potential of this therapeutic strategy and to alleviate human disease.

Teaching clinical pharmacology and therapeutics with an emphasis on the therapeutic reasoning of undergraduate medical students

PubMed Central

Richir, Milan C.; Tichelaar, Jelle; Geijteman, Eric C. T.

2008-01-01

Background The rational prescribing of drugs is an essential skill of medical doctors. Clinical pharmacologists play an important role in the development of these skills by teaching clinical pharmacology and therapeutics (CP&T) to undergraduate medical students. Although the approaches to teaching CP&T have undergone many changes over the last decennia, it is essential that the actual teaching of CP&T continues to be a major part of the undergraduate medical curriculum. Objectives The learning objectives of CP&T teaching in terms of developing the therapeutic competencies of undergraduate medical students are described, with an emphasis on therapeutic decision-making. On the basis of current theories of cognitive psychology and medical education, context-learning is presented as an effective approach by which to achieve therapeutic competencies. An example of a CP&T curriculum is presented. PMID:18228012

Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: lessons from the DALI Study.

PubMed

Roberts, J A; Stove, V; De Waele, J J; Sipinkoski, B; McWhinney, B; Ungerer, J P J; Akova, M; Bassetti, M; Dimopoulos, G; Kaukonen, K-M; Koulenti, D; Martin, C; Montravers, P; Rello, J; Rhodes, A; Starr, T; Wallis, S C; Lipman, J

2014-05-01

The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10-30 mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2-26.0) and free 1.5 (0.7-2.5); trough, total 11.9 (10.2-22.7) and free 1.8 (0.6-2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5-15.6%) and 8.2% (5.5-16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint (ρ = 0.79, P = 0.0021) and trough (ρ = 0.63, P = 0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concentrations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Maximal likelihood correspondence estimation for face recognition across pose.

PubMed

Li, Shaoxin; Liu, Xin; Chai, Xiujuan; Zhang, Haihong; Lao, Shihong; Shan, Shiguang

2014-10-01

Due to the misalignment of image features, the performance of many conventional face recognition methods degrades considerably in across pose scenario. To address this problem, many image matching-based methods are proposed to estimate semantic correspondence between faces in different poses. In this paper, we aim to solve two critical problems in previous image matching-based correspondence learning methods: 1) fail to fully exploit face specific structure information in correspondence estimation and 2) fail to learn personalized correspondence for each probe image. To this end, we first build a model, termed as morphable displacement field (MDF), to encode face specific structure information of semantic correspondence from a set of real samples of correspondences calculated from 3D face models. Then, we propose a maximal likelihood correspondence estimation (MLCE) method to learn personalized correspondence based on maximal likelihood frontal face assumption. After obtaining the semantic correspondence encoded in the learned displacement, we can synthesize virtual frontal images of the profile faces for subsequent recognition. Using linear discriminant analysis method with pixel-intensity features, state-of-the-art performance is achieved on three multipose benchmarks, i.e., CMU-PIE, FERET, and MultiPIE databases. Owe to the rational MDF regularization and the usage of novel maximal likelihood objective, the proposed MLCE method can reliably learn correspondence between faces in different poses even in complex wild environment, i.e., labeled face in the wild database.

Formation Control of the MAXIM L2 Libration Orbit Mission

NASA Technical Reports Server (NTRS)

Folta, David; Hartman, Kate; Howell, Kathleen; Marchand, Belinda

2004-01-01

The Micro-Arcsecond X-ray Imaging Mission (MAXIM), a proposed concept for the Structure and Evolution of the Universe (SEU) Black Hole Imager mission, is designed to make a ten million-fold improvement in X-ray image clarity of celestial objects by providing better than 0.1 micro-arcsecond imaging. Currently the mission architecture comprises 25 spacecraft, 24 as optics modules and one as the detector, which will form sparse sub-apertures of a grazing incidence X-ray interferometer covering the 0.3-10 keV bandpass. This formation must allow for long duration continuous science observations and also for reconfiguration that permits re-pointing of the formation. To achieve these mission goals, the formation is required to cooperatively point at desired targets. Once pointed, the individual elements of the MAXIM formation must remain stable, maintaining their relative positions and attitudes below a critical threshold. These pointing and formation stability requirements impact the control and design of the formation. In this paper, we provide analysis of control efforts that are dependent upon the stability and the configuration and dimensions of the MAXIM formation. We emphasize the utilization of natural motions in the Lagrangian regions to minimize the control efforts and we address continuous control via input feedback linearization (IFL). Results provide control cost, configuration options, and capabilities as guidelines for the development of this complex mission.

Anxiety responses to maximal exercise testing.

PubMed Central

O'Connor, P J; Petruzzello, S J; Kubitz, K A; Robinson, T L

1995-01-01

The influence of maximal exercise testing on state anxiety was examined in three separate studies. Highly trained male distance runners (Study 1, n = 12) as well as college students with average (Study 2, n = 16) and below average (Study 3, n = 32) physical fitness levels completed graded maximal exercise tests. This last group was also randomly assigned to either a control or an 8 week training programme in order to determine the effect of increased fitness on the psychological responses to maximal exercise testing. Physical fitness was determined by the measurement of maximal oxygen uptake. State anxiety (State-Trait Anxiety Inventory) was assessed before and from 2-15 min following exercise. It was found that the state anxiety responses to maximal exercise testing were not influenced by re-testing or by 8 weeks of endurance training. Across the three study groups, the anxiety response was variable during the first 5 min following exercise testing; increases, decreases and no changes in anxiety were observed when compared to pre-exercise levels. The anxiety response to maximal exercise appeared to be dependent on the pre-exercise anxiety levels as well as the timing of the post-exercise assessments. It is concluded that maximal exercise testing can be associated with negative mood shifts during the first 5 min after exercise; however, this response is transitory and followed by positive mood shifts 10-15 min following such tests. PMID:7551769

Control Strategies for Distributed Energy Resources to Maximize the Use of Wind Power in Rural Microgrids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Shuai; Elizondo, Marcelo A.; Samaan, Nader A.

2011-10-10

The focus of this paper is to design control strategies for distributed energy resources (DERs) to maximize the use of wind power in a rural microgrid. In such a system, it may be economical to harness wind power to reduce the consumption of fossil fuels for electricity production. In this work, we develop control strategies for DERs, including diesel generators, energy storage and demand response, to achieve high penetration of wind energy in a rural microgrid. Combinations of centralized (direct control) and decentralized (autonomous response) control strategies are investigated. Detailed dynamic models for a rural microgrid are built to conductmore » simulations. The system response to large disturbances and frequency regulation are tested. It is shown that optimal control coordination of DERs can be achieved to maintain system frequency while maximizing wind power usage and reducing the wear and tear on fossil fueled generators.« less

A rational model for maximizing the effects of therapeutic relationship regulation in personality disorders with poor metacognition and over-regulation of affects.

PubMed

Dimaggio, Giancarlo; Carcione, Antonino; Salvatore, Giampaolo; Semerari, Antonio; Nicolò, Giuseppe

2010-11-01

The therapeutic relationship plays a key role in personality disorder (PD) psychotherapy. Some aspects of therapeutic relationship regulation appear important for treatment of PD clients, including those with constricted relational schemas, poor metacognition, and over-regulation of affects described here. AIM.: To propose a rational model for how and when to work on the therapeutic relationship by treating the underlying personality pathology. Formalize a step-by-step procedure for performing operations such as validation of clients' experiences, creating a sense of sharedness, assessing the quality of the therapeutic relationship in order to prevent and repair ruptures in the alliance, self-disclosing by the therapist, and metacommunication on the basis of clients' responses to treatment. We discuss the implications of this model for further research into the PD therapy process. 2010 The British Psychological Society.

Further reduction of minimal first-met bad markings for the computationally efficient synthesis of a maximally permissive controller

NASA Astrophysics Data System (ADS)

Liu, GaiYun; Chao, Daniel Yuh

2015-08-01

To date, research on the supervisor design for flexible manufacturing systems focuses on speeding up the computation of optimal (maximally permissive) liveness-enforcing controllers. Recent deadlock prevention policies for systems of simple sequential processes with resources (S3PR) reduce the computation burden by considering only the minimal portion of all first-met bad markings (FBMs). Maximal permissiveness is ensured by not forbidding any live state. This paper proposes a method to further reduce the size of minimal set of FBMs to efficiently solve integer linear programming problems while maintaining maximal permissiveness using a vector-covering approach. This paper improves the previous work and achieves the simplest structure with the minimal number of monitors.

Maximal oxygen uptake and cardiorespiratory response to maximal 400-m free swimming, running and cycling tests in competitive swimmers.

PubMed

Rodríguez, F A

2000-06-01

This study compared the cardiorespiratory response of trained swimmers to 400-m unimpeded front crawl swimming (SW), treadmill running (TR) and ergometer cycling (EC) maximal exercise tests, and evaluated the validity and specificity of a method to measure maximal aerobic power in swimming. Two series of experiments were conducted. In series A (n=15), comparisons were made between VO2peak and other cardiorespiratory variables in three maximal tests: after 400-m SW, and during incremental TR and EC. In series B, VO2 peak and related variables were measured after SW and during EC (n=33). No significant differences were observed between VO2peak and VE in the three modes of exercise, although SW values tended to be higher. After SW, maximal ventilatory response was characterized by higher tidal volumes (VT) and lower respiratory rates (fR) as compared with TR and EC. The highest heart rate values (fH) were also observed in TR, followed by EC and SW. In series B, no significant differences were observed either in peak VO2 or VE, but fH was also lower in SW. A maximal 400-m unimpeded freestyle SW test yields essentially equal or nonsignificantly higher peak VO2 and VE values than during maximal TR or EC tests in trained swimmers. The specific maximal cardiorespiratory response to the SW test is characterized by higher VT, lower fR, and lower fH. Breath-by-breath measurements during the immediate recovery after a 400-m voluntary maximal swim is proposed as a valid and specific test for directly measuring maximal metabolic parameters and evaluating specific maximal aerobic power in swimming.

Quantum-Inspired Maximizer

NASA Technical Reports Server (NTRS)

Zak, Michail

2008-01-01

A report discusses an algorithm for a new kind of dynamics based on a quantum- classical hybrid-quantum-inspired maximizer. The model is represented by a modified Madelung equation in which the quantum potential is replaced by different, specially chosen 'computational' potential. As a result, the dynamics attains both quantum and classical properties: it preserves superposition and entanglement of random solutions, while allowing one to measure its state variables, using classical methods. Such optimal combination of characteristics is a perfect match for quantum-inspired computing. As an application, an algorithm for global maximum of an arbitrary integrable function is proposed. The idea of the proposed algorithm is very simple: based upon the Quantum-inspired Maximizer (QIM), introduce a positive function to be maximized as the probability density to which the solution is attracted. Then the larger value of this function will have the higher probability to appear. Special attention is paid to simulation of integer programming and NP-complete problems. It is demonstrated that the problem of global maximum of an integrable function can be found in polynomial time by using the proposed quantum- classical hybrid. The result is extended to a constrained maximum with applications to integer programming and TSP (Traveling Salesman Problem).

Society already achieves economic benefits from generic substitution but fails to do the same for therapeutic substitution.

PubMed

Gumbs, Pearl D; Verschuren, W M Monique; Souverein, Patrick C; Mantel-Teeuwisse, Aukje K; de Wit, G Ardine; de Boer, Anthonius; Klungel, Olaf H

2007-11-01

To assess the potential annual savings due to generic and therapeutic substitution of statin therapy for the general Dutch population, taking the patients medical history into account. We conducted a population-based costing study using the PHARMO Record Linkage System (RLS). PHARMO RLS contains drug dispensing records from a representative sample of pharmacies located in more than 50 regions in the Netherlands. We selected all statin users in the database since 2003. The cost-savings of generic substitution of statin therapy for all simvastatin and pravastatin users, and of therapeutic substitution of statin therapy for other statin users were calculated. Substituting current users and new users of statins were considered separately. Therapeutic substitution was based on the medical history of the individual patient. Patients were only substituted if there was an appropriate substitute available. The appropriateness of substitution was based on drug-drug interactions between statins and possible comedication and the availability of an equipotent alternative. Substituting (generic and therapeutic) statin therapy for all current users would lead to potential annual savings of approximately 87 million euros. Substituting (generic and therapeutic) all starters on statin therapy would lead to potential annual savings of around 51 million euros. In the case of generic substitution only, the potential annual savings for all current simvastatin and pravastatin users would be 2.4 million euros and for the new users about 1.8 million euros. From an economic point of view, society could gain a lot from substituting statin therapy, especially from therapeutic substitution.

Recent Progress in Functional Micellar Carriers with Intrinsic Therapeutic Activities for Anticancer Drug Delivery.

PubMed

Qu, Ying; Chu, BingYang; Shi, Kun; Peng, JinRong; Qian, ZhiYong

2017-12-01

Polymeric micelles have presented superior delivery properties for poorly water-soluble chemotherapeutic agents. However, it remains discouraging that there may be some additional short or long-term toxicities caused by the metabolites of high quantities of carriers. If carriers had simultaneous therapeutic effects with the drug, these issues would not be a concern. For this, carriers not only simply act as drug carriers, but also exert an intrinsic therapeutic effect as a therapeutic agent. The functional micellar carriers would be beneficial to maximize the anticancer effect, overcome the drug resistance and reduce the systemic toxicity. In this review, we aim to summarize the recent progress on the development of functional micellar carriers with intrinsic anticancer activities for the delivery of anticancer drugs. This review focuses on the design strategies, properties of carriers and the drug loading behavior. In addition, the combinational therapeutic effects between carriers and chemotherapeutic agents are also discussed.

Impacts of Maximizing Tendencies on Experience-Based Decisions.

PubMed

Rim, Hye Bin

2017-06-01

Previous research on risky decisions has suggested that people tend to make different choices depending on whether they acquire the information from personally repeated experiences or from statistical summary descriptions. This phenomenon, called as a description-experience gap, was expected to be moderated by the individual difference in maximizing tendencies, a desire towards maximizing decisional outcome. Specifically, it was hypothesized that maximizers' willingness to engage in extensive information searching would lead maximizers to make experience-based decisions as payoff distributions were given explicitly. A total of 262 participants completed four decision problems. Results showed that maximizers, compared to non-maximizers, drew more samples before making a choice but reported lower confidence levels on both the accuracy of knowledge gained from experiences and the likelihood of satisfactory outcomes. Additionally, maximizers exhibited smaller description-experience gaps than non-maximizers as expected. The implications of the findings and unanswered questions for future research were discussed.

Auctions with Dynamic Populations: Efficiency and Revenue Maximization

NASA Astrophysics Data System (ADS)

Said, Maher

We study a stochastic sequential allocation problem with a dynamic population of privately-informed buyers. We characterize the set of efficient allocation rules and show that a dynamic VCG mechanism is both efficient and periodic ex post incentive compatible; we also show that the revenue-maximizing direct mechanism is a pivot mechanism with a reserve price. We then consider sequential ascending auctions in this setting, both with and without a reserve price. We construct equilibrium bidding strategies in this indirect mechanism where bidders reveal their private information in every period, yielding the same outcomes as the direct mechanisms. Thus, the sequential ascending auction is a natural institution for achieving either efficient or optimal outcomes.

Delivery methods for site-specific nucleases: Achieving the full potential of therapeutic gene editing.

PubMed

Liu, Jia; Shui, Sai-Lan

2016-12-28

The advent of site-specific nucleases, particularly CRISPR/Cas9, provides researchers with the unprecedented ability to manipulate genomic sequences. These nucleases are used to create model cell lines, engineer metabolic pathways, produce transgenic animals and plants, perform genome-wide functional screen and, most importantly, treat human diseases that are difficult to tackle by traditional medications. Considerable efforts have been devoted to improving the efficiency and specificity of nucleases for clinical applications. However, safe and efficient delivery methods remain the major obstacle for therapeutic gene editing. In this review, we summarize the recent progress on nuclease delivery methods, highlight their impact on the outcomes of gene editing and discuss the potential of different delivery approaches for therapeutic gene editing. Copyright © 2016 Elsevier B.V. All rights reserved.

Strategically timing inhibition of phosphatidylinositol 3-kinase to maximize therapeutic index in estrogen receptor alpha-positive, PIK3CA-mutant breast cancer

PubMed Central

Yang, Wei; Hosford, Sarah R.; Dillon, Lloye M.; Shee, Kevin; Liu, Stephanie C.; Bean, Jennifer R.; Salphati, Laurent; Pang, Jodie; Zhang, Xiaolin; Nannini, Michelle A.; Demidenko, Eugene; Bates, Darcy; Lewis, Lionel D.; Marotti, Jonathan D.; Eastman, Alan R.; Miller, Todd W.

2016-01-01

Purpose Phosphatidylinositol 3-kinase (PI3K) inhibitors are being developed for the treatment of estrogen receptor α (ER)-positive breast cancer in combination with anti-estrogens. Understanding the temporal response and pharmacodynamic effects of PI3K inhibition in ER+ breast cancer will provide rationale for treatment scheduling to maximize therapeutic index. Experimental Design Anti-estrogen-sensitive and -resistant ER+ human breast cancer cell lines, and mice bearing PIK3CA-mutant xenografts were treated with the anti-estrogen fulvestrant, the PI3K inhibitor GDC-0941 (pictilisib; varied doses/schedules that provided similar amounts of drug each week), or combinations. Cell viability, signaling pathway inhibition, proliferation, apoptosis, tumor volume, and GDC-0941 concentrations in plasma and tumors were temporally measured. Results Treatment with the combination of fulvestrant and GDC-0941, regardless of dose/schedule, was significantly more effective than single-agent treatments in fulvestrant-resistant tumors. Short-term, complete PI3K inhibition blocked cell growth in vitro more effectively than chronic, incomplete inhibition. Longer-term PI3K inhibition hypersensitized cells to growth factor signaling upon drug withdrawal. Different schedules of GDC-0941 elicited similar tumor responses. While weekly high-dose GDC-0941 with fulvestrant continuously suppressed PI3K signaling for 72 hours, inducing a bolus of apoptosis and inhibiting proliferation, PI3K reactivation upon GDC-0941 washout induced a proliferative burst. Fulvestrant with daily low-dose GDC-0941 metronomically suppressed PI3K for 6–9 hours/day, repeatedly inducing small amounts of apoptosis and temporarily inhibiting proliferation, followed by proliferative rebound compared to fulvestrant alone. Conclusions Continuous and metronomic PI3K inhibition elicit robust anti-cancer effects in ER+, PIK3CA-mutant breast cancer. Clinical exploration of alternate treatment schedules of PI3K inhibitors

Big Data Transforms Discovery-Utilization Therapeutics Continuum.

PubMed

Waldman, S A; Terzic, A

2016-03-01

Enabling omic technologies adopt a holistic view to produce unprecedented insights into the molecular underpinnings of health and disease, in part, by generating massive high-dimensional biological data. Leveraging these systems-level insights as an engine driving the healthcare evolution is maximized through integration with medical, demographic, and environmental datasets from individuals to populations. Big data analytics has accordingly emerged to add value to the technical aspects of storage, transfer, and analysis required for merging vast arrays of omic-, clinical-, and eco-datasets. In turn, this new field at the interface of biology, medicine, and information science is systematically transforming modern therapeutics across discovery, development, regulation, and utilization. © 2015 ASCPT.

A matrix-algebraic formulation of distributed-memory maximal cardinality matching algorithms in bipartite graphs

DOE PAGES

Azad, Ariful; Buluç, Aydın

2016-05-16

We describe parallel algorithms for computing maximal cardinality matching in a bipartite graph on distributed-memory systems. Unlike traditional algorithms that match one vertex at a time, our algorithms process many unmatched vertices simultaneously using a matrix-algebraic formulation of maximal matching. This generic matrix-algebraic framework is used to develop three efficient maximal matching algorithms with minimal changes. The newly developed algorithms have two benefits over existing graph-based algorithms. First, unlike existing parallel algorithms, cardinality of matching obtained by the new algorithms stays constant with increasing processor counts, which is important for predictable and reproducible performance. Second, relying on bulk-synchronous matrix operations,more » these algorithms expose a higher degree of parallelism on distributed-memory platforms than existing graph-based algorithms. We report high-performance implementations of three maximal matching algorithms using hybrid OpenMP-MPI and evaluate the performance of these algorithm using more than 35 real and randomly generated graphs. On real instances, our algorithms achieve up to 200 × speedup on 2048 cores of a Cray XC30 supercomputer. Even higher speedups are obtained on larger synthetically generated graphs where our algorithms show good scaling on up to 16,384 cores.« less

Maximizing Exosome Colloidal Stability Following Electroporation

PubMed Central

Hood, Joshua L.; Scott, Michael J.; Wickline, Samuel A.

2014-01-01

Development of exosome based semi-synthetic nanovesicles for diagnostic and therapeutic purposes requires novel approaches to load exosomes with cargo. Electroporation has previously been used to load exosomes with RNA. However, investigations into exosome colloidal stability following electroporation have not been considered. Herein, we report the development of a unique trehalose pulse media (TPM) that minimizes exosome aggregation following electroporation. Dynamic light scattering (DLS) and RNA absorbance were employed to determine the extent of exosome aggregation and electroextraction post electroporation in TPM compared to common PBS pulse media or sucrose pulse media (SPM). Use of TPM to disaggregate melanoma exosomes post electroporation was dependent on both exosome concentration and electric field strength. TPM maximized exosome dispersal post electroporation for both homogenous B16 melanoma and heterogeneous human serum derived populations of exosomes. Moreover, TPM enabled heavy cargo loading of melanoma exosomes with 5 nm superparamagnetic iron oxide nanoparticles (SPION5) while maintaining original exosome size and minimizing exosome aggregation as evidenced by transmission electron microscopy. Loading exosomes with SPION5 increased exosome density on sucrose gradients. This provides a simple, label free means to enrich exogenously modified exosomes and introduces the potential for MRI driven theranostic exosome investigations in vivo. PMID:24333249

Maximizing exosome colloidal stability following electroporation.

PubMed

Hood, Joshua L; Scott, Michael J; Wickline, Samuel A

2014-03-01

Development of exosome-based semisynthetic nanovesicles for diagnostic and therapeutic purposes requires novel approaches to load exosomes with cargo. Electroporation has previously been used to load exosomes with RNA. However, investigations into exosome colloidal stability following electroporation have not been considered. Herein, we report the development of a unique trehalose pulse media (TPM) that minimizes exosome aggregation following electroporation. Dynamic light scattering (DLS) and RNA absorbance were employed to determine the extent of exosome aggregation and electroextraction post electroporation in TPM compared to common PBS pulse media or sucrose pulse media (SPM). Use of TPM to disaggregate melanoma exosomes post electroporation was dependent on both exosome concentration and electric field strength. TPM maximized exosome dispersal post electroporation for both homogenous B16 melanoma and heterogeneous human serum-derived populations of exosomes. Moreover, TPM enabled heavy cargo loading of melanoma exosomes with 5nm superparamagnetic iron oxide nanoparticles (SPION5) while maintaining original exosome size and minimizing exosome aggregation as evidenced by transmission electron microscopy. Loading exosomes with SPION5 increased exosome density on sucrose gradients. This provides a simple, label-free means of enriching exogenously modified exosomes and introduces the potential for MRI-driven theranostic exosome investigations in vivo. Copyright © 2013 Elsevier Inc. All rights reserved.

The Stress of Black Male Achievement: Ten Nonnegotiables

ERIC Educational Resources Information Center

Henfield, Malik S.

2012-01-01

Oftentimes, when the subject of Black students' talent maximization in gifted and advanced courses and programs is broached, students are treated as a monolithic entity. In fact, there is considerable evidence to suggest that unsuccessful achievement of academic excellence may be more troublesome for males than females at many points along the…

Erectile hydraulics: maximizing inflow while minimizing outflow.

PubMed

Meldrum, David R; Burnett, Arthur L; Dorey, Grace; Esposito, Katherine; Ignarro, Louis J

2014-05-01

Penile rigidity depends on maximizing inflow while minimizing outflow. The aim of this review is to describe the principal factors and mechanisms involved. Erectile quality is the main outcome measure. Data from the pertinent literature were examined to inform our conclusions. Nitric oxide (NO) is the principal factor increasing blood flow into the penis. Penile engorgement and the pelvic floor muscles maintain an adequate erection by impeding outflow of blood by exerting pressure on the penile veins from within and from outside of the penile tunica. Extrinsic pressure by the pelvic floor muscles further raises intracavernosal pressure above maximum inflow pressure to achieve full penile rigidity. Aging and poor lifestyle choices are associated with metabolic impediments to NO production. Aging is also associated with fewer smooth muscle cells and increased fibrosis within the corpora cavernosa, preventing adequate penile engorgement and pressure on the penile veins. Those same penile structural changes occur rapidly following the penile nerve injury that accompanies even "nerve-sparing" radical prostatectomy and are largely prevented in animal models by early chronic use of a phosphodiesterase type 5 (PDE5) inhibitor. Pelvic floor muscles may also decrease in tone and bulk with age, and pelvic floor muscle exercises have been shown to improve erectile function to a similar degree compared with a PDE5 inhibitor in men with erectile dysfunction (ED). Because NO is critical for vascular health and ED is strongly associated with cardiovascular disease, maximal attention should be focused on measures known to increase vascular NO production, including the use of PDE5 inhibitors. Attention should also be paid to early, regular use of PDE5 inhibition to reduce the incidence of ED following penile nerve injury and to assuring normal function of the pelvic floor muscles. These approaches to maximizing erectile function are complementary rather than competitive, as they

Are all maximally entangled states pure?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cavalcanti, D.; Brandao, F.G.S.L.; Terra Cunha, M.O.

We study if all maximally entangled states are pure through several entanglement monotones. In the bipartite case, we find that the same conditions which lead to the uniqueness of the entropy of entanglement as a measure of entanglement exclude the existence of maximally mixed entangled states. In the multipartite scenario, our conclusions allow us to generalize the idea of the monogamy of entanglement: we establish the polygamy of entanglement, expressing that if a general state is maximally entangled with respect to some kind of multipartite entanglement, then it is necessarily factorized of any other system.

Are all maximally entangled states pure?

NASA Astrophysics Data System (ADS)

Cavalcanti, D.; Brandão, F. G. S. L.; Terra Cunha, M. O.

2005-10-01

We study if all maximally entangled states are pure through several entanglement monotones. In the bipartite case, we find that the same conditions which lead to the uniqueness of the entropy of entanglement as a measure of entanglement exclude the existence of maximally mixed entangled states. In the multipartite scenario, our conclusions allow us to generalize the idea of the monogamy of entanglement: we establish the polygamy of entanglement, expressing that if a general state is maximally entangled with respect to some kind of multipartite entanglement, then it is necessarily factorized of any other system.

An Efficient and Effective Design of InP Nanowires for Maximal Solar Energy Harvesting

NASA Astrophysics Data System (ADS)

Wu, Dan; Tang, Xiaohong; Wang, Kai; He, Zhubing; Li, Xianqiang

2017-11-01

Solar cells based on subwavelength-dimensions semiconductor nanowire (NW) arrays promise a comparable or better performance than their planar counterparts by taking the advantages of strong light coupling and light trapping. In this paper, we present an accurate and time-saving analytical design for optimal geometrical parameters of vertically aligned InP NWs for maximal solar energy absorption. Short-circuit current densities are calculated for each NW array with different geometrical dimensions under solar illumination. Optimal geometrical dimensions are quantitatively presented for single, double, and multiple diameters of the NW arrays arranged both squarely and hexagonal achieving the maximal short-circuit current density of 33.13 mA/cm2. At the same time, intensive finite-difference time-domain numerical simulations are performed to investigate the same NW arrays for the highest light absorption. Compared with time-consuming simulations and experimental results, the predicted maximal short-circuit current densities have tolerances of below 2.2% for all cases. These results unambiguously demonstrate that this analytical method provides a fast and accurate route to guide high performance InP NW-based solar cell design.

Gaussian maximally multipartite-entangled states

NASA Astrophysics Data System (ADS)

Facchi, Paolo; Florio, Giuseppe; Lupo, Cosmo; Mancini, Stefano; Pascazio, Saverio

2009-12-01

We study maximally multipartite-entangled states in the context of Gaussian continuous variable quantum systems. By considering multimode Gaussian states with constrained energy, we show that perfect maximally multipartite-entangled states, which exhibit the maximum amount of bipartite entanglement for all bipartitions, only exist for systems containing n=2 or 3 modes. We further numerically investigate the structure of these states and their frustration for n≤7 .

Activity versus outcome maximization in time management.

PubMed

Malkoc, Selin A; Tonietto, Gabriela N

2018-04-30

Feeling time-pressed has become ubiquitous. Time management strategies have emerged to help individuals fit in more of their desired and necessary activities. We provide a review of these strategies. In doing so, we distinguish between two, often competing, motives people have in managing their time: activity maximization and outcome maximization. The emerging literature points to an important dilemma: a given strategy that maximizes the number of activities might be detrimental to outcome maximization. We discuss such factors that might hinder performance in work tasks and enjoyment in leisure tasks. Finally, we provide theoretically grounded recommendations that can help balance these two important goals in time management. Published by Elsevier Ltd.

Black disk, maximal Odderon and unitarity

NASA Astrophysics Data System (ADS)

Khoze, V. A.; Martin, A. D.; Ryskin, M. G.

2018-05-01

We argue that the so-called maximal Odderon contribution breaks the 'black disk' behavior of the asymptotic amplitude, since the cross section of the events with Large Rapidity Gaps grows faster than the total cross section. That is the 'maximal Odderon' is not consistent with unitarity.

The state-of-play and future of antibody therapeutics.

PubMed

Elgundi, Zehra; Reslan, Mouhamad; Cruz, Esteban; Sifniotis, Vicki; Kayser, Veysel

2017-12-01

It has been over four decades since the development of monoclonal antibodies (mAbs) using a hybridoma cell line was first reported. Since then more than thirty therapeutic antibodies have been marketed, mostly as oncology, autoimmune and inflammatory therapeutics. While antibodies are very efficient, their cost-effectiveness has always been discussed owing to their high costs, accumulating to more than one billion dollars from preclinical development through to market approval. Because of this, therapeutic antibodies are inaccessible to some patients in both developed and developing countries. The growing interest in biosimilar antibodies as affordable versions of therapeutic antibodies may provide alternative treatment options as well potentially decreasing costs. As certain markets begin to capitalize on this opportunity, regulatory authorities continue to refine the requirements for demonstrating quality, efficacy and safety of biosimilar compared to originator products. In addition to biosimilars, innovations in antibody engineering are providing the opportunity to design biobetter antibodies with improved properties to maximize efficacy. Enhancing effector function, antibody drug conjugates (ADC) or targeting multiple disease pathways via multi-specific antibodies are being explored. The manufacturing process of antibodies is also moving forward with advancements relating to host cell production and purification processes. Studies into the physical and chemical degradation pathways of antibodies are contributing to the design of more stable proteins guided by computational tools. Moreover, the delivery and pharmacokinetics of antibody-based therapeutics are improving as optimized formulations are pursued through the implementation of recent innovations in the field. Copyright © 2016 Elsevier B.V. All rights reserved.

Bioeconomic of profit maximization of red tilapia (Oreochromis sp.) culture using polynomial growth model

NASA Astrophysics Data System (ADS)

Wijayanto, D.; Kurohman, F.; Nugroho, RA

2018-03-01

The research purpose was to develop a model bioeconomic of profit maximization that can be applied to red tilapia culture. The development of fish growth model used polynomial growth function. Profit maximization process used the first derivative of profit equation to time of culture equal to zero. This research has also developed the equations to estimate the culture time to reach the target size of the fish harvest. The research proved that this research model could be applied in the red tilapia culture. In the case of this study, red tilapia culture can achieve the maximum profit at 584 days and the profit of Rp. 28,605,731 per culture cycle. If used size target of 250 g, the culture of red tilapia need 82 days of culture time.

Maximizing mutagenesis with solubilized CRISPR-Cas9 ribonucleoprotein complexes.

PubMed

Burger, Alexa; Lindsay, Helen; Felker, Anastasia; Hess, Christopher; Anders, Carolin; Chiavacci, Elena; Zaugg, Jonas; Weber, Lukas M; Catena, Raul; Jinek, Martin; Robinson, Mark D; Mosimann, Christian

2016-06-01

CRISPR-Cas9 enables efficient sequence-specific mutagenesis for creating somatic or germline mutants of model organisms. Key constraints in vivo remain the expression and delivery of active Cas9-sgRNA ribonucleoprotein complexes (RNPs) with minimal toxicity, variable mutagenesis efficiencies depending on targeting sequence, and high mutation mosaicism. Here, we apply in vitro assembled, fluorescent Cas9-sgRNA RNPs in solubilizing salt solution to achieve maximal mutagenesis efficiency in zebrafish embryos. MiSeq-based sequence analysis of targeted loci in individual embryos using CrispRVariants, a customized software tool for mutagenesis quantification and visualization, reveals efficient bi-allelic mutagenesis that reaches saturation at several tested gene loci. Such virtually complete mutagenesis exposes loss-of-function phenotypes for candidate genes in somatic mutant embryos for subsequent generation of stable germline mutants. We further show that targeting of non-coding elements in gene regulatory regions using saturating mutagenesis uncovers functional control elements in transgenic reporters and endogenous genes in injected embryos. Our results establish that optimally solubilized, in vitro assembled fluorescent Cas9-sgRNA RNPs provide a reproducible reagent for direct and scalable loss-of-function studies and applications beyond zebrafish experiments that require maximal DNA cutting efficiency in vivo. © 2016. Published by The Company of Biologists Ltd.

Diurnal Variations in Maximal Oxygen Uptake.

ERIC Educational Resources Information Center

McClellan, Powell D.

A study attempted to determine if diurnal (daily cyclical) variations were present during maximal exercise. The subjects' (30 female undergraduate physical education majors) oxygen consumption and heart rates were monitored while they walked on a treadmill on which the grade was raised every minute. Each subject was tested for maximal oxygen…

[Therapeutic education in asthma management].

PubMed

Korta Murua, J; Valverde Molina, J; Praena Crespo, M; Figuerola Mulet, J; Rodríguez Fernández-Oliva, C R; Rueda Esteban, S; Neira Rodríguez, A; Vázquez Cordero, C; Martínez Gómez, M; Román Piñana, J M

2007-05-01

All guidelines, protocols and recommendations underline the importance of therapeutic education as a key element in asthma management and control. Considerable evidence supports the efficacy and effectiveness of this measure. Health personnel, as well as patients and their parents, can and should be educated with two main objectives: to achieve the best possible quality of life and to allow self control of the disease. These goals can be attained through an educational process that should be individually tailored, continuous, progressive, dynamic, and sequential. The process poses more than a few difficulties involving patients, health professionals, and the health systems. Knowledge of the various psychological factors that can be present in asthmatic patients, as well as the factors related to the highly prevalent phenomenon of non-adherence, is essential. Awareness of the factors influencing physician-patient-family communication is also highly important to achieve the objectives set in therapeutic education. The educational process helps knowledge and abilities to be acquired and allows attitudes and beliefs to be modified. Patients and caregivers should be provided with an individual written action plan based on symptoms and/or forced expiratory volume in 1 second. Periodic follow-up visits are also required.

Therapeutic Gene Editing Safety and Specificity.

PubMed

Lux, Christopher T; Scharenberg, Andrew M

2017-10-01

Therapeutic gene editing is significant for medical advancement. Safety is intricately linked to the specificity of the editing tools used to cut at precise genomic targets. Improvements can be achieved by thoughtful design of nucleases and repair templates, analysis of off-target editing, and careful utilization of viral vectors. Advancements in DNA repair mechanisms and development of new generations of tools improve targeting of specific sequences while minimizing risks. It is important to plot a safe course for future clinical trials. This article reviews safety and specificity for therapeutic gene editing to spur dialogue and advancement. Copyright © 2017 Elsevier Inc. All rights reserved.

Integrating epidemiology, psychology, and economics to achieve HPV vaccination targets.

PubMed

Basu, Sanjay; Chapman, Gretchen B; Galvani, Alison P

2008-12-02

Human papillomavirus (HPV) vaccines provide an opportunity to reduce the incidence of cervical cancer. Optimization of cervical cancer prevention programs requires anticipation of the degree to which the public will adhere to vaccination recommendations. To compare vaccination levels driven by public perceptions with levels that are optimal for maximizing the community's overall utility, we develop an epidemiological game-theoretic model of HPV vaccination. The model is parameterized with survey data on actual perceptions regarding cervical cancer, genital warts, and HPV vaccination collected from parents of vaccine-eligible children in the United States. The results suggest that perceptions of survey respondents generate vaccination levels far lower than those that maximize overall health-related utility for the population. Vaccination goals may be achieved by addressing concerns about vaccine risk, particularly those related to sexual activity among adolescent vaccine recipients. In addition, cost subsidizations and shifts in federal coverage plans may compensate for perceived and real costs of HPV vaccination to achieve public health vaccination targets.

Alternative trailer configurations for maximizing payloads

Treesearch

Jason D. Thompson; Dana Mitchell; John Klepac

2017-01-01

In order for harvesting contractors to stay ahead of increasing costs, it is imperative that they employ all options to maximize productivity and efficiency. Transportation can account for half the cost to deliver wood to a mill. Contractors seek to maximize truck payload to increase productivity. The Forest Operations Research Unit, Southern Research Station, USDA...

On the Achievable Throughput Over TVWS Sensor Networks

PubMed Central

Caleffi, Marcello; Cacciapuoti, Angela Sara

2016-01-01

In this letter, we study the throughput achievable by an unlicensed sensor network operating over TV white space spectrum in presence of coexistence interference. Through the letter, we first analytically derive the achievable throughput as a function of the channel ordering. Then, we show that the problem of deriving the maximum expected throughput through exhaustive search is computationally unfeasible. Finally, we derive a computational-efficient algorithm characterized by polynomial-time complexity to compute the channel set maximizing the expected throughput and, stemming from this, we derive a closed-form expression of the maximum expected throughput. Numerical simulations validate the theoretical analysis. PMID:27043565

An Efficient and Effective Design of InP Nanowires for Maximal Solar Energy Harvesting.

PubMed

Wu, Dan; Tang, Xiaohong; Wang, Kai; He, Zhubing; Li, Xianqiang

2017-11-25

Solar cells based on subwavelength-dimensions semiconductor nanowire (NW) arrays promise a comparable or better performance than their planar counterparts by taking the advantages of strong light coupling and light trapping. In this paper, we present an accurate and time-saving analytical design for optimal geometrical parameters of vertically aligned InP NWs for maximal solar energy absorption. Short-circuit current densities are calculated for each NW array with different geometrical dimensions under solar illumination. Optimal geometrical dimensions are quantitatively presented for single, double, and multiple diameters of the NW arrays arranged both squarely and hexagonal achieving the maximal short-circuit current density of 33.13 mA/cm 2 . At the same time, intensive finite-difference time-domain numerical simulations are performed to investigate the same NW arrays for the highest light absorption. Compared with time-consuming simulations and experimental results, the predicted maximal short-circuit current densities have tolerances of below 2.2% for all cases. These results unambiguously demonstrate that this analytical method provides a fast and accurate route to guide high performance InP NW-based solar cell design.

Hierarchical Micro/Nano-Porous Acupuncture Needles Offering Enhanced Therapeutic Properties

NASA Astrophysics Data System (ADS)

in, Su-Ll; Gwak, Young S.; Kim, Hye Rim; Razzaq, Abdul; Lee, Kyeong-Seok; Kim, Hee Young; Chang, Suchan; Lee, Bong Hyo; Grimes, Craig A.; Yang, Chae Ha

2016-10-01

Acupuncture as a therapeutic intervention has been widely used for treatment of many pathophysiological disorders. For achieving improved therapeutic effects, relatively thick acupuncture needles have been frequently used in clinical practice with, in turn, enhanced stimulation intensity. However due to the discomforting nature of the larger-diameter acupuncture needles there is considerable interest in developing advanced acupuncture therapeutical techniques that provide more comfort with improved efficacy. So motivated, we have developed a new class of acupuncture needles, porous acupuncture needles (PANs) with hierarchical micro/nano-scale conical pores upon the surface, fabricated via a simple and well known electrochemical process, with surface area approximately 20 times greater than conventional acupuncture needles. The performance of these high-surface-area PANs is evaluated by monitoring the electrophysiological and behavioral responses from the in vivo stimulation of Shenmen (HT7) points in Wistar rats, showing PANs to be more effective in controlling electrophysiological and behavioral responses than conventional acupuncture needles. Comparative analysis of cocaine induced locomotor activity using PANs and thick acupuncture needles shows enhanced performance of PANs with significantly less pain sensation. Our work offers a unique pathway for achieving a comfortable and improved acupuncture therapeutic effect.

Hierarchical Micro/Nano-Porous Acupuncture Needles Offering Enhanced Therapeutic Properties

PubMed Central

In, Su-ll; Gwak, Young S.; Kim, Hye Rim; Razzaq, Abdul; Lee, Kyeong-Seok; Kim, Hee Young; Chang, SuChan; Lee, Bong Hyo; Grimes, Craig A.; Yang, Chae Ha

2016-01-01

Acupuncture as a therapeutic intervention has been widely used for treatment of many pathophysiological disorders. For achieving improved therapeutic effects, relatively thick acupuncture needles have been frequently used in clinical practice with, in turn, enhanced stimulation intensity. However due to the discomforting nature of the larger-diameter acupuncture needles there is considerable interest in developing advanced acupuncture therapeutical techniques that provide more comfort with improved efficacy. So motivated, we have developed a new class of acupuncture needles, porous acupuncture needles (PANs) with hierarchical micro/nano-scale conical pores upon the surface, fabricated via a simple and well known electrochemical process, with surface area approximately 20 times greater than conventional acupuncture needles. The performance of these high-surface-area PANs is evaluated by monitoring the electrophysiological and behavioral responses from the in vivo stimulation of Shenmen (HT7) points in Wistar rats, showing PANs to be more effective in controlling electrophysiological and behavioral responses than conventional acupuncture needles. Comparative analysis of cocaine induced locomotor activity using PANs and thick acupuncture needles shows enhanced performance of PANs with significantly less pain sensation. Our work offers a unique pathway for achieving a comfortable and improved acupuncture therapeutic effect. PMID:27713547

A maximally stable extremal region based scene text localization method

NASA Astrophysics Data System (ADS)

Xiao, Chengqiu; Ji, Lixin; Gao, Chao; Li, Shaomei

2015-07-01

Text localization in natural scene images is an important prerequisite for many content-based image analysis tasks. This paper proposes a novel text localization algorithm. Firstly, a fast pruning algorithm is designed to extract Maximally Stable Extremal Regions (MSER) as basic character candidates. Secondly, these candidates are filtered by using the properties of fitting ellipse and the distribution properties of characters to exclude most non-characters. Finally, a new extremal regions projection merging algorithm is designed to group character candidates into words. Experimental results show that the proposed method has an advantage in speed and achieve relatively high precision and recall rates than the latest published algorithms.

Strategically Timing Inhibition of Phosphatidylinositol 3-Kinase to Maximize Therapeutic Index in Estrogen Receptor Alpha-Positive, PIK3CA-Mutant Breast Cancer.

PubMed

Yang, Wei; Hosford, Sarah R; Dillon, Lloye M; Shee, Kevin; Liu, Stephanie C; Bean, Jennifer R; Salphati, Laurent; Pang, Jodie; Zhang, Xiaolin; Nannini, Michelle A; Demidenko, Eugene; Bates, Darcy; Lewis, Lionel D; Marotti, Jonathan D; Eastman, Alan R; Miller, Todd W

2016-05-01

Phosphatidylinositol 3-kinase (PI3K) inhibitors are being developed for the treatment of estrogen receptor α (ER)-positive breast cancer in combination with antiestrogens. Understanding the temporal response and pharmacodynamic effects of PI3K inhibition in ER(+) breast cancer will provide a rationale for treatment scheduling to maximize therapeutic index. Antiestrogen-sensitive and antiestrogen-resistant ER(+) human breast cancer cell lines and mice bearing PIK3CA-mutant xenografts were treated with the antiestrogen fulvestrant, the PI3K inhibitor GDC-0941 (pictilisib; varied doses/schedules that provided similar amounts of drug each week), or combinations. Cell viability, signaling pathway inhibition, proliferation, apoptosis, tumor volume, and GDC-0941 concentrations in plasma and tumors were temporally measured. Treatment with the combination of fulvestrant and GDC-0941, regardless of dose/schedule, was significantly more effective than that with single-agent treatments in fulvestrant-resistant tumors. Short-term, complete PI3K inhibition blocked cell growth in vitro more effectively than chronic, incomplete inhibition. Longer-term PI3K inhibition hypersensitized cells to growth factor signaling upon drug withdrawal. Different schedules of GDC-0941 elicited similar tumor responses. While weekly high-dose GDC-0941 with fulvestrant continuously suppressed PI3K signaling for 72 hours, inducing a bolus of apoptosis and inhibiting proliferation, PI3K reactivation upon GDC-0941 washout induced a proliferative burst. Fulvestrant with daily low-dose GDC-0941 metronomically suppressed PI3K for 6 to 9 hours/day, repeatedly inducing small amounts of apoptosis and temporarily inhibiting proliferation, followed by proliferative rebound compared with fulvestrant alone. Continuous and metronomic PI3K inhibition elicits robust anticancer effects in ER(+), PIK3CA-mutant breast cancer. Clinical exploration of alternate treatment schedules of PI3K inhibitors with antiestrogens

The Cost-Effectiveness of 22 Approaches for Raising Student Achievement

ERIC Educational Resources Information Center

Yeh, Stuart S.

2011-01-01

As a consequence of the federal "No Child Left Behind" (NCLB) law, there is tremendous pressure on school principals, teachers, school superintendents, district staff, state departments of education and governors to maximize the increase in student achievement that is obtained with every dollar of expenditure. Currently, teachers are…

Maximally slicing a black hole.

NASA Technical Reports Server (NTRS)

Estabrook, F.; Wahlquist, H.; Christensen, S.; Dewitt, B.; Smarr, L.; Tsiang, E.

1973-01-01

Analytic and computer-derived solutions are presented of the problem of slicing the Schwarzschild geometry into asymptotically flat, asymptotically static, maximal spacelike hypersurfaces. The sequence of hypersurfaces advances forward in time in both halves (u greater than or equal to 0, u less than or equal to 0) of the Kruskal diagram, tending asymptotically to the hypersurface r = 3/2 M and avoiding the singularity at r = 0. Maximality is therefore a potentially useful condition to impose in obtaining computer solutions of Einstein's equations.

Impact of Pharmacy-Led Dyslipidemia Interventions on Medication Safety and Therapeutic Failure in Patients

DTIC Science & Technology

2005-05-01

Center (PEC) guidelines on therapeutic failure. Such guidelines recommend atorvastatin as an alternative agent in patients who had a bona fide failure...on simvastatin. Failures requiring atorvastatin as an alternate agent were defined as (a) patients not at their LDL goal on maximal doses of...simvastatin 20 atorvastatin 20 med changed 3 (2%) simvastatin 10 atorvastatin 10 med changed 1 (0.7%) simvastatin 10 atorvastatin 20 med changed 5 (3.3

The antiviral effects of RSV fusion inhibitor, MDT-637, on clinical isolates, vs its achievable concentrations in the human respiratory tract and comparison to ribavirin.

PubMed

Kim, Young-In; Pareek, Rajat; Murphy, Ryan; Harrison, Lisa; Farrell, Eric; Cook, Robert; DeVincenzo, John

2017-11-01

Respiratory syncytial virus (RSV) viral load and disease severity associate, and the timing of viral load and disease run in parallel. An antiviral must be broadly effective against the natural spectrum of RSV genotypes and must attain concentrations capable of inhibiting viral replication within the human respiratory tract. We evaluated a novel RSV fusion inhibitor, MDT-637, and compared it with ribavirin for therapeutic effect in vitro to identify relative therapeutic doses achievable in humans. MDT-637 and ribavirin were co-incubated with RSV in HEp-2 cells. Quantitative PCR assessed viral concentrations; 50% inhibitory concentrations (IC 50 ) were compared to achievable human MDT-637 and ribavirin peak and trough concentrations. The IC 50 for MDT-637 and ribavirin (against RSV-A Long) was 1.42 and 16 973 ng/mL, respectively. The ratio of achievable peak respiratory secretion concentration to IC 50 was 6041-fold for MDT-637 and 25-fold for aerosolized ribavirin. The ratio of trough concentration to IC 50 was 1481-fold for MDT-637 and 3.29-fold for aerosolized ribavirin. Maximal peak and trough levels of oral or intravenous ribavirin were significantly lower than their IC 50 s. We also measured MDT-637 IC 50 s in 3 lab strains and 4 clinical strains. The IC 50 s ranged from 0.36 to 3.4 ng/mL. Achievable human MDT-637 concentrations in respiratory secretions exceed the IC 50 s by factors from hundreds to thousands of times greater than does ribavirin. Furthermore, MDT-637 has broad in vitro antiviral activity on clinical strains of different RSV genotypes and clades. Together, these data imply that MDT-637 may produce a superior clinical effect compared to ribavirin on natural RSV infections. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Therapeutic Touch(®) in a geriatric Palliative Care Unit - A retrospective review.

PubMed

Senderovich, Helen; Ip, Mary Lou; Berall, Anna; Karuza, Jurgis; Gordon, Michael; Binns, Malcolm; Wignarajah, Shaira; Grossman, Daphna; Dunal, Lynda

2016-08-01

Complementary therapies are increasingly used in palliative care as an adjunct to the standard management of symptoms to achieve an overall well-being for patients with malignant and non-malignant terminal illnesses. A Therapeutic Touch Program was introduced to a geriatric Palliative Care Unit (PCU) in October 2010 with two volunteer Therapeutic Touch Practitioners providing treatment. To conduct a retrospective review of Therapeutic Touch services provided to patients in an in-patient geriatric palliative care unit in order to understand their responses to Therapeutic Touch. A retrospective medical chart review was conducted on both patients who received Therapeutic Touch as well as a random selection of patients who did not receive Therapeutic Touch from October 2010-June 2013. Client characteristics and the Therapeutic Touch Practitioners' observations of the patients' response to treatment were collected and analyzed. Patients who did not receive Therapeutic Touch tended to have lower admitting Palliative Performance Scale scores, shorter length of stay and were older. Based on a sample of responses provided by patients and observed by the Therapeutic Touch practitioner, the majority of patients receiving treatment achieved a state of relaxation or sleep. This retrospective chart review suggests that implementation of a TT program for an inpatient geriatric Palliative Care Unit is feasible, and appears to be safe, and well-tolerated. Moreover, patient responses, as recorded in the Therapeutic Touch practitioners' session notes, suggest beneficial effects of Therapeutic Touch for a significant number of participants with no evidence of negative sequelae. Therefore, the use of TT in this difficult setting appears to have potential value as an adjunct or complementary therapy to help patients relax. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Left ventricular oxygen extraction during submaximal and maximal exertion in ponies.

PubMed Central

Manohar, M

1988-01-01

1. Left ventricular (LV) myocardial O2 extraction was studied in five healthy ponies which had catheters implanted in the great cardiac vein and main pulmonary artery 15-30 days before the study. The abdominal aorta was percutaneously catheterized to sample arterial blood. 2. In addition, phasic LV and aortic pressures, LV dP/dtmax and rate-pressure product were also studied; dP/dtmax is the maximal rate of rise of the left ventricular pressure during the isovolumic phase, and is considered an index of myocardial contractility. Measurements were made at rest (control) and during adenosine infusion (3 mumol kg-1 min-1) at rest, moderate exercise (heart rate 169 +/- 10 beats min-1), heavy exercise (heart rate 198 +/- 7 beats min-1), maximal exercise (heart rate 232 +/- 7 beats min-1), and adenosine infusion (3 mumol kg-1 min-1) during maximal exercise (heart rate 230 +/- 6 beats min-1). 3. In resting ponies, LV arterial to coronary venous O2 content difference (delta LVa-v O2) was 8.9 +/- 0.5 ml dl-1 and O2 extraction was 59.9 +/- 2.2%. Adenosine infusion at rest decreased delta LVa-v O2 and O2 extraction precipitously (2.6 ml dl-1 and 14.3 +/- 1.7%, respectively), thereby indicating superfluous LV myocardial perfusion. 4. Moderate, heavy and maximal exercise increased delta LVa-v O2 to 185, 194 and 218% of its control value and O2 extraction rose to 71 +/- 2, 75 +/- 1.5 and 78 +/- 0.9%, respectively. The widening of the delta LVa-v O2 gradient was due to the increased arterial O2 content during exercise. 5. Combining these observations with equine myocardial perfusion, the LV O2 consumption was calculated to be 7.8, 47.9 and 103.6 ml min-1 100 g-1 at rest, moderate and maximal exercise. In order to achieve the 13.4-fold increase in LV O2 consumption, the LV perfusion rose only 6-fold; the rest being met by widening the delta LVa-v O2. 6. Adenosine infusion during maximal exercise decreased delta LVa-v O2 and O2 extraction (10.7 +/- 1 ml dl-1 and 45%, respectively; P

Sex differences in autonomic function following maximal exercise.

PubMed

Kappus, Rebecca M; Ranadive, Sushant M; Yan, Huimin; Lane-Cordova, Abbi D; Cook, Marc D; Sun, Peng; Harvey, I Shevon; Wilund, Kenneth R; Woods, Jeffrey A; Fernhall, Bo

2015-01-01

Heart rate variability (HRV), blood pressure variability, (BPV) and heart rate recovery (HRR) are measures that provide insight regarding autonomic function. Maximal exercise can affect autonomic function, and it is unknown if there are sex differences in autonomic recovery following exercise. Therefore, the purpose of this study was to determine sex differences in several measures of autonomic function and the response following maximal exercise. Seventy-one (31 males and 40 females) healthy, nonsmoking, sedentary normotensive subjects between the ages of 18 and 35 underwent measurements of HRV and BPV at rest and following a maximal exercise bout. HRR was measured at minute one and two following maximal exercise. Males have significantly greater HRR following maximal exercise at both minute one and two; however, the significance between sexes was eliminated when controlling for VO2 peak. Males had significantly higher resting BPV-low-frequency (LF) values compared to females and did not significantly change following exercise, whereas females had significantly increased BPV-LF values following acute maximal exercise. Although males and females exhibited a significant decrease in both HRV-LF and HRV-high frequency (HF) with exercise, females had significantly higher HRV-HF values following exercise. Males had a significantly higher HRV-LF/HF ratio at rest; however, both males and females significantly increased their HRV-LF/HF ratio following exercise. Pre-menopausal females exhibit a cardioprotective autonomic profile compared to age-matched males due to lower resting sympathetic activity and faster vagal reactivation following maximal exercise. Acute maximal exercise is a sufficient autonomic stressor to demonstrate sex differences in the critical post-exercise recovery period.

A multiple scales approach to maximal superintegrability

NASA Astrophysics Data System (ADS)

Gubbiotti, G.; Latini, D.

2018-07-01

In this paper we present a simple, algorithmic test to establish if a Hamiltonian system is maximally superintegrable or not. This test is based on a very simple corollary of a theorem due to Nekhoroshev and on a perturbative technique called the multiple scales method. If the outcome is positive, this test can be used to suggest maximal superintegrability, whereas when the outcome is negative it can be used to disprove it. This method can be regarded as a finite dimensional analog of the multiple scales method as a way to produce soliton equations. We use this technique to show that the real counterpart of a mechanical system found by Jules Drach in 1935 is, in general, not maximally superintegrable. We give some hints on how this approach could be applied to classify maximally superintegrable systems by presenting a direct proof of the well-known Bertrand’s theorem.

Optimal Battery Utilization Over Lifetime for Parallel Hybrid Electric Vehicle to Maximize Fuel Economy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patil, Chinmaya; Naghshtabrizi, Payam; Verma, Rajeev

This paper presents a control strategy to maximize fuel economy of a parallel hybrid electric vehicle over a target life of the battery. Many approaches to maximizing fuel economy of parallel hybrid electric vehicle do not consider the effect of control strategy on the life of the battery. This leads to an oversized and underutilized battery. There is a trade-off between how aggressively to use and 'consume' the battery versus to use the engine and consume fuel. The proposed approach addresses this trade-off by exploiting the differences in the fast dynamics of vehicle power management and slow dynamics of batterymore » aging. The control strategy is separated into two parts, (1) Predictive Battery Management (PBM), and (2) Predictive Power Management (PPM). PBM is the higher level control with slow update rate, e.g. once per month, responsible for generating optimal set points for PPM. The considered set points in this paper are the battery power limits and State Of Charge (SOC). The problem of finding the optimal set points over the target battery life that minimize engine fuel consumption is solved using dynamic programming. PPM is the lower level control with high update rate, e.g. a second, responsible for generating the optimal HEV energy management controls and is implemented using model predictive control approach. The PPM objective is to find the engine and battery power commands to achieve the best fuel economy given the battery power and SOC constraints imposed by PBM. Simulation results with a medium duty commercial hybrid electric vehicle and the proposed two-level hierarchical control strategy show that the HEV fuel economy is maximized while meeting a specified target battery life. On the other hand, the optimal unconstrained control strategy achieves marginally higher fuel economy, but fails to meet the target battery life.« less

KATTS: a framework for maximizing NCLEX-RN performance.

PubMed

McDowell, Betsy M

2008-04-01

A key indicator of the quality of a nursing education program is the performance of its graduates as first-time takers of the NCLEX-RN. As a result, nursing schools are open to strategies that strengthen the performance of their graduates on the examination. The Knowledge base, Anxiety control, Test-Taking Skills (KATTS) framework focuses on the three components of achieving a maximum score on an examination. In KATTS, all three components must be present and in proper balance to maximize a test taker's score. By strengthening not just one but all of these components, graduates can improve their overall test scores significantly. Suggested strategies for strengthening each component of KATTS are provided. This framework has been used successfully in designing remedial tutoring programs and in assisting first-time NCLEX test takers in preparing for the licensing examination.

Nonimaging optics maximizing exergy for hybrid solar system

NASA Astrophysics Data System (ADS)

Winston, Roland; Jiang, Lun; Abdelhamid, Mahmoud; Widyolar, Bennett K.; Ferry, Jonathan; Cygan, David; Abbasi, Hamid; Kozlov, Alexandr; Kirk, Alexander; Elarde, Victor; Osowski, Mark

2016-09-01

The project team of University of California at Merced (UC-Merced), Gas Technology Institute (GTI) and MicroLink Devices Inc. (MicroLink) are developing a hybrid solar system using a nonimaging compound parabolic concentrator (CPC) that maximizes the exergy by delivering direct electricity and on-demand heat. The hybrid solar system technology uses secondary optics in a solar receiver to achieve high efficiency at high temperature, collects heat in particles and uses reflective liftoff cooled double junction (2J) InGaP/GaAs solar cells with backside infrared (IR) reflectors on the secondary optical element to raise exergy efficiency. The nonimaging optics provides additional concentration towards the high temperature thermal stream and enables it to operate efficiently at 650 °C while the solar cell is maintained at 40 °C to operate as efficiently as possible.

Achieving better cooling of turbine blades using numerical simulation methods

NASA Astrophysics Data System (ADS)

Inozemtsev, A. A.; Tikhonov, A. S.; Sendyurev, C. I.; Samokhvalov, N. Yu.

2013-02-01

A new design of the first-stage nozzle vane for the turbine of a prospective gas-turbine engine is considered. The blade's thermal state is numerically simulated in conjugate statement using the ANSYS CFX 13.0 software package. Critical locations in the blade design are determined from the distribution of heat fluxes, and measures aimed at achieving more efficient cooling are analyzed. Essentially lower (by 50-100°C) maximal temperature of metal has been achieved owing to the results of the performed work.

Therapeutic Outcome of Achalasia Based on High-Resolution Manometry: A Korean Multicenter Study.

PubMed

Lee, Hyuk; Chung, Hyunsoo; Lee, Tae Hee; Hong, Kyoung Sup; Youn, Young Hoon; Park, Jung Ho; Park, Hyung Seok; Park, Hyojin

2017-09-11

Because achalasia subtype is associated with therapeutic response, it is possible that regional differences in subtype distribution could lead to differences in therapeutic outcomes. We aimed to evaluate and compare high-resolution manometry (HRM) profiles among the different subtypes of achalasia and to elucidate predictive factors associated with treatment outcomes. Patients who were diagnosed with achalasia using HRM at 4 Korean university hospitals were retrospectively identified and analyzed. Sixty-four patients with untreated achalasia were divided into 3 subtypes using the Chicago classification system. Clinical characteristics, manometric features, and treatment outcomes were compared. Among 64 patients diagnosed with achalasia, 31 patients were classified as type I, 27 as type II, and 6 as type III. Regarding HRM parameters, there were statistically significant differences in basal lower esophageal sphincter pressure, 4-second-integrated relaxation pressure, residual upper esophageal sphincter pressure, body amplitude, and maximal intrabolus pressure between subtypes. Regarding therapeutic outcome, type II patients (overall success rate of 80.0%) were more likely to respond than type I (55.2%) or type III (33.2%) patients. Multivariate analysis demonstrated that achalasia subtype (type I vs. III, P = 0.072; type II vs. III, P = 0.005), therapeutic modality (dilation vs. pharmacologic, P = 0.013; laparoscopic Heller's myotomy vs. pharmacologic, P = 0.006), and HRM-measured esophageal length (<27.5 vs. ≥27.5 cm, P = 0.014) are independent predictive factors for therapeutic failure. Patients with type II achalasia had better treatment outcomes than patients with other achalasia subtypes. Achalasia subtype, therapeutic modality, and esophageal length are independent predictive factors of therapeutic outcome.

Therapeutic applications of circadian rhythms for the cardiovascular system

PubMed Central

Tsimakouridze, Elena V.; Alibhai, Faisal J.; Martino, Tami A.

2015-01-01

The cardiovascular system exhibits dramatic time-of-day dependent rhythms, for example the diurnal variation of heart rate, blood pressure, and timing of onset of adverse cardiovascular events such as heart attack and sudden cardiac death. Over the past decade, the circadian clock mechanism has emerged as a crucial factor regulating these daily fluctuations. Most recently, these studies have led to a growing clinical appreciation that targeting circadian biology offers a novel therapeutic approach toward cardiovascular (and other) diseases. Here we describe leading-edge therapeutic applications of circadian biology including (1) timing of therapy to maximize efficacy in treating heart disease (chronotherapy); (2) novel biomarkers discovered by testing for genomic, proteomic, metabolomic, or other factors at different times of day and night (chronobiomarkers); and (3) novel pharmacologic compounds that target the circadian mechanism with potential clinical applications (new chronobiology drugs). Cardiovascular disease remains a leading cause of death worldwide and new approaches in the management and treatment of heart disease are clearly warranted and can benefit patients clinically. PMID:25941487

Cardiac Sarcoidosis: Clinical Manifestations, Imaging Characteristics, and Therapeutic Approach

PubMed Central

Houston, Brian A; Mukherjee, Monica

2014-01-01

Sarcoidosis is a multi-system disease pathologically characterized by the accumulation of T-lymphocytes and mononuclear phagocytes into the sine qua non pathologic structure of the noncaseating granuloma. Cardiac involvement remains a key source of morbidity and mortality in sarcoidosis. Definitive diagnosis of cardiac sarcoidosis, particularly early enough in the disease course to provide maximal therapeutic impact, has proven a particularly difficult challenge. However, major advancements in imaging techniques have been made in the last decade. Advancements in imaging modalities including echocardiography, nuclear spectroscopy, positron emission tomography, and magnetic resonance imaging all have improved our ability to diagnose cardiac sarcoidosis, and in many cases to provide a more accurate prognosis and thus targeted therapy. Likewise, therapy for cardiac sarcoidosis is beginning to advance past a “steroids-only” approach, as novel immunosuppressant agents provide effective steroid-sparing options. The following focused review will provide a brief discussion of the epidemiology and clinical presentation of cardiac sarcoidosis followed by a discussion of up-to-date imaging modalities employed in its assessment and therapeutic approaches. PMID:25452702

The slack test does not assess maximal shortening velocity of muscle fascicle in human.

PubMed

Hager, Robin; Dorel, Sylvain; Nordez, Antoine; Rabita, Giuseppe; Couturier, Antoine; Hauraix, Hugo; Duchateau, Jacques; Guilhem, Gaël

2018-06-14

The application of a series of extremely high accelerative motor-driven quick releases while muscles contract isometrically (i.e. slack test) has been proposed to assess unloaded velocity in human muscle. This study aimed to measure gastrocnemius medialis fascicle (V F ) and tendinous tissues shortening velocity during motor-driven quick releases performed at various activation levels to assess the applicability of the slack test method in human. Maximal fascicle shortening velocity and joint velocity recorded during quick releases and during fast contraction without external load (ballistic condition) were compared. Gastrocnemius medialis fascicle behaviour was investigated from 25 participants using high-frame rate ultrasound during quick releases performed at various activation levels (from 0% to 60% of maximal voluntary isometric torque) and ballistic contractions. Unloaded joint velocity calculated using the slack test method increased whereas V F decreased with muscle activation level (P≤0.03). Passive and low-level quick releases elicited higher V F values (≥ 41.4±9.7 cm.s -1 ) compared to ballistic condition (36.3±8.7 cm.s -1 ), while quick releases applied at 60% of maximal voluntary isometric torque produced the lowest V F These findings suggest that initial fascicle length, complex fascicle-tendon interactions, unloading reflex and motor-driven movement pattern strongly influence and limit the shortening velocity achieved during the slack test. Furthermore, V F elicited by quick releases is likely to reflect substantial contributions of passive processes. Therefore, the slack test is not appropriate to assess maximal muscle shortening velocity in vivo. © 2018. Published by The Company of Biologists Ltd.

Breast cancer stem cells, EMT and therapeutic targets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kotiyal, Srishti; Bhattacharya, Susinjan, E-mail: s.bhattacharya@jiit.ac.in

Highlights: • Therapeutic targeting or inhibition of the key molecules of signaling pathways can control growth of breast cancer stem cells (BCSCs). • Development of BCSCs also involves miRNA interactions. • Therapeutic achievement can be done by targeting identified targets in the BCSC pathways. - Abstract: A small heterogeneous population of breast cancer cells acts as seeds to induce new tumor growth. These seeds or breast cancer stem cells (BCSCs) exhibit great phenotypical plasticity which allows them to undergo “epithelial to mesenchymal transition” (EMT) at the site of primary tumor and a future reverse transition. Apart from metastasis they aremore » also responsible for maintaining the tumor and conferring it with drug and radiation resistance and a tendency for post-treatment relapse. Many of the signaling pathways involved in induction of EMT are involved in CSC generation and regulation. Here we are briefly reviewing the mechanism of TGF-β, Wnt, Notch, TNF-α, NF-κB, RTK signalling pathways which are involved in EMT as well as BCSCs maintenance. Therapeutic targeting or inhibition of the key/accessory players of these pathways could control growth of BCSCs and hence malignant cancer. Additionally several miRNAs are dysregulated in cancer stem cells indicating their roles as oncogenes or tumor suppressors. This review also lists the miRNA interactions identified in BCSCs and discusses on some newly identified targets in the BCSC regulatory pathways like SHIP2, nicastrin, Pin 1, IGF-1R, pro-inflammatory cytokines and syndecan which can be targeted for therapeutic achievements.« less

A new therapeutic community: development of a compassion-focussed and contextual behavioural environment.

PubMed

Veale, David; Gilbert, Paul; Wheatley, Jon; Naismith, Iona

2015-01-01

Social relationships and communities provide the context and impetus for a range of psychological developments, from genetic expression to the development of core self-identities. This suggests a need to think about the therapeutic changes and processes that occur within a community context and how communities can enable therapeutic change. However, the 'therapeutic communities' that have developed since the Second World War have been under-researched. We suggest that the concept of community, as a change process, should be revisited within mainstream scientific research. This paper briefly reviews the historical development of therapeutic communities and critically evaluates their current theory, practice and outcomes in a systematic review. Attention is drawn to recent research on the nature of evolved emotion regulation systems, the way these are entrained by social relationships, the importance of affiliative emotions in the regulation of threat and the role of fear of affiliative emotions in psychopathology. We draw on concepts from compassion-focussed therapy, social learning theory and functional analytical psychotherapy to consider how members of a therapeutic community can be aware of each other's acts of courage and respond using compassion. Living in structured and affiliative-orientated communities that are guided by scientific models of affect and self-regulation offers potential therapeutic advantages over individual outpatient therapy for certain client groups. This conclusion should be investigated further. Key Practitioner Message Current therapeutic community practice is not sufficiently evidence based and may not be maximizing the potential therapeutic value of a community. Compassion-focussed therapy and social learning theory offer new approaches for a therapeutic environment, involving an understanding of the role, nature and complexities of compassionate and affiliative relationships from staff and members, behavioural change guided by

Aging and loss decision making: increased risk aversion and decreased use of maximizing information, with correlated rationality and value maximization

PubMed Central

Kurnianingsih, Yoanna A.; Sim, Sam K. Y.; Chee, Michael W. L.; Mullette-Gillman, O’Dhaniel A.

2015-01-01

We investigated how adult aging specifically alters economic decision-making, focusing on examining alterations in uncertainty preferences (willingness to gamble) and choice strategies (what gamble information influences choices) within both the gains and losses domains. Within each domain, participants chose between certain monetary outcomes and gambles with uncertain outcomes. We examined preferences by quantifying how uncertainty modulates choice behavior as if altering the subjective valuation of gambles. We explored age-related preferences for two types of uncertainty, risk, and ambiguity. Additionally, we explored how aging may alter what information participants utilize to make their choices by comparing the relative utilization of maximizing and satisficing information types through a choice strategy metric. Maximizing information was the ratio of the expected value of the two options, while satisficing information was the probability of winning. We found age-related alterations of economic preferences within the losses domain, but no alterations within the gains domain. Older adults (OA; 61–80 years old) were significantly more uncertainty averse for both risky and ambiguous choices. OA also exhibited choice strategies with decreased use of maximizing information. Within OA, we found a significant correlation between risk preferences and choice strategy. This linkage between preferences and strategy appears to derive from a convergence to risk neutrality driven by greater use of the effortful maximizing strategy. As utility maximization and value maximization intersect at risk neutrality, this result suggests that OA are exhibiting a relationship between enhanced rationality and enhanced value maximization. While there was variability in economic decision-making measures within OA, these individual differences were unrelated to variability within examined measures of cognitive ability. Our results demonstrate that aging alters economic decision

Aging and loss decision making: increased risk aversion and decreased use of maximizing information, with correlated rationality and value maximization.

PubMed

Kurnianingsih, Yoanna A; Sim, Sam K Y; Chee, Michael W L; Mullette-Gillman, O'Dhaniel A

2015-01-01

We investigated how adult aging specifically alters economic decision-making, focusing on examining alterations in uncertainty preferences (willingness to gamble) and choice strategies (what gamble information influences choices) within both the gains and losses domains. Within each domain, participants chose between certain monetary outcomes and gambles with uncertain outcomes. We examined preferences by quantifying how uncertainty modulates choice behavior as if altering the subjective valuation of gambles. We explored age-related preferences for two types of uncertainty, risk, and ambiguity. Additionally, we explored how aging may alter what information participants utilize to make their choices by comparing the relative utilization of maximizing and satisficing information types through a choice strategy metric. Maximizing information was the ratio of the expected value of the two options, while satisficing information was the probability of winning. We found age-related alterations of economic preferences within the losses domain, but no alterations within the gains domain. Older adults (OA; 61-80 years old) were significantly more uncertainty averse for both risky and ambiguous choices. OA also exhibited choice strategies with decreased use of maximizing information. Within OA, we found a significant correlation between risk preferences and choice strategy. This linkage between preferences and strategy appears to derive from a convergence to risk neutrality driven by greater use of the effortful maximizing strategy. As utility maximization and value maximization intersect at risk neutrality, this result suggests that OA are exhibiting a relationship between enhanced rationality and enhanced value maximization. While there was variability in economic decision-making measures within OA, these individual differences were unrelated to variability within examined measures of cognitive ability. Our results demonstrate that aging alters economic decision-making for

Optimal Halbach Permanent Magnet Designs for Maximally Pulling and Pushing Nanoparticles

PubMed Central

Sarwar, A.; Nemirovski, A.; Shapiro, B.

2011-01-01

Optimization methods are presented to design Halbach arrays to maximize the forces applied on magnetic nanoparticles at deep tissue locations. In magnetic drug targeting, where magnets are used to focus therapeutic nanoparticles to disease locations, the sharp fall off of magnetic fields and forces with distances from magnets has limited the depth of targeting. Creating stronger forces at depth by optimally designed Halbach arrays would allow treatment of a wider class of patients, e.g. patients with deeper tumors. The presented optimization methods are based on semi-definite quadratic programming, yield provably globally optimal Halbach designs in 2 and 3-dimensions, for maximal pull or push magnetic forces (stronger pull forces can collect nano-particles against blood forces in deeper vessels; push forces can be used to inject particles into precise locations, e.g. into the inner ear). These Halbach designs, here tested in simulations of Maxwell’s equations, significantly outperform benchmark magnets of the same size and strength. For example, a 3-dimensional 36 element 2000 cm3 volume optimal Halbach design yields a ×5 greater force at a 10 cm depth compared to a uniformly magnetized magnet of the same size and strength. The designed arrays should be feasible to construct, as they have a similar strength (≤ 1 Tesla), size (≤ 2000 cm3), and number of elements (≤ 36) as previously demonstrated arrays, and retain good performance for reasonable manufacturing errors (element magnetization direction errors ≤ 5°), thus yielding practical designs to improve magnetic drug targeting treatment depths. PMID:23335834

Optimal Halbach Permanent Magnet Designs for Maximally Pulling and Pushing Nanoparticles.

PubMed

Sarwar, A; Nemirovski, A; Shapiro, B

2012-03-01

Optimization methods are presented to design Halbach arrays to maximize the forces applied on magnetic nanoparticles at deep tissue locations. In magnetic drug targeting, where magnets are used to focus therapeutic nanoparticles to disease locations, the sharp fall off of magnetic fields and forces with distances from magnets has limited the depth of targeting. Creating stronger forces at depth by optimally designed Halbach arrays would allow treatment of a wider class of patients, e.g. patients with deeper tumors. The presented optimization methods are based on semi-definite quadratic programming, yield provably globally optimal Halbach designs in 2 and 3-dimensions, for maximal pull or push magnetic forces (stronger pull forces can collect nano-particles against blood forces in deeper vessels; push forces can be used to inject particles into precise locations, e.g. into the inner ear). These Halbach designs, here tested in simulations of Maxwell's equations, significantly outperform benchmark magnets of the same size and strength. For example, a 3-dimensional 36 element 2000 cm(3) volume optimal Halbach design yields a ×5 greater force at a 10 cm depth compared to a uniformly magnetized magnet of the same size and strength. The designed arrays should be feasible to construct, as they have a similar strength (≤ 1 Tesla), size (≤ 2000 cm(3)), and number of elements (≤ 36) as previously demonstrated arrays, and retain good performance for reasonable manufacturing errors (element magnetization direction errors ≤ 5°), thus yielding practical designs to improve magnetic drug targeting treatment depths.

Engineered Hybrid Nanoparticles for On-Demand Diagnostics and Therapeutics.

PubMed

Nguyen, Kim Truc; Zhao, Yanli

2015-12-15

Together with the simultaneous development of nanomaterials and molecular biology, the bionano interface brings about various applications of hybrid nanoparticles in nanomedicine. The hybrid nanoparticles not only present properties of the individual components but also show synergistic effects for specialized applications. Thus, the development of advanced hybrid nanoparticles for targeted and on-demand diagnostics and therapeutics of diseases has rapidly become a hot research topic in nanomedicine. The research focus is to fabricate novel classes of programmable hybrid nanoparticles that are precisely engineered to maximize drug concentrations in diseased cells, leading to enhanced efficacy and reduced side effects of chemotherapy for the disease treatment. In particular, the hybrid nanoparticle platforms can simultaneously target diseased cells, enable the location to be imaged by optical methods, and release therapeutic drugs to the diseased cells by command. This Account specially discusses the rational fabrication of integrated hybrid nanoparticles and their applications in diagnostics and therapeutics. For diagnostics applications, hybrid nanoparticles can be utilized as imaging agents that enable detailed visualization at the molecular level. By the use of suitable targeting ligands incorporated on the nanoparticles, targeted optical imaging may be feasible with improved performance. Novel imaging techniques such as multiphoton excitation and photoacoustic imaging using near-infrared light have been developed using the intrinsic properties of particular nanoparticles. The use of longer-wavelength excitation sources allows deeper penetration into the human body for disease diagnostics and at the same time reduces the adverse effects on normal tissues. Furthermore, multimodal imaging techniques have been achieved by combining several types of components in nanoparticles, offering higher accuracy and better spatial views, with the aim of detecting life

Specificity of a Maximal Step Exercise Test

ERIC Educational Resources Information Center

Darby, Lynn A.; Marsh, Jennifer L.; Shewokis, Patricia A.; Pohlman, Roberta L.

2007-01-01

To adhere to the principle of "exercise specificity" exercise testing should be completed using the same physical activity that is performed during exercise training. The present study was designed to assess whether aerobic step exercisers have a greater maximal oxygen consumption (max VO sub 2) when tested using an activity specific, maximal step…

Maximizing entanglement in bosonic Josephson junctions using shortcuts to adiabaticity and optimal control

NASA Astrophysics Data System (ADS)

Stefanatos, Dionisis; Paspalakis, Emmanuel

2018-05-01

In this article we consider a bosonic Josephson junction, a model system composed by two coupled nonlinear quantum oscillators which can be implemented in various physical contexts, initially prepared in a product of weakly populated coherent states. We quantify the maximum achievable entanglement between the modes of the junction and then use shortcuts to adiabaticity, a method developed to speed up adiabatic quantum dynamics, as well as numerical optimization, to find time-dependent controls (the nonlinearity and the coupling of the junction) which bring the system to a maximally entangled state.

Why Contextual Preference Reversals Maximize Expected Value

PubMed Central

2016-01-01

Contextual preference reversals occur when a preference for one option over another is reversed by the addition of further options. It has been argued that the occurrence of preference reversals in human behavior shows that people violate the axioms of rational choice and that people are not, therefore, expected value maximizers. In contrast, we demonstrate that if a person is only able to make noisy calculations of expected value and noisy observations of the ordinal relations among option features, then the expected value maximizing choice is influenced by the addition of new options and does give rise to apparent preference reversals. We explore the implications of expected value maximizing choice, conditioned on noisy observations, for a range of contextual preference reversal types—including attraction, compromise, similarity, and phantom effects. These preference reversal types have played a key role in the development of models of human choice. We conclude that experiments demonstrating contextual preference reversals are not evidence for irrationality. They are, however, a consequence of expected value maximization given noisy observations. PMID:27337391

Gradient Dynamics and Entropy Production Maximization

NASA Astrophysics Data System (ADS)

Janečka, Adam; Pavelka, Michal

2018-01-01

We compare two methods for modeling dissipative processes, namely gradient dynamics and entropy production maximization. Both methods require similar physical inputs-how energy (or entropy) is stored and how it is dissipated. Gradient dynamics describes irreversible evolution by means of dissipation potential and entropy, it automatically satisfies Onsager reciprocal relations as well as their nonlinear generalization (Maxwell-Onsager relations), and it has statistical interpretation. Entropy production maximization is based on knowledge of free energy (or another thermodynamic potential) and entropy production. It also leads to the linear Onsager reciprocal relations and it has proven successful in thermodynamics of complex materials. Both methods are thermodynamically sound as they ensure approach to equilibrium, and we compare them and discuss their advantages and shortcomings. In particular, conditions under which the two approaches coincide and are capable of providing the same constitutive relations are identified. Besides, a commonly used but not often mentioned step in the entropy production maximization is pinpointed and the condition of incompressibility is incorporated into gradient dynamics.

Recovery of maximally entangled quantum states by weak-measurement reversal

NASA Astrophysics Data System (ADS)

Maleki, Yusef; Zheltikov, Aleksei M.

2018-05-01

Maximal quantum entanglement provided by N00N states is a unique resource in the quest for the ultimate precision in physical measurements. Such states, however, are fragile and prone to decoherence. Even in weak-measurement schemes, as we demonstrate in this work, the phase super-resolution provided by N00N states is achieved at a cost of an N-fold enhancement of amplitude damping. Still, as the analysis presented here shows, a partial collapse of N00N states induced by weak measurements can be reversed, despite the dramatic, N-fold enhancement of amplitude damping, through appropriate reversal operations on the post-measurement state, enabling a full restoration of the Heisenberg-limit phase super-resolution of N00N states.

Maximizing omnidirectional light harvesting in metal oxide hyperbranched array architectures

NASA Astrophysics Data System (ADS)

Wu, Wu-Qiang; Feng, Hao-Lin; Rao, Hua-Shang; Xu, Yang-Fan; Kuang, Dai-Bin; Su, Cheng-Yong

2014-05-01

The scrupulous design of nanoarchitectures and smart hybridization of specific active materials are closely related to the overall photovoltaic performance of an anode electrode. Here we present a solution-based strategy for the fabrication of well-aligned metal oxide-based nanowire-nanosheet-nanorod hyperbranched arrays on transparent conducting oxide substrates. For these hyperbranched arrays, we observe a twofold increment in dye adsorption and enhanced light trapping and scattering capability compared with the pristine titanium dioxide nanowires, and thus a power conversion efficiency of 9.09% is achieved. Our growth approach presents a strategy to broaden the photoresponse and maximize the light-harvesting efficiency of arrays architectures, and may lead to applications for energy conversion and storage, catalysis, water splitting and gas sensing.

Maximizing omnidirectional light harvesting in metal oxide hyperbranched array architectures.

PubMed

Wu, Wu-Qiang; Feng, Hao-Lin; Rao, Hua-Shang; Xu, Yang-Fan; Kuang, Dai-Bin; Su, Cheng-Yong

2014-05-29

The scrupulous design of nanoarchitectures and smart hybridization of specific active materials are closely related to the overall photovoltaic performance of an anode electrode. Here we present a solution-based strategy for the fabrication of well-aligned metal oxide-based nanowire-nanosheet-nanorod hyperbranched arrays on transparent conducting oxide substrates. For these hyperbranched arrays, we observe a twofold increment in dye adsorption and enhanced light trapping and scattering capability compared with the pristine titanium dioxide nanowires, and thus a power conversion efficiency of 9.09% is achieved. Our growth approach presents a strategy to broaden the photoresponse and maximize the light-harvesting efficiency of arrays architectures, and may lead to applications for energy conversion and storage, catalysis, water splitting and gas sensing.

Can Monkeys Make Investments Based on Maximized Pay-off?

PubMed Central

Steelandt, Sophie; Dufour, Valérie; Broihanne, Marie-Hélène; Thierry, Bernard

2011-01-01

Animals can maximize benefits but it is not known if they adjust their investment according to expected pay-offs. We investigated whether monkeys can use different investment strategies in an exchange task. We tested eight capuchin monkeys (Cebus apella) and thirteen macaques (Macaca fascicularis, Macaca tonkeana) in an experiment where they could adapt their investment to the food amounts proposed by two different experimenters. One, the doubling partner, returned a reward that was twice the amount given by the subject, whereas the other, the fixed partner, always returned a constant amount regardless of the amount given. To maximize pay-offs, subjects should invest a maximal amount with the first partner and a minimal amount with the second. When tested with the fixed partner only, one third of monkeys learned to remove a maximal amount of food for immediate consumption before investing a minimal one. With both partners, most subjects failed to maximize pay-offs by using different decision rules with each partner' quality. A single Tonkean macaque succeeded in investing a maximal amount to one experimenter and a minimal amount to the other. The fact that only one of over 21 subjects learned to maximize benefits in adapting investment according to experimenters' quality indicates that such a task is difficult for monkeys, albeit not impossible. PMID:21423777

Extension of the lower bound of monitor solutions of maximally permissive supervisors to non-α net systems

NASA Astrophysics Data System (ADS)

Wu, W. H.; Chao, D. Y.

2016-07-01

Traditional region-based liveness-enforcing supervisors focus on (1) maximal permissiveness of not losing legal states, (2) structural simplicity of minimal number of monitors, and (3) fast computation. Lately, a number of similar approaches can achieve minimal configuration using efficient linear programming. However, it is unclear as to the relationship between the minimal configuration and the net structure. It is important to explore the structures involved for the fewest monitors required. Once the lower bound is achieved, further iteration to merge (or reduce the number of) monitors is not necessary. The minimal strongly connected resource subnet (i.e., all places are resources) that contains the set of resource places in a basic siphon is an elementary circuit. Earlier, we showed that the number of monitors required for liveness-enforcing and maximal permissiveness equals that of basic siphons for a subclass of Petri nets modelling manufacturing, called α systems. This paper extends this to systems more powerful than the α one so that the number of monitors in a minimal configuration remains to be lower bounded by that of basic siphons. This paper develops the theory behind and shows examples.

Contribution of Group Therapeutic Factors to the Outcome of Cognitive-Behavioral Therapy for Patients with Panic Disorder.

PubMed

Behenck, Andressa; Wesner, Ana Cristina; Finkler, Débora; Heldt, Elizeth

2017-04-01

Investigating the contribution of therapeutic factors arising from the collective nature or group therapy to treat mental disorders may help therapists maximize the outcome of therapy. Studies about the role of therapeutic factors in cognitive-behavioral group therapy (CBGT) for panic disorder (PD) patients are still scarce. To identify the therapeutic factors rated as the most useful by patients during CBGT. Also, we aimed to investigate the relationship between patient rating of therapeutic factors and specific stages of CBGT. Non-controlled clinical trial. A 12-session CBGT protocol was set up, covering psychoeducation, techniques for anxiety coping, cognitive restructuring, interoceptive and naturalistic exposure, and live exposure to avoidant behavior. PD symptom severity was assessed before and after the CBGT protocol. Yalom's Curative Factors Questionnaire was self-administered at the end of each session to evaluate the 12 therapeutic factors. The sample consisted of 16 patients, who produced 192 assessments of therapeutic factors. Severity of symptoms improved at the end of CBGT, with a large effect size (>1.0). Different ratings were attributed to therapeutic factors at different phases of CBGT. Seven factors were rated as significantly helpful: altruism, interpersonal learning/input, guidance, identification, family reenactment, self-understanding, and existential factors. Therapeutic factors are dynamic and interdependent. Therefore, recognizing the impact of these factors during CBGT may potentially contribute to a better understanding of the therapeutic process. Copyright © 2016 Elsevier Inc. All rights reserved.

Maximizing gait and balance: behaviors and decision-making processes of persons with multiple sclerosis and physical therapists.

PubMed

Held Bradford, Elissa; Finlayson, Marcia; White Gorman, Andrea; Wagner, Joanne

2018-05-01

To describe the behavioral decisions used by persons with multiple sclerosis (MS) and physical therapists to maximize gait and balance following outpatient physical therapy. A multi-method case series with seven matched pairs (persons with MS-physical therapists). Quota sampling maximized variability among persons with MS (disease steps score range 3-6). Three of the four physical therapists were MS or neurology certified. Persons with MS completed a phone survey, follow-up interview, and standardized questionnaires. Physical therapists completed an interview. Data were collected 2-8 weeks following discharge. Content and constant comparison analyses were used for thematic development and triangulation. Core themes arose exemplifying the decision-making processes and actions of persons with MS (challenging self by pushing but respecting limits) and physical therapists (finding the right fit). One overarching theme, keeping their lived world large, or participation in valued life roles, emerged integrating both perspectives driving decision-making. Participants have a shared goal of maximizing gait and balance so persons with MS can participate in valued life roles. Understanding the differences in the behavioral decisions and optimizing skill sets in shared decision-making and self-management may enhance the therapeutic partnership and engagement in gait- and balance-enhancing behaviors. Implications for Rehabilitation Persons with MS and physical therapists have a shared goal of maximizing gait and balance so persons with MS can participate in valued activities and life roles, or more poetically, keep their lived world large. Knowledge that persons with MS aim to challenge themselves by pushing but respecting limits can provide physical therapists with greater insight in helping persons with MS resolve uncertainty, set meaningful goals, and build the routines and resilience needed for engagement in gait- and balance-enhancing behaviors. Enriching skill sets in

Therapeutic interventions and success in risk factor control for secondary prevention of stroke.

PubMed

Alvarez-Sabin, Jose; Quintana, Manuel; Hernandez-Presa, Miguel Angel; Alvarez, Carlos; Chaves, Jose; Ribo, Marc

2009-01-01

We sought to evaluate the success rates in achieving preventive therapeutic goals in patients who experienced an ischemic stroke (IS) and compare them with those achieved in patients with coronary artery disease (CAD). This was an observational multicenter case-control study (3 patients with IS and one control subject with CAD) performed in 1444 primary health centers in Spain. Preventive therapeutic objectives according to American Heart Association guidelines were predefined. Demographic data, vascular risk factors, and success/failure in achievement of objectives were recorded and compared between patients with IS and CAD. A total of 5458 patients were included, 4098 (75.1%) had IS and 1360 (24.9%) had CAD. Although more than 90% of patients with hypertension, diabetes, or dyslipidemia were under specific drug regimens, only about 25% achieved the recommended therapeutic objective for each risk factor. Success rate was especially low among patients with IS compared with CAD: hypertension (23.8% v 27.2%; P = .028); dyslipidemia (13.6% v 20.3%; P < .001); and abdominal obesity (49.1% v 54.6%; P = .002). The only objective widely achieved in both groups was the use of antithrombotic drugs in atrial fibrillation (97.2% v 94.7%; P = .125). Only 3.3% of patients with IS had all risk factors under control, compared with 5.6% of those with CAD (P = .006). For all patients, multivariate logistic regression model showed that independent predictors of full risk factor control were: presence of CAD as compared with IS (odds ratio [OR] 2.11; 95% confidence interval [CI] 1.35-3.29; P = .001), older age (OR 1.02; 95% CI 1.00-1.04; P = .028), and having less than 3 risk factors (OR 16.98; 95% CI 9.02-31.97; P < .001). Success in achieving preventive therapeutic objectives for secondary prevention of vascular events is low, especially among patients with IS. There is an urgent need to devise strategies to improve risk factor control.

An information maximization model of eye movements

NASA Technical Reports Server (NTRS)

Renninger, Laura Walker; Coughlan, James; Verghese, Preeti; Malik, Jitendra

2005-01-01

We propose a sequential information maximization model as a general strategy for programming eye movements. The model reconstructs high-resolution visual information from a sequence of fixations, taking into account the fall-off in resolution from the fovea to the periphery. From this framework we get a simple rule for predicting fixation sequences: after each fixation, fixate next at the location that minimizes uncertainty (maximizes information) about the stimulus. By comparing our model performance to human eye movement data and to predictions from a saliency and random model, we demonstrate that our model is best at predicting fixation locations. Modeling additional biological constraints will improve the prediction of fixation sequences. Our results suggest that information maximization is a useful principle for programming eye movements.

Does evolution lead to maximizing behavior?

PubMed

Lehmann, Laurent; Alger, Ingela; Weibull, Jörgen

2015-07-01

A long-standing question in biology and economics is whether individual organisms evolve to behave as if they were striving to maximize some goal function. We here formalize this "as if" question in a patch-structured population in which individuals obtain material payoffs from (perhaps very complex multimove) social interactions. These material payoffs determine personal fitness and, ultimately, invasion fitness. We ask whether individuals in uninvadable population states will appear to be maximizing conventional goal functions (with population-structure coefficients exogenous to the individual's behavior), when what is really being maximized is invasion fitness at the genetic level. We reach two broad conclusions. First, no simple and general individual-centered goal function emerges from the analysis. This stems from the fact that invasion fitness is a gene-centered multigenerational measure of evolutionary success. Second, when selection is weak, all multigenerational effects of selection can be summarized in a neutral type-distribution quantifying identity-by-descent between individuals within patches. Individuals then behave as if they were striving to maximize a weighted sum of material payoffs (own and others). At an uninvadable state it is as if individuals would freely choose their actions and play a Nash equilibrium of a game with a goal function that combines self-interest (own material payoff), group interest (group material payoff if everyone does the same), and local rivalry (material payoff differences). © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Active targeted delivery of immune therapeutics to lymph nodes.

PubMed

Bahmani, Baharak; Vohra, Ishaan; Kamaly, Nazila; Abdi, Reza

2018-02-01

Organ transplantation is a life-saving procedure and the only option for patients with end-organ failure. Immune therapeutics have been key to the success of organ transplantation. However, immune therapeutics are still unable to eliminate graft rejection and their toxicity has been implicated in poorer long-term transplant outcomes. Targeted nanodelivery has the potential to enhance not only the therapeutic index but also the bioavailability of the immune therapeutics. One of the key sites of immune therapeutics delivery is lymph node where the priming of immune cells occur. The focus of this review is on nanomedicine research to develop the targeted delivery of immune therapeutics to lymph nodes for controlling immune activation. As nanomedicine creates its niche in clinical care, it provides novel immunotherapy platforms for transplant recipients. Draining lymph nodes are the primary loci of immune activation and represent a formidable site for delivery of wide variety of immune therapeutics. There have been relentless efforts to improve the properties of nanomedicines, to have in-depth knowledge of antigen and drug loading, and, finally, to explore various routes of passive and active targeted delivery to lymph nodes. The application of nanotechnology principles in the delivery of immune therapeutics to the lymph node has created enormous excitement as a paradigm shifting approach that enables targeted delivery of a gamut of molecules to achieve a desired immune response. Therefore, innovative strategies that improve their efficacy while reducing their toxicity are among the highest unmet needs in transplantation.

Real-time topic-aware influence maximization using preprocessing.

PubMed

Chen, Wei; Lin, Tian; Yang, Cheng

2016-01-01

Influence maximization is the task of finding a set of seed nodes in a social network such that the influence spread of these seed nodes based on certain influence diffusion model is maximized. Topic-aware influence diffusion models have been recently proposed to address the issue that influence between a pair of users are often topic-dependent and information, ideas, innovations etc. being propagated in networks are typically mixtures of topics. In this paper, we focus on the topic-aware influence maximization task. In particular, we study preprocessing methods to avoid redoing influence maximization for each mixture from scratch. We explore two preprocessing algorithms with theoretical justifications. Our empirical results on data obtained in a couple of existing studies demonstrate that one of our algorithms stands out as a strong candidate providing microsecond online response time and competitive influence spread, with reasonable preprocessing effort.

Resources and energetics determined dinosaur maximal size

PubMed Central

McNab, Brian K.

2009-01-01

Some dinosaurs reached masses that were ≈8 times those of the largest, ecologically equivalent terrestrial mammals. The factors most responsible for setting the maximal body size of vertebrates are resource quality and quantity, as modified by the mobility of the consumer, and the vertebrate's rate of energy expenditure. If the food intake of the largest herbivorous mammals defines the maximal rate at which plant resources can be consumed in terrestrial environments and if that limit applied to dinosaurs, then the large size of sauropods occurred because they expended energy in the field at rates extrapolated from those of varanid lizards, which are ≈22% of the rates in mammals and 3.6 times the rates of other lizards of equal size. Of 2 species having the same energy income, the species that uses the most energy for mass-independent maintenance of necessity has a smaller size. The larger mass found in some marine mammals reflects a greater resource abundance in marine environments. The presumptively low energy expenditures of dinosaurs potentially permitted Mesozoic communities to support dinosaur biomasses that were up to 5 times those found in mammalian herbivores in Africa today. The maximal size of predatory theropods was ≈8 tons, which if it reflected the maximal capacity to consume vertebrates in terrestrial environments, corresponds in predatory mammals to a maximal mass less than a ton, which is what is observed. Some coelurosaurs may have evolved endothermy in association with the evolution of feathered insulation and a small mass. PMID:19581600

Resources and energetics determined dinosaur maximal size.

PubMed

McNab, Brian K

2009-07-21

Some dinosaurs reached masses that were approximately 8 times those of the largest, ecologically equivalent terrestrial mammals. The factors most responsible for setting the maximal body size of vertebrates are resource quality and quantity, as modified by the mobility of the consumer, and the vertebrate's rate of energy expenditure. If the food intake of the largest herbivorous mammals defines the maximal rate at which plant resources can be consumed in terrestrial environments and if that limit applied to dinosaurs, then the large size of sauropods occurred because they expended energy in the field at rates extrapolated from those of varanid lizards, which are approximately 22% of the rates in mammals and 3.6 times the rates of other lizards of equal size. Of 2 species having the same energy income, the species that uses the most energy for mass-independent maintenance of necessity has a smaller size. The larger mass found in some marine mammals reflects a greater resource abundance in marine environments. The presumptively low energy expenditures of dinosaurs potentially permitted Mesozoic communities to support dinosaur biomasses that were up to 5 times those found in mammalian herbivores in Africa today. The maximal size of predatory theropods was approximately 8 tons, which if it reflected the maximal capacity to consume vertebrates in terrestrial environments, corresponds in predatory mammals to a maximal mass less than a ton, which is what is observed. Some coelurosaurs may have evolved endothermy in association with the evolution of feathered insulation and a small mass.

Cardiorespiratory Coordination in Repeated Maximal Exercise

PubMed Central

Garcia-Retortillo, Sergi; Javierre, Casimiro; Hristovski, Robert; Ventura, Josep L.; Balagué, Natàlia

2017-01-01

Increases in cardiorespiratory coordination (CRC) after training with no differences in performance and physiological variables have recently been reported using a principal component analysis approach. However, no research has yet evaluated the short-term effects of exercise on CRC. The aim of this study was to delineate the behavior of CRC under different physiological initial conditions produced by repeated maximal exercises. Fifteen participants performed 2 consecutive graded and maximal cycling tests. Test 1 was performed without any previous exercise, and Test 2 6 min after Test 1. Both tests started at 0 W and the workload was increased by 25 W/min in males and 20 W/min in females, until they were not able to maintain the prescribed cycling frequency of 70 rpm for more than 5 consecutive seconds. A principal component (PC) analysis of selected cardiovascular and cardiorespiratory variables (expired fraction of O2, expired fraction of CO2, ventilation, systolic blood pressure, diastolic blood pressure, and heart rate) was performed to evaluate the CRC defined by the number of PCs in both tests. In order to quantify the degree of coordination, the information entropy was calculated and the eigenvalues of the first PC (PC1) were compared between tests. Although no significant differences were found between the tests with respect to the performed maximal workload (Wmax), maximal oxygen consumption (VO2 max), or ventilatory threshold (VT), an increase in the number of PCs and/or a decrease of eigenvalues of PC1 (t = 2.95; p = 0.01; d = 1.08) was found in Test 2 compared to Test 1. Moreover, entropy was significantly higher (Z = 2.33; p = 0.02; d = 1.43) in the last test. In conclusion, despite the fact that no significant differences were observed in the conventionally explored maximal performance and physiological variables (Wmax, VO2 max, and VT) between tests, a reduction of CRC was observed in Test 2. These results emphasize the interest of CRC evaluation in

Student academic achievement in college chemistry

NASA Astrophysics Data System (ADS)

Tabibzadeh, Kiana S.

General Chemistry is required for variety of baccalaureate degrees, including all medical related fields, engineering, and science majors. Depending on the institution, the prerequisite requirement for college level General Chemistry varies. The success rate for this course is low. The purpose of this study is to examine the factors influencing student academic achievement and retention in General Chemistry at the college level. In this study student achievement is defined by those students who earned grades of "C" or better. The dissertation contains in-depth studies on influence of Intermediate Algebra as a prerequisite compared to Fundamental Chemistry for student academic achievement and student retention in college General Chemistry. In addition the study examined the extent and manner in which student self-efficacy influences student academic achievement in college level General Chemistry. The sample for this part of the study is 144 students enrolled in first semester college level General Chemistry. Student surveys determined student self-efficacy level. The statistical analyses of study demonstrated that Fundamental Chemistry is a better prerequisite for student academic achievement and student retention. The study also found that student self-efficacy has no influence on student academic achievement. The significance of this study will be to provide data for the purpose of establishing a uniform and most suitable prerequisite for college level General Chemistry. Finally the variables identified to influence student academic achievement and enhance student retention will support educators' mission to maximize the students' ability to complete their educational goal at institutions of higher education.

Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Can Preconditioning Strategies Improve Therapeutic Efficacy?

PubMed

Schäfer, Richard; Spohn, Gabriele; Baer, Patrick C

2016-07-01

Mesenchymal stem/stromal cells (MSCs) are becoming increasingly important for the development of cell therapeutics in regenerative medicine. Featuring immunomodulatory potential as well as secreting a variety of trophic factors, MSCs showed remarkable therapeutic effects in numerous preclinical disease models. However, sustainable translation of MSC therapies to the clinic is hampered by heterogeneity of MSCs and non-standardized in vitro culture technologies. Moreover, potent MSC therapeutics require MSCs with maximum regenerative capacity. There is growing evidence that in vitro preconditioning strategies of MSCs can optimize their therapeutic potential. In the following we will discuss achievements and challenges of the development of MSC therapies in regenerative medicine highlighting specific in vitro preconditioning strategies prior to cell transplantation to increase their therapeutic efficacy.

Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Can Preconditioning Strategies Improve Therapeutic Efficacy?

PubMed Central

Schäfer, Richard; Spohn, Gabriele; Baer, Patrick C.

2016-01-01

Mesenchymal stem/stromal cells (MSCs) are becoming increasingly important for the development of cell therapeutics in regenerative medicine. Featuring immunomodulatory potential as well as secreting a variety of trophic factors, MSCs showed remarkable therapeutic effects in numerous preclinical disease models. However, sustainable translation of MSC therapies to the clinic is hampered by heterogeneity of MSCs and non-standardized in vitro culture technologies. Moreover, potent MSC therapeutics require MSCs with maximum regenerative capacity. There is growing evidence that in vitro preconditioning strategies of MSCs can optimize their therapeutic potential. In the following we will discuss achievements and challenges of the development of MSC therapies in regenerative medicine highlighting specific in vitro preconditioning strategies prior to cell transplantation to increase their therapeutic efficacy. PMID:27721701

How To: Maximize Google

ERIC Educational Resources Information Center

Branzburg, Jeffrey

2004-01-01

Google is shaking out to be the leading Web search engine, with recent research from Nielsen NetRatings reporting about 40 percent of all U.S. households using the tool at least once in January 2004. This brief article discusses how teachers and students can maximize their use of Google.

Response to selection while maximizing genetic variance in small populations.

PubMed

Cervantes, Isabel; Gutiérrez, Juan Pablo; Meuwissen, Theo H E

2016-09-20

Rare breeds represent a valuable resource for future market demands. These populations are usually well-adapted, but their low census compromises the genetic diversity and future of these breeds. Since improvement of a breed for commercial traits may also confer higher probabilities of survival for the breed, it is important to achieve good responses to artificial selection. Therefore, efficient genetic management of these populations is essential to ensure that they respond adequately to genetic selection in possible future artificial selection scenarios. Scenarios that maximize the maximum genetic variance in a unique population could be a valuable option. The aim of this work was to study the effect of the maximization of genetic variance to increase selection response and improve the capacity of a population to adapt to a new environment/production system. We simulated a random scenario (A), a full-sib scenario (B), a scenario applying the maximum variance total (MVT) method (C), a MVT scenario with a restriction on increases in average inbreeding (D), a MVT scenario with a restriction on average individual increases in inbreeding (E), and a minimum coancestry scenario (F). Twenty replicates of each scenario were simulated for 100 generations, followed by 10 generations of selection. Effective population size was used to monitor the outcomes of these scenarios. Although the best response to selection was achieved in scenarios B and C, they were discarded because they are unpractical. Scenario A was also discarded because of its low response to selection. Scenario D yielded less response to selection and a smaller effective population size than scenario E, for which response to selection was higher during early generations because of the moderately structured population. In scenario F, response to selection was slightly higher than in Scenario E in the last generations. Application of MVT with a restriction on individual increases in inbreeding resulted in the

Maximizing return on socioeconomic investment in phase II proof-of-concept trials.

PubMed

Chen, Cong; Beckman, Robert A

2014-04-01

Phase II proof-of-concept (POC) trials play a key role in oncology drug development, determining which therapeutic hypotheses will undergo definitive phase III testing according to predefined Go-No Go (GNG) criteria. The number of possible POC hypotheses likely far exceeds available public or private resources. We propose a design strategy for maximizing return on socioeconomic investment in phase II trials that obtains the greatest knowledge with the minimum patient exposure. We compare efficiency using the benefit-cost ratio, defined to be the risk-adjusted number of truly active drugs correctly identified for phase III development divided by the risk-adjusted total sample size in phase II and III development, for different POC trial sizes, powering schemes, and associated GNG criteria. It is most cost-effective to conduct small POC trials and set the corresponding GNG bars high, so that more POC trials can be conducted under socioeconomic constraints. If δ is the minimum treatment effect size of clinical interest in phase II, the study design with the highest benefit-cost ratio has approximately 5% type I error rate and approximately 20% type II error rate (80% power) for detecting an effect size of approximately 1.5δ. A Go decision to phase III is made when the observed effect size is close to δ. With the phenomenal expansion of our knowledge in molecular biology leading to an unprecedented number of new oncology drug targets, conducting more small POC trials and setting high GNG bars maximize the return on socioeconomic investment in phase II POC trials. ©2014 AACR.

Assessment of the Maximal Split-Half Coefficient to Estimate Reliability

ERIC Educational Resources Information Center

Thompson, Barry L.; Green, Samuel B.; Yang, Yanyun

2010-01-01

The maximal split-half coefficient is computed by calculating all possible split-half reliability estimates for a scale and then choosing the maximal value as the reliability estimate. Osburn compared the maximal split-half coefficient with 10 other internal consistency estimates of reliability and concluded that it yielded the most consistently…

Self-focusing therapeutic gene delivery with intelligent gene vector swarms: intra-swarm signalling through receptor transgene expression in targeted cells.

PubMed

Tolmachov, Oleg E

2015-01-01

Gene delivery in vivo that is tightly focused on the intended target cells is essential to maximize the benefits of gene therapy and to reduce unwanted side-effects. Cell surface markers are immediately available for probing by therapeutic gene vectors and are often used to direct gene transfer with these vectors to specific target cell populations. However, it is not unusual for the choice of available extra-cellular markers to be too scarce to provide a reliable definition of the desired therapeutically relevant set of target cells. Therefore, interrogation of intra-cellular determinants of cell-specificity, such as tissue-specific transcription factors, can be vital in order to provide detailed cell-guiding information to gene vector particles. An important improvement in cell-specific gene delivery can be achieved through auto-buildup in vector homing efficiency using intelligent 'self-focusing' of swarms of vector particles on target cells. Vector self-focusing was previously suggested to rely on the release of diffusible chemo-attractants after a successful target-specific hit by 'scout' vector particles. I hypothesize that intelligent self-focusing behaviour of swarms of cell-targeted therapeutic gene vectors can be accomplished without the employment of difficult-to-use diffusible chemo-attractants, instead relying on the intra-swarm signalling through cells expressing a non-diffusible extra-cellular receptor for the gene vectors. In the proposed model, cell-guiding information is gathered by the 'scout' gene vector particles, which: (1) attach to a variety of cells via a weakly binding (low affinity) receptor; (2) successfully facilitate gene transfer into these cells; (3) query intra-cellular determinants of cell-specificity with their transgene expression control elements and (4) direct the cell-specific biosynthesis of a vector-encoded strongly binding (high affinity) cell-surface receptor. Free members of the vector swarm loaded with therapeutic cargo

Therapeutic Use of Cannabis in Inflammatory Bowel Disease

PubMed Central

Katz, Seymour

2016-01-01

The marijuana plant Cannabis sativa and its derivatives, cannabinoids, have grown increasingly popular as a potential therapy for inflammatory bowel disease (IBD). Studies have shown that modulation of the endocannabinoid system, which regulates various functions in the body and has been shown to play a key role in the pathogenesis of IBD, has a therapeutic effect in mouse colitis. Epidemiologic data and human therapy studies reveal a possible role for cannabinoids in the symptomatic treatment of IBD, although it has yet to be determined in human populations whether cannabinoids have therapeutic anti-inflammatory effects in IBD or are simply masking its many debilitating symptoms. Large, double-blind, randomized, placebo-controlled trials using serial inflammatory markers, biopsy findings, and endoscopic disease severity to demonstrate objective improvement in IBD are necessary before cannabis can be empirically accepted and recommended as an IBD treatment option. Questions concerning its safety profile and adverse effects prompt the need for further research, particularly in regard to dosing and route of administration to maximize benefits and limit potential harms. Cannabis use should be reserved for symptomatic control in patients with severe IBD refractory to the currently available standard-of-care and complementary and alternative medicines. PMID:28035196

IMNN: Information Maximizing Neural Networks

NASA Astrophysics Data System (ADS)

Charnock, Tom; Lavaux, Guilhem; Wandelt, Benjamin D.

2018-04-01

This software trains artificial neural networks to find non-linear functionals of data that maximize Fisher information: information maximizing neural networks (IMNNs). As compressing large data sets vastly simplifies both frequentist and Bayesian inference, important information may be inadvertently missed. Likelihood-free inference based on automatically derived IMNN summaries produces summaries that are good approximations to sufficient statistics. IMNNs are robustly capable of automatically finding optimal, non-linear summaries of the data even in cases where linear compression fails: inferring the variance of Gaussian signal in the presence of noise, inferring cosmological parameters from mock simulations of the Lyman-α forest in quasar spectra, and inferring frequency-domain parameters from LISA-like detections of gravitational waveforms. In this final case, the IMNN summary outperforms linear data compression by avoiding the introduction of spurious likelihood maxima.

Nanoparticle-enabled, image-guided treatment planning of target specific RNAi therapeutics in an orthotopic prostate cancer model.

PubMed

Lin, Qiaoya; Jin, Cheng S; Huang, Huang; Ding, Lili; Zhang, Zhihong; Chen, Juan; Zheng, Gang

2014-08-13

The abilities to deliver siRNA to its intended action site and assess the delivery efficiency are challenges for current RNAi therapy, where effective siRNA delivery will join force with patient genetic profiling to achieve optimal treatment outcome. Imaging could become a critical enabler to maximize RNAi efficacy in the context of tracking siRNA delivery, rational dosimetry and treatment planning. Several imaging modalities have been used to visualize nanoparticle-based siRNA delivery but rarely did they guide treatment planning. We report a multimodal theranostic lipid-nanoparticle, HPPS(NIR)-chol-siRNA, which has a near-infrared (NIR) fluorescent core, enveloped by phospholipid monolayer, intercalated with siRNA payloads, and constrained by apoA-I mimetic peptides to give ultra-small particle size (<30 nm). Using fluorescence imaging, we demonstrated its cytosolic delivery capability for both NIR-core and dye-labeled siRNAs and its structural integrity in mice through intravenous administration, validating the usefulness of NIR-core as imaging surrogate for non-labeled therapeutic siRNAs. Next, we validated the targeting specificity of HPPS(NIR)-chol-siRNA to orthotopic tumor using sequential four-steps (in vivo, in situ, ex vivo and frozen-tissue) fluorescence imaging. The image co-registration of computed tomography and fluorescence molecular tomography enabled non-invasive assessment and treatment planning of siRNA delivery into the orthotopic tumor, achieving efficacious RNAi therapy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Maximal Outboxes of Quadrilaterals

ERIC Educational Resources Information Center

Zhao, Dongsheng

2011-01-01

An outbox of a quadrilateral is a rectangle such that each vertex of the given quadrilateral lies on one side of the rectangle and different vertices lie on different sides. We first investigate those quadrilaterals whose every outbox is a square. Next, we consider the maximal outboxes of rectangles and those quadrilaterals with perpendicular…

Designer Self-Assemble Peptides Maximize the Therapeutic Benefits of Neural Stem Cell Transplantation for Alzheimer's Disease via Enhancing Neuron Differentiation and Paracrine Action.

PubMed

Cui, Guo-hong; Shao, Shui-jin; Yang, Jia-jun; Liu, Jian-ren; Guo, Hai-dong

2016-03-01

maximize the therapeutic benefits of NSC transplantation for AD through improving the survival and differentiation of transplanted stem cells and promoting the effects of neuroprotection, anti-neuroinflammatory and paracrine action. Our results may have important clinical implications for the design of future NSC-based strategies using the biomaterials for various neurodegenerative diseases including AD.

Does Maximizing Information at the Cut Score Always Maximize Classification Accuracy and Consistency?

ERIC Educational Resources Information Center

Wyse, Adam E.; Babcock, Ben

2016-01-01

A common suggestion made in the psychometric literature for fixed-length classification tests is that one should design tests so that they have maximum information at the cut score. Designing tests in this way is believed to maximize the classification accuracy and consistency of the assessment. This article uses simulated examples to illustrate…

Maximizing propulsive thrust of a driven filament at low Reynolds number via variable flexibility.

PubMed

Peng, Zhiwei; Elfring, Gwynn J; Pak, On Shun

2017-03-22

At low Reynolds numbers the locomotive capability of a body can be dramatically hindered by the absence of inertia. In this work, we show how propulsive performance in this regime can be significantly enhanced by employing spatially varying flexibility. As a prototypical example, we consider the propulsive thrust generated by a filament periodically driven at one end. The rigid case leads to zero propulsion, as so constrained by Purcell's scallop theorem, while for uniform filaments there exists a bending stiffness maximizing the propulsive force at a given frequency; here we demonstrate explicitly how considerable further improvement can be achieved by simply varying the stiffness along the filament. The optimal flexibility distribution is strongly configuration-dependent: while increasing the flexibility towards the tail-end enhances the propulsion of a clamped filament, for a hinged filament decreasing the flexibility towards the tail-end is instead favorable. The results reveal new design principles for maximizing propulsion at low Reynolds numbers, potentially useful for developing synthetic micro-swimmers requiring large propulsive force for various biomedical applications.

Current issues of RNAi therapeutics delivery and development.

PubMed

Haussecker, D

2014-12-10

12 years following the discovery of the RNAi mechanism in Man, a number of RNAi therapeutics development candidates have emerged with profiles suggesting that they could become drugs of significant medical importance for diseases like TTR amyloidosis, HBV, solid cancers, and hemophilia. Despite this robust progress, the perception of RNAi therapeutics has been on a roller-coaster ride driven not only by science, but also regulatory trends, the stock markets, and Big Pharma business development decisions [1]. This presentation provides an update on the current state of RNAi therapeutics development with a particular focus on what RNAi delivery can achieve today and key challenges to be overcome to expand therapeutic opportunities. The delivery of RNAi triggers to disease-relevant cell types clearly represents the rate-limiting factor in broadly expanding the applicability of RNAi therapeutics. Today, with at least 3 delivery options (lipid nanoparticles/LNPs, GalNAc-siRNA conjugates, Dynamic PolyConjugates/DPCs) for which profound gene knockdowns have been demonstrated in non-human primates and in the clinic, RNAi therapeutics should in principle be able to address most diseases related to gene expression in the liver. Given the central importance of the liver in systemic physiology, this already represents a significant therapeutic and commercial opportunity rivaling that of e.g. monoclonal antibodies. Beyond the liver, there is a reason to believe that current RNAi therapeutics technologies can address a number of solid tumors (e.g. LNPs), diseases of the eye (e.g. self-delivering RNAi triggers) as well as diseases involving the respiratory epithelium (e.g. aerosolized LNPs), certain phagocytic cells (LNPs), hematopoietic stem cells and their progeny (lentiviral DNA-directed RNAi), vascular endothelial cells (cationic lipoplexes), and certain cell types in the kidney (self-delivering RNAi triggers, DPCs; Table 1). Despite this success, there has been a sense that

Maximally-localized position, Euclidean path-integral, and thermodynamics in GUP quantum mechanics

NASA Astrophysics Data System (ADS)

Bernardo, Reginald Christian S.; Esguerra, Jose Perico H.

2018-04-01

In dealing with quantum mechanics at very high energies, it is essential to adapt to a quasiposition representation using the maximally-localized states because of the generalized uncertainty principle. In this paper, we look at maximally-localized states as eigenstates of the operator ξ = X + iβP that we refer to as the maximally-localized position. We calculate the overlap between maximally-localized states and show that the identity operator can be expressed in terms of the maximally-localized states. Furthermore, we show that the maximally-localized position is diagonal in momentum-space and that the maximally-localized position and its adjoint satisfy commutation and anti-commutation relations reminiscent of the harmonic oscillator commutation and anti-commutation relations. As application, we use the maximally-localized position in developing the Euclidean path-integral and introduce the compact form of the propagator for maximal localization. The free particle momentum-space propagator and the propagator for maximal localization are analytically evaluated up to quadratic-order in β. Finally, we obtain a path-integral expression for the partition function of a thermodynamic system using the maximally-localized states. The partition function of a gas of noninteracting particles is evaluated. At temperatures exceeding the Planck energy, we obtain the gas' maximum internal energy N / 2 β and recover the zero heat capacity of an ideal gas.

On Maximizing the Throughput of Packet Transmission under Energy Constraints.

PubMed

Wu, Weiwei; Dai, Guangli; Li, Yan; Shan, Feng

2018-06-23

More and more Internet of Things (IoT) wireless devices have been providing ubiquitous services over the recent years. Since most of these devices are powered by batteries, a fundamental trade-off to be addressed is the depleted energy and the achieved data throughput in wireless data transmission. By exploiting the rate-adaptive capacities of wireless devices, most existing works on energy-efficient data transmission try to design rate-adaptive transmission policies to maximize the amount of transmitted data bits under the energy constraints of devices. Such solutions, however, cannot apply to scenarios where data packets have respective deadlines and only integrally transmitted data packets contribute. Thus, this paper introduces a notion of weighted throughput, which measures how much total value of data packets are successfully and integrally transmitted before their own deadlines. By designing efficient rate-adaptive transmission policies, this paper aims to make the best use of the energy and maximize the weighted throughput. What is more challenging but with practical significance, we consider the fading effect of wireless channels in both offline and online scenarios. In the offline scenario, we develop an optimal algorithm that computes the optimal solution in pseudo-polynomial time, which is the best possible solution as the problem undertaken is NP-hard. In the online scenario, we propose an efficient heuristic algorithm based on optimal properties derived for the optimal offline solution. Simulation results validate the efficiency of the proposed algorithm.

Massage Therapy Education Online: Student Satisfaction and Achievement, Part I

PubMed Central

McQuillan, David James

2010-01-01

In recent years, providers of massage therapy education have, in growing numbers, started to use online technologies to support the learning processes of their students. Using a narrative review of the existing online learning literature, this paper aims to provide a solid pedagogical foundation for these early explorations. It identifies five key factors—instructional pedagogy, quality of instruction, interaction and communication, individual learner qualities, and the online interface—that contribute to student satisfaction and achievement in the online context. The relationships between those factors and the experience of the online learner are discussed with reference to maximization of student satisfaction and achievement. PMID:21589705

Generic and therapeutic substitutions in the UK: are they a good thing?

PubMed Central

Duerden, Martin G; Hughes, Dyfrig A

2010-01-01

There is considerable interest and debate concerning the place of generic substitution (switching from a brand to generic product); and on therapeutic substitution, that is, switching to a cheaper, but apparently equivalent, product, usually within the drug class. Generic substitution by pharmacists is standard practice in UK hospital settings, and is being proposed for implementation in primary care. Although most prescriptions are already written generically (83% in the community in England in 2008), there are still cost savings that could be made if generic medicines are substituted against prescriptions written by branded name or by getting prescribers to adhere to advice to prescribe generically. Therapeutic substitution is more contentious, as direct evidence to support equivalence is normally lacking. However, the price differential between established drugs whose patents have expired and for which generics are available and newer, branded medicines within the same therapeutic class, makes therapeutic substitution an attractive application of cost-minimization analysis for the more efficient use of healthcare resources. Here we explore the tension that exists between the clinical appropriateness and safety of switching from an individual patient perspective and the consideration of value for money which is required to maximize population health from a health service perspective. Although substitution may affect individual patients (such as, for instance, reduced adherence, increased potential for medication error), it might be a price worth paying given the opportunity cost associated with the use of medicines that are clinically no better than cheaper alternatives. PMID:20716231

Maximizing optical efficacy and color gamut in projection applications by combining four laser wavelengths

NASA Astrophysics Data System (ADS)

Wallhead, Ian; Ocaña, Roberto

2014-05-01

Laser projection devices should be designed to maximize their luminous efficacy and color gamut. This is for two main reasons. Firstly, being either stand alone devices or embedded in other products, they could be powered by battery, and lifetime is an important factor. Secondly, the increasing use of lasers to project images calls for a consideration of eye safety issues. The brightness of the projected image may be limited by the Class II accessible emission limit. There is reason to believe that current laser beam scanning projection technology is already close to the power ceiling based on eye safety limits. Consequently, it would be desirable to improve luminous efficacy to increase the output luminous flux whilst maintaining or improving color gamut for the same eye-safe optical power limit. Here we present a novel study about the combination of four laser wavelengths in order to maximize both color gamut and efficacy to produce the color white. Firstly, an analytic method to calculate efficacy as function of both four laser wavelengths and four laser powers is derived. Secondly we provide a new way to present the results by providing the diagram efficacy vs color gamut area that summarizes the performance of any wavelength combination for projection purposes. The results indicate that the maximal efficacy for the D65 white is only achievable by using a suitable combination of both laser power ratios and wavelengths.

CRISPR therapeutic tools for complex genetic disorders and cancer (Review)

PubMed Central

Baliou, Stella; Adamaki, Maria; Kyriakopoulos, Anthony M.; Spandidos, Demetrios A.; Panayiotidis, Mihalis; Christodoulou, Ioannis; Zoumpourlis, Vassilis

2018-01-01

One of the fundamental discoveries in the field of biology is the ability to modulate the genome and to monitor the functional outputs derived from genomic alterations. In order to unravel new therapeutic options, scientists had initially focused on inducing genetic alterations in primary cells, in established cancer cell lines and mouse models using either RNA interference or cDNA overexpression or various programmable nucleases [zinc finger nucleases (ZNF), transcription activator-like effector nucleases (TALEN)]. Even though a huge volume of data was produced, its use was neither cheap nor accurate. Therefore, the clustered regularly interspaced short palindromic repeats (CRISPR) system was evidenced to be the next step in genome engineering tools. CRISPR-associated protein 9 (Cas9)-mediated genetic perturbation is simple, precise and highly efficient, empowering researchers to apply this method to immortalized cancerous cell lines, primary cells derived from mouse and human origins, xenografts, induced pluripotent stem cells, organoid cultures, as well as the generation of genetically engineered animal models. In this review, we assess the development of the CRISPR system and its therapeutic applications to a wide range of complex diseases (particularly distinct tumors), aiming at personalized therapy. Special emphasis is given to organoids and CRISPR screens in the design of innovative therapeutic approaches. Overall, the CRISPR system is regarded as an eminent genome engineering tool in therapeutics. We envision a new era in cancer biology during which the CRISPR-based genome engineering toolbox will serve as the fundamental conduit between the bench and the bedside; nonetheless, certain obstacles need to be addressed, such as the eradication of side-effects, maximization of efficiency, the assurance of delivery and the elimination of immunogenicity. PMID:29901119

The key kinematic determinants of undulatory underwater swimming at maximal velocity.

PubMed

Connaboy, Chris; Naemi, Roozbeh; Brown, Susan; Psycharakis, Stelios; McCabe, Carla; Coleman, Simon; Sanders, Ross

2016-01-01

The optimisation of undulatory underwater swimming is highly important in competitive swimming performance. Nineteen kinematic variables were identified from previous research undertaken to assess undulatory underwater swimming performance. The purpose of the present study was to determine which kinematic variables were key to the production of maximal undulatory underwater swimming velocity. Kinematic data at maximal undulatory underwater swimming velocity were collected from 17 skilled swimmers. A series of separate backward-elimination analysis of covariance models was produced with cycle frequency and cycle length as dependent variables (DVs) and participant as a fixed factor, as including cycle frequency and cycle length would explain 100% of the maximal swimming velocity variance. The covariates identified in the cycle-frequency and cycle-length models were used to form the saturated model for maximal swimming velocity. The final parsimonious model identified three covariates (maximal knee joint angular velocity, maximal ankle angular velocity and knee range of movement) as determinants of the variance in maximal swimming velocity (adjusted-r2 = 0.929). However, when participant was removed as a fixed factor there was a large reduction in explained variance (adjusted r2 = 0.397) and only maximal knee joint angular velocity continued to contribute significantly, highlighting its importance to the production of maximal swimming velocity. The reduction in explained variance suggests an emphasis on inter-individual differences in undulatory underwater swimming technique and/or anthropometry. Future research should examine the efficacy of other anthropometric, kinematic and coordination variables to better understand the production of maximal swimming velocity and consider the importance of individual undulatory underwater swimming techniques when interpreting the data.

Protein-Based Therapeutic Killing for Cancer Therapies.

PubMed

Serna, Naroa; Sánchez-García, Laura; Unzueta, Ugutz; Díaz, Raquel; Vázquez, Esther; Mangues, Ramón; Villaverde, Antonio

2018-03-01

The treatment of some high-incidence human diseases is based on therapeutic cell killing. In cancer this is mainly achieved by chemical drugs that are systemically administered to reach effective toxic doses. As an innovative alternative, cytotoxic proteins identified in nature can be adapted as precise therapeutic agents. For example, individual toxins and venom components, proapoptotic factors, and antimicrobial peptides from bacteria, animals, plants, and humans have been engineered as highly potent drugs. In addition to the intrinsic cytotoxic activities of these constructs, their biological fabrication by DNA recombination allows the recruitment, in single pharmacological entities, of diverse functions of clinical interest such as specific cell-surface receptor binding, self-activation, and self-assembling as nanoparticulate materials, with wide applicability in cell-targeted oncotherapy and theragnosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Maximal Sprinting Speed of Elite Soccer Players During Training and Matches.

PubMed

Djaoui, Leo; Chamari, Karim; Owen, Adam L; Dellal, Alexandre

2017-06-01

The aim of the present study was to compare (a) the maximal sprinting speed (MSS) attained by soccer players during matches (MSSmatch) according to their level of play (professional first French division vs. elite amateur fourth French division) and the playing positions and (b) the MSS attained by professional soccer players during 14 different types of small-sided games (SSG, MSSSSG) and match-play. All players monitored through the study performed a 40-m sprint test to assess individual MSS (MSStest) and compare it to the training and match activity, with the calculation of the percentage of MSStest (%MSStest) reached. No differences were found according to the level of play; however, positional wide players achieved a higher MSSmatch, %MSStest, and MSSSSG than central players (both defenders and midfielders) during matches and SSG. MSSmatch were higher than all MSSSSG, and MSSSSG were positively correlated with the area of the pitch (0.45, p < 0.001), its length (0.53, p < 0.001), and the number of players involved (0.38, p < 0.001). The closer SSG was to match situation in terms of rules, the higher the MSSSSG. Wide players reached higher MSS in match and SSG than central players, confirming the relevance of using SSG close to match situation to specifically prepare elite players to the maximal running speed demand of the match.

Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes

PubMed Central

Petrosino, Jennifer M.; Heiss, Valerie J.; Maurya, Santosh K.; Kalyanasundaram, Anuradha; Periasamy, Muthu; LaFountain, Richard A.; Wilson, Jacob M.; Simonetti, Orlando P.; Ziouzenkova, Ouliana

2016-01-01

Functional assessments of cardiovascular fitness (CVF) are needed to establish animal models of dysfunction, test the effects of novel therapeutics, and establish the cardio-metabolic phenotype of mice. In humans, the graded maximal exercise test (GXT) is a standardized diagnostic for assessing CVF and mortality risk. These tests, which consist of concurrent staged increases in running speed and inclination, provide diagnostic cardio-metabolic parameters, such as, VO2max, anaerobic threshold, and metabolic crossover. Unlike the human-GXT, published mouse treadmill tests have set, not staged, increases in inclination as speed progress until exhaustion (PXT). Additionally, they often lack multiple cardio-metabolic parameters. Here, we developed a mouse-GXT with the intent of improving mouse-exercise testing sensitivity and developing translatable parameters to assess CVF in healthy and dysfunctional mice. The mouse-GXT, like the human-GXT, incorporated staged increases in inclination, speed, and intensity; and, was designed by considering imitations of the PXT and differences between human and mouse physiology. The mouse-GXT and PXTs were both tested in healthy mice (C57BL/6J, FVBN/J) to determine their ability to identify cardio-metabolic parameters (anaerobic threshold, VO2max, metabolic crossover) observed in human-GXTs. Next, theses assays were tested on established diet-induced (obese-C57BL/6J) and genetic (cardiac isoform Casq2-/-) models of cardiovascular dysfunction. Results showed that both tests reported VO2max and provided reproducible data about performance. Only the mouse-GXT reproducibly identified anaerobic threshold, metabolic crossover, and detected impaired CVF in dysfunctional models. Our findings demonstrated that the mouse-GXT is a sensitive, non-invasive, and cost-effective method for assessing CVF in mice. This new test can be used as a functional assessment to determine the cardio-metabolic phenotype of various animal models or the effects of

Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes.

PubMed

Petrosino, Jennifer M; Heiss, Valerie J; Maurya, Santosh K; Kalyanasundaram, Anuradha; Periasamy, Muthu; LaFountain, Richard A; Wilson, Jacob M; Simonetti, Orlando P; Ziouzenkova, Ouliana

2016-01-01

Functional assessments of cardiovascular fitness (CVF) are needed to establish animal models of dysfunction, test the effects of novel therapeutics, and establish the cardio-metabolic phenotype of mice. In humans, the graded maximal exercise test (GXT) is a standardized diagnostic for assessing CVF and mortality risk. These tests, which consist of concurrent staged increases in running speed and inclination, provide diagnostic cardio-metabolic parameters, such as, VO2max, anaerobic threshold, and metabolic crossover. Unlike the human-GXT, published mouse treadmill tests have set, not staged, increases in inclination as speed progress until exhaustion (PXT). Additionally, they often lack multiple cardio-metabolic parameters. Here, we developed a mouse-GXT with the intent of improving mouse-exercise testing sensitivity and developing translatable parameters to assess CVF in healthy and dysfunctional mice. The mouse-GXT, like the human-GXT, incorporated staged increases in inclination, speed, and intensity; and, was designed by considering imitations of the PXT and differences between human and mouse physiology. The mouse-GXT and PXTs were both tested in healthy mice (C57BL/6J, FVBN/J) to determine their ability to identify cardio-metabolic parameters (anaerobic threshold, VO2max, metabolic crossover) observed in human-GXTs. Next, theses assays were tested on established diet-induced (obese-C57BL/6J) and genetic (cardiac isoform Casq2-/-) models of cardiovascular dysfunction. Results showed that both tests reported VO2max and provided reproducible data about performance. Only the mouse-GXT reproducibly identified anaerobic threshold, metabolic crossover, and detected impaired CVF in dysfunctional models. Our findings demonstrated that the mouse-GXT is a sensitive, non-invasive, and cost-effective method for assessing CVF in mice. This new test can be used as a functional assessment to determine the cardio-metabolic phenotype of various animal models or the effects of

Efficient Wideband Spectrum Sensing with Maximal Spectral Efficiency for LEO Mobile Satellite Systems

PubMed Central

Li, Feilong; Li, Zhiqiang; Li, Guangxia; Dong, Feihong; Zhang, Wei

2017-01-01

The usable satellite spectrum is becoming scarce due to static spectrum allocation policies. Cognitive radio approaches have already demonstrated their potential towards spectral efficiency for providing more spectrum access opportunities to secondary user (SU) with sufficient protection to licensed primary user (PU). Hence, recent scientific literature has been focused on the tradeoff between spectrum reuse and PU protection within narrowband spectrum sensing (SS) in terrestrial wireless sensing networks. However, those narrowband SS techniques investigated in the context of terrestrial CR may not be applicable for detecting wideband satellite signals. In this paper, we mainly investigate the problem of joint designing sensing time and hard fusion scheme to maximize SU spectral efficiency in the scenario of low earth orbit (LEO) mobile satellite services based on wideband spectrum sensing. Compressed detection model is established to prove that there indeed exists one optimal sensing time achieving maximal spectral efficiency. Moreover, we propose novel wideband cooperative spectrum sensing (CSS) framework where each SU reporting duration can be utilized for its following SU sensing. The sensing performance benefits from the novel CSS framework because the equivalent sensing time is extended by making full use of reporting slot. Furthermore, in respect of time-varying channel, the spatiotemporal CSS (ST-CSS) is presented to attain space and time diversity gain simultaneously under hard decision fusion rule. Computer simulations show that the optimal sensing settings algorithm of joint optimization of sensing time, hard fusion rule and scheduling strategy achieves significant improvement in spectral efficiency. Additionally, the novel ST-CSS scheme performs much higher spectral efficiency than that of general CSS framework. PMID:28117712

Factors associated with therapeutic success in HIV-positive individuals in southern Brazil.

PubMed

Silveira, M P T; Maurer, P; Guttier, M C; Moreira, L B

2015-04-01

Therapeutic success is characterized by undetectable viral load, immune reconstitution confirmed by CD4+ T-cell count and no clinical manifestations of disease. High treatment adherence is a major determinant of therapeutic success that needs prevention of viral replication, allowing immune reconstitution. Adherence to treatment <95% has been associated with both immune and viral failure. The objective of this study was to evaluate factors associated with therapeutic success in adult patients on highly active antiretroviral therapy (HAART) in a specialized centre for HIV-AIDS in southern Brazil, being defined therapeutic success as achieving and maintaining undetectable viral load, stable immune status (CD4+ T lymphocyte count ≥200 cells/mm(3) ) and adherence to HAART ≥ 95%. We conducted a historical cohort study nested in the PC-HIV randomized clinical trial of PC-HIV. We included adults who were on HAART at Pelotas HIV/AIDS Assistance Service between June 2006 and July 2007 and for whom information on treatment adherence, viral load and CD4+ cell count was available. Pregnant women were excluded. We obtained clinical data from medical records and socio-demographic information in an interview. Therapeutic success was defined as achieving and maintaining undetectable viral load, stable immune status (CD4+ T lymphocyte count ≥200 cells/mm(3) ) and adherence to HAART ≥95%. We included 136 patients (60% male) in the cohort study. Mean age was 40 ± 10 years, and median treatment duration was 59 months (IQR 25-93). Family income varied from 0 to 8 times the minimum wage (IQR 1·0-2·3). Therapeutic success was achieved by 90% (122 patients), and it was associated with previously undetectable viral load (PR = 1·30; 95% CI = 1·13-1·49) and treatment adherence prior to study entry (PR = 1·34; 95% CI = 1·07-1·69), independently of sex, age and previous immune status. When undetectable viral load, CD4+ cell count ≥200 cells/mm(3) and treatment

An innovative and highly drug-tolerant approach for detecting neutralizing antibodies directed to therapeutic antibodies.

PubMed

Sloan, John H; Conway, Richard G; Pottanat, Thomas G; Troutt, Jason S; Higgs, Richard E; Konrad, Robert J; Qian, Yue-Wei

2016-10-01

Immunogenicity testing of biotherapeutic drugs is a regulatory requirement. Herein, we describe a drug-tolerant assay for detecting neutralizing antibodies against a therapeutic antibody. Excess target of the therapeutic antibody was incorporated into the detection step of an affinity capture elution assay. Signal generated from binding of antidrug antibody (ADA) to the therapeutic antibody was compared with signal from binding of ADA to the therapeutic antibody preincubated with its target. The results demonstrated that the target blocked binding of the therapeutic antibody to neutralizing monkey ADA and to two anti-idiotypic antibodies. This highly drug-tolerant novel approach enables the detection of neutralizing antibodies and allows for one basic assay format to achieve complete characterization of ADA responses.

Clustering performance comparison using K-means and expectation maximization algorithms.

PubMed

Jung, Yong Gyu; Kang, Min Soo; Heo, Jun

2014-11-14

Clustering is an important means of data mining based on separating data categories by similar features. Unlike the classification algorithm, clustering belongs to the unsupervised type of algorithms. Two representatives of the clustering algorithms are the K -means and the expectation maximization (EM) algorithm. Linear regression analysis was extended to the category-type dependent variable, while logistic regression was achieved using a linear combination of independent variables. To predict the possibility of occurrence of an event, a statistical approach is used. However, the classification of all data by means of logistic regression analysis cannot guarantee the accuracy of the results. In this paper, the logistic regression analysis is applied to EM clusters and the K -means clustering method for quality assessment of red wine, and a method is proposed for ensuring the accuracy of the classification results.

Designing Acellular Injectable Biomaterial Therapeutics for Treating Myocardial Infarction and Peripheral Artery Disease

PubMed Central

Hernandez, Melissa J.; Christman, Karen L.

2017-01-01

Summary As the number of global deaths attributed to cardiovascular disease continues to rise, viable treatments for cardiovascular events such as myocardial infarction (MI) or conditions like peripheral artery disease (PAD) are critical. Recent studies investigating injectable biomaterials have shown promise in promoting tissue regeneration and functional improvement, and in some cases, incorporating other therapeutics further augments the beneficial effects of these biomaterials. In this review, we aim to emphasize the advantages of acellular injectable biomaterial-based therapies, specifically material-alone approaches or delivery of acellular biologics, in regards to manufacturability and the capacity of these biomaterials to regenerate or repair diseased tissue. We will focus on design parameters and mechanisms that maximize therapeutic efficacy, particularly, improved functional perfusion and neovascularization regarding PAD and improved cardiac function and reduced negative left ventricular (LV) remodeling post-MI. We will then discuss the rationale and challenges of designing new injectable biomaterial-based therapies for the clinic. PMID:29057375

From Guide to Practice: Improving Your After School Science Program to Increase Student Academic Achievement

NASA Astrophysics Data System (ADS)

Taylor, J.

2013-12-01

Numerous science organizations, such as NASA, offer educational outreach activities geared towards after school. For some programs, the primary goal is to grow students' love of science. For others, the programs are also intended to increase academic achievement. For those programs looking to support student learning in out-of-school time environments, aligning the program with learning during the classroom day can be a challenge. The Institute for Education Sciences, What Works Clearinghouse, put together a 'Practice Guide' for maximizing learning time beyond the regular school day. These practice guides provide concrete recommendations for educators supported by research. While this guide is not specific to any content or subject-area, the recommendations provided align very well with science education. After school science is often viewed as a fun, dynamic environment for students. Indeed, one of the recommendations to ensure time is structured according to students' needs is to provide relevant and interesting experiences. Given that our after school programs provide such creative environments for students, what other components are needed to promote increased academic achievement? The recommendations provided to academic achievement, include: 1. Align Instruction, 2. Maximize Attendance and Participation, 3. Adapt Instruction, 4. Provide Engaging Experiences, and 5. Evaluate Program. In this session we will examine these five recommendations presented in the Practice Guide, discuss how these strategies align with science programs, and examine what questions each program should address in order to provide experiences that lend themselves to maximizing instruction. Roadblocks and solutions for overcoming challenges in each of the five areas will be presented. Jessica Taylor will present this research based on her role as an author on the Practice Guide, 'Improving Academic Achievement in Out-of-School Time' and her experience working in various informal science

An Analytic Approach for Optimal Geometrical Design of GaAs Nanowires for Maximal Light Harvesting in Photovoltaic Cells

PubMed Central

Wu, Dan; Tang, Xiaohong; Wang, Kai; Li, Xianqiang

2017-01-01

Semiconductor nanowires(NWs) with subwavelength scale diameters have demonstrated superior light trapping features, which unravel a new pathway for low cost and high efficiency future generation solar cells. Unlike other published work, a fully analytic design is for the first time proposed for optimal geometrical parameters of vertically-aligned GaAs NW arrays for maximal energy harvesting. Using photocurrent density as the light absorbing evaluation standard, 2 μm length NW arrays whose multiple diameters and periodicity are quantitatively identified achieving the maximal value of 29.88 mA/cm2 under solar illumination. It also turns out that our method has wide suitability for single, double and four different diameters of NW arrays for highest photon energy harvesting. To validate this analytical method, intensive numerical three-dimensional finite-difference time-domain simulations of the NWs’ light harvesting are also carried out. Compared with the simulation results, the predicted maximal photocurrent densities lie within 1.5% tolerance for all cases. Along with the high accuracy, through directly disclosing the exact geometrical dimensions of NW arrays, this method provides an effective and efficient route for high performance photovoltaic design. PMID:28425488

Deterministic quantum annealing expectation-maximization algorithm

NASA Astrophysics Data System (ADS)

Miyahara, Hideyuki; Tsumura, Koji; Sughiyama, Yuki

2017-11-01

Maximum likelihood estimation (MLE) is one of the most important methods in machine learning, and the expectation-maximization (EM) algorithm is often used to obtain maximum likelihood estimates. However, EM heavily depends on initial configurations and fails to find the global optimum. On the other hand, in the field of physics, quantum annealing (QA) was proposed as a novel optimization approach. Motivated by QA, we propose a quantum annealing extension of EM, which we call the deterministic quantum annealing expectation-maximization (DQAEM) algorithm. We also discuss its advantage in terms of the path integral formulation. Furthermore, by employing numerical simulations, we illustrate how DQAEM works in MLE and show that DQAEM moderate the problem of local optima in EM.

Terminal altitude maximization for Mars entry considering uncertainties

NASA Astrophysics Data System (ADS)

Cui, Pingyuan; Zhao, Zeduan; Yu, Zhengshi; Dai, Juan

2018-04-01

Uncertainties present in the Mars atmospheric entry process may cause state deviations from the nominal designed values, which will lead to unexpected performance degradation if the trajectory is designed merely based on the deterministic dynamic model. In this paper, a linear covariance based entry trajectory optimization method is proposed considering the uncertainties presenting in the initial states and parameters. By extending the elements of the state covariance matrix as augmented states, the statistical behavior of the trajectory is captured to reformulate the performance metrics and path constraints. The optimization problem is solved by the GPOPS-II toolbox in MATLAB environment. Monte Carlo simulations are also conducted to demonstrate the capability of the proposed method. Primary trading performances between the nominal deployment altitude and its dispersion can be observed by modulating the weights on the dispersion penalty, and a compromised result referring to maximizing the 3σ lower bound of the terminal altitude is achieved. The resulting path constraints also show better satisfaction in a disturbed environment compared with the nominal situation.

Relationship between arterial oxygen desaturation and ventilation during maximal exercise.

PubMed

Miyachi, M; Tabata, I

1992-12-01

The purpose of the present study was to investigate the contribution of ventilation to arterial O2 desaturation during maximal exercise. Nine untrained subjects and 22 trained long-distance runners [age 18-36 yr, maximal O2 uptake (VO2max) 48-74 ml.min-1 x kg-1] volunteered to participate in the study. The subjects performed an incremental exhaustive cycle ergometry test at 70 rpm of pedaling frequency, during which arterial O2 saturation (SaO2) and ventilatory data were collected every minute. SaO2 was estimated with a pulse oximeter. A significant positive correlation was found between SaO2 and end-tidal PO2 (PETO2; r = 0.72, r2 = 0.52, P < 0.001) during maximal exercise. These statistical results suggest that approximately 50% of the variability of SaO2 can be accounted for by differences in PETO2, which reflects alveolar PO2. Furthermore, PETO2 was highly correlated with the ventilatory equivalent for O2 (VE/VO2; r = 0.91, P < 0.001), which indicates that PETO2 could be the result of ventilation stimulated by maximal exercise. Finally, SaO2 was positively related to VE/VO2 during maximal exercise (r = 0.74, r2 = 0.55, P < 0.001). Therefore, one-half of the arterial O2 desaturation occurring during maximal exercise may be explained by less hyperventilation, specifically for our subjects, who demonstrated a wide range of trained states. Furthermore, we found an indirect positive correlation between SaO2 and ventilatory response to CO2 at rest (r = 0.45, P < 0.05), which was mediated by ventilation during maximal exercise. These data also suggest that ventilation is an important factor for arterial O2 desaturation during maximal exercise.

A new augmentation based algorithm for extracting maximal chordal subgraphs

DOE PAGES

Bhowmick, Sanjukta; Chen, Tzu-Yi; Halappanavar, Mahantesh

2014-10-18

If every cycle of a graph is chordal length greater than three then it contains an edge between non-adjacent vertices. Chordal graphs are of interest both theoretically, since they admit polynomial time solutions to a range of NP-hard graph problems, and practically, since they arise in many applications including sparse linear algebra, computer vision, and computational biology. A maximal chordal subgraph is a chordal subgraph that is not a proper subgraph of any other chordal subgraph. Existing algorithms for computing maximal chordal subgraphs depend on dynamically ordering the vertices, which is an inherently sequential process and therefore limits the algorithms’more » parallelizability. In our paper we explore techniques to develop a scalable parallel algorithm for extracting a maximal chordal subgraph. We demonstrate that an earlier attempt at developing a parallel algorithm may induce a non-optimal vertex ordering and is therefore not guaranteed to terminate with a maximal chordal subgraph. We then give a new algorithm that first computes and then repeatedly augments a spanning chordal subgraph. After proving that the algorithm terminates with a maximal chordal subgraph, we then demonstrate that this algorithm is more amenable to parallelization and that the parallel version also terminates with a maximal chordal subgraph. That said, the complexity of the new algorithm is higher than that of the previous parallel algorithm, although the earlier algorithm computes a chordal subgraph which is not guaranteed to be maximal. Finally, we experimented with our augmentation-based algorithm on both synthetic and real-world graphs. We provide scalability results and also explore the effect of different choices for the initial spanning chordal subgraph on both the running time and on the number of edges in the maximal chordal subgraph.« less

A New Augmentation Based Algorithm for Extracting Maximal Chordal Subgraphs.

PubMed

Bhowmick, Sanjukta; Chen, Tzu-Yi; Halappanavar, Mahantesh

2015-02-01

A graph is chordal if every cycle of length greater than three contains an edge between non-adjacent vertices. Chordal graphs are of interest both theoretically, since they admit polynomial time solutions to a range of NP-hard graph problems, and practically, since they arise in many applications including sparse linear algebra, computer vision, and computational biology. A maximal chordal subgraph is a chordal subgraph that is not a proper subgraph of any other chordal subgraph. Existing algorithms for computing maximal chordal subgraphs depend on dynamically ordering the vertices, which is an inherently sequential process and therefore limits the algorithms' parallelizability. In this paper we explore techniques to develop a scalable parallel algorithm for extracting a maximal chordal subgraph. We demonstrate that an earlier attempt at developing a parallel algorithm may induce a non-optimal vertex ordering and is therefore not guaranteed to terminate with a maximal chordal subgraph. We then give a new algorithm that first computes and then repeatedly augments a spanning chordal subgraph. After proving that the algorithm terminates with a maximal chordal subgraph, we then demonstrate that this algorithm is more amenable to parallelization and that the parallel version also terminates with a maximal chordal subgraph. That said, the complexity of the new algorithm is higher than that of the previous parallel algorithm, although the earlier algorithm computes a chordal subgraph which is not guaranteed to be maximal. We experimented with our augmentation-based algorithm on both synthetic and real-world graphs. We provide scalability results and also explore the effect of different choices for the initial spanning chordal subgraph on both the running time and on the number of edges in the maximal chordal subgraph.

The Therapeutic School.

ERIC Educational Resources Information Center

Rice, John Steadman

2002-01-01

Contributes to the recent research on specific institutional carriers of the therapeutic culture, such as the state, the corporation, and the self- help movement, defining therapeutic discourse and discussing the therapeutic ethic, the therapeutic school, schools of education and their critics, and disappointing results of therapeutic schooling.…

Maximization, learning, and economic behavior

PubMed Central

Erev, Ido; Roth, Alvin E.

2014-01-01

The rationality assumption that underlies mainstream economic theory has proved to be a useful approximation, despite the fact that systematic violations to its predictions can be found. That is, the assumption of rational behavior is useful in understanding the ways in which many successful economic institutions function, although it is also true that actual human behavior falls systematically short of perfect rationality. We consider a possible explanation of this apparent inconsistency, suggesting that mechanisms that rest on the rationality assumption are likely to be successful when they create an environment in which the behavior they try to facilitate leads to the best payoff for all agents on average, and most of the time. Review of basic learning research suggests that, under these conditions, people quickly learn to maximize expected return. This review also shows that there are many situations in which experience does not increase maximization. In many cases, experience leads people to underweight rare events. In addition, the current paper suggests that it is convenient to distinguish between two behavioral approaches to improve economic analyses. The first, and more conventional approach among behavioral economists and psychologists interested in judgment and decision making, highlights violations of the rational model and proposes descriptive models that capture these violations. The second approach studies human learning to clarify the conditions under which people quickly learn to maximize expected return. The current review highlights one set of conditions of this type and shows how the understanding of these conditions can facilitate market design. PMID:25024182

Maximization, learning, and economic behavior.

PubMed

Erev, Ido; Roth, Alvin E

2014-07-22

The rationality assumption that underlies mainstream economic theory has proved to be a useful approximation, despite the fact that systematic violations to its predictions can be found. That is, the assumption of rational behavior is useful in understanding the ways in which many successful economic institutions function, although it is also true that actual human behavior falls systematically short of perfect rationality. We consider a possible explanation of this apparent inconsistency, suggesting that mechanisms that rest on the rationality assumption are likely to be successful when they create an environment in which the behavior they try to facilitate leads to the best payoff for all agents on average, and most of the time. Review of basic learning research suggests that, under these conditions, people quickly learn to maximize expected return. This review also shows that there are many situations in which experience does not increase maximization. In many cases, experience leads people to underweight rare events. In addition, the current paper suggests that it is convenient to distinguish between two behavioral approaches to improve economic analyses. The first, and more conventional approach among behavioral economists and psychologists interested in judgment and decision making, highlights violations of the rational model and proposes descriptive models that capture these violations. The second approach studies human learning to clarify the conditions under which people quickly learn to maximize expected return. The current review highlights one set of conditions of this type and shows how the understanding of these conditions can facilitate market design.

Maximal tree size of few-qubit states

NASA Astrophysics Data System (ADS)

Le, Huy Nguyen; Cai, Yu; Wu, Xingyao; Rabelo, Rafael; Scarani, Valerio

2014-06-01

Tree size (TS) is an interesting measure of complexity for multiqubit states: not only is it in principle computable, but one can obtain lower bounds for it. In this way, it has been possible to identify families of states whose complexity scales superpolynomially in the number of qubits. With the goal of progressing in the systematic study of the mathematical property of TS, in this work we characterize the tree size of pure states for the case where the number of qubits is small, namely, 3 or 4. The study of three qubits does not hold great surprises, insofar as the structure of entanglement is rather simple; the maximal TS is found to be 8, reached for instance by the |W> state. The study of four qubits yields several insights: in particular, the most economic description of a state is found not to be recursive. The maximal TS is found to be 16, reached for instance by a state called |Ψ(4)> which was already discussed in the context of four-photon down-conversion experiments. We also find that the states with maximal tree size form a set of zero measure: a smoothed version of tree size over a neighborhood of a state (ɛ-TS) reduces the maximal values to 6 and 14, respectively. Finally, we introduce a notion of tree size for mixed states and discuss it for a one-parameter family of states.

Biomedical applications of microneedles in therapeutics: recent advancements and implications in drug delivery.

PubMed

Rejinold, N Sanoj; Shin, Ju-Hyung; Seok, Hae Yong; Kim, Yeu-Chun

2016-01-01

The skin, as the largest organ, is a better option for drug delivery in many diseases. However, most transdermal delivery is difficult due to the low permeability of therapeutics across the various skin layers. There have been many innovations in transdermal drug delivery to enhance the therapeutic efficacy of the drugs administered. Microneedles (MN), micron sized needles, are of great interest to scientists as a new therapeutic vehicle through transdermal routes, especially for vaccines, drugs, small molecules, etc. This review covers new insights into different types of MNs such as solid, hollow, coated and dissolving MNs (SMNs, HMNs, CMNs, and DMNs) for selected biomedical applications in detail. Specific focus has been given to CMNs and DMNs for vaccine and drug delivery applications with recent developments in new MNs covered. This review explores the feasibility of innovative MNs used as a drug delivery carrier. Because most of the SMNs and HMNs have many limitations, it is difficult to achieve therapeutic efficacy. Therefore, many scientists are investigating functional modifications of MNs through covalent and non-covalent methods, especially for CMNs and DMNs. The biomedical applications of MNs are growing and new exciting improvements could be achieved, thus resulting in better micro/nano technologies in the near future.

Renal Sympathetic Denervation System via Intraluminal Ultrasonic Ablation: Therapeutic Intravascular Ultrasound Design and Preclinical Evaluation.

PubMed

Chernin, Gil; Szwarcfiter, Iris; Bausback, Yvonne; Jonas, Michael

2017-05-01

To assess the safety and performance of a nonfocused and nonballooned ultrasonic (US) catheter-based renal sympathetic denervation (RDN) system in normotensive swine. RDN with the therapeutic intravascular US catheter was evaluated in 3 experiments: (i) therapeutic intravascular US RDN vs a control group of untreated animals with follow-up of 30, 45, and 90 days (n = 6; n = 12 renal arteries for each group); (ii) therapeutic intravascular US RDN vs radiofrequency (RF) RDN in the contralateral artery in the same animal (n = 2; n = 4 renal arteries); and (iii) therapeutic intravascular US RDN in a recently stent-implanted renal artery (n = 2; n = 4 renal arteries). In the first experiment, therapeutic intravascular US RDN was safe, without angiographic evidence of dissection or renal artery stenosis. Neuronal tissue vacuolization, nuclei pyknosis, and perineuronal inflammation were evident after RDN, without renal artery wall damage. Norepinephrine levels were significantly lower after therapeutic intravascular US RDN after 30, 45, and 90 days compared with the control group (200.17 pg/mg ± 63.35, 184.75 pg/mg ± 44.51, and 203.43 pg/mg ± 58.54, respectively, vs 342.42 pg/mg ± 79.97). In the second experiment, deeper neuronal ablation penetrance was found with therapeutic intravascular US RDN vs RF RDN (maximal penetrance from endothelium of 7.0 mm vs 3.5 mm, respectively). There was less damage to the artery wall after therapeutic intravascular US RDN than with RF RDN, after which edema and injured endothelium were seen. In the third experiment, denervation inside the stent-implanted segments was feasible without damage to the renal artery wall or stent. The therapeutic intravascular US system performed safely and reduced norepinephrine levels. Deeper penetrance and better preservation of vessel wall were observed with therapeutic intravascular US RDN vs RF RDN. Neuronal ablations were observed in stent-implanted renal arteries. Copyright © 2017 SIR. Published

Maximal volume behind horizons without curvature singularity

NASA Astrophysics Data System (ADS)

Wang, Shao-Jun; Guo, Xin-Xuan; Wang, Towe

2018-01-01

The black hole information paradox is related to the area of event horizon, and potentially to the volume and singularity behind it. One example is the complexity/volume duality conjectured by Stanford and Susskind. Accepting the proposal of Christodoulou and Rovelli, we calculate the maximal volume inside regular black holes, which are free of curvature singularity, in asymptotically flat and anti-de Sitter spacetimes respectively. The complexity/volume duality is then applied to anti-de Sitter regular black holes. We also present an analytical expression for the maximal volume outside the de Sitter horizon.

Does Maximal External Tibial Component Rotation Influence Tibiofemoral Load Distribution in the Primary Knee Arthroplasty Setting: A Comparison of Neutral vs Maximal Anatomical External Rotatory States.

PubMed

Manning, William A; Ghosh, Kanishka M; Blain, Alasdair P; Longstaff, Lee M; Rushton, Steven P; Deehan, David J

2017-06-01

Tibial component rotation at time of knee arthroplasty can influence conformity, load transmission across the polyethylene surface, and perhaps ultimately determined survivorship. Optimal tibial component rotation on the cut surface is reliant on standard per operative manual stressing. This subjective assessment aims to balance constraint and stability of the articulation through a full arc of movement. Using a cadaveric model, computer navigation and under defined, previously validated loaded conditions mimicking the in vivo setting, the influence of maximal tibial component external rotation compared with the neutral state was examined for changes in laxity and tibiofemoral continuous load using 3D displacement measurement and an orthosensor continuous load sensor implanted within the polyethylene spacer in a simulated single radius total knee arthroplasty. No significant difference was found throughout arc of motion (0-115 degrees of flexion) for maximal varus and/or valgus or rotatory laxity between the 2 states. The neutral state achieved equivalence for mediolateral load distribution at each point of flexion. We have found that external rotation of the tibial component increased medial compartment load in comparison with the neutral position. Compared with the neutral state, external rotation consistently effected a marginal, but not significant reduction in lateral load under similar loading conditions. The effects were most pronounced in midflexion. On the basis of these findings, we would advocate for the midtibial tubercle point to determine tibial component rotation and caution against component external rotation. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantum speedup in solving the maximal-clique problem

NASA Astrophysics Data System (ADS)

Chang, Weng-Long; Yu, Qi; Li, Zhaokai; Chen, Jiahui; Peng, Xinhua; Feng, Mang

2018-03-01

The maximal-clique problem, to find the maximally sized clique in a given graph, is classically an NP-complete computational problem, which has potential applications ranging from electrical engineering, computational chemistry, and bioinformatics to social networks. Here we develop a quantum algorithm to solve the maximal-clique problem for any graph G with n vertices with quadratic speedup over its classical counterparts, where the time and spatial complexities are reduced to, respectively, O (√{2n}) and O (n2) . With respect to oracle-related quantum algorithms for the NP-complete problems, we identify our algorithm as optimal. To justify the feasibility of the proposed quantum algorithm, we successfully solve a typical clique problem for a graph G with two vertices and one edge by carrying out a nuclear magnetic resonance experiment involving four qubits.

Therapeutic management of cutaneous and genital warts.

PubMed

Ockenfels, Hans Michael

2016-09-01

During their lifetime, at least 10 % of the population will be infected by human papillomaviruses (HPV), clinically characterized by the formation of cutaneous or genital warts. Although warts are ubiquitous, there are no defined treatments. Especially in the first six months, warts frequently resolve without therapeutic intervention. This complicates the interpretation of study data, given that many studies do not differentiate between newly infected patients and those with infections that have persisted for a long time. Similarly, most studies do not take location, size, and thickness of lesions into account, either. The objective of the present review article is to analyze the study data currently available, taking into consideration both subtypes and locations - factors exceedingly crucial in clinical practice. In particular, the distinction between new-onset and chronic recalcitrant warts is reflected in a therapeutic algorithm. In the case of genital warts, the algorithm is more clearly determined by the extent of the area affected rather than the longevity of lesions. In immunocompetent individuals, any therapeutic intervention must be aimed at achieving complete resolution. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Big Data Transforms Discovery-Utilization Therapeutics Continuum

PubMed Central

Waldman, SA; Terzic, A

2015-01-01

Enabling omic technologies adopt a holistic view to produce unprecedented insights into the molecular underpinnings of health and disease, in part, by generating massive high-dimensional biological data. Leveraging these systems-level insights as an engine driving the healthcare evolution is maximized through integration with medical, demographic, and environmental datasets from individuals to populations. Big data analytics has accordingly emerged to add value to the technical aspects of storage, transfer, and analysis required for merging vast arrays of omic-, clinical- and eco-datasets. In turn, this new field at the interface of biology, medicine, and information science is systematically transforming modern therapeutics across discovery, development, regulation, and utilization. “…a man's discourse was like to a rich Persian carpet, the beautiful figures and patterns of which can be shown only by spreading and extending it out; when it is contracted and folded up, they are obscured and lost” Themistocles quoted by Plutarch AD 46 – AD 120 PMID:26888297

[The use of therapeutic writing in an institutional context].

PubMed

Reyes-Iraola, Adriana

2014-01-01

This article aims to explain the effect of the use of writing, in an institutional therapeutic space, as a means to achieve the therapeutic change in the patient and a greater efficiency in time and in institutional spaces. Different forms of using the written document are shown and supported theoretically in the context of narrative and collaborative therapy, as well as examples with the presentation of excerpts of writings of the participants. The sample was composed of patients attending the Hospital de Psiquiatría, Unidad Morelos, to receive treatment in any of the forms (commital and/or outpatient consultation). Written and oral language exchange meaning continuously, showing that the therapeutic process takes place beyond institutional and therapeutic spaces (and times). This encourages the advantages offered by the use of written language in oral psychotherapeutic processes. Writing is an intellectual resource which facilitates thinking, since when we write our own experiences the events that constitutes them are organized in time. This produces a perception of change, a representation of meanings, and stimulates self-efficiency, since it produces several stories of the events and experiences.

Basic principles of maximizing dental office productivity.

PubMed

Mamoun, John

2012-01-01

To maximize office productivity, dentists should focus on performing tasks that only they can perform and not spend office hours performing tasks that can be delegated to non-dentist personnel. An important element of maximizing productivity is to arrange the schedule so that multiple patients are seated simultaneously in different operatories. Doing so allows the dentist to work on one patient in one operatory without needing to wait for local anesthetic to take effect on another patient in another operatory, or for assistants to perform tasks (such as cleaning up, taking radiographs, performing prophylaxis, or transporting and preparing equipment and supplies) in other operatories. Another way to improve productivity is to structure procedures so that fewer steps are needed to set up and implement them. In addition, during procedures, four-handed dental passing methods can be used to provide the dentist with supplies or equipment when needed. This article reviews basic principles of maximizing dental office productivity, based on the author's observations of business logistics used by various dental offices.

Real-time, aptamer-based tracking of circulating therapeutic agents in living animals

PubMed Central

Ferguson, B. Scott; Hoggarth, David A.; Maliniak, Dan; Ploense, Kyle; White, Ryan J.; Woodward, Nick; Hsieh, Kuangwen; Bonham, Andrew J.; Eisenstein, Michael; Kippin, Tod; Plaxco, Kevin W.; Soh, H. Tom

2014-01-01

A sensor capable of continuously measuring specific molecules in the bloodstream in vivo would give clinicians a valuable window into patients’ health and their response to therapeutics. Such technology would enable truly personalized medicine, wherein therapeutic agents could be tailored with optimal doses for each patient to maximize efficacy and minimize side effects. Unfortunately, continuous, real-time measurement is currently only possible for a handful of targets, such as glucose, lactose, and oxygen, and the few existing platforms for continuous measurement are not generalizable for the monitoring of other analytes, such as small-molecule therapeutics. In response, we have developed a real-time biosensor capable of continuously tracking a wide range of circulating drugs in living subjects. Our microfluidic electrochemical detector for in vivo continuous monitoring (MEDIC) requires no exogenous reagents, operates at room temperature, and can be reconfigured to measure different target molecules by exchanging probes in a modular manner. To demonstrate the system's versatility, we measured therapeutic in vivo concentrations of doxorubicin (a chemotherapeutic) and kanamycin (an antibiotic) in live rats and in human whole blood for several hours with high sensitivity and specificity at sub-minute temporal resolution. Importantly, we show that MEDIC can also obtain pharmacokineticparameters for individual animals in real-time. Accordingly, just as continuous glucose monitoring technology is currently revolutionizing diabetes care, we believe MEDIC could be a powerful enabler for personalized medicine by ensuring delivery of optimal drug doses for individual patients based on direct detection of physiological parameters. PMID:24285484

Maximal Ethics in Counselor Education.

ERIC Educational Resources Information Center

Engels, Dennis W.

1981-01-01

Discusses the concept of maximal ethics as a basis of counselor behavior and describes the need for ethics development in counselor education training. Notes modeling aspects of counselor educator behavior and considers programming for ethical development in counselor training. Suggests resource materials for counselor training in ethics. (RC)

Detrimental Relations of Maximization with Academic and Career Attitudes

ERIC Educational Resources Information Center

Dahling, Jason J.; Thompson, Mindi N.

2013-01-01

Maximization refers to a decision-making style that involves seeking the single best option when making a choice, which is generally dysfunctional because people are limited in their ability to rationally evaluate all options and identify the single best outcome. The vocational consequences of maximization are examined in two samples, college…

Enumerating all maximal frequent subtrees in collections of phylogenetic trees.

PubMed

Deepak, Akshay; Fernández-Baca, David

2014-01-01

A common problem in phylogenetic analysis is to identify frequent patterns in a collection of phylogenetic trees. The goal is, roughly, to find a subset of the species (taxa) on which all or some significant subset of the trees agree. One popular method to do so is through maximum agreement subtrees (MASTs). MASTs are also used, among other things, as a metric for comparing phylogenetic trees, computing congruence indices and to identify horizontal gene transfer events. We give algorithms and experimental results for two approaches to identify common patterns in a collection of phylogenetic trees, one based on agreement subtrees, called maximal agreement subtrees, the other on frequent subtrees, called maximal frequent subtrees. These approaches can return subtrees on larger sets of taxa than MASTs, and can reveal new common phylogenetic relationships not present in either MASTs or the majority rule tree (a popular consensus method). Our current implementation is available on the web at https://code.google.com/p/mfst-miner/. Our computational results confirm that maximal agreement subtrees and all maximal frequent subtrees can reveal a more complete phylogenetic picture of the common patterns in collections of phylogenetic trees than maximum agreement subtrees; they are also often more resolved than the majority rule tree. Further, our experiments show that enumerating maximal frequent subtrees is considerably more practical than enumerating ordinary (not necessarily maximal) frequent subtrees.

Statistical mechanics of influence maximization with thermal noise

NASA Astrophysics Data System (ADS)

Lynn, Christopher W.; Lee, Daniel D.

2017-03-01

The problem of optimally distributing a budget of influence among individuals in a social network, known as influence maximization, has typically been studied in the context of contagion models and deterministic processes, which fail to capture stochastic interactions inherent in real-world settings. Here, we show that by introducing thermal noise into influence models, the dynamics exactly resemble spins in a heterogeneous Ising system. In this way, influence maximization in the presence of thermal noise has a natural physical interpretation as maximizing the magnetization of an Ising system given a budget of external magnetic field. Using this statistical mechanical formulation, we demonstrate analytically that for small external-field budgets, the optimal influence solutions exhibit a highly non-trivial temperature dependence, focusing on high-degree hub nodes at high temperatures and on easily influenced peripheral nodes at low temperatures. For the general problem, we present a projected gradient ascent algorithm that uses the magnetic susceptibility to calculate locally optimal external-field distributions. We apply our algorithm to synthetic and real-world networks, demonstrating that our analytic results generalize qualitatively. Our work establishes a fruitful connection with statistical mechanics and demonstrates that influence maximization depends crucially on the temperature of the system, a fact that has not been appreciated by existing research.

Therapeutic hypothermia for out-of-hospital ventricular fibrillation survivors: a feasibility study comparing time to achieve target core temperature using conventional conductive cooling versus combined conductive plus pericranial convective cooling.

PubMed

Wass, C Thomas; White, Roger D; Schroeder, Darrell R; Mirzoyev, Sultan A; Warfield, Karen T

2013-04-01

Mild to moderate therapeutic hypothermia (TH) has been shown to improve survival and neurologic outcome, as well as to reduce healthcare costs in patients resuscitated from out-of-hospital cardiac arrest (OHCA) with ventricular fibrillation. Accordingly, the American Heart Association has categorized this as a Class IB intervention. The therapeutic window for initiating TH is narrow, and thus, achieving target temperature expeditiously is of paramount importance to improve postresuscitative neurologic outcome. The present investigation is a feasibility study designed to assess the practicality and efficacy of including pericranial cooling in our postresuscitative TH protocol. Specifically, we compared time required to achieve target temperature (33°C) using our present standard of TH care (ie, conductive body cooling, conventional TH group) versus combined conductive body cooling plus convective (forced-air) head and neck cooling (combined TH group). Adult patients who experienced OHCA were included in the study provided TH could be initiated within 4 hours of resuscitation from ventricular fibrillation. Patients enrolled in both groups were cooled using the servo-controlled Arctic Sun conductive cooling system (Medivance, Inc, Louisville, CO). However, patients enrolled in the combined TH group also received forced-air pericranial cooling with an ambient temperature of approximately 13°C. In all cases, the target core (bladder) temperature was 33°C. The primary endpoint (ie, time required to achieve a core temperature of 33°C) was analyzed as a continuous variable and compared between groups using the rank sum test, whereas categorical variables were compared between groups using the chi-square test. Cardiac intensive care unit at a major tertiary care teaching center in Rochester, MN. Adult patients who experienced OHCA were included in the study. Patients enrolled in both groups were cooled using the servo-controlled Arctic Sun conductive cooling system

Contact refusal by children following acrimonious separation: therapeutic approaches with children and parents.

PubMed

Dejong, Margaret; Davies, Hilary

2013-04-01

This paper aims to build on the existing literature, by presenting some thoughts based on clinical experience with nine families of children referred for intractable contact refusal with one parent following marital separation. This particular group of high-conflict divorce cases engenders an inordinate amount of frustration both within the courts and therapeutic agencies. We outline here our assessment process and therapeutic strategies, as well as consideration of the role of the wider professional system and the courts. We conclude that whether or not direct contact with the rejected parent is achieved, useful therapeutic work can be carried out to assist children in moving on with their lives.

Maximizing Total QoS-Provisioning of Image Streams with Limited Energy Budget

NASA Astrophysics Data System (ADS)

Lee, Wan Yeon; Kim, Kyong Hoon; Ko, Young Woong

To fully utilize the limited battery energy of mobile electronic devices, we propose an adaptive adjustment method of processing quality for multiple image stream tasks running with widely varying execution times. This adjustment method completes the worst-case executions of the tasks with a given budget of energy, and maximizes the total reward value of processing quality obtained during their executions by exploiting the probability distribution of task execution times. The proposed method derives the maximum reward value for the tasks being executable with arbitrary processing quality, and near maximum value for the tasks being executable with a finite number of processing qualities. Our evaluation on a prototype system shows that the proposed method achieves larger reward values, by up to 57%, than the previous method.

The self-paced VO2max test to assess maximal oxygen uptake in highly trained runners.

PubMed

Hogg, James S; Hopker, James G; Mauger, Alexis R

2015-03-01

The novel self-paced maximal-oxygen-uptake (VO2max) test (SPV) may be a more suitable alternative to traditional maximal tests for elite athletes due to the ability to self-regulate pace. This study aimed to examine whether the SPV can be administered on a motorized treadmill. Fourteen highly trained male distance runners performed a standard graded exercise test (GXT), an incline-based SPV (SPVincline), and a speed-based SPV (SPVspeed). The GXT included a plateau-verification stage. Both SPV protocols included 5×2-min stages (and a plateau-verification stage) and allowed for self-pacing based on fixed increments of rating of perceived exertion: 11, 13, 15, 17, and 20. The participants varied their speed and incline on the treadmill by moving between different marked zones in which the tester would then adjust the intensity. There was no significant difference (P=.319, ES=0.21) in the VO2max achieved in the SPVspeed (67.6±3.6 mL·kg(-1)·min(-1), 95%CI=65.6-69.7 mL·kg(-1)·min(-1)) compared with that achieved in the GXT (68.6±6.0 mL·kg(-1)·min(-1), 95%CI=65.1-72.1 mL·kg(-1)·min(-1)). Participants achieved a significantly higher VO2max in the SPVincline (70.6±4.3 mL·kg(-1)·min(-1), 95%CI=68.1-73.0 mL·kg(-1)·min(-1)) than in either the GXT (P=.027, ES=0.39) or SPVspeed (P=.001, ES=0.76). The SPVspeed protocol produces VO2max values similar to those obtained in the GXT and may represent a more appropriate and athlete-friendly test that is more oriented toward the variable speed found in competitive sport.

Integrating Multiple Correlated Phenotypes for Genetic Association Analysis by Maximizing Heritability

PubMed Central

Zhou, Jin J.; Cho, Michael H.; Lange, Christoph; Lutz, Sharon; Silverman, Edwin K.; Laird, Nan M.

2015-01-01

Many correlated disease variables are analyzed jointly in genetic studies in the hope of increasing power to detect causal genetic variants. One approach involves assessing the relationship between each phenotype and each single nucleotide polymorphism (SNP) individually and using a Bonferroni correction for the effective number of tests conducted. Alternatively, one can apply a multivariate regression or a dimension reduction technique, such as principal component analysis (PCA), and test for the association with the principal components (PC) of the phenotypes rather than the individual phenotypes. Inspired by the previous approaches of combining phenotypes to maximize heritability at individual SNPs, in this paper, we propose to construct a maximally heritable phenotype (MaxH) by taking advantage of the estimated total heritability and co-heritability. The heritability and co-heritability only need to be estimated once, therefore our method is applicable to genome-wide scans. MaxH phenotype is a linear combination of the individual phenotypes with increased heritability and power over the phenotypes being combined. Simulations show that the heritability and power achieved agree well with the theory for large samples and two phenotypes. We compare our approach with commonly used methods and assess both the heritability and the power of the MaxH phenotype. Moreover we provide suggestions for how to choose the phenotypes for combination. An application of our approach to a COPD genome-wide association study shows the practical relevance. PMID:26111731

Power Converters Maximize Outputs Of Solar Cell Strings

NASA Technical Reports Server (NTRS)

Frederick, Martin E.; Jermakian, Joel B.

1993-01-01

Microprocessor-controlled dc-to-dc power converters devised to maximize power transferred from solar photovoltaic strings to storage batteries and other electrical loads. Converters help in utilizing large solar photovoltaic arrays most effectively with respect to cost, size, and weight. Main points of invention are: single controller used to control and optimize any number of "dumb" tracker units and strings independently; power maximized out of converters; and controller in system is microprocessor.

Maximizing the physical use of the office.

PubMed

Levin, Roger

2004-10-01

When referring to the physical plant in a dental practice, I am referring mainly to the use of dental chairs, because this is where dental practice production occurs. By maximizing the use of chairs or adding the necessary number of chairs to a practice, any office can grow and experience a proper patient flow. Since most offices have significantly high rates of no-shows, last-minute cancellations and overdue patients, the potential for growth is enormous. By using the schedule and chairs properly, the office has the opportunity to maximize production, create convenient appointments for patients and significantly increase practice profitability.

Single maximal versus combination punch kinematics.

PubMed

Piorkowski, Barry A; Lees, Adrian; Barton, Gabor J

2011-03-01

The aim of this study was to determine the influence of punch type (Jab, Cross, Lead Hook and Reverse Hook) and punch modality (Single maximal, 'In-synch' and 'Out of synch' combination) on punch speed and delivery time. Ten competition-standard volunteers performed punches with markers placed on their anatomical landmarks for 3D motion capture with an eight-camera optoelectronic system. Speed and duration between key moments were computed. There were significant differences in contact speed between punch types (F(2,18,84.87) = 105.76, p = 0.001) with Lead and Reverse Hooks developing greater speed than Jab and Cross. There were significant differences in contact speed between punch modalities (F(2,64,102.87) = 23.52, p = 0.001) with the Single maximal (M+/- SD: 9.26 +/- 2.09 m/s) higher than 'Out of synch' (7.49 +/- 2.32 m/s), 'In-synch' left (8.01 +/- 2.35 m/s) or right lead (7.97 +/- 2.53 m/s). Delivery times were significantly lower for Jab and Cross than Hook. Times were significantly lower 'In-synch' than a Single maximal or 'Out of synch' combination mode. It is concluded that a defender may have more evasion-time than previously reported. This research could be of use to performers and coaches when considering training preparations.

Prevalence of Obesity and Its Influence on Achievement of Cardiometabolic Therapeutic Goals in Chinese Type 2 Diabetes Patients: An Analysis of the Nationwide, Cross-Sectional 3B Study.

PubMed

Zhou, Xianghai; Ji, Linong; Ran, Xingwu; Su, Benli; Ji, Qiuhe; Pan, Changyu; Weng, Jianping; Ma, Changsheng; Hao, Chuanming; Zhang, Danyi; Hu, Dayi

2016-01-01

There are few data on the prevalence of obesity and its influence on achieving blood glucose, blood pressure, and blood lipid (3B) goals in Chinese type 2 diabetes outpatients. Patient demographic data, anthropometric measurements, medications, and blood glucose and lipid profiles of 24,512 type 2 diabetes patients from a large, geographically diverse study (CCMR-3B) were analyzed. Using cut-points for body mass index (BMI) and waist circumference (WC) recommended by the Working Group on Obesity in China, overweight and obesity were defined as BMIs of 24-27.9 kg/m2 and ≥28.0 kg/m2. Central obesity was defined as a waist circumference ≥80 cm in women and ≥85 cm in men. The 3B therapeutic goals were HbA1c<7.0%, BP<140/90 mmHg and LDL-C<2.6 mmol/L. Overall, 43.0% of type 2 diabetes patients were overweight and 16.7% were obese; 13.3% of overweight and and 10.1% of obese patients achieved all the 3B target goals. Overweight or obese patients were less likely to achieve 3B goals than those with normal BMIs. More than a half the overweight or obese patients (69.6%) were centrally obese. Patients with abdominal obesity were less likely to achieve cardiometabolic targets than those without abdominal obesity. In multivariate logistic regression analysis, female, higher BMI and waist circumference, smoking, drinking, sedentary lifestyle, and longer diabetes duration were significantly correlated with failure to achieve 3B control goals. Obesity is highly prevalent and associated with poor 3B control in Chinese type 2 diabetes patients. In clinical practice, more attention and resources should focus on weight loss for such patients.

Delivery of local therapeutics to the brain: working toward advancing treatment for malignant gliomas.

PubMed

Chaichana, Kaisorn L; Pinheiro, Leon; Brem, Henry

2015-03-01

Malignant gliomas, including glioblastoma and anaplastic astrocytomas, are characterized by their propensity to invade surrounding brain parenchyma, making curative resection difficult. These tumors typically recur within two centimeters of the resection cavity even after gross total removal. As a result, there has been an emphasis on developing therapeutics aimed at achieving local disease control. In this review, we will summarize the current developments in the delivery of local therapeutics, namely direct injection, convection-enhanced delivery and implantation of drug-loaded polymers, as well as the application of these therapeutics in future methods including microchip drug delivery and local gene therapy.

Delivery of local therapeutics to the brain: working toward advancing treatment for malignant gliomas

PubMed Central

Chaichana, Kaisorn L; Pinheiro, Leon; Brem, Henry

2015-01-01

Malignant gliomas, including glioblastoma and anaplastic astrocytomas, are characterized by their propensity to invade surrounding brain parenchyma, making curative resection difficult. These tumors typically recur within two centimeters of the resection cavity even after gross total removal. As a result, there has been an emphasis on developing therapeutics aimed at achieving local disease control. In this review, we will summarize the current developments in the delivery of local therapeutics, namely direct injection, convection-enhanced delivery and implantation of drug-loaded polymers, as well as the application of these therapeutics in future methods including microchip drug delivery and local gene therapy. PMID:25853310

[Therapeutic hypothermia for severe traumatic brain injury].

PubMed

Bouzat, P; Francony, G; Oddo, M; Payen, J-F

2013-11-01

Therapeutic hypothermia (TH) is considered a standard of care in the post-resuscitation phase of cardiac arrest. In experimental models of traumatic brain injury (TBI), TH was found to have neuroprotective properties. However, TH failed to demonstrate beneficial effects on neurological outcome in patients with TBI. The absence of benefits of TH uniformly applied in TBI patients should not question the use of TH as a second-tier therapy to treat elevated intracranial pressure. The management of all the practical aspects of TH is a key factor to avoid side effects and to optimize the potential benefit of TH in the treatment of intracranial hypertension. Induction of TH can be achieved with external surface cooling or with intra-vascular devices. The therapeutic target should be set at a 35°C using brain temperature as reference, and should be maintained at least during 48 hours and ideally over the entire period of elevated intracranial pressure. The control of the rewarming phase is crucial to avoid temperature overshooting and should not exceed 1°C/day. Besides its use in the management of intracranial hypertension, therapeutic cooling is also essential to treat hyperthermia in brain-injured patients. In this review, we will discuss the benefit-risk balance and practical aspects of therapeutic temperature management in TBI patients. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Comparison of changes in the mobility of the pelvic floor muscle on during the abdominal drawing-in maneuver, maximal expiration, and pelvic floor muscle maximal contraction.

PubMed

Jung, Halim; Jung, Sangwoo; Joo, Sunghee; Song, Changho

2016-01-01

[Purpose] The purpose of this study was to compare changes in the mobility of the pelvic floor muscle during the abdominal drawing-in maneuver, maximal expiration, and pelvic floor muscle maximal contraction. [Subjects] Thirty healthy adults participated in this study (15 men and 15 women). [Methods] All participants performed a bridge exercise and abdominal curl-up during the abdominal drawing-in maneuver, maximal expiration, and pelvic floor muscle maximal contraction. Pelvic floor mobility was evaluated as the distance from the bladder base using ultrasound. [Results] According to exercise method, bridge exercise and abdominal curl-ups led to significantly different pelvic floor mobility. The pelvic floor muscle was elevated during the abdominal drawing-in maneuver and descended during maximal expiration. Finally, pelvic floor muscle mobility was greater during abdominal curl-up than during the bridge exercise. [Conclusion] According to these results, the abdominal drawing-in maneuver induced pelvic floor muscle contraction, and pelvic floor muscle contraction was greater during the abdominal curl-up than during the bridge exercise.

Self-tuning bistable parametric feedback oscillator: Near-optimal amplitude maximization without model information

NASA Astrophysics Data System (ADS)

Braun, David J.; Sutas, Andrius; Vijayakumar, Sethu

2017-01-01

Theory predicts that parametrically excited oscillators, tuned to operate under resonant condition, are capable of large-amplitude oscillation useful in diverse applications, such as signal amplification, communication, and analog computation. However, due to amplitude saturation caused by nonlinearity, lack of robustness to model uncertainty, and limited sensitivity to parameter modulation, these oscillators require fine-tuning and strong modulation to generate robust large-amplitude oscillation. Here we present a principle of self-tuning parametric feedback excitation that alleviates the above-mentioned limitations. This is achieved using a minimalistic control implementation that performs (i) self-tuning (slow parameter adaptation) and (ii) feedback pumping (fast parameter modulation), without sophisticated signal processing past observations. The proposed approach provides near-optimal amplitude maximization without requiring model-based control computation, previously perceived inevitable to implement optimal control principles in practical application. Experimental implementation of the theory shows that the oscillator self-tunes itself near to the onset of dynamic bifurcation to achieve extreme sensitivity to small resonant parametric perturbations. As a result, it achieves large-amplitude oscillations by capitalizing on the effect of nonlinearity, despite substantial model uncertainties and strong unforeseen external perturbations. We envision the present finding to provide an effective and robust approach to parametric excitation when it comes to real-world application.

National GDP, Science Interest and Science Achievement: A Person-by-Nation Interaction

PubMed Central

Drob, Elliot M. Tucker; Cheung, Amanda K.; Briley, Daniel A.

2014-01-01

Maximizing science achievement is a critical target of educational policy, with important implications for national and international economic and technological competitiveness. Previous research has identified both science interest and socioeconomic status (SES) as robust predictors of science achievement, but little research has examined their joint effects. In a dataset drawn from approximately 400,000 high school students from 57 countries, we document large interest by SES and interest by per capita gross domestic product (GDP) interactions in the prediction of science achievement. Student interest in science is a substantially stronger predictor of science achievement in higher socioeconomic contexts and in higher GDP nations. Our results are consistent with the hypothesis that, in higher opportunity contexts, motivational factors play larger roles in learning and achievement. They add to the growing body of evidence indicating that substantial cross national differences in psychological effect sizes are not simply a logical possibility, but in many cases, an empirical reality. PMID:25304883

The evolving landscape of therapeutic drug development for hepatocellular carcinoma.

PubMed

Chong, Dawn Qingqing; Tan, Iain Beehuat; Choo, Su-Pin; Toh, Han Chong

2013-11-01

Currently, only one drug, sorafenib, is FDA approved for the treatment of advanced hepatocellular carcinoma (HCC), achieving modest objective response rates while still conferring an overall survival benefit. Unlike other solid tumors, no oncogenic addiction loops have been validated as clinically actionable targets in HCC. Outcomes of HCC could potentially be improved if critical molecular subclasses with distinct therapeutic vulnerabilities can be identified, biomarkers that predict recurrence or progression early can be determined and key epigenetic, genetic or microenvironment drivers that determine best response to a specific targeting treatment can be uncovered. Our group and others have examined the molecular heterogeneity of hepatocellular carcinoma. We have developed a panel of patient derived xenograft models to enable focused pre-clinical drug development of rationally designed therapies in specific molecular subgroups. We observed unique patterns, including synergies, of drug activity across our molecularly diverse HCC xenografts, pointing to specific therapeutic vulnerabilities for individual tumors. These efforts inform clinical trial designs and catalyze therapeutic development. It also argues for efficient strategic allocation of patients into appropriate enriched clinical trials. Here, we will discuss some of the recent important therapeutic studies in advanced HCC and also some of the potential strategies to optimize clinical therapeutic development moving forward. Copyright © 2013 Elsevier Inc. All rights reserved.

Quantization with maximally degenerate Poisson brackets: the harmonic oscillator!

NASA Astrophysics Data System (ADS)

Nutku, Yavuz

2003-07-01

Nambu's construction of multi-linear brackets for super-integrable systems can be thought of as degenerate Poisson brackets with a maximal set of Casimirs in their kernel. By introducing privileged coordinates in phase space these degenerate Poisson brackets are brought to the form of Heisenberg's equations. We propose a definition for constructing quantum operators for classical functions, which enables us to turn the maximally degenerate Poisson brackets into operators. They pose a set of eigenvalue problems for a new state vector. The requirement of the single-valuedness of this eigenfunction leads to quantization. The example of the harmonic oscillator is used to illustrate this general procedure for quantizing a class of maximally super-integrable systems.

Maximizers in Lipschitz spacetimes are either timelike or null

NASA Astrophysics Data System (ADS)

Graf, Melanie; Ling, Eric

2018-04-01

We prove that causal maximizers in C 0,1 spacetimes are either timelike or null. This question was posed in Sämann and Steinbauer (2017 arXiv:1710.10887) since bubbling regions in C0, α spacetimes (α <1 ) can produce causal maximizers that contain a segment which is timelike and a segment which is null, see Chruściel and Grant (2012 Class. Quantum Grav. 29 145001). While C 0,1 spacetimes do not produce bubbling regions, the causal character of maximizers for spacetimes with regularity at least C 0,1 but less than C 1,1 was unknown until now. As an application we show that timelike geodesically complete spacetimes are C 0,1-inextendible.

Are running speeds maximized with simple-spring stance mechanics?

PubMed

Clark, Kenneth P; Weyand, Peter G

2014-09-15

Are the fastest running speeds achieved using the simple-spring stance mechanics predicted by the classic spring-mass model? We hypothesized that a passive, linear-spring model would not account for the running mechanics that maximize ground force application and speed. We tested this hypothesis by comparing patterns of ground force application across athletic specialization (competitive sprinters vs. athlete nonsprinters, n = 7 each) and running speed (top speeds vs. slower ones). Vertical ground reaction forces at 5.0 and 7.0 m/s, and individual top speeds (n = 797 total footfalls) were acquired while subjects ran on a custom, high-speed force treadmill. The goodness of fit between measured vertical force vs. time waveform patterns and the patterns predicted by the spring-mass model were assessed using the R(2) statistic (where an R(2) of 1.00 = perfect fit). As hypothesized, the force application patterns of the competitive sprinters deviated significantly more from the simple-spring pattern than those of the athlete, nonsprinters across the three test speeds (R(2) <0.85 vs. R(2) ≥ 0.91, respectively), and deviated most at top speed (R(2) = 0.78 ± 0.02). Sprinters attained faster top speeds than nonsprinters (10.4 ± 0.3 vs. 8.7 ± 0.3 m/s) by applying greater vertical forces during the first half (2.65 ± 0.05 vs. 2.21 ± 0.05 body wt), but not the second half (1.71 ± 0.04 vs. 1.73 ± 0.04 body wt) of the stance phase. We conclude that a passive, simple-spring model has limited application to sprint running performance because the swiftest runners use an asymmetrical pattern of force application to maximize ground reaction forces and attain faster speeds. Copyright © 2014 the American Physiological Society.

Maximizing Pharmacy's Contribution to Society.

ERIC Educational Resources Information Center

Marston, Robert Q.

1978-01-01

It is argued that the role of colleges in the effort to maximize pharmacy's contribution to society requires an emphasis on research in the pharmaceutical sciences, in the clinical use of drugs, and in the socioeconomic aspects of drug therapy. This will produce more qualified pharmacists and greater credibility for the profession. (JMD)

Enumerating all maximal frequent subtrees in collections of phylogenetic trees

PubMed Central

2014-01-01

Background A common problem in phylogenetic analysis is to identify frequent patterns in a collection of phylogenetic trees. The goal is, roughly, to find a subset of the species (taxa) on which all or some significant subset of the trees agree. One popular method to do so is through maximum agreement subtrees (MASTs). MASTs are also used, among other things, as a metric for comparing phylogenetic trees, computing congruence indices and to identify horizontal gene transfer events. Results We give algorithms and experimental results for two approaches to identify common patterns in a collection of phylogenetic trees, one based on agreement subtrees, called maximal agreement subtrees, the other on frequent subtrees, called maximal frequent subtrees. These approaches can return subtrees on larger sets of taxa than MASTs, and can reveal new common phylogenetic relationships not present in either MASTs or the majority rule tree (a popular consensus method). Our current implementation is available on the web at https://code.google.com/p/mfst-miner/. Conclusions Our computational results confirm that maximal agreement subtrees and all maximal frequent subtrees can reveal a more complete phylogenetic picture of the common patterns in collections of phylogenetic trees than maximum agreement subtrees; they are also often more resolved than the majority rule tree. Further, our experiments show that enumerating maximal frequent subtrees is considerably more practical than enumerating ordinary (not necessarily maximal) frequent subtrees. PMID:25061474

Emerging insights into barriers to effective brain tumor therapeutics.

PubMed

Woodworth, Graeme F; Dunn, Gavin P; Nance, Elizabeth A; Hanes, Justin; Brem, Henry

2014-01-01

There is great promise that ongoing advances in the delivery of therapeutics to the central nervous system (CNS) combined with rapidly expanding knowledge of brain tumor patho-biology will provide new, more effective therapies. Brain tumors that form from brain cells, as opposed to those that come from other parts of the body, rarely metastasize outside of the CNS. Instead, the tumor cells invade deep into the brain itself, causing disruption in brain circuits, blood vessel and blood flow changes, and tissue swelling. Patients with the most common and deadly form, glioblastoma (GBM) rarely live more than 2 years even with the most aggressive treatments and often with devastating neurological consequences. Current treatments include maximal safe surgical removal or biopsy followed by radiation and chemotherapy to address the residual tumor mass and invading tumor cells. However, delivering effective and sustained treatments to these invading cells without damaging healthy brain tissue is a major challenge and focus of the emerging fields of nanomedicine and viral and cell-based therapies. New treatment strategies, particularly those directed against the invasive component of this devastating CNS disease, are sorely needed. In this review, we (1) discuss the history and evolution of treatments for GBM, (2) define and explore three critical barriers to improving therapeutic delivery to invasive brain tumors, specifically, the neuro-vascular unit as it relates to the blood brain barrier, the extra-cellular space in regard to the brain penetration barrier, and the tumor genetic heterogeneity and instability in association with the treatment efficacy barrier, and (3) identify promising new therapeutic delivery approaches that have the potential to address these barriers and create sustained, meaningful efficacy against GBM.

Pace's Maxims for Homegrown Library Projects. Coming Full Circle

ERIC Educational Resources Information Center

Pace, Andrew K.

2005-01-01

This article discusses six maxims by which to run library automation. The following maxims are discussed: (1) Solve only known problems; (2) Avoid changing data to fix display problems; (3) Aut viam inveniam aut faciam; (4) If you cannot make it yourself, buy something; (5) Kill the alligator closest to the boat; and (6) Just because yours is…

General form of a cooperative gradual maximal covering location problem

NASA Astrophysics Data System (ADS)

Bagherinejad, Jafar; Bashiri, Mahdi; Nikzad, Hamideh

2018-07-01

Cooperative and gradual covering are two new methods for developing covering location models. In this paper, a cooperative maximal covering location-allocation model is developed (CMCLAP). In addition, both cooperative and gradual covering concepts are applied to the maximal covering location simultaneously (CGMCLP). Then, we develop an integrated form of a cooperative gradual maximal covering location problem, which is called a general CGMCLP. By setting the model parameters, the proposed general model can easily be transformed into other existing models, facilitating general comparisons. The proposed models are developed without allocation for physical signals and with allocation for non-physical signals in discrete location space. Comparison of the previously introduced gradual maximal covering location problem (GMCLP) and cooperative maximal covering location problem (CMCLP) models with our proposed CGMCLP model in similar data sets shows that the proposed model can cover more demands and acts more efficiently. Sensitivity analyses are performed to show the effect of related parameters and the model's validity. Simulated annealing (SA) and a tabu search (TS) are proposed as solution algorithms for the developed models for large-sized instances. The results show that the proposed algorithms are efficient solution approaches, considering solution quality and running time.

Overview of systematic reviews of therapeutic ranges: methodologies and recommendations for practice.

PubMed

Cooney, Lewis; Loke, Yoon K; Golder, Su; Kirkham, Jamie; Jorgensen, Andrea; Sinha, Ian; Hawcutt, Daniel

2017-06-02

Many medicines are dosed to achieve a particular therapeutic range, and monitored using therapeutic drug monitoring (TDM). The evidence base for a therapeutic range can be evaluated using systematic reviews, to ensure it continues to reflect current indications, doses, routes and formulations, as well as updated adverse effect data. There is no consensus on the optimal methodology for systematic reviews of therapeutic ranges. An overview of systematic reviews of therapeutic ranges was undertaken. The following databases were used: Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts and Reviews of Effects (DARE) and MEDLINE. The published methodologies used when systematically reviewing the therapeutic range of a drug were analyzed. Step by step recommendations to optimize such systematic reviews are proposed. Ten systematic reviews that investigated the correlation between serum concentrations and clinical outcomes encompassing a variety of medicines and indications were assessed. There were significant variations in the methodologies used (including the search terms used, data extraction methods, assessment of bias, and statistical analyses undertaken). Therapeutic ranges should be population and indication specific and based on clinically relevant outcomes. Recommendations for future systematic reviews based on these findings have been developed. Evidence based therapeutic ranges have the potential to improve TDM practice. Current systematic reviews investigating therapeutic ranges have highly variable methodologies and there is no consensus of best practice when undertaking systematic reviews in this field. These recommendations meet a need not addressed by standard protocols.

A Therapeutic Approach to Teaching Poetry: Individual Development, Psychology, and Social Reparation. Psychoanalysis, Education and Social Transformation

ERIC Educational Resources Information Center

Williams, Todd O.

2012-01-01

A Therapeutic Approach to Teaching Poetry develops a poetry pedagogy that offers significant benefits to students by helping them to achieve a sense of renewal (a deeper awareness of self and potentials) and reparation (a realistic, but positive and proactive worldview). Todd O. Williams offers a thorough examination of the therapeutic potential…

Moderate-to-Vigorous Physical Activity, Indices of Cognitive Control, and Academic Achievement in Preadolescents.

PubMed

Pindus, Dominika M; Drollette, Eric S; Scudder, Mark R; Khan, Naiman A; Raine, Lauren B; Sherar, Lauren B; Esliger, Dale W; Kramer, Arthur F; Hillman, Charles H

2016-06-01

To assess whether preadolescents' objectively measured moderate-to-vigorous physical activity (MVPA) is associated with cognitive control and academic achievement, independent of aerobic fitness. A sample of 74 children (Meanage = 8.64 years, SD = .58, 46% girls) were included in the analyses. Daily MVPA (min/d) was measured over 7 days using ActiGraph wGT3X+ accelerometer. Aerobic fitness was measured using a maximal graded exercise test and expressed as maximal oxygen uptake (mL*kg(-1)*min(-1)). Inhibitory control was measured with a modified Eriksen flanker task (reaction time and accuracy), and working memory with an Operation Span Task (accuracy scores). Academic achievement (in reading, mathematics, and spelling) was expressed as standardized scores on the Kaufman Test of Educational Achievement. The relationships were assessed using hierarchical regression models adjusting for aerobic fitness and other covariates. No significant associations were found between MVPA and inhibition, working memory, or academic achievement. Aerobic fitness was positively associated with inhibitory control (P = .02) and spelling (P = .04) but not with other cognitive or academic variables (all P > .05). Aerobic fitness, rather than daily MVPA, is positively associated with childhood ability to manage perceptual interference and spelling. Further research into the associations between objectively measured MVPA and cognitive and academic outcomes in children while controlling for important covariates is needed. Copyright © 2016 Elsevier Inc. All rights reserved.

In patients with extensive subcutaneous emphysema, which technique achieves maximal clinical resolution: infraclavicular incisions, subcutaneous drain insertion or suction on in situ chest drain?

PubMed

Johnson, Charles H N; Lang, Sommer A; Bilal, Haris; Rammohan, Kandadai S

2014-06-01

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: 'In patients with extensive subcutaneous emphysema, which technique achieves maximal clinical resolution: infraclavicular incisions, subcutaneous drain insertion or suction on in situ chest drain?'. Altogether more than 200 papers were found using the reported search, of which 14 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Subcutaneous emphysema is usually a benign, self-limiting condition only requiring conservative management. Interventions are useful in the context of severe patient discomfort, respiratory distress or persistent air leak. In the absence of any comparative study, it is not possible to choose definitively between infraclavicular incisions, drain insertion and increasing suction on an in situ drain as the best method for managing severe subcutaneous emphysema. All the three techniques described have been shown to provide effective relief. Increasing suction on a chest tube already in situ provided rapid relief in patients developing SE following pulmonary resection. A retrospective study showed resolution in 66%, increasing to 98% in those who underwent video-assisted thoracic surgery with identification and closure of the leak. Insertion of a drain into the subcutaneous tissue also provided rapid sustained relief. Several studies aided drainage by using regular compressive massage. Infraclavicular incisions were also shown to provide rapid relief, but were noted to be more invasive and carried the potential for cosmetic defect. No major complications were illustrated. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Therapeutic landscapes and longevity: Wellness tourism in Bama.

PubMed

Huang, Liyuan; Xu, Honggang

2018-01-01

Due to the rising demand for healthcare products and concern over environmental pollution, wellness tourism has been booming in China in recent years. The therapeutic landscape theory provides a multi-scale interpretation of wellness tourism to explore how wellness tourists achieve health in healing places. By presenting the results of 83 interviews conducted in Bama, China, this study reveals that the "longevity village" Bama, endorsed by centenarians, provides a retreat that combines natural beauty and a harmonious neighbourhood for wellness tourists. This article argues that although three themes-natural environment, social interaction and symbolic landscape-work together in the healing process of tourists, the symbolic landscape, which is significantly shaped by the longevity culture, plays a dominant role. Longevity in Chinese culture symbolizes the alignment of a strong body, graceful mind, and pleasant habitat. Furthermore, tourism reinforces the importance of symbols and imagination (of a place), the perception of longevity demonstrates the symbolic landscape and thus increases tourists' attachment to the place, and the unusual environment leads to a different therapeutic landscape from that of daily life. Finally, since to date there has been very few works on therapeutic landscapes in China, it is expected that this study will fill the knowledge gap and broaden the scope of application as well as conceptualization of the therapeutic landscape. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Pharmacokinetic alterations in pregnancy and use of therapeutic drug monitoring].

PubMed

Panchaud, Alice; Weisskopf, Etienne; Winterfeld, Ursula; Baud, David; Guidi, Monia; Eap, Chin B; Csajka, Chantal; Widmer, Nicolas

2014-01-01

Following the thalidomide tragedy, pharmacological research in pregnant women focused primarily on drug safety for the unborn child and remains only limited regarding the efficacy and safety of treatment for the mother. Significant physiological changes during pregnancy may yet affect the pharmacokinetics of drugs and thus compromise its efficacy and/or safety. Therapeutic drug monitoring (TDM) would maximize the potential effectiveness of treatments, while minimizing the potential risk of toxicity for the mother and the fetus. At present, because of the lack of concentration-response relationship studies in pregnant women, TDM can rely only on individual assessment (based on an effective concentration before pregnancy) and remains reserved only to unexpected situations such as signs of toxicity or unexplained inefficiency. © 2014 Société Française de Pharmacologie et de Thérapeutique.

Therapeutic drug monitoring in pregnancy.

PubMed

Matsui, Doreen M

2012-10-01

Therapeutic drug monitoring (TDM) is commonly recommended to optimize drug dosing regimens of various medications. It has been proposed to guide therapy in pregnant women, in whom physiological changes may lead to altered pharmacokinetics resulting in difficulty in predicting the appropriate drug dosage. Ideally, TDM may play a role in enhancing the effectiveness of treatment while minimizing toxicity of both the mother and fetus. Monitoring of drug levels may also be helpful in assessing adherence to prescribed therapy in selected cases. Limitations exist as therapeutic ranges have only been defined for a limited number of drugs and are based on data obtained in nonpregnant patients. TDM has been suggested for anticonvulsants, antidepressants, and antiretroviral drugs, based on pharmacokinetic studies that have shown reduced drug concentrations. However, there is only relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Further studies are required to determine whether implementation of TDM during pregnancy improves outcome and is associated with any benefit beyond that achieved by clinical judgment alone. The cost effectiveness of TDM programs during pregnancy also remains to be examined.

Nonadditive entropy maximization is inconsistent with Bayesian updating

NASA Astrophysics Data System (ADS)

Pressé, Steve

2014-11-01

The maximum entropy method—used to infer probabilistic models from data—is a special case of Bayes's model inference prescription which, in turn, is grounded in basic propositional logic. By contrast to the maximum entropy method, the compatibility of nonadditive entropy maximization with Bayes's model inference prescription has never been established. Here we demonstrate that nonadditive entropy maximization is incompatible with Bayesian updating and discuss the immediate implications of this finding. We focus our attention on special cases as illustrations.

Nonadditive entropy maximization is inconsistent with Bayesian updating.

PubMed

Pressé, Steve

2014-11-01

The maximum entropy method-used to infer probabilistic models from data-is a special case of Bayes's model inference prescription which, in turn, is grounded in basic propositional logic. By contrast to the maximum entropy method, the compatibility of nonadditive entropy maximization with Bayes's model inference prescription has never been established. Here we demonstrate that nonadditive entropy maximization is incompatible with Bayesian updating and discuss the immediate implications of this finding. We focus our attention on special cases as illustrations.

Les Ambivalences du Silence: Les "Maximes" de la Rochefoucauld Par Quatre Chemins

ERIC Educational Resources Information Center

Turcat, Eric

2012-01-01

Maxims are famous for their moral pronouncements, yet La Rochefoucauld's "Maximes" (1678) have become infamous for offering little moral guidance. Morally ambivalent at best, the "Maximes" are also less known for their other forms of ambivalence, whether rhetorical, psychological, anthropological or linguistic. Such are…

Role of Vertical Jumps and Anthropometric Variables in Maximal Kicking Ball Velocities in Elite Soccer Players

PubMed Central

Rodríguez-Lorenzo, Lois; Fernandez-del-Olmo, Miguel; Sanchez-Molina, José Andrés

2016-01-01

Abstract Kicking is one of the most important skills in soccer and the ability to achieve ma ximal kicking velocity with both legs leads to an advantage for the soccer player. This study examined the relationship be tween kicking ball velocity with both legs using anthropometric measurements and vertical jumps (a squat jump (SJ); a countermovement jump without (CMJ) and with the arm swing (CMJA) and a reactive jump (RJ)). Anthropome tric measurements did not correlate with kicking ball velocity. Vertical jumps correlated significantly with kicking ball velocity using the dominant leg only (r = .47, r = .58, r = .44, r = .51, for SJ, CMJ, CMJA and RJ, respectively) . Maximal kicking velocity with the dominant leg was significantly higher than with the non-dominant leg (t = 18.0 4, p < 0.001). Our results suggest that vertical jumps may be an optimal test to assess neuromuscular skills involved in kicking at maximal speed. Lack of the relationship between vertical jumps and kicking velocity with the non-dominant leg may reflect a difficulty to exhibit the neuromuscular skills during dominant leg kicking. PMID:28149419

Influence of simulated weightlessness on maximal oxygen uptake of untrained rats

NASA Technical Reports Server (NTRS)

Overton, J. Michael; Tipton, Charles M.

1987-01-01

The purpose of this study was to determine the effect of hindlimb suspension on maximal oxygen uptake of rodents. Male Sprague-Dawley rats were assigned to head-down (HD) suspension, horizontal (HOZ) suspension, or cage (C) control for 6-9 days. Rats were tested for maximal oxygen uptake before and after surgical instrumentation (Doppler flow probes, carotid and jugular cannulae), and after suspension. Body weight was significantly decreased after suspension in both HD and HOZ groups, but was significantly increased in the C group. Absolute maximal O2 uptake (ml/min) was not different in the C group. However, because of their increased weight, relative maximal O2 uptake (ml/min per kg) was significantly reduced. In contrast, both relative and absolute maximal O2 uptake were significantly lower, following suspension, for the HD and HOZ groups. These preliminary results support the use of hindlimb suspension as an effective model to study the mechanism(s) of cardiovascular deconditioning.

Maximally random discrete-spin systems with symmetric and asymmetric interactions and maximally degenerate ordering

NASA Astrophysics Data System (ADS)

Atalay, Bora; Berker, A. Nihat

2018-05-01

Discrete-spin systems with maximally random nearest-neighbor interactions that can be symmetric or asymmetric, ferromagnetic or antiferromagnetic, including off-diagonal disorder, are studied, for the number of states q =3 ,4 in d dimensions. We use renormalization-group theory that is exact for hierarchical lattices and approximate (Migdal-Kadanoff) for hypercubic lattices. For all d >1 and all noninfinite temperatures, the system eventually renormalizes to a random single state, thus signaling q ×q degenerate ordering. Note that this is the maximally degenerate ordering. For high-temperature initial conditions, the system crosses over to this highly degenerate ordering only after spending many renormalization-group iterations near the disordered (infinite-temperature) fixed point. Thus, a temperature range of short-range disorder in the presence of long-range order is identified, as previously seen in underfrustrated Ising spin-glass systems. The entropy is calculated for all temperatures, behaves similarly for ferromagnetic and antiferromagnetic interactions, and shows a derivative maximum at the short-range disordering temperature. With a sharp immediate contrast of infinitesimally higher dimension 1 +ɛ , the system is as expected disordered at all temperatures for d =1 .

In vivo maximal fascicle-shortening velocity during plantar flexion in humans.

PubMed

Hauraix, Hugo; Nordez, Antoine; Guilhem, Gaël; Rabita, Giuseppe; Dorel, Sylvain

2015-12-01

Interindividual variability in performance of fast movements is commonly explained by a difference in maximal muscle-shortening velocity due to differences in the proportion of fast-twitch fibers. To provide a better understanding of the capacity to generate fast motion, this study aimed to 1) measure for the first time in vivo the maximal fascicle-shortening velocity of human muscle; 2) evaluate the relationship between angular velocity and fascicle-shortening velocity from low to maximal angular velocities; and 3) investigate the influence of musculo-articular features (moment arm, tendinous tissues stiffness, and muscle architecture) on maximal angular velocity. Ultrafast ultrasound images of the gastrocnemius medialis were obtained from 31 participants during maximal isokinetic and light-loaded plantar flexions. A strong linear relationship between fascicle-shortening velocity and angular velocity was reported for all subjects (mean R(2) = 0.97). The maximal shortening velocity (V(Fmax)) obtained during the no-load condition (NLc) ranged between 18.8 and 43.3 cm/s. V(Fmax) values were very close to those of the maximal shortening velocity (V(max)), which was extrapolated from the F-V curve (the Hill model). Angular velocity reached during the NLc was significantly correlated with this V(Fmax) (r = 0.57; P < 0.001). This finding was in agreement with assumptions about the role of muscle fiber type, whereas interindividual comparisons clearly support the fact that other parameters may also contribute to performance during fast movements. Nevertheless, none of the biomechanical features considered in the present study were found to be directly related to the highest angular velocity, highlighting the complexity of the upstream mechanics that lead to maximal-velocity muscle contraction. Copyright © 2015 the American Physiological Society.

[Ultrasonography-guided therapeutic procedures in the neck region].

PubMed

Brzac, Hrvojka Tomić

2009-12-01

Minimally invasive therapeutic procedures in medicine have become very popular because of the reduced risk compared to classic surgical treatment, speed of recovery, little or no side effects, and frequently lower cost. One of these methods is ultrasonography-guided percutaneous injection of 95% ethanol (PEIT, percutaneous ethanol injection therapy), which is especially suitable for the neck region. Other methods like laser photocoagulation (ILP) or radiofrequency ablation (RFA) are more aggressive and expensive. The procedure of sterile 95% ethanol injecting is performed on an outpatient basis, without preparation. A specific amount of alcohol is injected into the lesion using a thin spinal needle, under ultrasonography guidance. The amount of alcohol depends on the size of the lesion. Complications are rare and the procedure can be repeated several times. PEIT is used in the treatment of parathyroid glands, especially secondary hyperparathyroidism, thyroid nodules (toxic adenoma, goiters and cysts), other cysts on the neck, and cervical metastases of thyroid cancer. Direct ethanol injection into the tissue causes cellular dehydration and protein denaturation, followed by the development of necrosis, fibrosis, and thrombosis of the small blood vessels. In this way, reduction or disappearance of the nodes can be achieved, along with functional normalization (for parathyroid glands and toxic adenoma), with longer or shorter disease remission or complete recovery. Today, PEIT is mostly used in dialyzed patients with secondary hyperparathyroidism. The treatment gives best results in combination with vitamin D analogs, if 1-2 parathyroid glands are enlarged, and for residual parathyroid gland after parathyroidectomy. A success rate of 50%-70% has been reported, depending on the number of enlarged parathyroid glands. Therapeutic effect is manifested in the size reduction or complete fibrozation of the gland, reduction or disappearance of vascularization, and a decrease

Comparison of changes in the mobility of the pelvic floor muscle on during the abdominal drawing-in maneuver, maximal expiration, and pelvic floor muscle maximal contraction

PubMed Central

Jung, Halim; Jung, Sangwoo; Joo, Sunghee; Song, Changho

2016-01-01

[Purpose] The purpose of this study was to compare changes in the mobility of the pelvic floor muscle during the abdominal drawing-in maneuver, maximal expiration, and pelvic floor muscle maximal contraction. [Subjects] Thirty healthy adults participated in this study (15 men and 15 women). [Methods] All participants performed a bridge exercise and abdominal curl-up during the abdominal drawing-in maneuver, maximal expiration, and pelvic floor muscle maximal contraction. Pelvic floor mobility was evaluated as the distance from the bladder base using ultrasound. [Results] According to exercise method, bridge exercise and abdominal curl-ups led to significantly different pelvic floor mobility. The pelvic floor muscle was elevated during the abdominal drawing-in maneuver and descended during maximal expiration. Finally, pelvic floor muscle mobility was greater during abdominal curl-up than during the bridge exercise. [Conclusion] According to these results, the abdominal drawing-in maneuver induced pelvic floor muscle contraction, and pelvic floor muscle contraction was greater during the abdominal curl-up than during the bridge exercise. PMID:27065532

Rational maximizing by humans (Homo sapiens) in an ultimatum game.

PubMed

Smith, Phillip; Silberberg, Alan

2010-07-01

In the human mini-ultimatum game, a proposer splits a sum of money with a responder. If the responder accepts, both are paid. If not, neither is paid. Typically, responders reject inequitable distributions, favoring punishing over maximizing. In Jensen et al.'s (Science 318:107-109, 2007) adaptation with apes, a proposer selects between two distributions of raisins. Despite inequitable offers, responders often accept, thereby maximizing. The rejection response differs between the human and ape versions of this game. For humans, rejection is instantaneous; for apes, it requires 1 min of inaction. We replicate Jensen et al.'s procedure in humans with money. When waiting 1 min to reject, humans favor punishing over maximizing; however, when rejection requires 5 min of inaction, humans, like apes, maximize. If species differences in time horizons are accommodated, Jensen et al.'s ape data are reproducible in humans.

Chamaebatiaria millefolium (Torr.) Maxim.: fernbush

Treesearch

Nancy L. Shaw; Emerenciana G. Hurd

2008-01-01

Fernbush - Chamaebatiaria millefolium (Torr.) Maxim. - the only species in its genus, is endemic to the Great Basin, Colorado Plateau, and adjacent areas of the western United States. It is an upright, generally multistemmed, sweetly aromatic shrub 0.3 to 2 m tall. Bark of young branches is brown and becomes smooth and gray with age. Leaves are leathery, alternate,...

Task complexity and maximal isometric strength gains through motor learning

PubMed Central

McGuire, Jessica; Green, Lara A.; Gabriel, David A.

2014-01-01

Abstract This study compared the effects of a simple versus complex contraction pattern on the acquisition, retention, and transfer of maximal isometric strength gains and reductions in force variability. A control group (N = 12) performed simple isometric contractions of the wrist flexors. An experimental group (N = 12) performed complex proprioceptive neuromuscular facilitation (PNF) contractions consisting of maximal isometric wrist extension immediately reversing force direction to wrist flexion within a single trial. Ten contractions were completed on three consecutive days with a retention and transfer test 2‐weeks later. For the retention test, the groups performed their assigned contraction pattern followed by a transfer test that consisted of the other contraction pattern for a cross‐over design. Both groups exhibited comparable increases in strength (20.2%, P < 0.01) and reductions in mean torque variability (26.2%, P < 0.01), which were retained and transferred. There was a decrease in the coactivation ratio (antagonist/agonist muscle activity) for both groups, which was retained and transferred (35.2%, P < 0.01). The experimental group exhibited a linear decrease in variability of the torque‐ and sEMG‐time curves, indicating transfer to the simple contraction pattern (P < 0.01). The control group underwent a decrease in variability of the torque‐ and sEMG‐time curves from the first day of training to retention, but participants returned to baseline levels during the transfer condition (P < 0.01). However, the difference between torque RMS error versus the variability in torque‐ and sEMG‐time curves suggests the demands of the complex task were transferred, but could not be achieved in a reproducible way. PMID:25428951

Short, unit-memory, Byte-oriented, binary convolutional codes having maximal free distance

NASA Technical Reports Server (NTRS)

Lee, L. N.

1975-01-01

It is shown that (n sub 0, k sub 0) convolutional codes with unit memory always achieve the largest free distance among all codes of the same rate k sub 0/n sub 0 and same number 2MK sub 0 of encoder states, where M is the encoder memory. A unit-memory code with maximal free distance is given at each place where this free distance exceeds that of the best code with k sub 0 and n sub 0 relatively prime, for all Mk sub 0 less than or equal to 6 and for R = 1/2, 1/3, 1/4, 2/3. It is shown that the unit-memory codes are byte-oriented in such a way as to be attractive for use in concatenated coding systems.

Maximal near-field radiative heat transfer between two plates

NASA Astrophysics Data System (ADS)

Nefzaoui, Elyes; Ezzahri, Younès; Drévillon, Jérémie; Joulain, Karl

2013-09-01

Near-field radiative transfer is a promising way to significantly and simultaneously enhance both thermo-photovoltaic (TPV) devices power densities and efficiencies. A parametric study of Drude and Lorentz models performances in maximizing near-field radiative heat transfer between two semi-infinite planes separated by nanometric distances at room temperature is presented in this paper. Optimal parameters of these models that provide optical properties maximizing the radiative heat flux are reported and compared to real materials usually considered in similar studies, silicon carbide and heavily doped silicon in this case. Results are obtained by exact and approximate (in the extreme near-field regime and the electrostatic limit hypothesis) calculations. The two methods are compared in terms of accuracy and CPU resources consumption. Their differences are explained according to a mesoscopic description of nearfield radiative heat transfer. Finally, the frequently assumed hypothesis which states a maximal radiative heat transfer when the two semi-infinite planes are of identical materials is numerically confirmed. Its subsequent practical constraints are then discussed. Presented results enlighten relevant paths to follow in order to choose or design materials maximizing nano-TPV devices performances.

Obesity, Inflammation, and Postmenopausal Breast Cancer: Therapeutic Implications

PubMed Central

Macciò, Antonio; Madeddu, Clelia

2011-01-01

Breast cancer is the female malignant neoplasia with the highest incidence in the industrialized world. Although early diagnosis has contributed to therapeutic success, breast cancer remains a major health issue. In the last few year the hormone therapy for estrogen-dependent breast cancer has evolved achieving significant clinical results; at the same time, it has enabled us to better define the role of estrogens in the etiopathogenesis of this tumour. Weight increase and obesity have been identified as the most important risk and prognostic factors for breast cancer in postmenopausal women. Several hypotheses have been proposed to explain the association of obesity with postmenopausal breast cancer. Specific obesity-associated factors, including leptin, insulin and inflammatory mediators, seem to influence breast cancer growth and prognosis independently of estrogens and at least in part by interacting with estrogen signalling at a cellular level. Therefore, a careful assessment of the nutritional status and body composition is paramount for a proper therapeutic approach for postmenopausal breast carcinoma. The use of antidiabetic and anti-inflammatory drugs associated with conventional hormone therapies and dietary/physical interventions could offer a new therapeutic approach for breast carcinoma that develops in the context of adiposity. PMID:22125453

Neuroscience-driven discovery and development of sleep therapeutics.

PubMed

Dresler, M; Spoormaker, V I; Beitinger, P; Czisch, M; Kimura, M; Steiger, A; Holsboer, F

2014-03-01

Until recently, neuroscience has given sleep research and discovery of better treatments of sleep disturbances little attention, despite the fact that disturbed sleep has overwhelming impact on human health. Sleep is a complex phenomenon in which specific psychological, electrophysiological, neurochemical, endocrinological, immunological and genetic factors are involved. The brain as both the generator and main object of sleep is obviously of particular interest, which makes a neuroscience-driven view the most promising approach to evaluate clinical implications and applications of sleep research. Polysomnography as the gold standard of sleep research, complemented by brain imaging, neuroendocrine testing, genomics and other laboratory measures can help to create composite biomarkers that allow maximizing the effects of individualized therapies while minimizing adverse effects. Here we review the current state of the neuroscience of sleep, sleep disorders and sleep therapeutics and will give some leads to promote the discovery and development of sleep medicines that are better than those we have today. Copyright © 2013 Elsevier Inc. All rights reserved.

Maximizing tibial coverage is detrimental to proper rotational alignment.

PubMed

Martin, Stacey; Saurez, Alex; Ismaily, Sabir; Ashfaq, Kashif; Noble, Philip; Incavo, Stephen J

2014-01-01

Traditionally, the placement of the tibial component in total knee arthroplasty (TKA) has focused on maximizing coverage of the tibial surface. However, the degree to which maximal coverage affects correct rotational placement of symmetric and asymmetric tibial components has not been well defined and might represent an implant design issue worthy of further inquiry. Using four commercially available tibial components (two symmetric, two asymmetric), we sought to determine (1) the overall amount of malrotation that would occur if components were placed for maximal tibial coverage; and (2) whether the asymmetric designs would result in less malrotation than the symmetric designs when placed for maximal coverage in a computer model using CT reconstructions. CT reconstructions of 30 tibial specimens were used to generate three-dimensional tibia reconstructions with attention to the tibial anatomic axis, the tibial tubercle, and the resected tibial surface. Using strict criteria, four commercially available tibial designs (two symmetric, two asymmetric) were placed on the resected tibial surface. The resulting component rotation was examined. Among all four designs, 70% of all tibial components placed in orientation maximizing fit to resection surface were internally malrotated (average 9°). The asymmetric designs had fewer cases of malrotation (28% and 52% for the two asymmetric designs, 100% and 96% for the two symmetric designs; p < 0.001) and less malrotation on average (2° and 5° for the asymmetric designs, 14° for both symmetric designs; p < 0.001). Maximizing tibial coverage resulted in implant malrotation in a large percentage of cases. Given similar amounts of tibial coverage, correct rotational positioning was more likely to occur with the asymmetric designs. Malrotation of components is an important cause of failure in TKA. Priority should be given to correct tibial rotational positioning. This study suggested that it is easier to balance rotation and

Instructional Patterns: Strategies for Maximizing Student Learning [with CD-ROM

ERIC Educational Resources Information Center

Holt, Larry Charles; Kysilka, Marcella L.

2005-01-01

"Instructional Patterns: Strategies for Maximizing Student Learning" examines instruction from the learners' point of view by showing how instructional patterns can be used to maximize the potential for students to learn. This book explores the interactive patterns that exist in today's classroom and demonstrates how teachers can…

Evidence for surprise minimization over value maximization in choice behavior

PubMed Central

Schwartenbeck, Philipp; FitzGerald, Thomas H. B.; Mathys, Christoph; Dolan, Ray; Kronbichler, Martin; Friston, Karl

2015-01-01

Classical economic models are predicated on the idea that the ultimate aim of choice is to maximize utility or reward. In contrast, an alternative perspective highlights the fact that adaptive behavior requires agents’ to model their environment and minimize surprise about the states they frequent. We propose that choice behavior can be more accurately accounted for by surprise minimization compared to reward or utility maximization alone. Minimizing surprise makes a prediction at variance with expected utility models; namely, that in addition to attaining valuable states, agents attempt to maximize the entropy over outcomes and thus ‘keep their options open’. We tested this prediction using a simple binary choice paradigm and show that human decision-making is better explained by surprise minimization compared to utility maximization. Furthermore, we replicated this entropy-seeking behavior in a control task with no explicit utilities. These findings highlight a limitation of purely economic motivations in explaining choice behavior and instead emphasize the importance of belief-based motivations. PMID:26564686

Achieving High Throughput for Data Transfer over ATM Networks

NASA Technical Reports Server (NTRS)

Johnson, Marjory J.; Townsend, Jeffrey N.

1996-01-01

File-transfer rates for ftp are often reported to be relatively slow, compared to the raw bandwidth available in emerging gigabit networks. While a major bottleneck is disk I/O, protocol issues impact performance as well. Ftp was developed and optimized for use over the TCP/IP protocol stack of the Internet. However, TCP has been shown to run inefficiently over ATM. In an effort to maximize network throughput, data-transfer protocols can be developed to run over UDP or directly over IP, rather than over TCP. If error-free transmission is required, techniques for achieving reliable transmission can be included as part of the transfer protocol. However, selected image-processing applications can tolerate a low level of errors in images that are transmitted over a network. In this paper we report on experimental work to develop a high-throughput protocol for unreliable data transfer over ATM networks. We attempt to maximize throughput by keeping the communications pipe full, but still keep packet loss under five percent. We use the Bay Area Gigabit Network Testbed as our experimental platform.

A Maximal Entropy Distribution Derivation of the Sharma-Taneja-Mittal Entropic Form

NASA Astrophysics Data System (ADS)

Scarfone, Antonio M.

In this letter we derive the distribution maximizing the Sharma-Taneja-Mittal entropy under certain constrains by using an information inequality satisfied by the Br`egman divergence associated to this entropic form. The resulting maximal entropy distribution coincides with the one derived from the calculus according to the maximal entropy principle à la Jaynes.

Intramuscular Heating Characteristics of Multihour Low-Intensity Therapeutic Ultrasound.

PubMed

Rigby, Justin H; Taggart, Rebecca M; Stratton, Kelly L; Lewis, George K; Draper, David O

2015-11-01

The heating characteristics of a stationary device delivering sustained acoustic medicine with low-intensity therapeutic ultrasound (LITUS) are unknown. To measure intramuscular (IM) heating produced by a LITUS device developed for long-duration treatment of musculoskeletal injuries. Controlled laboratory study. University research laboratory. A total of 26 healthy volunteers (16 men, 10 women; age = 23.0 ± 2.1 years, height = 1.74 ± 0.09 m, mass = 73.48 ± 14.65 kg). Participants were assigned randomly to receive active (n = 20) or placebo (n = 6) LITUS at a frequency of 3 MHz and an energy intensity of 0.132 W/cm(2) continuously for 3 hours with a single transducer or dual transducers on the triceps surae muscle. We measured IM temperature using thermocouples inserted at 1.5- and 3-cm depths into muscle. Temperatures were recorded throughout treatment and 30 minutes posttreatment. We used 2-sample t tests to determine the heating curve of the LITUS treatment and differences in final temperatures between depth and number of transducers. A mild IM temperature increase of 1 °C was reached 10 ± 5 minutes into the treatment, and a more vigorous temperature increase of 4 °C was reached 80 ± 10 minutes into the treatment. The maximal steady-state IM temperatures produced during the final 60 minutes of treatment at the 1.5-cm depth were 4.42 °C ± 0.08 °C and 3.92 °C ± 0.06 °C using 1 and 2 transducers, respectively. At the 3.0-cm depth, the maximal steady-state IM temperatures during the final 60 minutes of treatment were 3.05 °C ± 0.09 °C and 3.17 °C ± 0.05 °C using 1 and 2 transducers, respectively. We observed a difference between the temperatures measured at each depth (t78 = -2.45, P = .02), but the number of transducers used to generate heating was not different (t78 = 1.79, P = .08). The LITUS device elicited tissue heating equivalent to traditional ultrasound but could be sustained for multiple hours. It is a safe and effective alternative tool

The therapeutic workplace to promote treatment engagement and drug abstinence in out-of-treatment injection drug users: a randomized controlled trial.

PubMed

Holtyn, August F; Koffarnus, Mikhail N; DeFulio, Anthony; Sigurdsson, Sigurdur O; Strain, Eric C; Schwartz, Robert P; Leoutsakos, Jeannie-Marie S; Silverman, Kenneth

2014-11-01

Determine if employment-based reinforcement can increase methadone treatment engagement and drug abstinence in out-of-treatment injection drug users. This study was conducted from 2008 to 2012 in a therapeutic workplace in Baltimore, MD. After a 4-week induction, participants (N=98) could work and earn pay for 26 weeks and were randomly assigned to Work Reinforcement, Methadone & Work Reinforcement, and Abstinence, Methadone & Work Reinforcement conditions. Work Reinforcement participants had to work to earn pay. Methadone & Work Reinforcement and Abstinence, Methadone, & Work Reinforcement participants had to enroll in methadone treatment to work and maximize pay. Abstinence, Methadone, & Work Reinforcement participants had to provide opiate- and cocaine-negative urine samples to maximize pay. Most participants (92%) enrolled in methadone treatment during induction. Drug abstinence increased as a graded function of the addition of the methadone and abstinence contingencies. Abstinence, Methadone & Work Reinforcement participants provided significantly more urine samples negative for opiates (75% versus 54%) and cocaine (57% versus 32%) than Work Reinforcement participants. Methadone & Work Reinforcement participants provided significantly more cocaine-negative samples than Work Reinforcement participants (55% versus 32%). The therapeutic workplace can promote drug abstinence in out-of-treatment injection drug users. Clinical trial registration number: NCT01416584. Copyright © 2014 Elsevier Inc. All rights reserved.

The Therapeutic Workplace to Promote Treatment Engagement and Drug Abstinence in Out-of-Treatment Injection Drug Users: A Randomized Controlled Trial

PubMed Central

Holtyn, August F.; Koffarnus, Mikhail N.; DeFulio, Anthony; Sigurdsson, Sigurdur O.; Strain, Eric C.; Schwartz, Robert P.; Leoutsakos, Jeannie-Marie S.; Silverman, Kenneth

2014-01-01

Objective Determine if employment-based reinforcement can increase methadone treatment engagement and drug abstinence in out-of-treatment injection drug users. Method This study was conducted from 2008–2012 in a therapeutic workplace in Baltimore, MD. After a 4-week induction, participants (N=98) could work and earn pay for 26 weeks and were randomly assigned to Work Reinforcement, Methadone & Work Reinforcement, and Abstinence, Methadone & Work Reinforcement conditions. Work Reinforcement participants had to work to earn pay. Methadone & Work Reinforcement, and Abstinence, Methadone, & Work Reinforcement participants had to enroll in methadone treatment to work and maximize pay. Abstinence, Methadone, & Work Reinforcement participants had to provide opiate- and cocaine-negative urine samples to maximize pay. Results Most participants (92%) enrolled in methadone treatment during induction. Drug abstinence increased as a graded function of the addition of the methadone and abstinence contingencies. Abstinence, Methadone & Work Reinforcement participants provided significantly more urine samples negative for opiates (75% versus 54%) and cocaine (57% versus 32%) than Work Reinforcement participants. Methadone & Work Reinforcement participants provided significantly more cocaine-negative samples than Work Reinforcement participants (55% versus 32%). Conclusion The therapeutic workplace can promote drug abstinence in out-of-treatment injection drug users. PMID:24607365

Gross domestic product, science interest, and science achievement: a person × nation interaction.

PubMed

Tucker-Drob, Elliot M; Cheung, Amanda K; Briley, Daniel A

2014-11-01

Maximizing science achievement is a critical target of educational policy and has important implications for national and international economic and technological competitiveness. Previous research has identified both science interest and socioeconomic status (SES) as robust predictors of science achievement, but little research has examined their joint effects. In a data set drawn from approximately 400,000 high school students from 57 countries, we documented large Science Interest × SES and Science Interest × Per Capita Gross Domestic Product (GDP) interactions in the prediction of science achievement. Student interest in science is a substantially stronger predictor of science achievement in higher socioeconomic contexts and in higher-GDP nations. Our results are consistent with the hypothesis that in higher-opportunity contexts, motivational factors play larger roles in learning and achievement. They add to the growing body of evidence indicating that substantial cross-national differences in psychological effect sizes are not simply a logical possibility but, in many cases, an empirical reality. © The Author(s) 2014.

Clinical differences among nonsteroidal antiinflammatory drugs: implications for therapeutic substitution in ambulatory patients.

PubMed

Levy, R A; Smith, D L

1989-01-01

The practice of therapeutic substitution, i.e., replacing one drug with another chemically different drug from the same therapeutic class, represents an important therapeutic modification with potential clinical significance far beyond that of generic substitution. Adverse consequences following therapeutic substitution of nonsteroidal antiinflammatory drugs (NSAID) is of special concern because of substantial differences among these agents in pharmacokinetic, pharmacological, and clinical properties. Therapeutic substitution of NSAID for ambulatory patients may result in compromised clinical outcome because (1) patient response is unpredictable and selection of the optimal agent must be tailored for each patient; (2) substantial differences exist in adverse reaction profiles; (3) drug interaction studies are lacking; and (4) selection of an agent must be individualized to ensure compliance with the dosing regimen. Cost savings achieved through therapeutic substitution of NSAID may be lost by additional overall treatment costs due to adverse reactions or suboptimal therapy. The occurrence of adverse or suboptimal effects in ambulatory patients is more likely if NSAID are substituted without full knowledge of the patient's medical history and clinical status. Communication between the pharmacy and prescribing physician regarding a patient's specific needs is essential for rational substitution among NSAID.

The Holy Grail of Polymer Therapeutics for Cancer Therapy: An Overview on the Pharmacokinetics and Bio Distribution.

PubMed

Dyawanapelly, Sathish; Junnuthula, Vijayabhaskar Reddy; Singh, AkhileshVikram

2015-01-01

In recent years, multifaceted clinical benefits of polymeric therapeutics have been reported. Over the past decades, cancer has been one of the leading causes of mortality in the world. Many clinically approved chemotherapeutics encounter potential challenges against deadly cancer. Moreover, safety and efficacy of anticancer agents have been limited by undesirable pharmacokinetics and biodistribution. To address these limitations, various polymer drug conjugates are being studied and developed to improve the antitumor efficacy. Among other therapeutics, polymer therapeutics are well established platforms that circumvent anticancer therapeutics from enzymatic metabolism via direct conjugation to therapeutic molecules. Interestingly, polymer therapeutics meets an unmet need of small molecules. Further clinical study showed that polymer-drug conjugation can achieve desired pharmacokinetics and biodistribution properties of several anticancer drugs. The present retrospective review mainly enlightens the most recent preclinical and clinical studies include safety, stability, pharmacokinetic behavior and distribution of polymer therapeutics.

Optimal quantum error correcting codes from absolutely maximally entangled states

NASA Astrophysics Data System (ADS)

Raissi, Zahra; Gogolin, Christian; Riera, Arnau; Acín, Antonio

2018-02-01

Absolutely maximally entangled (AME) states are pure multi-partite generalizations of the bipartite maximally entangled states with the property that all reduced states of at most half the system size are in the maximally mixed state. AME states are of interest for multipartite teleportation and quantum secret sharing and have recently found new applications in the context of high-energy physics in toy models realizing the AdS/CFT-correspondence. We work out in detail the connection between AME states of minimal support and classical maximum distance separable (MDS) error correcting codes and, in particular, provide explicit closed form expressions for AME states of n parties with local dimension \

Worst-Case Energy Efficiency Maximization in a 5G Massive MIMO-NOMA System.

PubMed

Chinnadurai, Sunil; Selvaprabhu, Poongundran; Jeong, Yongchae; Jiang, Xueqin; Lee, Moon Ho

2017-09-18

In this paper, we examine the robust beamforming design to tackle the energy efficiency (EE) maximization problem in a 5G massive multiple-input multiple-output (MIMO)-non-orthogonal multiple access (NOMA) downlink system with imperfect channel state information (CSI) at the base station. A novel joint user pairing and dynamic power allocation (JUPDPA) algorithm is proposed to minimize the inter user interference and also to enhance the fairness between the users. This work assumes imperfect CSI by adding uncertainties to channel matrices with worst-case model, i.e., ellipsoidal uncertainty model (EUM). A fractional non-convex optimization problem is formulated to maximize the EE subject to the transmit power constraints and the minimum rate requirement for the cell edge user. The designed problem is difficult to solve due to its nonlinear fractional objective function. We firstly employ the properties of fractional programming to transform the non-convex problem into its equivalent parametric form. Then, an efficient iterative algorithm is proposed established on the constrained concave-convex procedure (CCCP) that solves and achieves convergence to a stationary point of the above problem. Finally, Dinkelbach's algorithm is employed to determine the maximum energy efficiency. Comprehensive numerical results illustrate that the proposed scheme attains higher worst-case energy efficiency as compared with the existing NOMA schemes and the conventional orthogonal multiple access (OMA) scheme.

Worst-Case Energy Efficiency Maximization in a 5G Massive MIMO-NOMA System

PubMed Central

Jeong, Yongchae; Jiang, Xueqin; Lee, Moon Ho

2017-01-01

In this paper, we examine the robust beamforming design to tackle the energy efficiency (EE) maximization problem in a 5G massive multiple-input multiple-output (MIMO)-non-orthogonal multiple access (NOMA) downlink system with imperfect channel state information (CSI) at the base station. A novel joint user pairing and dynamic power allocation (JUPDPA) algorithm is proposed to minimize the inter user interference and also to enhance the fairness between the users. This work assumes imperfect CSI by adding uncertainties to channel matrices with worst-case model, i.e., ellipsoidal uncertainty model (EUM). A fractional non-convex optimization problem is formulated to maximize the EE subject to the transmit power constraints and the minimum rate requirement for the cell edge user. The designed problem is difficult to solve due to its nonlinear fractional objective function. We firstly employ the properties of fractional programming to transform the non-convex problem into its equivalent parametric form. Then, an efficient iterative algorithm is proposed established on the constrained concave-convex procedure (CCCP) that solves and achieves convergence to a stationary point of the above problem. Finally, Dinkelbach’s algorithm is employed to determine the maximum energy efficiency. Comprehensive numerical results illustrate that the proposed scheme attains higher worst-case energy efficiency as compared with the existing NOMA schemes and the conventional orthogonal multiple access (OMA) scheme. PMID:28927019

Uncountably many maximizing measures for a dense subset of continuous functions

NASA Astrophysics Data System (ADS)

Shinoda, Mao

2018-05-01

Ergodic optimization aims to single out dynamically invariant Borel probability measures which maximize the integral of a given ‘performance’ function. For a continuous self-map of a compact metric space and a dense set of continuous functions, we show the existence of uncountably many ergodic maximizing measures. We also show that, for a topologically mixing subshift of finite type and a dense set of continuous functions there exist uncountably many ergodic maximizing measures with full support and positive entropy.

Laparohysteroscopy in female infertility: A diagnostic cum therapeutic tool in Indian setting.

PubMed

Puri, Suman; Jain, Dinesh; Puri, Sandeep; Kaushal, Sandeep; Deol, Satjeet Kaur

2015-01-01

To evaluate the role of laparohysteroscopy in female infertility andto study the effect of therapeutic procedures in achieving fertility. Patients with female infertility presenting to outpatient Department of Obstetrics and Gynecology were evaluated over a period of 18 months. Fifty consenting subjects excluding male factor infertility with normal hormonal profile and no contraindication to laparoscopy were subject to diagnostic laparoscopy and hysteroscopy. T-test. We studied 50 patients comprising of 24 (48%) cases of primary infertility and 26 (52%) patients of secondary infertility. The average age of active married life for 50 patients was between 8 and 9 years. In our study, the most commonly found pathologies were PCOD, endometroisis and tubal blockage. 11 (28.2) patients conceived after laparohysteroscopy followed by artificial reproductive techniques. This study demonstrates the benefit of laparohysteroscopy for diagnosis and as a therapeutic tool in patients with primary and secondary infertility. We were able to achieve a higher conception rate of 28.2%.

Association between therapeutic alliance, care satisfaction, and pharmacological adherence in bipolar disorder.

PubMed

Sylvia, Louisa G; Hay, Aleena; Ostacher, Michael J; Miklowitz, David J; Nierenberg, Andrew A; Thase, Michael E; Sachs, Gary S; Deckersbach, Thilo; Perlis, Roy H

2013-06-01

We sought to understand the association of specific aspects of care satisfaction, such as patients' perceived relationship with their psychiatrist and access to their psychiatrist and staff, and therapeutic alliance with participants' likelihood to adhere to their medication regimens among patients with bipolar disorder. We examined data from the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder, an effectiveness study investigating the course and treatment of bipolar disorder. We expected that participants (n = 3037) with positive perceptions of their relationship with their psychiatrist and quality of psychopharmacologic care, as assessed by the Helping Alliance Questionnaire and Care Satisfaction Questionnaire, would be associated with better medication adherence. We utilized logistic regression models controlling for already established factors associated with poor adherence. Patients' perceptions of collaboration, empathy, and accessibility were significantly associated with adherence to treatment in individuals with bipolar disorder completing at least 1 assessment. Patients' perceptions of their psychiatrists' experience, as well as of their degree of discussing medication risks and benefits, were not associated with medication adherence. Patients' perceived therapeutic alliance and treatment environment impact their adherence to pharmacotherapy recommendations. This study may enable psychopharmacologists' practices to be structured to maximize features associated with greater medication adherence.

Knowledge discovery by accuracy maximization

PubMed Central

Cacciatore, Stefano; Luchinat, Claudio; Tenori, Leonardo

2014-01-01

Here we describe KODAMA (knowledge discovery by accuracy maximization), an unsupervised and semisupervised learning algorithm that performs feature extraction from noisy and high-dimensional data. Unlike other data mining methods, the peculiarity of KODAMA is that it is driven by an integrated procedure of cross-validation of the results. The discovery of a local manifold’s topology is led by a classifier through a Monte Carlo procedure of maximization of cross-validated predictive accuracy. Briefly, our approach differs from previous methods in that it has an integrated procedure of validation of the results. In this way, the method ensures the highest robustness of the obtained solution. This robustness is demonstrated on experimental datasets of gene expression and metabolomics, where KODAMA compares favorably with other existing feature extraction methods. KODAMA is then applied to an astronomical dataset, revealing unexpected features. Interesting and not easily predictable features are also found in the analysis of the State of the Union speeches by American presidents: KODAMA reveals an abrupt linguistic transition sharply separating all post-Reagan from all pre-Reagan speeches. The transition occurs during Reagan’s presidency and not from its beginning. PMID:24706821

Reversal of cognitive decline: A novel therapeutic program

PubMed Central

Bredesen, Dale E.

2014-01-01

This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system. PMID:25324467

Volume versus value maximization illustrated for Douglas-fir with thinning

Treesearch

Kurt H. Riitters; J. Douglas Brodie; Chiang Kao

1982-01-01

Economic and physical criteria for selecting even-aged rotation lengths are reviewed with examples of their optimizations. To demonstrate the trade-off between physical volume, economic return, and stand diameter, examples of thinning regimes for maximizing volume, forest rent, and soil expectation are compared with an example of maximizing volume without thinning. The...

Trust Maximization in Social Networks

NASA Astrophysics Data System (ADS)

Zhan, Justin; Fang, Xing

Trust is a human-related phenomenon in social networks. Trust research on social networks has gained much attention on its usefulness, and on modeling propagations. There is little focus on finding maximum trust in social networks which is particularly important when a social network is oriented by certain tasks. In this paper, we propose a trust maximization algorithm based on the task-oriented social networks.

Partial agonists for α4β2 nicotinic receptors stimulate dopaminergic neuron firing with relatively enhanced maximal effects

PubMed Central

Chen, Ying; Broad, Lisa M; Phillips, Keith G; Zwart, Ruud

2012-01-01

BACKGROUND AND PURPOSE Partial agonists selective for α4β2 nicotinic ACh receptors have been developed for smoking cessation as they induce weak activation of native α4β2* receptors and inhibit effect of nicotine. However, it is unclear whether at brain functions there is an existence of receptor reserve that allows weak receptor activation to induce maximum physiological effects. We assessed the extent of α4β2 partial agonist-induced increase of firing rate in dopaminergic neurons and evaluated the influence of receptor reserve. EXPERIMENTAL APPROACH The relative maximal effects and potencies of six nicotinic agonists were assessed on recombinant human α4β2 and α7 receptors expressed in mammalian cell lines by measuring calcium influx. Agonist-induced increase of the spontaneous firing rate of dopaminergic neurons was recorded using microelectrodes in the ventral tegmental area of rat brain slices. KEY RESULTS All α4β2 partial and full agonists increased the firing rate concentration-dependently. Their sensitivity to subtype-selective antagonists showed predominant activation of native α4β2* receptors. However, partial agonists with relative maximal effects as low as 33% on α4β2 receptors maximally increased the firing rate and induced additional depolarization block of firing, demonstrating that partial activation of receptors caused the maximum increase in firing rate in the presence of a receptor reserve. CONCLUSIONS AND IMPLICATIONS Partial α4β2 agonists induced relatively enhanced effects on the firing rate of dopaminergic neurons, and the effect was mainly attributed to the existence of native α4β2* receptor reserve. The results have implications in the understanding of physiological effects and therapeutic efficacies of α4β2 partial agonists. PMID:21838750

Nondecoupling of maximal supergravity from the superstring.

PubMed

Green, Michael B; Ooguri, Hirosi; Schwarz, John H

2007-07-27

We consider the conditions necessary for obtaining perturbative maximal supergravity in d dimensions as a decoupling limit of type II superstring theory compactified on a (10-d) torus. For dimensions d=2 and d=3, it is possible to define a limit in which the only finite-mass states are the 256 massless states of maximal supergravity. However, in dimensions d>or=4, there are infinite towers of additional massless and finite-mass states. These correspond to Kaluza-Klein charges, wound strings, Kaluza-Klein monopoles, or branes wrapping around cycles of the toroidal extra dimensions. We conclude that perturbative supergravity cannot be decoupled from string theory in dimensions>or=4. In particular, we conjecture that pure N=8 supergravity in four dimensions is in the Swampland.

Non-linear optical response by functionalized gold nanospheres: identifying design principles to maximize the molecular photo-release.

PubMed

Bergamini, Luca; Voliani, Valerio; Cappello, Valentina; Nifosì, Riccardo; Corni, Stefano

2015-08-28

In a recent study by Voliani et al. [Small, 2011, 7, 3271], the electromagnetic field enhancement in the vicinity of the gold nanoparticle surface has been exploited to achieve photocontrolled release of a molecular cargo conjugated to the nanoparticles via 1,2,3-triazole, a photocleavable moiety. The aim of the present study is to investigate the mechanism of the photorelease by characterizing the nanoparticle aggregation status within the cells and simulating the electric field enhancement in a range of experimentally realistic geometries, such as single Au nanoparticles, dimers, trimers and random aggregates. Two plasmon-enhanced processes are examined for triazole photocleavage, i.e. three-photon excitation and third-harmonic-generation (one-photon) excitation. Taking into account the absorption cross sections of the triazole, we conclude that the latter mechanism is more efficient, and provides a photocleavage rate that explains the experimental findings. Moreover, we determine which aggregate geometries are required to maximize the field enhancement, and the dependence of such enhancement on the excitation wavelength. Our results provide design principles for maximizing the multiphoton molecular photorelease by such functionalized gold nanoparticles.

Maximizing the Range of a Projectile.

ERIC Educational Resources Information Center

Brown, Ronald A.

1992-01-01

Discusses solutions to the problem of maximizing the range of a projectile. Presents three references that solve the problem with and without the use of calculus. Offers a fourth solution suitable for introductory physics courses that relies more on trigonometry and the geometry of the problem. (MDH)

Nanoparticles for targeted delivery of therapeutics and small interfering RNAs in hepatocellular carcinoma

PubMed Central

Varshosaz, Jaleh; Farzan, Maryam

2015-01-01

Hepatocellular carcinoma (HCC) is the 5th most common malignancy which is responsible for more than half million annual mortalities; also, it is the third leading cause of cancer related death. Unfavorable systemic side-effects of chemotherapeutic agents and susceptibility to the degradation of small interfering RNAs (siRNAs), which can knock down a specific gene involved in the disease, have hampered their clinical application. So, it could be beneficial to develop an efficient carrier for the stabilization and specific delivery of drugs and siRNA to cells. Targeted nanoparticles have gained considerable attention as an efficient drug and gene delivery system, which is due to their capability in achieving the highest accumulation of cytotoxic agents in tumor tissue, modifiable drug pharmacokinetic- and bio-distribution, improved effectiveness of treatment, and limited side-effects. Recent studies have shed more light on the advantages of novel drug loaded carrier systems vs free drugs. Most of the animal studies have reported improvement in treatment efficacy and survival rate using novel carrier systems. Targeted delivery may be achieved passively or actively. In passive targeting, no ligand as homing device is used, while targeting is achieved by incorporating the therapeutic agent into a macromolecule or nanoparticle that passively reaches the target organ. However, in active targeting, the therapeutic agent or carrier system is conjugated to a tissue or cell-specific receptor which is over-expressed in a special malignancy using a ligand called a homing device. This review covers a broad spectrum of targeted nanoparticles as therapeutic and non-viral siRNA delivery systems, which are developed for enhanced cellular uptake and targeted gene silencing in vitro and in vivo and their characteristics and opportunities for the clinical applications of drugs and therapeutic siRNA are discussed in this article. Asialoglycoprotein receptors, low-density lipoprotein

Comparison of Periodized and Non-Periodized Resistance Training on Maximal Strength: A Meta-Analysis.

PubMed

Williams, Tyler D; Tolusso, Danilo V; Fedewa, Michael V; Esco, Michael R

2017-10-01

Periodization is a logical method of organizing training into sequential phases and cyclical time periods in order to increase the potential for achieving specific performance goals while minimizing the potential for overtraining. Periodized resistance training plans are proposed to be superior to non-periodized training plans for enhancing maximal strength. The primary aim of this study was to examine the previous literature comparing periodized resistance training plans to non-periodized resistance training plans and determine a quantitative estimate of effect on maximal strength. All studies included in the meta-analysis met the following inclusion criteria: (1) peer-reviewed publication; (2) published in English; (3) comparison of a periodized resistance training group to a non-periodized resistance training group; (4) maximal strength measured by 1-repetition maximum (1RM) squat, bench press, or leg press. Data were extracted and independently coded by two authors. Random-effects models were used to aggregate a mean effect size (ES), 95% confidence intervals (CIs) and potential moderators. The cumulative results of 81 effects gathered from 18 studies published between 1988 and 2015 indicated that the magnitude of improvement in 1RM following periodized resistance training was greater than non-periodized resistance training (ES = 0.43, 95% CI 0.27-0.58; P < 0.001). Periodization model (β = 0.51; P = 0.0010), training status (β = -0.59; P = 0.0305), study length (β = 0.03; P = 0.0067), and training frequency (β = 0.46; P = 0.0123) were associated with a change in 1RM. These results indicate that undulating programs were more favorable for strength gains. Improvements in 1RM were greater among untrained participants. Additionally, higher training frequency and longer study length were associated with larger improvements in 1RM. These results suggest that periodized resistance training plans have a moderate effect on 1RM compared to non

Effect of Age and Other Factors on Maximal Heart Rate.

ERIC Educational Resources Information Center

Londeree, Ben R.; Moeschberger, Melvin L.

1982-01-01

To reduce confusion regarding reported effects of age on maximal exercise heart rate, a comprehensive review of the relevant English literature was conducted. Data on maximal heart rate after exercising with a bicycle, a treadmill, and after swimming were analyzed with regard to physical fitness and to age, sex, and racial differences. (Authors/PP)

Recent advances in cancer therapeutics.

PubMed

Chessum, Nicola; Jones, Keith; Pasqua, Elisa; Tucker, Michael

2015-01-01

In the past 20 years, cancer therapeutics has undergone a paradigm shift away from the traditional cytotoxic drugs towards the targeting of proteins intimately involved in driving the cancer phenotype. The poster child for this alternative approach to the treatment of cancer is imatinib, a small-molecule kinase inhibitor designed to target chronic myeloid leukaemia driven by the BCR-ABL translocation in a defined patient population. The improvement in survival achieved by treatment of this patient cohort with imatinib is impressive. Thus, the aim is to provide efficacy but with low toxicity. The role of the medicinal chemist in oncology drug discovery is now closely aligned with the role in most other therapeutic areas with high-throughput and/or fragment-based screening, structure-based design, selectivity, pharmacokinetic optimisation and pharmacodynamic biomarker modulation, all playing a familiar part in the process. In this chapter, we selected four areas in which compounds are either approved drugs or in clinical trials. These are chaperone inhibitors, kinase inhibitors, histone deacetylase inhibitors and inhibitors of protein-protein interactions. Even within these areas, we have been selective, particularly for kinase inhibitors, and our aim has been to exemplify newer approaches and novel aspects of medicinal chemistry. © 2015 Elsevier B.V. All rights reserved.

Dynamic Cerebral Autoregulation Is Acutely Impaired during Maximal Apnoea in Trained Divers

PubMed Central

Cross, Troy J.; Kavanagh, Justin J.; Breskovic, Toni; Johnson, Bruce D.; Dujic, Zeljko

2014-01-01

Aims To examine whether dynamic cerebral autoregulation is acutely impaired during maximal voluntary apnoea in trained divers. Methods Mean arterial pressure (MAP), cerebral blood flow-velocity (CBFV) and end-tidal partial pressures of O2 and CO2 (PETO2 and PETCO2) were measured in eleven trained, male apnoea divers (28±2 yr; 182±2 cm, 76±7 kg) during maximal “dry” breath holding. Dynamic cerebral autoregulation was assessed by determining the strength of phase synchronisation between MAP and CBFV during maximal apnoea. Results The strength of phase synchronisation between MAP and CBFV increased from rest until the end of maximal voluntary apnoea (P<0.05), suggesting that dynamic cerebral autoregulation had weakened by the apnoea breakpoint. The magnitude of impairment in dynamic cerebral autoregulation was strongly, and positively related to the rise in PETCO2 observed during maximal breath holding (R 2 = 0.67, P<0.05). Interestingly, the impairment in dynamic cerebral autoregulation was not related to the fall in PETO2 induced by apnoea (R 2 = 0.01, P = 0.75). Conclusions This study is the first to report that dynamic cerebral autoregulation is acutely impaired in trained divers performing maximal voluntary apnoea. Furthermore, our data suggest that the impaired autoregulatory response is related to the change in PETCO2, but not PETO2, during maximal apnoea in trained divers. PMID:24498340

Reserve design to maximize species persistence

Treesearch

Robert G. Haight; Laurel E. Travis

2008-01-01

We develop a reserve design strategy to maximize the probability of species persistence predicted by a stochastic, individual-based, metapopulation model. Because the population model does not fit exact optimization procedures, our strategy involves deriving promising solutions from theory, obtaining promising solutions from a simulation optimization heuristic, and...

Using enzyme folding to explore the mechanism of therapeutic touch: a feasibility study.

PubMed

Strickland, Mallory L; Boylan, Helen M

2010-07-01

The goal of this research is to design a novel model using protein folding to study Therapeutic Touch, a noncontact form of energy manipulation healing. Presented is a feasibility study suggesting that the denaturation path of ribonuclease A may be a useful model to study the energy exchange underlying therapeutic touch. The folding of ribonuclease A serves as a controlled energy-requiring system in which energy manipulation can be measured by the degree of folding achieved. A kinetic assay and fluorescence spectroscopy are used to assess the enzyme-folding state. The data suggest that the kinetic assay is a useful means of assessing the degree of refolding, and specifically, the enzyme function. However, fluorescence spectroscopy was not shown to be an effective measurement of enzyme structure for the purposes of this work. More research is needed to assess the underlying mechanism of therapeutic touch to complement the existing studies. An enzyme-folding model may provide a useful means of studying the energy exchange in therapeutic touch.

Combining Immune Checkpoint Inhibitors and Kinase-Inhibiting Supramolecular Therapeutics for Enhanced Anticancer Efficacy.

PubMed

Kulkarni, Ashish; Natarajan, Siva Kumar; Chandrasekar, Vineethkrishna; Pandey, Prithvi Raj; Sengupta, Shiladitya

2016-09-29

A major limitation of immune checkpoint inhibitors is that only a small subset of patients achieve durable clinical responses. This necessitates the development of combinatorial regimens with immunotherapy. However, some combinations, such as MEK- or PI3K-inhibitors with a PD1-PDL1 checkpoint inhibitor, are pharmacologically challenging to implement. We rationalized that such combinations can be enabled using nanoscale supramolecular targeted therapeutics, which spatially home into tumors and exert temporally sustained inhibition of the target. Here we describe two case studies where nanoscale MEK- and PI3K-targeting supramolecular therapeutics were engineered using a quantum mechanical all-atomistic simulation-based approach. The combinations of nanoscale MEK- and PI3K-targeting supramolecular therapeutics with checkpoint PDL1 and PD1 inhibitors exert enhanced antitumor outcome in melanoma and breast cancers in vivo, respectively. Additionally, the temporal sequence of administration impacts the outcome. The combination of supramolecular therapeutics and immunotherapy could emerge as a paradigm shift in the treatment of cancer.

Maximizing Health or Sufficient Capability in Economic Evaluation? A Methodological Experiment of Treatment for Drug Addiction.

PubMed

Goranitis, Ilias; Coast, Joanna; Day, Ed; Copello, Alex; Freemantle, Nick; Frew, Emma

2017-07-01

Conventional practice within the United Kingdom and beyond is to conduct economic evaluations with "health" as evaluative space and "health maximization" as the decision-making rule. However, there is increasing recognition that this evaluative framework may not always be appropriate, and this is particularly the case within public health and social care contexts. This article presents a methodological case study designed to explore the impact of changing the evaluative space within an economic evaluation from health to capability well-being and the decision-making rule from health maximization to the maximization of sufficient capability. Capability well-being is an evaluative space grounded on Amartya Sen's capability approach and assesses well-being based on individuals' ability to do and be the things they value in life. Sufficient capability is an egalitarian approach to decision making that aims to ensure everyone in society achieves a normatively sufficient level of capability well-being. The case study is treatment for drug addiction, and the cost-effectiveness of 2 psychological interventions relative to usual care is assessed using data from a pilot trial. Analyses are undertaken from a health care and a government perspective. For the purpose of the study, quality-adjusted life years (measured using the EQ-5D-5L) and years of full capability equivalent and years of sufficient capability equivalent (both measured using the ICECAP-A [ICEpop CAPability measure for Adults]) are estimated. The study concludes that different evaluative spaces and decision-making rules have the potential to offer opposing treatment recommendations. The implications for policy makers are discussed.

Curriculum and Testing Strategies to Maximize STAAR Achievement

ERIC Educational Resources Information Center

Johnson, William L.; Johnson, Annabel M.; Johnson, Jared W.

2014-01-01

The document is from a presentation at the 2014 annual conference of the Science Teachers Association of Texas (STAT). The presenter noted that the 2001 No Child Left Behind (NCLB) law was the most far-reaching education legislation in over four decades. To address the requirements of this legislation, the presenter examined the third-generation…

New Business Models to Accelerate Innovation in Pediatric Oncology Therapeutics: A Review.

PubMed

Das, Sonya; Rousseau, Raphaël; Adamson, Peter C; Lo, Andrew W

2018-06-02

Few patient populations are as helpless and in need of advocacy as children with cancer. Pharmaceutical companies have historically faced significant financial disincentives to pursue pediatric oncology therapeutics, including low incidence, high costs of conducting pediatric trials, and a lack of funding for early-stage research. Review of published studies of pediatric oncology research and the cost of drug development, as well as clinical trials of pediatric oncology therapeutics at ClinicalTrials.gov, identified 77 potential drug development projects to be included in a hypothetical portfolio. The returns of this portfolio were simulated so as to compute the financial returns and risk. Simulated business strategies include combining projects at different clinical phases of development, obtaining partial funding from philanthropic grants, and obtaining government guarantees to reduce risk. The purely private-sector portfolio exhibited expected returns ranging from -24.2% to 10.2%, depending on the model variables assumed. This finding suggests significant financial disincentives for pursuing pediatric oncology therapeutics and implies that financial support from the public and philanthropic sectors is essential. Phase diversification increases the likelihood of a successful drug and yielded expected returns of -5.3% to 50.1%. Standard philanthropic grants had a marginal association with expected returns, and government guarantees had a greater association by reducing downside exposure. An assessment of a proposed venture philanthropy fund demonstrated stronger performance than the purely private-sector-funded portfolio or those with traditional amounts of philanthropic support. A combination of financial and business strategies has the potential to maximize expected return while eliminating some downside risk-in certain cases enabling expected returns as high as 50.1%-that can overcome current financial disincentives and accelerate the development of pediatric

Salinity effect on the maximal growth temperature of some bacteria isolated from marine enviroments.

PubMed

Stanley, S O; Morita, R Y

1968-01-01

Salinity of the growth medium was found to have a marked effect on the maximal growth temperature of four bacteria isolated from marine sources. Vibrio marinus MP-1 had a maximal growth temperature of 21.2 C at a salinity of 35% and a maximal growth temperature of 10.5 C at a salinity of 7%, the lowest salinity at which it would grow. This effect was shown to be due to the presence of various cations in the medium. The order of effectiveness of cations in restoring the normal maximal growth temperature, when added to dilute seawater, was Na(+) > Li(+) > Mg(++) > K(+) > Rb(+) > NH(4) (+). The anions tested, with the exception of SO(4)=, had no marked effect on the maximal growth temperature response. In a completely defined medium, the highest maximal growth temperature was 20.0 C at 0.40 m NaCl. A decrease in the maximal growth temperature was observed at both low and high concentrations of NaCl.

Bioengineering and Coordination of Regulatory Networks and Intracellular Complexes to Maximize Hydrogen Production by Phototrophic Microorganisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tabita, F. Robert

2013-07-30

In this study, the Principal Investigator, F.R. Tabita has teamed up with J. C. Liao from UCLA. This project's main goal is to manipulate regulatory networks in phototrophic bacteria to affect and maximize the production of large amounts of hydrogen gas under conditions where wild-type organisms are constrained by inherent regulatory mechanisms from allowing this to occur. Unrestrained production of hydrogen has been achieved and this will allow for the potential utilization of waste materials as a feed stock to support hydrogen production. By further understanding the means by which regulatory networks interact, this study will seek to maximize themore » ability of currently available “unrestrained” organisms to produce hydrogen. The organisms to be utilized in this study, phototrophic microorganisms, in particular nonsulfur purple (NSP) bacteria, catalyze many significant processes including the assimilation of carbon dioxide into organic carbon, nitrogen fixation, sulfur oxidation, aromatic acid degradation, and hydrogen oxidation/evolution. Moreover, due to their great metabolic versatility, such organisms highly regulate these processes in the cell and since virtually all such capabilities are dispensable, excellent experimental systems to study aspects of molecular control and biochemistry/physiology are available.« less

Tapping the RNA world for therapeutics.

PubMed

Lieberman, Judy

2018-05-01

A recent revolution in RNA biology has led to the identification of new RNA classes with unanticipated functions, new types of RNA modifications, an unexpected multiplicity of alternative transcripts and widespread transcription of extragenic regions. This development in basic RNA biology has spawned a corresponding revolution in RNA-based strategies to generate new types of therapeutics. Here, I review RNA-based drug design and discuss barriers to broader applications and possible ways to overcome them. Because they target nucleic acids rather than proteins, RNA-based drugs promise to greatly extend the domain of 'druggable' targets beyond what can be achieved with small molecules and biologics.

A Model of College Tuition Maximization

ERIC Educational Resources Information Center

Bosshardt, Donald I.; Lichtenstein, Larry; Zaporowski, Mark P.

2009-01-01

This paper develops a series of models for optimal tuition pricing for private colleges and universities. The university is assumed to be a profit maximizing, price discriminating monopolist. The enrollment decision of student's is stochastic in nature. The university offers an effective tuition rate, comprised of stipulated tuition less financial…

The jet-disk symbiosis without maximal jets: 1D hydrodynamical jets revisited

NASA Astrophysics Data System (ADS)

Crumley, Patrick; Ceccobello, Chiara; Connors, Riley M. T.; Cavecchi, Yuri

2017-05-01

In this work we discuss the recent criticism by Zdziarski (2016, A&A, 586, A18) of the maximal jet model derived in Falcke & Biermann (1995, A&A, 293, 665). We agree with Zdziarski that in general a jet's internal energy is not bounded by its rest-mass energy density. We describe the effects of the mistake on conclusions that have been made using the maximal jet model and show when a maximal jet is an appropriate assumption. The maximal jet model was used to derive a 1D hydrodynamical model of jets in agnjet, a model that does multiwavelength fitting of quiescent/hard state X-ray binaries and low-luminosity active galactic nuclei. We correct algebraic mistakes made in the derivation of the 1D Euler equation and relax the maximal jet assumption. We show that the corrections cause minor differences as long as the jet has a small opening angle and a small terminal Lorentz factor. We find that the major conclusion from the maximal jet model, the jet-disk symbiosis, can be generally applied to astrophysical jets. We also show that isothermal jets are required to match the flat radio spectra seen in low-luminosity X-ray binaries and active galactic nuclei, in agreement with other works.

[Psychiatry with open doors. Part 2: Therapeutic challenges].

PubMed

Sollberger, D; Lang, U E

2014-03-01

In the previous part of the issue we argued that opening the doors of acute psychiatric inpatient wards is actually one of the anchor points on the way to an innovative psychiatry. It focuses on the patient's personality in a sense that this is taken as seriously as the psychiatric disorder itself. Patients and relatives should be enabled to participate in treatment decisions as they should experience that treatment teams are concerned about reliance, liability and security in therapeutic relationships in an empathetic way. The second part of the issue contributes to the therapeutic measures, the different skills and modifications of treatment frameworks in acute psychiatry (e.g. prevention of crowding in acute psychiatric inpatient units, education of staff, assessment of the risks of violence, de-escalation strategies and coping with suicidality). They might be helpful in implementing the outlined confidence about the essence of therapeutic relationships, autonomy and codetermination of patients in treatment. These suggestions might enhance a professional approach particularly with respect to prevention and also concerning acute interventions in situations of endangerment to self and others and of aggression and violence in the units. In this way they help to achieve the goal of open doors in psychiatry.

Tumor Radiation Therapy Creates Therapeutic Vaccine Responses to the Colorectal Cancer Antigen GUCY2C

DOE Office of Scientific and Technical Information (OSTI.GOV)

Witek, Matthew; Blomain, Erik S.; Magee, Michael S.

Purpose: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. Methods and Materials: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responsesmore » were assessed by tumor size and incidence. Results: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P<.05), tumor eradication was maximized (P<.01), and tumor volumes were minimized (P<.001) in mice whose tumors were irradiated before, compared with after, Ad5-GUCY2C vaccination. The immunologic and antitumor efficacy of Ad5-GUCY2C was amplified comparably by unfractionated (8 Gy × 1), or biologically equivalent doses of fractionated (3.5 Gy × 3), RT. The antitumor effects of sequential RT and IT (RT-IT) depended on expression of GUCY2C by tumor cells and the adenoviral vaccine vector, and tumor volumes were inversely related to the magnitude of GUCY2C-specific T cell responses. Moreover, mice cured of CT26-GUCY2C tumors by RT-IT showed long-lasting antigen-dependent protection, resisting tumors formed by GUCY2C-expressing 4T1 breast cancer cells inoculated 50 days after CT26 cells. Conclusions: Optimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

PubMed

Straube, Andreas; Aicher, Bernhard; Fiebich, Bernd L; Haag, Gunther

2011-03-31

Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.As an example the fixed-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

PubMed Central

2011-01-01

Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden the array of therapeutic

Update on Huntington's disease: advances in care and emerging therapeutic options.

PubMed

Zielonka, Daniel; Mielcarek, Michal; Landwehrmeyer, G Bernhard

2015-03-01

Huntington's disease (HD) is the most common hereditary neurodegenerative disorder. Despite the fact that both the gene and the mutation causing this monogenetic disorder were identified more than 20 years ago, disease-modifying therapies for HD have not yet been established. While intense preclinical research and large cohort studies in HD have laid foundations for tangible improvements in understanding HD and caring for HD patients, identifying targets for therapeutic interventions and developing novel therapeutic modalities (new chemical entities and advanced therapies using DNA and RNA molecules as therapeutic agents) continues to be an ongoing process. The authors review recent achievements in HD research and focus on approaches towards disease-modifying therapies, ranging from huntingtin-lowering strategies to improving huntingtin clearance that may be promoted by posttranslational HTT modifications. The nature and number of upcoming clinical studies/trials in HD is a reason for hope for HD patients and their families. Copyright © 2014 Elsevier Ltd. All rights reserved.

Maximal voluntary isometric contraction tests for normalizing electromyographic data from different regions of supraspinatus and infraspinatus muscles: Identifying reliable combinations.

PubMed

Alenabi, Talia; Whittaker, Rachel; Kim, Soo Y; Dickerson, Clark R

2018-04-25

This study aimed to identify optimal sets of maximal voluntary isometric contractions (MVICs) for normalizing EMG data from anterior and posterior regions of the supraspinatus, and superior, middle and inferior regions of the infraspinatus. 31 right-handed young healthy individuals (15 males, 16 females) participated. EMG activity was obtained from two regions of supraspinatus and three regions of infraspinatus muscles via fine wire electrodes. Participants performed 15 MVIC tests against manual resistance. The EMG data were normalized to the maximum values. Optimal sets of MVIC combinations, defined as those which elicited >90% MVIC activation in the muscles of interest in >80% and >90% of the population, were obtained. EMG data from the inferior region of infraspinatus were removed from analysis due to technical problem. No single test achieved maximal activation of both regions of either the supraspinatus or infraspinatus. Instead, a combination of 6-8 MVICs were required to reach >90% MVIC activation in both parts of those muscles. In all regions of the rotator cuff muscles, the optimal combination was obtained with 8-10 MVICs. The proposed combinations can reduce inter-participant variability in generating maximal activation from different regions of the supraspinatus and infraspinatus muscles. Copyright © 2018 Elsevier Ltd. All rights reserved.

Turning the gene tap off; implications of regulating gene expression for cancer therapeutics

PubMed Central

Curtin, James F.; Candolfi, Marianela; Xiong, Weidong; Lowenstein, Pedro R.; Castro, Maria G.

2008-01-01

Cancer poses a tremendous therapeutic challenge worldwide, highlighting the critical need for developing novel therapeutics. A promising cancer treatment modality is gene therapy, which is a form of molecular medicine designed to introduce into target cells genetic material with therapeutic intent. Anticancer gene therapy strategies currently used in preclinical models, and in some cases in the clinic, include proapoptotic genes, oncolytic/replicative vectors, conditional cytotoxic approaches, inhibition of angiogenesis, inhibition of growth factor signaling, inactivation of oncogenes, inhibition of tumor invasion and stimulation of the immune system. The translation of these novel therapeutic modalities from the preclinical setting to the clinic has been driven by encouraging preclinical efficacy data and advances in gene delivery technologies. One area of intense research involves the ability to accurately regulate the levels of therapeutic gene expression to achieve enhanced efficacy and provide the capability to switch gene expression off completely if adverse side effects should arise. This feature could also be implemented to switch gene expression off when a successful therapeutic outcome ensues. Here, we will review recent developments related to the engineering of transcriptional switches within gene delivery systems, which could be implemented in clinical gene therapy applications directed at the treatment of cancer. PMID:18347132

Using return on investment to maximize conservation effectiveness in Argentine grasslands

PubMed Central

Murdoch, William; Ranganathan, Jai; Polasky, Stephen; Regetz, James

2010-01-01

The rapid global loss of natural habitats and biodiversity, and limited resources, place a premium on maximizing the expected benefits of conservation actions. The scarcity of information on the fine-grained distribution of species of conservation concern, on risks of loss, and on costs of conservation actions, especially in developing countries, makes efficient conservation difficult. The distribution of ecosystem types (unique ecological communities) is typically better known than species and arguably better represents the entirety of biodiversity than do well-known taxa, so we use conserving the diversity of ecosystem types as our conservation goal. We define conservation benefit to include risk of conversion, spatial effects that reward clumping of habitat, and diminishing returns to investment in any one ecosystem type. Using Argentine grasslands as an example, we compare three strategies: protecting the cheapest land (“minimize cost”), maximizing conservation benefit regardless of cost (“maximize benefit”), and maximizing conservation benefit per dollar (“return on investment”). We first show that the widely endorsed goal of saving some percentage (typically 10%) of a country or habitat type, although it may inspire conservation, is a poor operational goal. It either leads to the accumulation of areas with low conservation benefit or requires infeasibly large sums of money, and it distracts from the real problem: maximizing conservation benefit given limited resources. Second, given realistic budgets, return on investment is superior to the other conservation strategies. Surprisingly, however, over a wide range of budgets, minimizing cost provides more conservation benefit than does the maximize-benefit strategy. PMID:21098281

Using return on investment to maximize conservation effectiveness in Argentine grasslands.

PubMed

Murdoch, William; Ranganathan, Jai; Polasky, Stephen; Regetz, James

2010-12-07

The rapid global loss of natural habitats and biodiversity, and limited resources, place a premium on maximizing the expected benefits of conservation actions. The scarcity of information on the fine-grained distribution of species of conservation concern, on risks of loss, and on costs of conservation actions, especially in developing countries, makes efficient conservation difficult. The distribution of ecosystem types (unique ecological communities) is typically better known than species and arguably better represents the entirety of biodiversity than do well-known taxa, so we use conserving the diversity of ecosystem types as our conservation goal. We define conservation benefit to include risk of conversion, spatial effects that reward clumping of habitat, and diminishing returns to investment in any one ecosystem type. Using Argentine grasslands as an example, we compare three strategies: protecting the cheapest land ("minimize cost"), maximizing conservation benefit regardless of cost ("maximize benefit"), and maximizing conservation benefit per dollar ("return on investment"). We first show that the widely endorsed goal of saving some percentage (typically 10%) of a country or habitat type, although it may inspire conservation, is a poor operational goal. It either leads to the accumulation of areas with low conservation benefit or requires infeasibly large sums of money, and it distracts from the real problem: maximizing conservation benefit given limited resources. Second, given realistic budgets, return on investment is superior to the other conservation strategies. Surprisingly, however, over a wide range of budgets, minimizing cost provides more conservation benefit than does the maximize-benefit strategy.

Supramolecular Nanoparticles for Molecular Diagnostics and Therapeutics

NASA Astrophysics Data System (ADS)

Chen, Kuan-Ju

Over the past decades, significant efforts have been devoted to explore the use of various nanoparticle-based systems in the field of nanomedicine, including molecular imaging and therapy. Supramolecular synthetic approaches have attracted lots of attention due to their flexibility, convenience, and modularity for producing nanoparticles. In this dissertation, the developmental story of our size-controllable supramolecular nanoparticles (SNPs) will be discussed, as well as their use in specific biomedical applications. To achieve the self-assembly of SNPs, the well-characterized molecular recognition system (i.e., cyclodextrin/adamantane recognition) was employed. The resulting SNPs, which were assembled from three molecular building blocks, possess incredible stability in various physiological conditions, reversible size-controllability and dynamic disassembly that were exploited for various in vitro and in vivo applications. An advantage of using the supramolecular approach is that it enables the convenient incorporation of functional ligands onto SNP surface that confers functionality ( e.g., targeting, cell penetration) to SNPs. We utilized SNPs for molecular imaging such as magnetic resonance imaging (MRI) and positron emission tomography (PET) by introducing reporter systems (i.e., radio-isotopes, MR contrast agents, and fluorophores) into SNPs. On the other hand, the incorporation of various payloads, including drugs, genes and proteins, into SNPs showed improved delivery performance and enhanced therapeutic efficacy for these therapeutic agents. Leveraging the powers of (i) a combinatorial synthetic approach based on supramolecular assembly and (ii) a digital microreactor, a rapid developmental pathway was developed that is capable of screening SNP candidates for the ideal structural and functional properties that deliver optimal performance. Moreover, SNP-based theranostic delivery systems that combine reporter systems and therapeutic payloads into a

Structurally Based Therapeutic Evaluation: A Therapeutic and Practical Approach to Teaching Medicinal Chemistry.

ERIC Educational Resources Information Center

Alsharif, Naser Z.; And Others

1997-01-01

Explains structurally based therapeutic evaluation of drugs, which uses seven therapeutic criteria in translating chemical and structural knowledge into therapeutic decision making in pharmaceutical care. In a Creighton University (Nebraska) medicinal chemistry course, students apply the approach to solve patient-related therapeutic problems in…

Algal biofuels from urban wastewaters: maximizing biomass yield using nutrients recycled from hydrothermal processing of biomass.

PubMed

Selvaratnam, T; Pegallapati, A K; Reddy, H; Kanapathipillai, N; Nirmalakhandan, N; Deng, S; Lammers, P J

2015-04-01

Recent studies have proposed algal cultivation in urban wastewaters for the dual purpose of waste treatment and bioenergy production from the resulting biomass. This study proposes an enhancement to this approach that integrates cultivation of an acidophilic strain, Galdieria sulphuraria 5587.1, in a closed photobioreactor (PBR); hydrothermal liquefaction (HTL) of the wet algal biomass; and recirculation of the nutrient-rich aqueous product (AP) of HTL to the PBR to achieve higher biomass productivity than that could be achieved with raw wastewater. The premise is that recycling nutrients in the AP can maintain optimal C, N and P levels in the PBR to maximize biomass growth to increase energy returns. Growth studies on the test species validated growth on AP derived from HTL at temperatures from 180 to 300°C. Doubling N and P concentrations over normal levels in wastewater resulted in biomass productivity gains of 20-25% while N and P removal rates also doubled. Copyright © 2015 Elsevier Ltd. All rights reserved.

Uncovering the overlapping community structure of complex networks by maximal cliques

NASA Astrophysics Data System (ADS)

Li, Junqiu; Wang, Xingyuan; Cui, Yaozu

2014-12-01

In this paper, a unique algorithm is proposed to detect overlapping communities in the un-weighted and weighted networks with considerable accuracy. The maximal cliques, overlapping vertex, bridge vertex and isolated vertex are introduced. First, all the maximal cliques are extracted by the algorithm based on the deep and bread searching. Then two maximal cliques can be merged into a larger sub-graph by some given rules. In addition, the proposed algorithm successfully finds overlapping vertices and bridge vertices between communities. Experimental results using some real-world networks data show that the performance of the proposed algorithm is satisfactory.

RNAi therapeutics and applications of microRNAs in cancer treatment.

PubMed

Uchino, Keita; Ochiya, Takahiro; Takeshita, Fumitaka

2013-06-01

RNA interference-based therapies are proving to be powerful tools for combating various diseases, including cancer. Scientists are researching the development of safe and efficient systems for the delivery of small RNA molecules, which are extremely fragile in serum, to target organs and cells in the human body. A dozen pre-clinical and clinical trials have been under way over the past few years involving biodegradable nanoparticles, lipids, chemical modification and conjugation. On the other hand, microRNAs, which control the balance of cellular biological processes, have been studied as attractive therapeutic targets in cancer treatment. In this review, we provide an overview of RNA interference-based therapeutics in clinical trials and discuss the latest technology for the systemic delivery of nucleic acid drugs. Furthermore, we focus on dysregulated microRNAs in human cancer, which have progressed in pre-clinical trials as therapeutic targets, and describe a wide range of strategies to control the expression levels of endogenous microRNAs. Further development of RNA interference technologies and progression of clinical trials will contribute to the achievement of practical applications of nucleic acid drugs.

Inpatient group therapeutic interventions for patients with intellectual disabilities.

PubMed

Reddy, Vilash

2015-03-01

Group therapy can be an effective mode of therapy, used on an inpatient unit, as it can allow patients to become allies in their journey to understand and overcome their mental health needs. The therapeutic principles discussed by Dr Irvin Yalom illustrate the significance and importance of group therapy, which was strongly incorporated into interactive behavior therapy (IBT) developed by Dr Daniel J Tomasulo. IBT is a type of group therapy, more action oriented, created to allow patients with intellectual disabilities (IDs) to better comprehend discussed topics, by designing and tailoring activities to meet their cognitive and linguistic capabilities. Additional details found in this article will illustrate the methods by which IBT is capable of meeting the needs of patients with ID. Such adjustments include shorter duration of activities to maximize concentration, proactive role-playing involving the synergistic effort of all members of the group, and limiting the authoritative role of the therapist in a group environment. © The Author(s) 2014.

Maxime A. Faget Portrait

NASA Image and Video Library

1953-02-18

L59-1497-6 Maxime A. Faget was born in British Honduras in 1921, the son of an honored physician of the U.S. Public Health Service. In 1943 he earned a B.S. in mechanical engineering from Louisiana State University. After service as a navy submarine officer, he joined the Langley staff in 1946 as a member of the Pilotless Aircraft Research Division. His early work for PARD involved the invention of choking inlets for ramjets and a flight Mach meter. Photograph published in Engineer in Charge: A History of the Langley Aeronautical Laboratory, 1917-1958 by James R. Hansen. Page 379.

The pragmatics of therapeutic interaction: an empirical study.

PubMed

Lepper, Georgia

2009-10-01

The research reported in this article aims to demonstrate a method for the systematic study of the therapist/patient interaction in psychoanalytic psychotherapy, drawing upon the tradition and methods of 'pragmatics'--the study of language in interaction. A brief introduction to the discipline of pragmatics demonstrates its relevance to the contemporary focus of clinical theory on the here-and-now dynamics of the relationship between analyst and patient. This is followed by a detailed study of five segments from the transcript of a therapeutic dialogue, drawn from a brief psychoanalytic psychotherapy, in which therapist and patient negotiate the meaning of the patient's symptom: Is it psychosomatic? The research seeks to show how the therapeutic process can be observed and studied as an interactional achievement, grounded in general and well-studied procedures through which meaning is intersubjectively developed and shared. Implications of the analysis for clinical theory and practice, and further research, are discussed.

Gold Nanoparticles-enabled Efficient Dual Delivery of Anticancer Therapeutics to HeLa Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farooq, Muhammad U.; Novosad, Valentyn; Rozhkova, Elena A.

Colloidal gold nanoparticles (AuNPs) are of interest as non-toxic carriers for drug delivery owing to their advanced properties, such as extensive surface-to-volume ratio and possibilities for tailoring their charge, hydrophilicity and functionality through surface chemistries. To date, various biocompatible polymers have been used for surface decoration of AuNPs to enhance their stability, payloads capacity and cellular uptake. This study describes a facile one-step method to synthesize stable AuNPs loaded with combination of two anticancer therapeutics, -bleomycin and doxorubicin. Anticancer activities, cytotoxicity, uptake and intracellular localization of the AuNPs were demonstrated in HeLa cells. We show that the therapeutic efficacy ofmore » the nanohybrid drug was strongly enhanced by the active targeting by the nanoscale delivery system to HeLa cells with a significant decrease of the half-maximal effective drug concentration, through blockage of HeLa cancer cell cycle. These results provide rationale for further progress of AuNPs-assisted combination chemotherapy using two drugs at optimized effective concentrations which act via different mechanisms thus decreasing possibilities of development of the cancer drug resistance, reduction of systemic drug toxicity and improvement of outcomes of chemotherapy.« less

Gold Nanoparticles-enabled Efficient Dual Delivery of Anticancer Therapeutics to HeLa Cells

DOE PAGES

Farooq, Muhammad U.; Novosad, Valentyn; Rozhkova, Elena A.; ...

2018-02-13

Colloidal gold nanoparticles (AuNPs) are of interest as non-toxic carriers for drug delivery owing to their advanced properties, such as extensive surface-to-volume ratio and possibilities for tailoring their charge, hydrophilicity and functionality through surface chemistries. To date, various biocompatible polymers have been used for surface decoration of AuNPs to enhance their stability, payloads capacity and cellular uptake. This study describes a facile one-step method to synthesize stable AuNPs loaded with combination of two anticancer therapeutics, -bleomycin and doxorubicin. Anticancer activities, cytotoxicity, uptake and intracellular localization of the AuNPs were demonstrated in HeLa cells. We show that the therapeutic efficacy ofmore » the nanohybrid drug was strongly enhanced by the active targeting by the nanoscale delivery system to HeLa cells with a significant decrease of the half-maximal effective drug concentration, through blockage of HeLa cancer cell cycle. These results provide rationale for further progress of AuNPs-assisted combination chemotherapy using two drugs at optimized effective concentrations which act via different mechanisms thus decreasing possibilities of development of the cancer drug resistance, reduction of systemic drug toxicity and improvement of outcomes of chemotherapy.« less

Energy Efficiency Maximization for WSNs with Simultaneous Wireless Information and Power Transfer

PubMed Central

Yu, Hongyan; Zhang, Yongqiang; Yang, Yuanyuan; Ji, Luyue

2017-01-01

Recently, the simultaneous wireless information and power transfer (SWIPT) technique has been regarded as a promising approach to enhance performance of wireless sensor networks with limited energy supply. However, from a green communication perspective, energy efficiency optimization for SWIPT system design has not been investigated in Wireless Rechargeable Sensor Networks (WRSNs). In this paper, we consider the tradeoffs between energy efficiency and three factors including spectral efficiency, the transmit power and outage target rate for two different modes, i.e., power splitting (PS) and time switching modes (TS), at the receiver. Moreover, we formulate the energy efficiency maximization problem subject to the constraints of minimum Quality of Service (QoS), minimum harvested energy and maximum transmission power as non-convex optimization problem. In particular, we focus on optimizing power control and power allocation policy in PS and TS modes to maximize energy efficiency of data transmission. For PS and TS modes, we propose the corresponding algorithm to characterize a non-convex optimization problem that takes into account the circuit power consumption and the harvested energy. By exploiting nonlinear fractional programming and Lagrangian dual decomposition, we propose suboptimal iterative algorithms to obtain the solutions of non-convex optimization problems. Furthermore, we derive the outage probability and effective throughput from the scenarios that the transmitter does not or partially know the channel state information (CSI) of the receiver. Simulation results illustrate that the proposed optimal iterative algorithm can achieve optimal solutions within a small number of iterations and various tradeoffs between energy efficiency and spectral efficiency, transmit power and outage target rate, respectively. PMID:28820496

Energy Efficiency Maximization for WSNs with Simultaneous Wireless Information and Power Transfer.

PubMed

Yu, Hongyan; Zhang, Yongqiang; Guo, Songtao; Yang, Yuanyuan; Ji, Luyue

2017-08-18

Recently, the simultaneous wireless information and power transfer (SWIPT) technique has been regarded as a promising approach to enhance performance of wireless sensor networks with limited energy supply. However, from a green communication perspective, energy efficiency optimization for SWIPT system design has not been investigated in Wireless Rechargeable Sensor Networks (WRSNs). In this paper, we consider the tradeoffs between energy efficiency and three factors including spectral efficiency, the transmit power and outage target rate for two different modes, i.e., power splitting (PS) and time switching modes (TS), at the receiver. Moreover, we formulate the energy efficiency maximization problem subject to the constraints of minimum Quality of Service (QoS), minimum harvested energy and maximum transmission power as non-convex optimization problem. In particular, we focus on optimizing power control and power allocation policy in PS and TS modes to maximize energy efficiency of data transmission. For PS and TS modes, we propose the corresponding algorithm to characterize a non-convex optimization problem that takes into account the circuit power consumption and the harvested energy. By exploiting nonlinear fractional programming and Lagrangian dual decomposition, we propose suboptimal iterative algorithms to obtain the solutions of non-convex optimization problems. Furthermore, we derive the outage probability and effective throughput from the scenarios that the transmitter does not or partially know the channel state information (CSI) of the receiver. Simulation results illustrate that the proposed optimal iterative algorithm can achieve optimal solutions within a small number of iterations and various tradeoffs between energy efficiency and spectral efficiency, transmit power and outage target rate, respectively.

Targeted polymeric therapeutic nanoparticles: design, development and clinical translation†

PubMed Central

Kamaly, Nazila; Xiao, Zeyu; Valencia, Pedro M.; Radovic-Moreno, Aleksandar F.; Farokhzad, Omid C.

2013-01-01

Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this optimization of drug pharmacology as aided by careful design of multifunctional NPs can lead to improved drug safety and efficacy, and may be complimentary to drug enhancements that are traditionally achieved by medicinal chemistry. In this regard, polymeric NPs have the potential to result in a highly differentiated new class of therapeutics, distinct from the original active drugs used in their composition, and distinct from first generation NPs that largely facilitated drug formulation. A greater flexibility in the design of drug molecules themselves may also be facilitated following their incorporation into NPs, as drug properties (solubility, metabolism, plasma binding, biodistribution, target tissue accumulation) will no longer be constrained to the same extent by drug chemical composition, but also become in-part the function of the physicochemical properties of the NP. The combination of optimally designed drugs with optimally engineered polymeric NPs opens up the possibility of improved clinical outcomes that may not be achievable with the administration of drugs in their conventional form. In this critical review, we aim to provide insights into the design and development

Analysis of elliptically polarized maximally entangled states for bell inequality tests

NASA Astrophysics Data System (ADS)

Martin, A.; Smirr, J.-L.; Kaiser, F.; Diamanti, E.; Issautier, A.; Alibart, O.; Frey, R.; Zaquine, I.; Tanzilli, S.

2012-06-01

When elliptically polarized maximally entangled states are considered, i.e., states having a non random phase factor between the two bipartite polarization components, the standard settings used for optimal violation of Bell inequalities are no longer adapted. One way to retrieve the maximal amount of violation is to compensate for this phase while keeping the standard Bell inequality analysis settings. We propose in this paper a general theoretical approach that allows determining and adjusting the phase of elliptically polarized maximally entangled states in order to optimize the violation of Bell inequalities. The formalism is also applied to several suggested experimental phase compensation schemes. In order to emphasize the simplicity and relevance of our approach, we also describe an experimental implementation using a standard Soleil-Babinet phase compensator. This device is employed to correct the phase that appears in the maximally entangled state generated from a type-II nonlinear photon-pair source after the photons are created and distributed over fiber channels.

Stability region maximization by decomposition-aggregation method. [Skylab stability

NASA Technical Reports Server (NTRS)

Siljak, D. D.; Cuk, S. M.

1974-01-01

This work is to improve the estimates of the stability regions by formulating and resolving a proper maximization problem. The solution of the problem provides the best estimate of the maximal value of the structural parameter and at the same time yields the optimum comparison system, which can be used to determine the degree of stability of the Skylab. The analysis procedure is completely computerized, resulting in a flexible and powerful tool for stability considerations of large-scale linear as well as nonlinear systems.

Maximizing the Impact of e-Therapy and Serious Gaming: Time for a Paradigm Shift.

PubMed

Fleming, Theresa M; de Beurs, Derek; Khazaal, Yasser; Gaggioli, Andrea; Riva, Giuseppe; Botella, Cristina; Baños, Rosa M; Aschieri, Filippo; Bavin, Lynda M; Kleiboer, Annet; Merry, Sally; Lau, Ho Ming; Riper, Heleen

2016-01-01

Internet interventions for mental health, including serious games, online programs, and apps, hold promise for increasing access to evidence-based treatments and prevention. Many such interventions have been shown to be effective and acceptable in trials; however, uptake and adherence outside of trials is seldom reported, and where it is, adherence at least, generally appears to be underwhelming. In response, an international Collaboration On Maximizing the impact of E-Therapy and Serious Gaming (COMETS) was formed. In this perspectives' paper, we call for a paradigm shift to increase the impact of internet interventions toward the ultimate goal of improved population mental health. We propose four pillars for change: (1) increased focus on user-centered approaches, including both user-centered design of programs and greater individualization within programs, with the latter perhaps utilizing increased modularization; (2) Increased emphasis on engagement utilizing processes such as gaming, gamification, telepresence, and persuasive technology; (3) Increased collaboration in program development, testing, and data sharing, across both sectors and regions, in order to achieve higher quality, more sustainable outcomes with greater reach; and (4) Rapid testing and implementation, including the measurement of reach, engagement, and effectiveness, and timely implementation. We suggest it is time for researchers, clinicians, developers, and end-users to collaborate on these aspects in order to maximize the impact of e-therapies and serious gaming.

Maximizing the Impact of e-Therapy and Serious Gaming: Time for a Paradigm Shift

PubMed Central

Fleming, Theresa M.; de Beurs, Derek; Khazaal, Yasser; Gaggioli, Andrea; Riva, Giuseppe; Botella, Cristina; Baños, Rosa M.; Aschieri, Filippo; Bavin, Lynda M.; Kleiboer, Annet; Merry, Sally; Lau, Ho Ming; Riper, Heleen

2016-01-01

Internet interventions for mental health, including serious games, online programs, and apps, hold promise for increasing access to evidence-based treatments and prevention. Many such interventions have been shown to be effective and acceptable in trials; however, uptake and adherence outside of trials is seldom reported, and where it is, adherence at least, generally appears to be underwhelming. In response, an international Collaboration On Maximizing the impact of E-Therapy and Serious Gaming (COMETS) was formed. In this perspectives’ paper, we call for a paradigm shift to increase the impact of internet interventions toward the ultimate goal of improved population mental health. We propose four pillars for change: (1) increased focus on user-centered approaches, including both user-centered design of programs and greater individualization within programs, with the latter perhaps utilizing increased modularization; (2) Increased emphasis on engagement utilizing processes such as gaming, gamification, telepresence, and persuasive technology; (3) Increased collaboration in program development, testing, and data sharing, across both sectors and regions, in order to achieve higher quality, more sustainable outcomes with greater reach; and (4) Rapid testing and implementation, including the measurement of reach, engagement, and effectiveness, and timely implementation. We suggest it is time for researchers, clinicians, developers, and end-users to collaborate on these aspects in order to maximize the impact of e-therapies and serious gaming. PMID:27148094

The Maximal Oxygen Uptake Verification Phase: a Light at the End of the Tunnel?

PubMed

Schaun, Gustavo Z

2017-12-08

Commonly performed during an incremental test to exhaustion, maximal oxygen uptake (V̇O 2max ) assessment has become a recurring practice in clinical and experimental settings. To validate the test, several criteria were proposed. In this context, the plateau in oxygen uptake (V̇O 2 ) is inconsistent in its frequency, reducing its usefulness as a robust method to determine "true" V̇O 2max . Moreover, secondary criteria previously suggested, such as expiratory exchange ratios or percentages of maximal heart rate, are highly dependent on protocol design and often are achieved at V̇O 2 percentages well below V̇O 2max . Thus, an alternative method termed verification phase was proposed. Currently, it is clear that the verification phase can be a practical and sensitive method to confirm V̇O 2max ; however, procedures to conduct it are not standardized across the literature and no previous research tried to summarize how it has been employed. Therefore, in this review the knowledge on the verification phase was updated, while suggestions on how it can be performed (e.g. intensity, duration, recovery) were provided according to population and protocol design. Future studies should focus to identify a verification protocol feasible for different populations and to compare square-wave and multistage verification phases. Additionally, studies assessing verification phases in different patient populations are still warranted.

Cardiovascular consequences of bed rest: effect on maximal oxygen uptake

NASA Technical Reports Server (NTRS)

Convertino, V. A.

1997-01-01

Maximal oxygen uptake (VO2max) is reduced in healthy individuals confined to bed rest, suggesting it is independent of any disease state. The magnitude of reduction in VO2max is dependent on duration of bed rest and the initial level of aerobic fitness (VO2max), but it appears to be independent of age or gender. Bed rest induces an elevated maximal heart rate which, in turn, is associated with decreased cardiac vagal tone, increased sympathetic catecholamine secretion, and greater cardiac beta-receptor sensitivity. Despite the elevation in heart rate, VO2max is reduced primarily from decreased maximal stroke volume and cardiac output. An elevated ejection fraction during exercise following bed rest suggests that the lower stroke volume is not caused by ventricular dysfunction but is primarily the result of decreased venous return associated with lower circulating blood volume, reduced central venous pressure, and higher venous compliance in the lower extremities. VO2max, stroke volume, and cardiac output are further compromised by exercise in the upright posture. The contribution of hypovolemia to reduced cardiac output during exercise following bed rest is supported by the close relationship between the relative magnitude (% delta) and time course of change in blood volume and VO2max during bed rest, and also by the fact that retention of plasma volume is associated with maintenance of VO2max after bed rest. Arteriovenous oxygen difference during maximal exercise is not altered by bed rest, suggesting that peripheral mechanisms may not contribute significantly to the decreased VO2max. However reduction in baseline and maximal muscle blood flow, red blood cell volume, and capillarization in working muscles represent peripheral mechanisms that may contribute to limited oxygen delivery and, subsequently, lowered VO2max. Thus, alterations in cardiac and vascular functions induced by prolonged confinement to bed rest contribute to diminution of maximal oxygen uptake

Towards a new era in medicine: therapeutic genome editing.

PubMed

Porteus, Matthew H

2015-12-22

Genome editing is the process of precisely modifying the nucleotide sequence of the genome. It has provided a powerful approach to research questions but, with the development of a new set of tools, it is now possible to achieve frequencies of genome editing that are high enough to be useful therapeutically. Genome editing is being developed to treat not only monogenic diseases but also infectious diseases and diseases that have both a genetic and an environmental component.

Gamma loop contributing to maximal voluntary contractions in man.

PubMed Central

Hagbarth, K E; Kunesch, E J; Nordin, M; Schmidt, R; Wallin, E U

1986-01-01

A local anaesthetic drug was injected around the peroneal nerve in healthy subjects in order to investigate whether the resulting loss in foot dorsiflexion power in part depended on a gamma-fibre block preventing 'internal' activation of spindle end-organs and thereby depriving the alpha-motoneurones of an excitatory spindle inflow during contraction. The motor outcome of maximal dorsiflexion efforts was assessed by measuring firing rates of individual motor units in the anterior tibial (t.a.) muscle, mean voltage e.m.g. from the pretibial muscles, dorsiflexion force and range of voluntary foot dorsiflexion movements. The tests were performed with and without peripheral conditioning stimuli, such as agonist or antagonist muscle vibration or imposed stretch of the contracting muscles. As compared to control values of t.a. motor unit firing rates in maximal isometric voluntary contractions, the firing rates were lower and more irregular during maximal dorsiflexion efforts performed during subtotal peroneal nerve blocks. During the development of paresis a gradual reduction of motor unit firing rates was observed before the units ceased responding to the voluntary commands. This change in motor unit behaviour was accompanied by a reduction of the mean voltage e.m.g. activity in the pretibial muscles. At a given stage of anaesthesia the e.m.g. responses to maximal voluntary efforts were more affected than the responses evoked by electric nerve stimuli delivered proximal to the block, indicating that impaired impulse transmission in alpha motor fibres was not the sole cause of the paresis. The inability to generate high and regular motor unit firing rates during peroneal nerve blocks was accentuated by vibration applied over the antagonistic calf muscles. By contrast, in eight out of ten experiments agonist stretch or vibration caused an enhancement of motor unit firing during the maximal force tasks. The reverse effects of agonist and antagonist vibration on the

The Relationship of Religious Involvement to a Variety of Indicators of Cognitive Ability and Achievement in College Students.

ERIC Educational Resources Information Center

Zern, David S.

1987-01-01

Undergraduates reported anonymously their degree of religiousness, their Scholastic Aptitude Test (SAT) scores, and their grade point averages (GPAs). Found religiousness negatively related to ability, and not related to achievement. The students' capacity to maximize their potential, measured by the standard score difference between GPA and SAT,…

Prediction equations for maximal respiratory pressures of Brazilian adolescents.

PubMed

Mendes, Raquel E F; Campos, Tania F; Macêdo, Thalita M F; Borja, Raíssa O; Parreira, Verônica F; Mendonça, Karla M P P

2013-01-01

The literature emphasizes the need for studies to provide reference values and equations able to predict respiratory muscle strength of Brazilian subjects at different ages and from different regions of Brazil. To develop prediction equations for maximal respiratory pressures (MRP) of Brazilian adolescents. In total, 182 healthy adolescents (98 boys and 84 girls) aged between 12 and 18 years, enrolled in public and private schools in the city of Natal-RN, were evaluated using an MVD300 digital manometer (Globalmed®) according to a standardized protocol. Statistical analysis was performed using SPSS Statistics 17.0 software, with a significance level of 5%. Data normality was verified using the Kolmogorov-Smirnov test, and descriptive analysis results were expressed as the mean and standard deviation. To verify the correlation between the MRP and the independent variables (age, weight, height and sex), the Pearson correlation test was used. To obtain the prediction equations, stepwise multiple linear regression was used. The variables height, weight and sex were correlated to MRP. However, weight and sex explained part of the variability of MRP, and the regression analysis in this study indicated that these variables contributed significantly in predicting maximal inspiratory pressure, and only sex contributed significantly to maximal expiratory pressure. This study provides reference values and two models of prediction equations for maximal inspiratory and expiratory pressures and sets the necessary normal lower limits for the assessment of the respiratory muscle strength of Brazilian adolescents.

[Maximal isometric bite force and sports. Preliminary study].

PubMed

Sannajust, J P; Thiery, C; Poumarat, G; Vanneuville, G; Barthélémy, I; Mondie, J M

2002-06-01

The evaluation of the bite forces coupled with EMG activity of masseter muscles allows to point out temporo-mandibular joint disorders. The intense practice of sports induces stress which may affect the mandibular statics, due to an hyperfunction of the elevator masticatory muscles, especially the masseter muscles. This concept has led us to compare the maximum isometric bite forces of sedentary and physically trained subjects. The aim of this experimentation is to study the maximum isometric bite forces of the premolars, with a force transducer, for two groups of physically trained and sedentary volunteers (25 subjects), with distinction between male and female subjects. Subjects with normal denture and no temporo-mandibular joint disorder were retained. EMG and force recording were synchronized and recorded during 10 seconds of maximal contraction. The male subjects developed a maximal bite-force significantly higher (p < 0.05) compared to the female subjects. There is no significant difference between subjects practising a sport (at least 6 hours a week) and sedentary ones. The evolution of force during the contraction is different between sexes. EMG activity allowed to control that subjects developed a maximal force and an increase in muscular fatigability of physically active females compared to sedentary ones was noticed. The difference of maximal force between men and women is similar to the one found for the locomotor muscles. The analysis of the evolution of the force according to the contraction duration, might be linked to a different distribution of muscular fibers according to the sex. The practice of a sport might increase the fatigability of the masseter muscles and might be a factor inducing a muscular imbalance of the mandibular posture. But the relatively low number of subjects and the absence of well defined distinctions between different kinds of sport limit our conclusions.

Effect of sonic driving on maximal aerobic performance.

PubMed

Brilla, L.R.; Hatcher, Stefanie

2000-07-01

The study purpose was to evaluate antecedent binaural stimulation (ABS) on maximal aerobic physical performance. Twenty-two healthy, physically active subjects, 21-34 years, randomly received one of two preparations for each session: 15 min of quiet (BLANK) or percussive sonic driving at 200+ beats per minute (bpm) using a recorded compact disc (FSS, Mill Valley, CA) with headphones (ABS). Baseline HR, blood pressure (BP), and breathing frequency (f(br)) were obtained. During each condition, HR and f(br) were recorded at 3-min intervals. The graded maximal treadmill testing was administered immediately postpreparation session on separate days, with at least 48 h rest between sessions. There were significant differences in the antecedent period means between the two conditions, ABS (HR: 70.2 +/- 10.7 bpm; f(br): 18.5 +/- 3.3 br min(-1); BP: 134.5/87.9 +/- 13.6/9.2 mm Hg) and BLANK (HR: 64.6 +/- 7.9; f(br): 14.3 +/- 2.9; BP: 126.7/80.3 +/- 12.1/8.6). Differences were noted for each 3-min interval and pre- postantecedent period. The maximal graded exercise test (GXT) results showed that there was a small but significant (P < 0.05), increase in maximal VO(2) in the ABS (49.8 +/- 6.8 ml. kg(-1). min(-1)) vs. BLANK (46.7 +/- 8.7) conditions. Related to that finding was a slight increase (0.5 min) in time to exhaustion (P < 0.05). There were no significant differences in HR or RPE (P > 0.05). There may be a latency to ABS related to entrainment or imagery-enhanced warm-up. Am. J. Hum. Biol. 12:558-565, 2000. Copyright 2000 Wiley-Liss, Inc.

Laparohysteroscopy in female infertility: A diagnostic cum therapeutic tool in Indian setting

PubMed Central

Puri, Suman; Jain, Dinesh; Puri, Sandeep; Kaushal, Sandeep; Deol, Satjeet Kaur

2015-01-01

Aims: To evaluate the role of laparohysteroscopy in female infertility andto study the effect of therapeutic procedures in achieving fertility. Settings and Design: Patients with female infertility presenting to outpatient Department of Obstetrics and Gynecology were evaluated over a period of 18 months. Materials and Methods: Fifty consenting subjects excluding male factor infertility with normal hormonal profile and no contraindication to laparoscopy were subject to diagnostic laparoscopy and hysteroscopy. Statistical Analysis Used: T-test. Results: We studied 50 patients comprising of 24 (48%) cases of primary infertility and 26 (52%) patients of secondary infertility. The average age of active married life for 50 patients was between 8 and 9 years. In our study, the most commonly found pathologies were PCOD, endometroisis and tubal blockage. 11 (28.2) patients conceived after laparohysteroscopy followed by artificial reproductive techniques. Conclusions: This study demonstrates the benefit of laparohysteroscopy for diagnosis and as a therapeutic tool in patients with primary and secondary infertility. We were able to achieve a higher conception rate of 28.2%. PMID:25664268

Therapeutic apheresis for severe hypertriglyceridemia in pregnancy.

PubMed

Basar, Rafet; Uzum, Ayse Kubat; Canbaz, Bulent; Dogansen, Sema Ciftci; Kalayoglu-Besisik, Sevgi; Altay-Dadin, Senem; Aral, Ferihan; Ozbey, Nese Colak

2013-05-01

During pregnancy, a progressive increase in serum triglyceride (TG) and cholesterol levels is observed whereas TG levels mostly remain <300 mg/dl. In women with genetic forms of hypertriglyceridemia, pregnancy may cause extremely elevated TG levels leading to potentially life-threatening pancreatitis attacks and chylomicronemia syndrome. The only safe medical treatment option during pregnancy is ω-3 fatty acids, which have moderate TG lowering effects. Therapeutic apheresis could be used as primary treatment approach during pregnancy. We reported the effect of double filtration apheresis in one pregnant women with severe hypertriglyceridemia, therapeutic plasmapheresis and double filtration methods in the other severe hypertriglyceridemic pregnant woman; a 32-year-old pregnant woman (patient 1) with a history of hypertriglyceridemia-induced acute pancreatitis during pregnancy and a 30-year-old pregnant woman with extremely high TG levels (12,000 mg/dl) leading to chylomicronemia syndrome (patient 2). Medical nutrition therapy and ω-3 fatty acids were also provided. Double filtration apheresis (patient 1) and plasmapheresis + double filtration apheresis (patient 2) were used. When we calculated the TG levels before and after therapeutic apheresis, maximum decrease achieved with double filtration apheresis was 46.3 % for patient 1 and 37.3 % for patient 2. However, with plasmapheresis TG level declined by 72 % in patient 2. Plasmapheresis seemed to be more efficient to decrease TG levels. Iron deficiency anemia was the main complication apart from technical difficulties by lipemic obstruction of tubing system. Healthy babies were born. Delivery led to decreases in TG levels. It is concluded that during pregnancy therapeutic apheresis is an effective method to decrease extremely high TG levels and risks of its potentially life-threatening complications.

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions.

PubMed

Sofia, M Anthony; Rubin, David T

2017-04-01

The development of therapeutic antibodies represents a revolutionary change in medical therapy for digestive diseases. Beginning with the initial studies that confirmed the pathogenicity of cytokines in inflammatory bowel disease, the development and application of therapeutic antibodies brought challenges and insights into their potential and optimal use. Infliximab was the first biological drug approved for use in Crohn's disease and ulcerative colitis. The lessons learned from infliximab include the importance of immunogenicity and the influence of pharmacokinetics on disease response and outcomes. Building on this foundation, other therapeutic antibodies achieved approval for inflammatory bowel disease and many more are in development for several digestive diseases. In this review, we reflect on the history of therapeutic antibodies and discuss current practice and future directions for the field.

Cardiovascular Fitness and Maximal Heart Rate Differences Among Three Ethnic Groups.

ERIC Educational Resources Information Center

Farrell, S. W.

1988-01-01

Examination of differences in maximal heart rate and treadmill time among three ethnic groups revealed no significant age-adjusted differences among white, black, and Mexican-American males, and suggested that black females' lower maximal heart rate may be explained by their lower cardiovascular fitness level when compared to those of other…

Comparative analysis of success of psoriasis treatment with standard therapeutic modalities and balneotherapy.

PubMed

Baros, Duka Ninković; Gajanin, Vesna S; Gajanin, Radoslav B; Zrnić, Bogdan

2014-01-01

Psoriasis is a chronic, inflammatory, immune-mediated skin disease. In addition to standard therapeutic modalities (antibiotics, cytostatics, phototherapy, photochemotherapy and retinoids), nonstandard methods can be used in the treatment of psoriasis. This includes balneotherapy which is most commonly used in combination with therapeutic resources. The aim of this research was to determine the length of remission of psoriasis in patients treated with standard therapeutic modalities, balneotherapy, and combined treatment (standard therapeutic modalities and balneotherapy). The study analyzed 60 adult patients, of both sexes, with different clinical forms of psoriasis, who were divided into three groups according to the applied therapeutic modalities: the first group (treated with standard therapeutic modalities), the second group (treated with balneotherapy) and the third group (treated with combined therapy-standard methods therapy and balneotherapy). The Psoriasis Area and Severity Index was determined in first, third and sixth week of treatment for all patients. The following laboratory analysis were performed and monitored: C reactive protein, iron with total iron binding capacity, unsaturated iron binding capacity and ferritin, uric acid, rheumatoid factors and antibodies to streptolysin O in the first and sixth week of treatment. The average length of remission in patients treated with standard therapeutic modalities and in those treated with balneotherapy was 1.77 +/- 0.951 months and 1.79 +/- 0.918 months, respectively. There was a statistically significant difference in the duration of remission between the patients treated with combination therapy and patients treated with standard therapeutic modalities (p = 0.019) and balneotherapy (p = 0.032). The best results have been achieved when the combination therapy was administered.

Blood lactate clearance after maximal exercise depends on active recovery intensity.

PubMed

Devlin, J; Paton, B; Poole, L; Sun, W; Ferguson, C; Wilson, J; Kemi, O J

2014-06-01

High-intensity exercise is time-limited by onset of fatigue, marked by accumulation of blood lactate. This is accentuated at maximal, all-out exercise that rapidly accumulates high blood lactate. The optimal active recovery intensity for clearing lactate after such maximal, all-out exercise remains unknown. Thus, we studied the intensity-dependence of lactate clearance during active recovery after maximal exercise. We constructed a standardized maximal, all-out treadmill exercise protocol that predictably lead to voluntary exhaustion and blood lactate concentration>10 mM. Next, subjects ran series of all-out bouts that increased blood lactate concentration to 11.5±0.2 mM, followed by recovery exercises ranging 0% (passive)-100% of the lactate threshold. Repeated measurements showed faster lactate clearance during active versus passive recovery (P<0.01), and that active recovery at 60-100% of lactate threshold was more efficient for lactate clearance than lower intensity recovery (P<0.05). Active recovery at 80% of lactate threshold had the highest rate of and shortest time constant for lactate clearance (P<0.05), whereas the response during the other intensities was graded (100%=60%>40%>passive recovery, P<0.05). Active recovery after maximal all-out exercise clears accumulated blood lactate faster than passive recovery in an intensity-dependent manner, with maximum clearance occurring at active recovery of 80% of lactate threshold.

Cardio-Respiratory Responses to Maximal Work During Arm and Bicycle Ergometry.

ERIC Educational Resources Information Center

Israel, Richard G.; Hardison, George T.

This study compared cardio-respiratory responses during maximal arm work using a Monarch Model 880 Rehab Trainer to cardio-respiratory responses during maximal leg work on a Monarch Model 850 Bicycle Ergometer. Subjects for the investigation were 17 male university students ranging from 18 to 28 years of age. The specific variables compared…

A simple method for measurement of maximal downstroke power on friction-loaded cycle ergometer.

PubMed

Morin, Jean-Benoît; Belli, Alain

2004-01-01

The aim of this study was to propose and validate a post-hoc correction method to obtain maximal power values taking into account inertia of the flywheel during sprints on friction-loaded cycle ergometers. This correction method was obtained from a basic postulate of linear deceleration-time evolution during the initial phase (until maximal power) of a sprint and included simple parameters as flywheel inertia, maximal velocity, time to reach maximal velocity and friction force. The validity of this model was tested by comparing measured and calculated maximal power values for 19 sprint bouts performed by five subjects against 0.6-1 N kg(-1) friction loads. Non-significant differences between measured and calculated maximal power (1151+/-169 vs. 1148+/-170 W) and a mean error index of 1.31+/-1.20% (ranging from 0.09% to 4.20%) showed the validity of this method. Furthermore, the differences between measured maximal power and power neglecting inertia (20.4+/-7.6%, ranging from 9.5% to 33.2%) emphasized the usefulness of power correcting in studies about anaerobic power which do not include inertia, and also the interest of this simple post-hoc method.

Maximizing algebraic connectivity in air transportation networks

NASA Astrophysics Data System (ADS)

Wei, Peng

In air transportation networks the robustness of a network regarding node and link failures is a key factor for its design. An experiment based on the real air transportation network is performed to show that the algebraic connectivity is a good measure for network robustness. Three optimization problems of algebraic connectivity maximization are then formulated in order to find the most robust network design under different constraints. The algebraic connectivity maximization problem with flight routes addition or deletion is first formulated. Three methods to optimize and analyze the network algebraic connectivity are proposed. The Modified Greedy Perturbation Algorithm (MGP) provides a sub-optimal solution in a fast iterative manner. The Weighted Tabu Search (WTS) is designed to offer a near optimal solution with longer running time. The relaxed semi-definite programming (SDP) is used to set a performance upper bound and three rounding techniques are discussed to find the feasible solution. The simulation results present the trade-off among the three methods. The case study on two air transportation networks of Virgin America and Southwest Airlines show that the developed methods can be applied in real world large scale networks. The algebraic connectivity maximization problem is extended by adding the leg number constraint, which considers the traveler's tolerance for the total connecting stops. The Binary Semi-Definite Programming (BSDP) with cutting plane method provides the optimal solution. The tabu search and 2-opt search heuristics can find the optimal solution in small scale networks and the near optimal solution in large scale networks. The third algebraic connectivity maximization problem with operating cost constraint is formulated. When the total operating cost budget is given, the number of the edges to be added is not fixed. Each edge weight needs to be calculated instead of being pre-determined. It is illustrated that the edge addition and the

Optimal technique for maximal forward rotating vaults in men's gymnastics.

PubMed

Hiley, Michael J; Jackson, Monique I; Yeadon, Maurice R

2015-08-01

In vaulting a gymnast must generate sufficient linear and angular momentum during the approach and table contact to complete the rotational requirements in the post-flight phase. This study investigated the optimization of table touchdown conditions and table contact technique for the maximization of rotation potential for forwards rotating vaults. A planar seven-segment torque-driven computer simulation model of the contact phase in vaulting was evaluated by varying joint torque activation time histories to match three performances of a handspring double somersault vault by an elite gymnast. The closest matching simulation was used as a starting point to maximize post-flight rotation potential (the product of angular momentum and flight time) for a forwards rotating vault. It was found that the maximized rotation potential was sufficient to produce a handspring double piked somersault vault. The corresponding optimal touchdown configuration exhibited hip flexion in contrast to the hyperextended configuration required for maximal height. Increasing touchdown velocity and angular momentum lead to additional post-flight rotation potential. By increasing the horizontal velocity at table touchdown, within limits obtained from recorded performances, the handspring double somersault tucked with one and a half twists, and the handspring triple somersault tucked became theoretically possible. Copyright © 2015 Elsevier B.V. All rights reserved.

On the advancement of therapeutic penality: therapeutic authority, personality science and the therapeutic community.

PubMed

McBride, Ruari-Santiago

2017-09-01

In this article I examine the advancement of therapeutic penality in the UK, a penal philosophy that reimagines prison policy, practices and environments utilising psychological knowledge. Adopting a historical approach, I show how modern therapeutic penality is linked to the emergence of personality science in the nineteenth century and the development of the democratic therapeutic community (DTC) model in the twentieth century. I outline how at the turn of the twenty-first century a catalytic event generated a moral panic that led the British government to mobilise psychological knowledge and technologies in an attempt to manage dangerous people with severe personality disorder. Tracing subsequent developments, I argue psychological ways of talking, thinking and acting have obtained unparalleled salience in domains of penality and, in turn, radically transformed the conditions of imprisonment. © 2017 Foundation for the Sociology of Health & Illness.

[Bladder endometriosis. Diagnostic and therapeutic approximation].

PubMed

Monllor Gisbert, J; Merino Hernaez, C; Olivier Gómez, C; Carballido Rodríguez, J

1991-01-01

Endometriosis is defined by the presence of functionally active endometria in ectopic position; so when its clinical behaviour adopts the characteristics of tumoration, endometrioma is accepted as an alternative name. Location of this pathology in the urinary apparatus is uncommon in terms of incidence, since the bladder is a selected site. This condition implies a high morbidity rate because it requires a high level of suspicion in order to be diagnosed. It is acknowledged that no image study (CAT, Echography, MNR, etc.) is pathognomonic for endometriosis and it is necessary to perform endoscopy and biopsy to achieve a correct diagnosis. The paper includes the strategy to follow, both with regard to diagnosis and the current therapeutic approaches.

Therapeutic Fc-fusion proteins and peptides as successful alternatives to antibodies.

PubMed

Beck, Alain; Reichert, Janice M

2011-01-01

Therapeutic antibodies have captured substantial attention due to the relatively high rate at which these products reach marketing approval, and the subsequent commercial success they frequently achieve. In the 2000s, a total of 20 antibodies (18 full-length IgG and 2 Fab) were approved by the Food and Drug Administration (FDA) or European Medicines Agency (EMA). In the 2010s to date, an additional 3 antibodies (denosumab, belimumab, ipilimumab) have been approved and one antibody-drug conjugate (brentuximab vedotin) is undergoing regulatory review and may be approved in the US by August 30, 2011. However, a less heralded group of antibody-based therapeutics comprising proteins or peptides fused with an Fc is following the success of classical antibodies.

Optimal Energy Management for a Smart Grid using Resource-Aware Utility Maximization

NASA Astrophysics Data System (ADS)

Abegaz, Brook W.; Mahajan, Satish M.; Negeri, Ebisa O.

2016-06-01

Heterogeneous energy prosumers are aggregated to form a smart grid based energy community managed by a central controller which could maximize their collective energy resource utilization. Using the central controller and distributed energy management systems, various mechanisms that harness the power profile of the energy community are developed for optimal, multi-objective energy management. The proposed mechanisms include resource-aware, multi-variable energy utility maximization objectives, namely: (1) maximizing the net green energy utilization, (2) maximizing the prosumers' level of comfortable, high quality power usage, and (3) maximizing the economic dispatch of energy storage units that minimize the net energy cost of the energy community. Moreover, an optimal energy management solution that combines the three objectives has been implemented by developing novel techniques of optimally flexible (un)certainty projection and appliance based pricing decomposition in an IBM ILOG CPLEX studio. A real-world, per-minute data from an energy community consisting of forty prosumers in Amsterdam, Netherlands is used. Results show that each of the proposed mechanisms yields significant increases in the aggregate energy resource utilization and welfare of prosumers as compared to traditional peak-power reduction methods. Furthermore, the multi-objective, resource-aware utility maximization approach leads to an optimal energy equilibrium and provides a sustainable energy management solution as verified by the Lagrangian method. The proposed resource-aware mechanisms could directly benefit emerging energy communities in the world to attain their energy resource utilization targets.

Maximal Oxygen Uptake, Sweating and Tolerance to Exercise in the Heat

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Castle, B. L.; Ruff, W. K.

1972-01-01

The physiological mechanisms that facilitate acute acclimation to heat have not been fully elucidated, but the result is the establishment of a more efficient cardiovascular system to increase heat dissipation via increased sweating that allows the acclimated man to function with a cooler internal environment and to extend his performance. Men in good physical condition with high maximal oxygen uptakes generally acclimate to heat more rapidly and retain it longer than men in poorer condition. Also, upon first exposure trained men tolerate exercise in the heat better than untrained men. Both resting in heat and physical training in a cool environment confer only partial acclimation when first exposed to work in the heat. These observations suggest separate additive stimuli of metabolic heat from exercise and environmental heat to increase sweating during the acclimation process. However, the necessity of utilizing physical exercise during acclimation has been questioned. Bradbury et al. (1964) have concluded exercise has no effect on the course of heat acclimation since increased sweating can be induced by merely heating resting subjects. Preliminary evidence suggests there is a direct relationship between the maximal oxygen uptake and the capacity to maintain thermal regulation, particularly through the control of sweating. Since increased sweating is an important mechanism for the development of heat acclimation, and fit men have high sweat rates, it follows that upon initial exposure to exercise in the heat, men with high maximal oxygen uptakes should exhibit less strain than men with lower maximal oxygen uptakes. The purpose of this study was: (1) to determine if men with higher maximal oxygen uptakes exhibit greater tolerance than men with lower oxygen uptakes during early exposure to exercise in the heat, and (2) to investigate further the mechanism of the relationship between sweating and maximal work capacity.

Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi

PubMed Central

Suraweera, Amila; O’Byrne, Kenneth J.; Richard, Derek J.

2018-01-01

Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, HDACi have shown limited success in treating solid tumors. The combination of HDACi with standard chemotherapeutic drugs has demonstrated promising anticancer effects in both preclinical and clinical studies. In this review, we summarize the research thus far on HDACi in combination therapy, with other anticancer agents and their translation into preclinical and clinical studies. We additionally highlight the side effects associated with HDACi in cancer therapy and discuss potential biomarkers to either select or predict a patient’s response to these agents, in order to limit the off-target toxicity associated with HDACi. PMID:29651407

A Maximal Element Theorem in FWC-Spaces and Its Applications

PubMed Central

Hu, Qingwen; Miao, Yulin

2014-01-01

A maximal element theorem is proved in finite weakly convex spaces (FWC-spaces, in short) which have no linear, convex, and topological structure. Using the maximal element theorem, we develop new existence theorems of solutions to variational relation problem, generalized equilibrium problem, equilibrium problem with lower and upper bounds, and minimax problem in FWC-spaces. The results represented in this paper unify and extend some known results in the literature. PMID:24782672

Field use of maximal sprint speed by collared lizards (Crotaphytus collaris): compensation and sexual selection.

PubMed

Husak, Jerry F; Fox, Stanley F

2006-09-01

To understand how selection acts on performance capacity, the ecological role of the performance trait being measured must be determined. Knowing if and when an animal uses maximal performance capacity may give insight into what specific selective pressures may be acting on performance, because individuals are expected to use close to maximal capacity only in contexts important to survival or reproductive success. Furthermore, if an ecological context is important, poor performers are expected to compensate behaviorally. To understand the relative roles of natural and sexual selection on maximal sprint speed capacity we measured maximal sprint speed of collared lizards (Crotaphytus collaris) in the laboratory and field-realized sprint speed for the same individuals in three different contexts (foraging, escaping a predator, and responding to a rival intruder). Females used closer to maximal speed while escaping predators than in the other contexts. Adult males, on the other hand, used closer to maximal speed while responding to an unfamiliar male intruder tethered within their territory. Sprint speeds during foraging attempts were far below maximal capacity for all lizards. Yearlings appeared to compensate for having lower absolute maximal capacity by using a greater percentage of their maximal capacity while foraging and escaping predators than did adults of either sex. We also found evidence for compensation within age and sex classes, where slower individuals used a greater percentage of their maximal capacity than faster individuals. However, this was true only while foraging and escaping predators and not while responding to a rival. Collared lizards appeared to choose microhabitats near refugia such that maximal speed was not necessary to escape predators. Although natural selection for predator avoidance cannot be ruled out as a selective force acting on locomotor performance in collared lizards, intrasexual selection for territory maintenance may be more

Therapeutic risk management of clinical-legal dilemmas: should it be a core competency?

PubMed

Simon, Robert I; Shuman, Daniel W

2009-01-01

Therapeutic risk management of clinical-legal dilemmas achieves an optimal alignment between clinical competence and an understanding of legal concerns applicable to psychiatric practice. Understanding how psychiatry and law interact in frequently occurring clinical situations is essential for effective patient care. Successful management of clinical-legal dilemmas also avoids unnecessary, counterproductive defensive practices.

Reversible increase in maximal cortisol secretion rate in septic shock.

PubMed

Dorin, Richard I; Qualls, Clifford R; Torpy, David J; Schrader, Ronald M; Urban, Frank K

2015-03-01

Cortisol clearance is reduced in sepsis and may contribute to the development of impaired adrenocortical function that is thought to contribute to the pathophysiology of critical illness-related corticosteroid insufficiency. We sought to assess adrenocortical function using computer-assisted numerical modeling methodology to characterize and compare maximal cortisol secretion rate and free cortisol half-life in septic shock, sepsis, and healthy control subjects. Post hoc analysis of previously published total cortisol, free cortisol, corticosteroid-binding globulin, and albumin concentration data. Single academic medical center. Subjects included septic shock (n = 45), sepsis (n = 25), and healthy controls (n = 10). I.v. cosyntropin (250 μg). Solutions for maximal cortisol secretion rate and free cortisol half-life were obtained by least squares solution of simultaneous, nonlinear differential equations that account for free cortisol appearance and elimination as well as reversible binding to corticosteroid-binding globulin and albumin. Maximal cortisol secretion rate was significantly greater in septic shock (0.83 nM/s [0.44, 1.58 nM/s] reported as median [lower quartile, upper quartile]) compared with sepsis (0.51 nM/s [0.36, 0.62 nM/s]; p = 0.007) and controls (0.49 nM/s [0.42, 0.62 nM/s]; p = 0.04). The variance of maximal cortisol secretion rate in septic shock was also greater than that of sepsis or control groups (F test, p < 0.001). Free cortisol half-life was significantly increased in septic shock (4.6 min [2.2, 6.3 min]) and sepsis (3.0 min [2.3, 4.8 min] when compared with controls (2.0 min [1.2, 2.6 min]) (both p < 0.004). Results obtained by numerical modeling are consistent with comparable measures obtained by the gold standard stable isotope dilution method. Septic shock is associated with generally not only higher levels but also greater variance of maximal cortisol secretion rate when compared with control and sepsis groups. Additional studies

Structural biomechanics of the craniomaxillofacial skeleton under maximal masticatory loading: Inferences and critical analysis based on a validated computational model.

PubMed

Pakdel, Amir R; Whyne, Cari M; Fialkov, Jeffrey A

2017-06-01

The trend towards optimizing stabilization of the craniomaxillofacial skeleton (CMFS) with the minimum amount of fixation required to achieve union, and away from maximizing rigidity, requires a quantitative understanding of craniomaxillofacial biomechanics. This study uses computational modeling to quantify the structural biomechanics of the CMFS under maximal physiologic masticatory loading. Using an experimentally validated subject-specific finite element (FE) model of the CMFS, the patterns of stress and strain distribution as a result of physiological masticatory loading were calculated. The trajectories of the stresses were plotted to delineate compressive and tensile regimes over the entire CMFS volume. The lateral maxilla was found to be the primary vertical buttress under maximal bite force loading, with much smaller involvement of the naso-maxillary buttress. There was no evidence that the pterygo-maxillary region is a buttressing structure, counter to classical buttress theory. The stresses at the zygomatic sutures suggest that two-point fixation of zygomatic complex fractures may be sufficient for fixation under bite force loading. The current experimentally validated biomechanical FE model of the CMFS is a practical tool for in silico optimization of current practice techniques and may be used as a foundation for the development of design criteria for future technologies for the treatment of CMFS injury and disease. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Can artificial parthenogenesis sidestep ethical pitfalls in human therapeutic cloning? An historical perspective

PubMed Central

Fangerau, H

2005-01-01

The aim of regenerative medicine is to reconstruct tissue that has been lost or pathologically altered. Therapeutic cloning seems to offer a method of achieving this aim; however, the ethical debate surrounding human therapeutic cloning is highly controversial. Artificial parthenogenesis—obtaining embryos from unfertilised eggs—seems to offer a way to sidestep these ethical pitfalls. Jacques Loeb (1859–1924), the founding father of artificial parthogenesis, faced negative public opinion when he published his research in 1899. His research, the public's response to his findings, and his ethical foundations serve as an historical argument both for the communication of science and compromise in biological research. PMID:16319240

Therapeutic drug levels

MedlinePlus

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Decalogue of the Spanish Society of Arteriosclerosis to reduce therapeutic inertia.

PubMed

Blasco, Mariano; Pérez-Martínez, Pablo; Lahoz, Carlos

Therapeutic inertia (TI) is defined as the failure of the physician to initiate or intensify a treatment when the therapeutic goal has not been achieved. TI can be of 2types: inertia due to lack of prescription of drugs and inertia in the absence of control of a risk factor. The consequences of TI are poor control of risk factors, an increase in potentially preventable events and an increase in costs. There are factors of the doctor himself, the patient and the care organization that determine the presence of TI. Ten measures are proposed to reduce TI: to promote continuing education, to define clearly therapeutic objectives, to establish audits, to implement computerized medical records with alerts, to encourage research in this field, to disseminate clinical practice guidelines, to create motivational incentives, to organize care, to improve the doctor-patient relationship and to involve other health care providers. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

When Medicine Meets Engineering—Paradigm Shifts in Diagnostics and Therapeutics

PubMed Central

Wang, Hann; Silva, Aleidy; Ho, Chih-Ming

2013-01-01

During the last two decades, the manufacturing techniques of microfluidics-based devices have been phenomenally advanced, offering unlimited potential for bio-medical technologies. However, the direct applications of these technologies toward diagnostics and therapeutics are still far from maturity. The present challenges lay at the interfaces between the engineering systems and the biocomplex systems. A precisely designed engineering system with narrow dynamic range is hard to seamlessly integrate with the adaptive biological system in order to achieve the design goals. These differences remain as the roadblock between two fundamentally non-compatible systems. This paper will not extensively review the existing microfluidic sensors and actuators; rather, we will discuss the sources of the gaps for integration. We will also introduce system interface technologies for bridging the differences to lead toward paradigm shifts in diagnostics and therapeutics. PMID:26835672

On differential operators generating iterative systems of linear ODEs of maximal symmetry algebra

NASA Astrophysics Data System (ADS)

Ndogmo, J. C.

2017-06-01

Although every iterative scalar linear ordinary differential equation is of maximal symmetry algebra, the situation is different and far more complex for systems of linear ordinary differential equations, and an iterative system of linear equations need not be of maximal symmetry algebra. We illustrate these facts by examples and derive families of vector differential operators whose iterations are all linear systems of equations of maximal symmetry algebra. Some consequences of these results are also discussed.

Local Hamiltonians for maximally multipartite-entangled states

NASA Astrophysics Data System (ADS)

Facchi, P.; Florio, G.; Pascazio, S.; Pepe, F.

2010-10-01

We study the conditions for obtaining maximally multipartite-entangled states (MMESs) as nondegenerate eigenstates of Hamiltonians that involve only short-range interactions. We investigate small-size systems (with a number of qubits ranging from 3 to 5) and show some example Hamiltonians with MMESs as eigenstates.

Maximally Expressive Task Modeling

NASA Technical Reports Server (NTRS)

Japp, John; Davis, Elizabeth; Maxwell, Theresa G. (Technical Monitor)

2002-01-01

Planning and scheduling systems organize "tasks" into a timeline or schedule. The tasks are defined within the scheduling system in logical containers called models. The dictionary might define a model of this type as "a system of things and relations satisfying a set of rules that, when applied to the things and relations, produce certainty about the tasks that are being modeled." One challenging domain for a planning and scheduling system is the operation of on-board experiment activities for the Space Station. The equipment used in these experiments is some of the most complex hardware ever developed by mankind, the information sought by these experiments is at the cutting edge of scientific endeavor, and the procedures for executing the experiments are intricate and exacting. Scheduling is made more difficult by a scarcity of space station resources. The models to be fed into the scheduler must describe both the complexity of the experiments and procedures (to ensure a valid schedule) and the flexibilities of the procedures and the equipment (to effectively utilize available resources). Clearly, scheduling space station experiment operations calls for a "maximally expressive" modeling schema. Modeling even the simplest of activities cannot be automated; no sensor can be attached to a piece of equipment that can discern how to use that piece of equipment; no camera can quantify how to operate a piece of equipment. Modeling is a human enterprise-both an art and a science. The modeling schema should allow the models to flow from the keyboard of the user as easily as works of literature flowed from the pen of Shakespeare. The Ground Systems Department at the Marshall Space Flight Center has embarked on an effort to develop a new scheduling engine that is highlighted by a maximally expressive modeling schema. This schema, presented in this paper, is a synergy of technological advances and domain-specific innovations.

Influence of Lumber Volume Maximization on Value in Sawing Hardwood Sawlogs

Treesearch

Philip H. Steele; Francis G. Wagner; Lalit Kumar; Philip A. Araman

1992-01-01

Research based on applying volume-maximizing sawing solutions to idealized hardwood log forms has shown that average lumber yield can be increased by 6 percent. It is possible, however, that a lumber volume-maximizing solution may result in a decrease in lumber grade and a net reduction in total value of sawn lumber. The objective of this study was to determine the...

Characterization of maximally entangled two-qubit states via the Bell-Clauser-Horne-Shimony-Holt inequality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Zeqian

2004-08-01

Maximally entangled states should maximally violate the Bell inequality. It is proved that all two-qubit states that maximally violate the Bell-Clauser-Horne-Shimony-Holt inequality are exactly Bell states and the states obtained from them by local transformations. The proof is obtained by using the certain algebraic properties that Pauli's matrices satisfy. The argument is extended to the three-qubit system. Since all states obtained by local transformations of a maximally entangled state are equally valid entangled states, we thus give the characterizations of maximally entangled states in both the two-qubit and three-qubit systems in terms of the Bell inequality.

Stroke maximizing and high efficient hysteresis hybrid modeling for a rhombic piezoelectric actuator

NASA Astrophysics Data System (ADS)

Shao, Shubao; Xu, Minglong; Zhang, Shuwen; Xie, Shilin

2016-06-01

Rhombic piezoelectric actuator (RPA), which employs a rhombic mechanism to amplify the small stroke of PZT stack, has been widely used in many micro-positioning machineries due to its remarkable properties such as high displacement resolution and compact structure. In order to achieve large actuation range along with high accuracy, the stroke maximizing and compensation for the hysteresis are two concerns in the use of RPA. However, existing maximization methods based on theoretical model can hardly accurately predict the maximum stroke of RPA because of approximation errors that are caused by the simplifications that must be made in the analysis. Moreover, despite the high hysteresis modeling accuracy of Preisach model, its modeling procedure is trivial and time-consuming since a large set of experimental data is required to determine the model parameters. In our research, to improve the accuracy of theoretical model of RPA, the approximation theory is employed in which the approximation errors can be compensated by two dimensionless coefficients. To simplify the hysteresis modeling procedure, a hybrid modeling method is proposed in which the parameters of Preisach model can be identified from only a small set of experimental data by using the combination of discrete Preisach model (DPM) with particle swarm optimization (PSO) algorithm. The proposed novel hybrid modeling method can not only model the hysteresis with considerable accuracy but also significantly simplified the modeling procedure. Finally, the inversion of hysteresis is introduced to compensate for the hysteresis non-linearity of RPA, and consequently a pseudo-linear system can be obtained.

The results of therapeutic plasma exchange in patients with severe hyperthyroidism: a retrospective multicenter study.

PubMed

Keklik, Muzaffer; Kaynar, Leylagul; Yilmaz, Mehmet; Sivgin, Serdar; Solmaz, Musa; Pala, Cigdem; Aribas, Sulbiye; Akyol, Gulsah; Unluhizarci, Kursat; Cetin, Mustafa; Eser, Bulent; Unal, Ali

2013-06-01

Hyperthyroidism characterized by elevated serum levels of circulating thyroid hormones. The aim of hyperthyroidism treatment is to achieve a euthyroid state as soon as possible and to maintain euthyroid status. However, drug withdrawal and utilization of alternative therapies are needed in cases in which leucopenia or impairment in liver functions is observed during medical therapy. In the present study, we aimed to present our cases which underwent therapeutic plasma exchange (TPE) due to severe hyperthyroidism. The results of 22 patients who underwent therapeutic plasma exchange due to hyperthyroidism in Apheresis Units of Erciyes University and Gaziantep University, between 2006 and 2012, were retrospectively reviewed. These cases had severe thyrotoxic values despite anti-thyroid drug use. After TPE, we observed a significant decrease in free thyroxin (FT4) (p<0.001) and free triiodotyhronin (FT3) (p<0.004) levels. There was statistically significant increase in the mean values of TSH levels after TPE (p<0.001). Clinical improvement was achieved in hyperthyroidism by TPE in 20 cases (91%). Both FT3 and FT4 levels remained above the normal limits in two of 22 patients. TPE should be considered as an effective and safe therapeutic option to achieve euthyroid state before surgery or radioactive iodine treatment. TPE is a useful option in cases with severe hyperthyroidism unresponsive to anti-thyroid agents and in those with clinical manifestations of cardiac failure and in patients with severe adverse events during anti-thyroid therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

How collaboration in therapy becomes therapeutic: the therapeutic collaboration coding system.

PubMed

Ribeiro, Eugénia; Ribeiro, António P; Gonçalves, Miguel M; Horvath, Adam O; Stiles, William B

2013-09-01

The quality and strength of the therapeutic collaboration, the core of the alliance, is reliably associated with positive therapy outcomes. The urgent challenge for clinicians and researchers is constructing a conceptual framework to integrate the dialectical work that fosters collaboration, with a model of how clients make progress in therapy. We propose a conceptual account of how collaboration in therapy becomes therapeutic. In addition, we report on the construction of a coding system - the therapeutic collaboration coding system (TCCS) - designed to analyse and track on a moment-by-moment basis the interaction between therapist and client. Preliminary evidence is presented regarding the coding system's psychometric properties. The TCCS evaluates each speaking turn and assesses whether and how therapists are working within the client's therapeutic zone of proximal development, defined as the space between the client's actual therapeutic developmental level and their potential developmental level that can be reached in collaboration with the therapist. We applied the TCCS to five cases: a good and a poor outcome case of narrative therapy, a good and a poor outcome case of cognitive-behavioural therapy, and a dropout case of narrative therapy. The TCCS offers markers that may help researchers better understand the therapeutic collaboration on a moment-to-moment basis and may help therapists better regulate the relationship. © 2012 The British Psychological Society.

Cancer Terminator Viruses and Approaches for Enhancing Therapeutic Outcomes

PubMed Central

Das, Swadesh K.; Sarkar, Siddik; Dash, Rupesh; Dent, Paul; Wang, Xiang-Yang; Sarkar, Devanand; Fisher, Paul B.

2015-01-01

No single or combinatorial therapeutic approach has proven effective in decreasing morbidity or engendering a cure of metastatic cancer. In principle, conditionally replication-competent adenoviruses that induce tumor oncolysis through cancer-specific replication hold promise for cancer therapy. However, a single-agent approach may not be adequate to completely eradicate cancer in a patient because most cancers arise from abnormalities in multiple genetic and signal transduction pathways and targeting disseminated metastases is difficult to achieve. Based on these considerations, a novel class of cancer destroying adenoviruses have been produced, cancer terminator viruses (CTVs), in which cancer-specific replication is controlled by the progression-elevated gene-3 promoter and replicating viruses produce a second transgene encoding an apoptosis-inducing and immunomodulatory cytokine, either melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) or interferon-γ. This review focuses on these viruses and ways to improve their delivery systemically and enhance their therapeutic efficacy. PMID:23021240

The behavioral economics of consumer brand choice: patterns of reinforcement and utility maximization.

PubMed

Foxall, Gordon R; Oliveira-Castro, Jorge M; Schrezenmaier, Teresa C

2004-06-30

Purchasers of fast-moving consumer goods generally exhibit multi-brand choice, selecting apparently randomly among a small subset or "repertoire" of tried and trusted brands. Their behavior shows both matching and maximization, though it is not clear just what the majority of buyers are maximizing. Each brand attracts, however, a small percentage of consumers who are 100%-loyal to it during the period of observation. Some of these are exclusively buyers of premium-priced brands who are presumably maximizing informational reinforcement because their demand for the brand is relatively price-insensitive or inelastic. Others buy exclusively the cheapest brands available and can be assumed to maximize utilitarian reinforcement since their behavior is particularly price-sensitive or elastic. Between them are the majority of consumers whose multi-brand buying takes the form of selecting a mixture of economy -- and premium-priced brands. Based on the analysis of buying patterns of 80 consumers for 9 product categories, the paper examines the continuum of consumers so defined and seeks to relate their buying behavior to the question of how and what consumers maximize.

Potential benefits of maximal exercise just prior to return from weightlessness

NASA Technical Reports Server (NTRS)

Convertino, Victor A.

1987-01-01

The purpose of this study was to determine whether performance of a single maximal bout of exercise during weightlessness within hours of return to earth would enhance recovery of aerobic fitness and physical work capacities under a 1G environment. Ten healthy men were subjected to a 10-d bedrest period in the 6-deg headdown position. A graded maximal supine cycle ergometer test was performed before and at the end of bedrest to simulate exercise during weightlessness. Following 3 h of resumption of the upright posture, a second maximal exercise test was performed on a treadmill to measure work capacity under conditions of 1G. Compared to before bedrest, peak oxygen consumption, V(O2), decreased by 8.7 percent and peak heart rate (HR) increased by 5.6 percent in the supine cycle test at the end of bedrest. However, there were no significant changes in peak V(O2) and peak HR in the upright treadmill test following bedrest. These data suggest that one bout of maximal leg exercise prior to return from 10 d of weightlessness may be adequate to restore preflight aerobic fitness and physical work capacity.

Maximizing Your Investment in Building Automation System Technology.

ERIC Educational Resources Information Center

Darnell, Charles

2001-01-01

Discusses how organizational issues and system standardization can be important factors that determine an institution's ability to fully exploit contemporary building automation systems (BAS). Further presented is management strategy for maximizing BAS investments. (GR)

Therapeutic Enzymes: Applications and Approaches to Pharmacological Improvement.

PubMed

Yari, Maryam; Ghoshoon, Mohammad B; Vakili, Bahareh; Ghasemi, Younes

2017-01-01

Among therapeutic proteins, enzymes represent small and of course profitable market. They can be used to treat important, rare, and deadly diseases. Enzyme therapy is the only available treatment for certain disorders. Here, pharmaceutical enzymes are reviewed. They are categorized in four main groups, enzymes in replacement therapy, enzymes in cancer treatment, enzymes for fibrinolysis, and finally enzymes that are used topically for various treatments. Furthermore, enzyme gene therapy and future perspective of therapeutic enzymes are mentioned in brief. There are many important approved enzymes in pharmaceutical market. Several approaches such as point mutation, fusion protein designing, glycoengineering, and PEGylation were used to achieve improved enzymes. Although sometimes enzymes were engineered to facilitate production and purification process, appropriate delivery to target sites, extending half-life, and reducing immunogenicity are among the main goals of engineering approaches. Overall, enzymes play a critical role in treatment of common and rare diseases. Evaluation of new enzymes as well as improvement of approved enzymes are of the most important challenges in biotechnology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Acceptability of locally produced ready-to-use therapeutic foods in Ethiopia, Ghana, Pakistan and India

USDA-ARS?s Scientific Manuscript database

Successful treatment of severe acute malnutrition has been achieved with ready-to-use therapeutic food (RUTF), but only 15% of children with severe acute malnutrition receive RUTF. The objective of this study was to determine whether new formulations of RUTF produced using locally available ingredie...

[Therapeutic nursing: a systematic review].

PubMed

Lautenschläger, S; Müller, C; Immenschuh, U; Muser, J; Behrens, J

2014-08-01

For some years therapeutic service catalogues have been established in medical rehabilitation which have broadened our previous understanding of nursing actions. Currently, therapeutic nursing plays a prominent role in neurological early rehabilitation because the operations and procedures coding system (OPS) 8-552 within the DRG-System (Diagnosis Related Groups) states that therapeutic nursing must be carried out by specially trained nursing personnel. This requirement leads to inconsistencies in nursing practice and the medical service of the health insurance (MDK) since a definition of therapeutic nursing is lacking. A previous review of therapeutic nursing in 2003 focused primarily on the development of the therapeutic nursing role, but not on therapeutic nursing itself. The following article contains the first systematic review of the current state of research regarding a definition of therapeutic nursing. For this purpose, a systematic study was conducted to examine if there are, nationally or internationally, any definitions of therapeutic nursing and to identify what the therapeutic aspects of nursing are. The research included following database; Medline, Cinahl and Embase. Additionally, a research by hand of several German journals as well as textbooks and specialized literature was carried out. 5 studies were selected which define the term "therapeutic nursing". Among these are one review, one primary study, one theoretical discussion and one dissertation. Further twenty four studies were identified which do not define the term, but are closely related to the subject, and use or characterize the term in various contexts. The publications examined provided indications of duties, interventions and roles nurses should perform, but not how to carry these out, nor what is therapeutic about the nursing. At the same time, the low number of studies reveals that therapeutic nursing has barely been examined and demonstrates the lack of theoretically grounding

High Intensity Interval Training for Maximizing Health Outcomes.

PubMed

Karlsen, Trine; Aamot, Inger-Lise; Haykowsky, Mark; Rognmo, Øivind

Regular physical activity and exercise training are important actions to improve cardiorespiratory fitness and maintain health throughout life. There is solid evidence that exercise is an effective preventative strategy against at least 25 medical conditions, including cardiovascular disease, stroke, hypertension, colon and breast cancer, and type 2 diabetes. Traditionally, endurance exercise training (ET) to improve health related outcomes has consisted of low- to moderate ET intensity. However, a growing body of evidence suggests that higher exercise intensities may be superior to moderate intensity for maximizing health outcomes. The primary objective of this review is to discuss how aerobic high-intensity interval training (HIIT) as compared to moderate continuous training may maximize outcomes, and to provide practical advices for successful clinical and home-based HIIT. Copyright © 2017. Published by Elsevier Inc.

Therapeutic burst-suppression coma in pediatric febrile refractory status epilepticus.

PubMed

Lin, Jainn-Jim; Chou, Cheng-Che; Lan, Shih-Yun; Hsiao, Hsiang-Ju; Wang, Yu; Chan, Oi-Wa; Hsia, Shao-Hsuan; Wang, Huei-Shyong; Lin, Kuang-Lin

2017-09-01

Evidence for the beneficial effect of therapeutic burst-suppression coma in pediatric patients with febrile refractory status epilepticus is limited, and the clinical outcomes of this treatment strategy are largely unknown. Therefore, the aim of this study was to explore the outcomes of therapeutic burst-suppression coma in a series of children with febrile refractory status epilepticus. We retrospectively reviewed consecutive pediatric patients with febrile refractory status epilepticus admitted to our pediatric intensive care unit between January 2000 and December 2013. The clinical characteristics were analyzed. Thirty-five patients (23 boys; age range: 1-18years) were enrolled, of whom 28 (80%) developed super-refractory status epilepticus. All of the patients received the continuous administration of intravenous antiepileptic drugs for febrile refractory status epilepticus, and 26 (74.3%) achieved therapeutic burst-suppression coma. All of the patients received mechanical ventilatory support, and 26 (74.3%) received inotropic agents. Eight (22.9%) patients died within 1month. The neurologically functional outcomes at 6months were good in six (27.3%) of the 22 survivors, of whom two returned to clinical baseline. The patients with therapeutic burst-suppression coma were significantly associated with hemodynamic support than the patients with electrographic seizures control (p=0.03), and had a trend of higher 1-month mortality rate, worse 6months outcomes, and a longer duration of hospitalization. Our results suggest that therapeutic burst-suppression coma to treat febrile refractory status epilepticus may lead to an increased risk of hemodynamic instability and a trend of worse outcomes. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Relationships between maximal anaerobic power of the arms and legs and javelin performance.

PubMed

Bouhlel, E; Chelly, M S; Tabka, Z; Shephard, R

2007-06-01

The aim of this study was to examine relationships between maximal anaerobic power, as measured by leg and arm force-velocity tests, estimates of local muscle volume and javelin performance. Ten trained national level male javelin throwers (mean age 19.6+/- 2 years) participated in this study. Maximal anaerobic power, maximal force and maximal velocity were measured during leg (Wmax-L) and arm (Wmax-A) force-velocity tests, performed on appropriately modified forms of Monark cycle ergometer. Estimates of leg and arm muscle volume were made using a standard anthropometric kit. Maximal force of the leg (Fmax-L) was significantly correlated with estimated leg muscle volume (r=0.71, P<0.05). Wmax-L and Wmax-A were both significantly correlated with javelin performance (r=0.76, P<0.01; r=0.71, P <0.05, respectively). Maximal velocity of the leg (Vmax-L) was also significantly correlated with throwing performance (r=0.83; P<0.001). Wmax of both legs and arms were significantly correlated with javelin performance, the closest correlation being for Wmax-L; this emphasizes the importance of the leg muscles in this sport. Fmax-L and Vmax-L were related to muscle volume and to javelin performance, respectively. Force-velocity testing may have value in regulating conditioning and rehabilitation in sports involving throwing.

Silk hydrogels for sustained ocular delivery of anti-vascular endothelial growth factor (anti-VEGF) therapeutics.

PubMed

Lovett, Michael L; Wang, Xiaoqin; Yucel, Tuna; York, Lyndsey; Keirstead, Marc; Haggerty, Linda; Kaplan, David L

2015-09-01

Silk hydrogels were formulated with anti-vascular endothelial growth factor (anti-VEGF) therapeutics for sustained ocular drug delivery. Using silk fibroin as a vehicle for delivery, bevacizumab-loaded hydrogel formulations demonstrated sustained release of 3 months or greater in experiments in vitro as well as in vivo using an intravitreal injection model in Dutch-belted rabbits. Using both standard dose (1.25mg bevacizumab/50 μL injection) and high dose (5.0mg bevacizumab/50 μL injection) hydrogel formulations, release concentrations were achieved at day 90 that were equivalent or greater than those achieved at day 30 with the positive standard dose control (single injection (50 μL) of 1.25mg bevacizumab solution), which is estimated to be the therapeutic threshold based on the current dosage administration schedule of 1 injection/month. These gels also demonstrated signs of biodegradation after 3 months, suggesting that repeated injections may be possible (e.g., one injection every 3-6 months or longer). Due to its pharmacokinetic and biodegradation profiles, this delivery system may be used to reduce the frequency of dosing for patients currently enduring treatment using bevacizumab or other anti-VEGF therapeutics. Copyright © 2015 Elsevier B.V. All rights reserved.

Maximizing the probability of satisfying the clinical goals in radiation therapy treatment planning under setup uncertainty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fredriksson, Albin, E-mail: albin.fredriksson@raysearchlabs.com; Hårdemark, Björn; Forsgren, Anders

2015-07-15

Purpose: This paper introduces a method that maximizes the probability of satisfying the clinical goals in intensity-modulated radiation therapy treatments subject to setup uncertainty. Methods: The authors perform robust optimization in which the clinical goals are constrained to be satisfied whenever the setup error falls within an uncertainty set. The shape of the uncertainty set is included as a variable in the optimization. The goal of the optimization is to modify the shape of the uncertainty set in order to maximize the probability that the setup error will fall within the modified set. Because the constraints enforce the clinical goalsmore » to be satisfied under all setup errors within the uncertainty set, this is equivalent to maximizing the probability of satisfying the clinical goals. This type of robust optimization is studied with respect to photon and proton therapy applied to a prostate case and compared to robust optimization using an a priori defined uncertainty set. Results: Slight reductions of the uncertainty sets resulted in plans that satisfied a larger number of clinical goals than optimization with respect to a priori defined uncertainty sets, both within the reduced uncertainty sets and within the a priori, nonreduced, uncertainty sets. For the prostate case, the plans taking reduced uncertainty sets into account satisfied 1.4 (photons) and 1.5 (protons) times as many clinical goals over the scenarios as the method taking a priori uncertainty sets into account. Conclusions: Reducing the uncertainty sets enabled the optimization to find better solutions with respect to the errors within the reduced as well as the nonreduced uncertainty sets and thereby achieve higher probability of satisfying the clinical goals. This shows that asking for a little less in the optimization sometimes leads to better overall plan quality.« less

Utilization of diagnostic ultrasound and intravenous lipid-encapsulated perfluorocarbons in non-invasive targeted cardiovascular therapeutics.

PubMed

Porter, Thomas R; Choudhury, Songita A; Xie, Feng

2016-01-01

Diagnostic ultrasound (DUS) pressures have the ability to induce inertial cavitation (IC) of systemically administered microbubbles; this bioeffect has many diagnostic and therapeutic implications in cardiovascular care. Diagnostically, commercially available lipid-encapsulated perfluorocarbons (LEP) can be utilized to improve endocardial and vascular border delineation as well as assess myocardial perfusion. Therapeutically, the liquid jets induced by IC can alter endothelial function and dissolve thrombi within the immediate vicinity of the cavitating microbubbles. The cavitating LEP can also result in the localized release of any bound therapeutic substance at the site of insonation. DUS-induced IC has been tested in pre-clinical studies to determine what effect it has on acute vascular and microvascular thrombosis as well as nitric oxide (NO) release. These pre-clinical studies have consistently shown that DUS-induced IC of LEP is effective in restoring coronary vascular and microvascular flow in acute ST segment elevation myocardial infarction (STEMI), with microvascular flow improving even if upstream large vessel flow has not been achieved. The initial clinical trials examining the efficacy of short pulse duration DUS high mechanical index impulses in patients with STEMI are underway, and preliminary studies have suggested that earlier epicardial vessel recanalization can be achieved prior to arriving in the cardiac catheterization laboratory. DUS high mechanical index impulses have also been effective in pre-clinical studies for targeting DNA delivery that has restored islet cell function in type I diabetes and restored vascular flow in the extremities downstream from a peripheral vascular occlusion. Improvements in this technique will come from three dimensional arrays for therapeutic applications, more automated delivery techniques that can be applied in the field, and use of submicron-sized acoustically activated LEP droplets that may better permeate the

Future research and therapeutic applications of human stem cells: general, regulatory, and bioethical aspects.

PubMed

Liras, Antonio

2010-12-10

There is much to be investigated about the specific characteristics of stem cells and about the efficacy and safety of the new drugs based on this type of cells, both embryonic as adult stem cells, for several therapeutic indications (cardiovascular and ischemic diseases, diabetes, hematopoietic diseases, liver diseases). Along with recent progress in transference of nuclei from human somatic cells, as well as iPSC technology, has allowed availability of lineages of all three germ layers genetically identical to those of the donor patient, which permits safe transplantation of organ-tissue-specific adult stem cells with no immune rejection. The main objective is the need for expansion of stem cell characteristics to maximize stem cell efficacy (i.e. the proper selection of a stem cell) and the efficacy (maximum effect) and safety of stem cell derived drugs. Other considerations to take into account in cell therapy will be the suitability of infrastructure and technical staff, biomaterials, production costs, biobanks, biosecurity, and the biotechnological industry. The general objectives in the area of stem cell research in the next few years, are related to identification of therapeutic targets and potential therapeutic tests, studies of cell differentiation and physiological mechanisms, culture conditions of pluripotent stem cells and efficacy and safety tests for stem cell-based drugs or procedures to be performed in both animal and human models in the corresponding clinical trials. A regulatory framework will be required to ensure patient accessibility to products and governmental assistance for their regulation and control. Bioethical aspects will be required related to the scientific and therapeutic relevance and cost of cryopreservation over time, but specially with respect to embryos which may ultimately be used for scientific uses of research as source of embryonic stem cells, in which case the bioethical conflict may be further aggravated.

Endurance training and maximal oxygen consumption with ageing: Role of maximal cardiac output and oxygen extraction.

PubMed

Montero, David; Díaz-Cañestro, Candela

2016-05-01

The increase in maximal oxygen consumption (VO2max) with endurance training is associated with that of maximal cardiac output (Qmax), but not oxygen extraction, in young individuals. Whether such a relationship is altered with ageing remains unclear. Therefore, we sought systematically to review and determine the effect of endurance training on and the associations among VO2max, Qmax and arteriovenous oxygen difference at maximal exercise (Ca-vO2max) in healthy aged individuals. We conducted a systematic search of MEDLINE, Scopus and Web of Science, from their inceptions until May 2015 for articles assessing the effect of endurance training lasting 3 weeks or longer on VO2max and Qmax and/or Ca-vO2max in healthy middle-aged and/or older individuals (mean age ≥40 years). Meta-analyses were performed to determine the standardised mean difference (SMD) in VO2max, Qmax and Ca-vO2max between post and pre-training measurements. Subgroup and meta-regression analyses were used to evaluate the associations among SMDs and potential moderating factors. Sixteen studies were included after systematic review, comprising a total of 153 primarily untrained healthy middle-aged and older subjects (mean age 42-71 years). Endurance training programmes ranged from 8 to 52 weeks of duration. After data pooling, VO2max (SMD 0.89; P < 0.0001) and Qmax (SMD 0.61; P < 0.0001) were increased after endurance training; no heterogeneity among studies was detected. Ca-vO2max was only increased with endurance training interventions lasting more than 12 weeks (SMD 0.62; P = 0.001). In meta-regression, the SMD in Qmax was positively associated with the SMD in VO2max (B = 0.79, P = 0.04). The SMD in Ca-vO2max was not associated with the SMD in VO2max (B = 0.09, P = 0.84). The improvement in VO2max following endurance training is a linear function of Qmax, but not Ca-vO2max, through healthy ageing. © The European Society of Cardiology 2015.

Current Status of Dengue Therapeutics Research and Development

PubMed Central

Ooi, Eng Eong; Vasudevan, Subhash G.

2017-01-01

Abstract Dengue is a significant global health problem. Even though a vaccine against dengue is now available, which is a notable achievement, its long-term protective efficacy against each of the 4 dengue virus serotypes remains to be definitively determined. Consequently, drugs directed at the viral targets or critical host mechanisms that can be used safely as prophylaxis or treatment to effectively ameliorate disease or reduce disease severity and fatalities are still needed to reduce the burden of dengue. This review will provide a brief account of the status of therapeutics research and development for dengue. PMID:28403438

Maximal muscular vascular conductances during whole body upright exercise in humans

PubMed Central

Calbet, J A L; Jensen-Urstad, M; van Hall, G; Holmberg, H -C; Rosdahl, H; Saltin, B

2004-01-01

That muscular blood flow may reach 2.5 l kg−1 min−1 in the quadriceps muscle has led to the suggestion that muscular vascular conductance must be restrained during whole body exercise to avoid hypotension. The main aim of this study was to determine the maximal arm and leg muscle vascular conductances (VC) during leg and arm exercise, to find out if the maximal muscular vasodilatory response is restrained during maximal combined arm and leg exercise. Six Swedish elite cross-country skiers, age (mean ± s.e.m.) 24 ± 2 years, height 180 ± 2 cm, weight 74 ± 2 kg, and maximal oxygen uptake (V̇O2,max) 5.1 ± 0.1 l min−1 participated in the study. Femoral and subclavian vein blood flows, intra-arterial blood pressure, cardiac output, as well as blood gases in the femoral and subclavian vein, right atrium and femoral artery were determined during skiing (roller skis) at ∼76% of V̇O2,max and at V̇O2,max with different techniques: diagonal stride (combined arm and leg exercise), double poling (predominantly arm exercise) and leg skiing (predominantly leg exercise). During submaximal exercise cardiac output (26–27 l min−1), mean blood pressure (MAP) (∼87 mmHg), systemic VC, systemic oxygen delivery and pulmonary V̇O2 (∼4 l min−1) attained similar values regardless of exercise mode. The distribution of cardiac output was modified depending on the musculature engaged in the exercise. There was a close relationship between VC and V̇O2 in arms (r = 0.99, P < 0.001) and legs (r = 0.98, P < 0.05). Peak arm VC (63.7 ± 5.6 ml min−1 mmHg−1) was attained during double poling, while peak leg VC was reached at maximal exercise with the diagonal technique (109.8 ± 11.5 ml min−1 mmHg−1) when arm VC was 38.8 ± 5.7 ml min−1 mmHg−1. If during maximal exercise arms and legs had been vasodilated to the observed maximal levels then mean arterial pressure would have dropped at least to 75–77 mmHg in our experimental conditions. It is concluded that

Challenges and Achievements in Prevention and Treatment of Smallpox

PubMed Central

Melamed, Sharon; Israely, Tomer; Paran, Nir

2018-01-01

Declaration of smallpox eradication by the WHO in 1980 led to discontinuation of the worldwide vaccination campaign. The increasing percentage of unvaccinated individuals, the existence of its causative infectious agent variola virus (VARV), and the recent synthetic achievements increase the threat of intentional or accidental release and reemergence of smallpox. Control of smallpox would require an emergency vaccination campaign, as no other protective measure has been approved to achieve eradication and ensure worldwide protection. Experimental data in surrogate animal models support the assumption, based on anecdotal, uncontrolled historical data, that vaccination up to 4 days postexposure confers effective protection. The long incubation period, and the uncertainty of the exposure status in the surrounding population, call for the development and evaluation of safe and effective methods enabling extension of the therapeutic window, and to reduce the disease manifestations and vaccine adverse reactions. To achieve these goals, we need to evaluate the efficacy of novel and already licensed vaccines as a sole treatment, or in conjunction with immune modulators and antiviral drugs. In this review, we address the available data, recent achievements, and open questions. PMID:29382130

Therapeutic friendliness and the development of therapeutic leverage by mental health nurses in community rehabilitation settings.

PubMed

Gardner, Andrew

2010-01-01

In a world dominated by technology and driven by fiscal policy emphasis, the therapeutic relationship as a healing modality is still a central theme to mental health nurses (MHN) in their everyday work. This research, as part of a PhD program, used a constructivist grounded theory approach to explore the process of therapeutic relationships and professional boundaries. The current paper outlines how therapeutic friendliness provides a connection for the therapeutic relationship to develop but in doing so requires a balancing of the therapeutic relationship and constant maintenance of the professional boundary. The authors also discuss how community mental health nurses (CMHN) invest in the therapeutic relationship in order to develop a therapeutic alliance and how the alliance between the CMHN and the client facilitates the use of therapeutic leverage applied by the CMHN as part of the therapeutic process.

Quantum Tasks with Non-maximally Quantum Channels via Positive Operator-Valued Measurement

NASA Astrophysics Data System (ADS)

Peng, Jia-Yin; Luo, Ming-Xing; Mo, Zhi-Wen

2013-01-01

By using a proper positive operator-valued measure (POVM), we present two new schemes for probabilistic transmission with non-maximally four-particle cluster states. In the first scheme, we demonstrate that two non-maximally four-particle cluster states can be used to realize probabilistically sharing an unknown three-particle GHZ-type state within either distant agent's place. In the second protocol, we demonstrate that a non-maximally four-particle cluster state can be used to teleport an arbitrary unknown multi-particle state in a probabilistic manner with appropriate unitary operations and POVM. Moreover the total success probability of these two schemes are also worked out.

Some methods for achieving more efficient performance of fuel assemblies

NASA Astrophysics Data System (ADS)

Boltenko, E. A.

2014-07-01

More efficient operation of reactor plant fuel assemblies can be achieved through the use of new technical solutions aimed at obtaining more uniform distribution of coolant over the fuel assembly section, more intense heat removal on convex heat-transfer surfaces, and higher values of departure from nucleate boiling ratio (DNBR). Technical solutions using which it is possible to obtain more intense heat removal on convex heat-transfer surfaces and higher DNBR values in reactor plant fuel assemblies are considered. An alternative heat removal arrangement is described using which it is possible to obtain a significantly higher power density in a reactor plant and essentially lower maximal fuel rod temperature.

Maximally Expressive Modeling

NASA Technical Reports Server (NTRS)

Jaap, John; Davis, Elizabeth; Richardson, Lea

2004-01-01

Planning and scheduling systems organize tasks into a timeline or schedule. Tasks are logically grouped into containers called models. Models are a collection of related tasks, along with their dependencies and requirements, that when met will produce the desired result. One challenging domain for a planning and scheduling system is the operation of on-board experiments for the International Space Station. In these experiments, the equipment used is among the most complex hardware ever developed; the information sought is at the cutting edge of scientific endeavor; and the procedures are intricate and exacting. Scheduling is made more difficult by a scarcity of station resources. The models to be fed into the scheduler must describe both the complexity of the experiments and procedures (to ensure a valid schedule) and the flexibilities of the procedures and the equipment (to effectively utilize available resources). Clearly, scheduling International Space Station experiment operations calls for a maximally expressive modeling schema.

Strong correlation of maximal squat strength with sprint performance and vertical jump height in elite soccer players

PubMed Central

Wisloff, U; Castagna, C; Helgerud, J; Jones, R; Hoff, J

2004-01-01

Background: A high level of strength is inherent in elite soccer play, but the relation between maximal strength and sprint and jumping performance has not been studied thoroughly. Objective: To determine whether maximal strength correlates with sprint and vertical jump height in elite male soccer players. Methods: Seventeen international male soccer players (mean (SD) age 25.8 (2.9) years, height 177.3 (4.1) cm, weight 76.5 (7.6) kg, and maximal oxygen uptake 65.7 (4.3) ml/kg/min) were tested for maximal strength in half squats and sprinting ability (0–30 m and 10 m shuttle run sprint) and vertical jumping height. Result: There was a strong correlation between maximal strength in half squats and sprint performance and jumping height. Conclusions: Maximal strength in half squats determines sprint performance and jumping height in high level soccer players. High squat strength did not imply reduced maximal oxygen consumption. Elite soccer players should focus on maximal strength training, with emphasis on maximal mobilisation of concentric movements, which may improve their sprinting and jumping performance. PMID:15155427

Maximizing Resource Utilization in Video Streaming Systems

ERIC Educational Resources Information Center

Alsmirat, Mohammad Abdullah

2013-01-01

Video streaming has recently grown dramatically in popularity over the Internet, Cable TV, and wire-less networks. Because of the resource demanding nature of video streaming applications, maximizing resource utilization in any video streaming system is a key factor to increase the scalability and decrease the cost of the system. Resources to…

Quantum correlations of two-qubit states with one maximally mixed marginal

NASA Astrophysics Data System (ADS)

Milne, Antony; Jennings, David; Jevtic, Sania; Rudolph, Terry

2014-08-01

We investigate the entanglement, CHSH nonlocality, fully entangled fraction, and symmetric extendibility of two-qubit states that have a single maximally mixed marginal. Within this set of states, the steering ellipsoid formalism has recently highlighted an interesting family of so-called maximally obese states. These are found to have extremal quantum correlation properties that are significant in the steering ellipsoid picture and for the study of two-qubit states in general.

Maximal liquid bridges between horizontal cylinders

NASA Astrophysics Data System (ADS)

Cooray, Himantha; Huppert, Herbert E.; Neufeld, Jerome A.

2016-08-01

We investigate two-dimensional liquid bridges trapped between pairs of identical horizontal cylinders. The cylinders support forces owing to surface tension and hydrostatic pressure that balance the weight of the liquid. The shape of the liquid bridge is determined by analytically solving the nonlinear Laplace-Young equation. Parameters that maximize the trapping capacity (defined as the cross-sectional area of the liquid bridge) are then determined. The results show that these parameters can be approximated with simple relationships when the radius of the cylinders is small compared with the capillary length. For such small cylinders, liquid bridges with the largest cross-sectional area occur when the centre-to-centre distance between the cylinders is approximately twice the capillary length. The maximum trapping capacity for a pair of cylinders at a given separation is linearly related to the separation when it is small compared with the capillary length. The meniscus slope angle of the largest liquid bridge produced in this regime is also a linear function of the separation. We additionally derive approximate solutions for the profile of a liquid bridge, using the linearized Laplace-Young equation. These solutions analytically verify the above-mentioned relationships obtained for the maximization of the trapping capacity.

Translational experimental therapeutics: The translation of laboratory-based discovery into disease-related therapy.

PubMed

Kieburtz, Karl; Olanow, C Warren

2007-04-01

In the past decade, there has been an increasing emphasis on laboratory-based translational research. This has led to significant scientific advances in our understanding of disease mechanisms and in the development of novel approaches to therapy such as gene therapy, RNA interference, and stem cells. However, the translation of these remarkable scientific achievements into new and effective disease-modifying therapies has lagged behind these scientific accomplishments. We use the term "translational experimental therapeutics" to describe the pathway between the discovery of a basic disease mechanism or novel therapeutic approach and its translation into an effective treatment for patients with a specific disease. In this article, we review the components of this pathway, and discuss issues that might impede this process. Only by optimizing this pathway can we realize the full therapeutic potential of current scientific discoveries and translate the astounding advances that have been accomplished in the laboratory into effective treatments for our patients. Copyright (c) 2007 Mount Sinai School of Medicine.

Applications of lipid based formulation technologies in the delivery of biotechnology-based therapeutics.

PubMed

du Plessis, Lissinda H; Marais, Etienne B; Mohammed, Faruq; Kotzé, Awie F

2014-01-01

In the last decades several new biotechnologically-based therapeutics have been developed due to progress in genetic engineering. A growing challenge facing pharmaceutical scientists is formulating these compounds into oral dosage forms with adequate bioavailability. An increasingly popular approach to formulate biotechnology-based therapeutics is the use of lipid based formulation technologies. This review highlights the importance of lipid based drug delivery systems in the formulation of oral biotechnology based therapeutics including peptides, proteins, DNA, siRNA and vaccines. The different production procedures used to achieve high encapsulation efficiencies of the bioactives are discussed, as well as the factors influencing the choice of excipient. Lipid based colloidal drug delivery systems including liposomes and solid lipid nanoparticles are reviewed with a focus on recent advances and updates. We further describe microemulsions and self-emulsifying drug delivery systems and recent findings on bioactive delivery. We conclude the review with a few examples on novel lipid based formulation technologies.

Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges.

PubMed

Mingozzi, Federico; High, Katherine A

2011-05-01

In vivo gene replacement for the treatment of inherited disease is one of the most compelling concepts in modern medicine. Adeno-associated virus (AAV) vectors have been extensively used for this purpose and have shown therapeutic efficacy in a range of animal models. Successful translation to the clinic was initially slow, but long-term expression of donated genes at therapeutic levels has now been achieved in patients with inherited retinal disorders and haemophilia B. Recent exciting results have raised hopes for the treatment of many other diseases. As we discuss here, the prospects and challenges for AAV gene therapy are to a large extent dependent on the target tissue and the specific disease.

Projection of two biphoton qutrits onto a maximally entangled state.

PubMed

Halevy, A; Megidish, E; Shacham, T; Dovrat, L; Eisenberg, H S

2011-04-01

Bell state measurements, in which two quantum bits are projected onto a maximally entangled state, are an essential component of quantum information science. We propose and experimentally demonstrate the projection of two quantum systems with three states (qutrits) onto a generalized maximally entangled state. Each qutrit is represented by the polarization of a pair of indistinguishable photons-a biphoton. The projection is a joint measurement on both biphotons using standard linear optics elements. This demonstration enables the realization of quantum information protocols with qutrits, such as teleportation and entanglement swapping. © 2011 American Physical Society

Hemodynamic and arterial stiffness differences between African-Americans and Caucasians after maximal exercise.

PubMed

Yan, Huimin; Ranadive, Sushant M; Heffernan, Kevin S; Lane, Abbi D; Kappus, Rebecca M; Cook, Marc D; Wu, Pei-Tzu; Sun, Peng; Harvey, Idethia S; Woods, Jeffrey A; Wilund, Kenneth R; Fernhall, Bo

2014-01-01

African-American (AA) men have higher arterial stiffness and augmentation index (AIx) than Caucasian-American (CA) men. Women have greater age-associated increases in arterial stiffness and AIx than men. This study examined racial and sex differences in arterial stiffness and central hemodynamics at rest and after an acute bout of maximal exercise in young healthy individuals. One hundred young, healthy individuals (28 AA men, 24 AA women, 25 CA men, and 23 CA women) underwent measurements of aortic blood pressure (BP) and arterial stiffness at rest and 15 and 30 min after an acute bout of graded maximal aerobic exercise. Aortic BP and AIx were derived from radial artery applanation tonometry. Aortic stiffness (carotid-femoral) was measured via pulse wave velocity. Aortic stiffness was increased in AA subjects but not in CA subjects (P < 0.05) after an acute bout of maximal cycling exercise, after controlling for body mass index. Aortic BP decreased after exercise in CA subjects but not in AA subjects (P < 0.05). Women exhibited greater reductions in AIx after maximal aerobic exercise compared with men (P < 0.05). In conclusion, race and sex impact vascular and central hemodynamic responses to exercise. Young AA and CA subjects exhibited differential responses in central stiffness and central BP after acute maximal exercise. Premenopausal women had greater augmented pressure at rest and after maximal aerobic exercise than men. Future research is needed to examine the potential mechanisms.

Hemodynamic and arterial stiffness differences between African-Americans and Caucasians after maximal exercise

PubMed Central

Ranadive, Sushant M.; Heffernan, Kevin S.; Lane, Abbi D.; Kappus, Rebecca M.; Cook, Marc D.; Wu, Pei-Tzu; Sun, Peng; Harvey, Idethia S.; Woods, Jeffrey A.; Wilund, Kenneth R.; Fernhall, Bo

2013-01-01

African-American (AA) men have higher arterial stiffness and augmentation index (AIx) than Caucasian-American (CA) men. Women have greater age-associated increases in arterial stiffness and AIx than men. This study examined racial and sex differences in arterial stiffness and central hemodynamics at rest and after an acute bout of maximal exercise in young healthy individuals. One hundred young, healthy individuals (28 AA men, 24 AA women, 25 CA men, and 23 CA women) underwent measurements of aortic blood pressure (BP) and arterial stiffness at rest and 15 and 30 min after an acute bout of graded maximal aerobic exercise. Aortic BP and AIx were derived from radial artery applanation tonometry. Aortic stiffness (carotid-femoral) was measured via pulse wave velocity. Aortic stiffness was increased in AA subjects but not in CA subjects (P < 0.05) after an acute bout of maximal cycling exercise, after controlling for body mass index. Aortic BP decreased after exercise in CA subjects but not in AA subjects (P < 0.05). Women exhibited greater reductions in AIx after maximal aerobic exercise compared with men (P < 0.05). In conclusion, race and sex impact vascular and central hemodynamic responses to exercise. Young AA and CA subjects exhibited differential responses in central stiffness and central BP after acute maximal exercise. Premenopausal women had greater augmented pressure at rest and after maximal aerobic exercise than men. Future research is needed to examine the potential mechanisms. PMID:24186094

MicroRNA therapeutics: towards a new era for the management of cancer and other diseases.

PubMed

Rupaimoole, Rajesha; Slack, Frank J

2017-03-01

In just over two decades since the discovery of the first microRNA (miRNA), the field of miRNA biology has expanded considerably. Insights into the roles of miRNAs in development and disease, particularly in cancer, have made miRNAs attractive tools and targets for novel therapeutic approaches. Functional studies have confirmed that miRNA dysregulation is causal in many cases of cancer, with miRNAs acting as tumour suppressors or oncogenes (oncomiRs), and miRNA mimics and molecules targeted at miRNAs (antimiRs) have shown promise in preclinical development. Several miRNA-targeted therapeutics have reached clinical development, including a mimic of the tumour suppressor miRNA miR-34, which reached phase I clinical trials for treating cancer, and antimiRs targeted at miR-122, which reached phase II trials for treating hepatitis. In this article, we describe recent advances in our understanding of miRNAs in cancer and in other diseases and provide an overview of current miRNA therapeutics in the clinic. We also discuss the challenge of identifying the most efficacious therapeutic candidates and provide a perspective on achieving safe and targeted delivery of miRNA therapeutics.

Optimal Loading for Maximizing Power During Sled-Resisted Sprinting.

PubMed

Cross, Matt R; Brughelli, Matt; Samozino, Pierre; Brown, Scott R; Morin, Jean-Benoit

2017-09-01

To ascertain whether force-velocity-power relationships could be compiled from a battery of sled-resisted overground sprints and to clarify and compare the optimal loading conditions for maximizing power production for different athlete cohorts. Recreational mixed-sport athletes (n = 12) and sprinters (n = 15) performed multiple trials of maximal sprints unloaded and towing a selection of sled masses (20-120% body mass [BM]). Velocity data were collected by sports radar, and kinetics at peak velocity were quantified using friction coefficients and aerodynamic drag. Individual force-velocity and power-velocity relationships were generated using linear and quadratic relationships, respectively. Mechanical and optimal loading variables were subsequently calculated and test-retest reliability assessed. Individual force-velocity and power-velocity relationships were accurately fitted with regression models (R 2 > .977, P < .001) and were reliable (ES = 0.05-0.50, ICC = .73-.97, CV = 1.0-5.4%). The normal loading that maximized peak power was 78% ± 6% and 82% ± 8% of BM, representing a resistance of 3.37 and 3.62 N/kg at 4.19 ± 0.19 and 4.90 ± 0.18 m/s (recreational athletes and sprinters, respectively). Optimal force and normal load did not clearly differentiate between cohorts, although sprinters developed greater maximal power (17.2-26.5%, ES = 0.97-2.13, P < .02) at much greater velocities (16.9%, ES = 3.73, P < .001). Mechanical relationships can be accurately profiled using common sled-training equipment. Notably, the optimal loading conditions determined in this study (69-96% of BM, dependent on friction conditions) represent much greater resistance than current guidelines (~7-20% of BM). This method has potential value in quantifying individualized training parameters for optimized development of horizontal power.

Issues in formulary management: therapeutic interchange. The value, cost, and quality of therapeutic interchange.

PubMed

Mahoney, C D

1992-10-01

Therapeutic interchange is a process of substituting a prescribed medication with one that offers therapeutic and cost benefits. The practice not only provides short-term savings but also is associated with decreases in lengths of stay in hospitals and total hospital drug expenses. There may be medicolegal implications when FDA-approved indications differ for interchanged drugs. The potential for liability is decreased when a standard of care is met, but since standards can change, guidelines should be reviewed regularly. High-tech, high-cost drugs are sometimes appropriate for therapeutic interchange. Pharmacy and therapeutics committees should assure best value by considering indirect expenses, quality, and therapeutic outcome, as well as product cost. Therapeutic interchange programs enable pharmacy managers to neutralize or at least slow the rate of drug cost increases, ensuring appropriate utilization of resources and more favorable patient outcomes.

Is the required therapeutic effect always achieved by racemic switch of proton-pump inhibitors?

PubMed Central

Zhou, Quan; Yan, Xiao-Feng; Pan, Wen-Sheng; Zeng, Su

2008-01-01

Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R(+)-rabeprazole] (10 mg) was found to be more effective than rabeprazole (20 mg) in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors (PPIs). A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships (QSARs) are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole. PMID:18442220

Optimum sample size allocation to minimize cost or maximize power for the two-sample trimmed mean test.

PubMed

Guo, Jiin-Huarng; Luh, Wei-Ming

2009-05-01

When planning a study, sample size determination is one of the most important tasks facing the researcher. The size will depend on the purpose of the study, the cost limitations, and the nature of the data. By specifying the standard deviation ratio and/or the sample size ratio, the present study considers the problem of heterogeneous variances and non-normality for Yuen's two-group test and develops sample size formulas to minimize the total cost or maximize the power of the test. For a given power, the sample size allocation ratio can be manipulated so that the proposed formulas can minimize the total cost, the total sample size, or the sum of total sample size and total cost. On the other hand, for a given total cost, the optimum sample size allocation ratio can maximize the statistical power of the test. After the sample size is determined, the present simulation applies Yuen's test to the sample generated, and then the procedure is validated in terms of Type I errors and power. Simulation results show that the proposed formulas can control Type I errors and achieve the desired power under the various conditions specified. Finally, the implications for determining sample sizes in experimental studies and future research are discussed.

Crossover and maximal fat-oxidation points in sedentary healthy subjects: methodological issues.

PubMed

Gmada, N; Marzouki, H; Haboubi, M; Tabka, Z; Shephard, R J; Bouhlel, E

2012-02-01

Our study aimed to assess the influence of protocol on the crossover point and maximal fat-oxidation (LIPOX(max)) values in sedentary, but otherwise healthy, young men. Maximal oxygen intake was assessed in 23 subjects, using a progressive maximal cycle ergometer test. Twelve sedentary males (aged 20.5±1.0 years) whose directly measured maximal aerobic power (MAP) values were lower than their theoretical maximal values (tMAP) were selected from this group. These individuals performed, in random sequence, three submaximal graded exercise tests, separated by three-day intervals; work rates were based on the tMAP in one test and on MAP in the remaining two. The third test was used to assess the reliability of data. Heart rate, respiratory parameters, blood lactate, the crossover point and LIPOX(max) values were measured during each of these tests. The crossover point and LIPOX(max) values were significantly lower when the testing protocol was based on tMAP rather than on MAP (P<0.001). Respiratory exchange ratios were significantly lower with MAP than with tMAP at 30, 40, 50 and 60% of maximal aerobic power (P<0.01). At the crossover point, lactate and 5-min postexercise oxygen consumption (EPOC(5 min)) values were significantly higher using tMAP rather than MAP (P<0.001). During the first 5 min of recovery, EPOC(5 min) and blood lactate were significantly correlated (r=0.89; P<0.001). Our data show that, to assess the crossover point and LIPOX(max) values for research purposes, the protocol must be based on the measured MAP rather than on a theoretical value. Such a determination should improve individualization of training for initially sedentary subjects. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Maximal radius of the aftershock zone in earthquake networks

NASA Astrophysics Data System (ADS)

Mezentsev, A. Yu.; Hayakawa, M.

2009-09-01

In this paper, several seismoactive regions were investigated (Japan, Southern California and two tectonically distinct Japanese subregions) and structural seismic constants were estimated for each region. Using the method for seismic clustering detection proposed by Baiesi and Paczuski [M. Baiesi, M. Paczuski, Phys. Rev. E 69 (2004) 066106; M. Baiesi, M. Paczuski, Nonlin. Proc. Geophys. (2005) 1607-7946], we obtained the equation of the aftershock zone (AZ). It was shown that the consideration of a finite velocity of seismic signal leads to the natural appearance of maximal possible radius of the AZ. We obtained the equation of maximal radius of the AZ as a function of the magnitude of the main event and estimated its values for each region.

Optimization of Second Fault Detection Thresholds to Maximize Mission POS

NASA Technical Reports Server (NTRS)

Anzalone, Evan

2018-01-01

In order to support manned spaceflight safety requirements, the Space Launch System (SLS) has defined program-level requirements for key systems to ensure successful operation under single fault conditions. To accommodate this with regards to Navigation, the SLS utilizes an internally redundant Inertial Navigation System (INS) with built-in capability to detect, isolate, and recover from first failure conditions and still maintain adherence to performance requirements. The unit utilizes multiple hardware- and software-level techniques to enable detection, isolation, and recovery from these events in terms of its built-in Fault Detection, Isolation, and Recovery (FDIR) algorithms. Successful operation is defined in terms of sufficient navigation accuracy at insertion while operating under worst case single sensor outages (gyroscope and accelerometer faults at launch). In addition to first fault detection and recovery, the SLS program has also levied requirements relating to the capability of the INS to detect a second fault, tracking any unacceptable uncertainty in knowledge of the vehicle's state. This detection functionality is required in order to feed abort analysis and ensure crew safety. Increases in navigation state error and sensor faults can drive the vehicle outside of its operational as-designed environments and outside of its performance envelope causing loss of mission, or worse, loss of crew. The criteria for operation under second faults allows for a larger set of achievable missions in terms of potential fault conditions, due to the INS operating at the edge of its capability. As this performance is defined and controlled at the vehicle level, it allows for the use of system level margins to increase probability of mission success on the operational edges of the design space. Due to the implications of the vehicle response to abort conditions (such as a potentially failed INS), it is important to consider a wide range of failure scenarios in terms of

Determinants of maximal oxygen uptake (VO2 max) in fire fighter testing.

PubMed

Vandersmissen, G J M; Verhoogen, R A J R; Van Cauwenbergh, A F M; Godderis, L

2014-07-01

The aim of this study was to evaluate current daily practice of aerobic capacity testing in Belgian fire fighters. The impact of personal and test-related parameters on the outcome has been evaluated. Maximal oxygen uptake (VO2 max) results of 605 male fire fighters gathered between 1999 and 2010 were analysed. The maximal cardio respiratory exercise tests were performed at 22 different centres using different types of tests (tread mill or bicycle), different exercise protocols and measuring equipment. Mean VO2 max was 43.3 (SD = 9.8) ml/kg.min. Besides waist circumference and age, the type of test, the degree of performance of the test and the test centre were statistically significant determinants of maximal oxygen uptake. Test-related parameters have to be taken into account when interpreting and comparing maximal oxygen uptake tests of fire fighters. It highlights the need for standardization of aerobic capacity testing in the medical evaluation of fire fighters. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Linear maps preserving maximal deviation and the Jordan structure of quantum systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamhalter, Jan

2012-12-15

In the algebraic approach to quantum theory, a quantum observable is given by an element of a Jordan algebra and a state of the system is modelled by a normalized positive functional on the underlying algebra. Maximal deviation of a quantum observable is the largest statistical deviation one can obtain in a particular state of the system. The main result of the paper shows that each linear bijective transformation between JBW algebras preserving maximal deviations is formed by a Jordan isomorphism or a minus Jordan isomorphism perturbed by a linear functional multiple of an identity. It shows that only onemore » numerical statistical characteristic has the power to determine the Jordan algebraic structure completely. As a consequence, we obtain that only very special maps can preserve the diameter of the spectra of elements. Nonlinear maps preserving the pseudometric given by maximal deviation are also described. The results generalize hitherto known theorems on preservers of maximal deviation in the case of self-adjoint parts of von Neumann algebras proved by Molnar.« less

Maximal strength and power assessment in novice weight trainers.

PubMed

Cronin, John B; Henderson, Melanie E

2004-02-01

The purpose of this study was to investigate whether changes in maximal strength and power output occurred over time in the absence of strength and power training in novice weight trainers. It also investigated whether differences existed between upper- and lower-body assessments and unilateral and bilateral assessments. The power output and maximal strength (1 repetition maximum [1RM]) of 10 male novice subjects were measured on 4 occasions, each assessment 7-10 days apart. The exercises used to measure the upper- and lower-body strength and power outputs were the bench press and supine squat, respectively. Significant (p < 0.05) changes in unilateral (9.8-16.8%) and bilateral 1RM (6.8-15.0%) leg strength were found, the first assessment being significantly different from all other assessments and assessment 2 significantly different from assessment 4. Changes in the upper body (10-13.6%) were also observed. The only significant difference was between assessment 1 and the other testing occasions. No differences in power output were observed for both the upper and lower body during the study. It would seem that considerable changes in maximal strength occur rapidly and in the absence of any formal strength training program in novice weight trainers.

Prediction of Maximal Aerobic Capacity in Severely Burned Children

PubMed Central

Porro, Laura; Rivero, Haidy G.; Gonzalez, Dante; Tan, Alai; Herndon, David N.; Suman, Oscar E.

2011-01-01

Introduction Maximal oxygen uptake (VO2 peak) is an indicator of cardiorespiratory fitness, but requires expensive equipment and a relatively high technical skill level. Purpose The aim of this study is to provide a formula for estimating VO2 peak in burned children, using information obtained without expensive equipment. Methods Children, with ≥40% total surface area burned (TBSA), underwent a modified Bruce treadmill test to asses VO2 peak at 6 months after injury. We recorded gender, age, %TBSA, %3rd degree burn, height, weight, treadmill time, maximal speed, maximal grade, and peak heart rate, and applied McHenry’s select algorithm to extract important independent variables and Robust multiple regression to establish prediction equations. Results 42 children; 7 to 17 years old were tested. Robust multiple regression model provided the equation: VO2=10.33 – 0.62 *Age (years) + 1.88 * Treadmill Time (min) + 2.3 (gender; Females = 0, Males = 1). The correlation between measured and estimated VO2 peak was R=0.80. We then validated the equation with a group of 33 burned children, which yielded a correlation between measured and estimated VO2 peak of R=0.79. Conclusions Using only a treadmill and easily gathered information, VO2 peak can be estimated in children with burns. PMID:21316155

Maximizing the Biochemical Resolving Power of Fluorescence Microscopy

PubMed Central

Esposito, Alessandro; Popleteeva, Marina; Venkitaraman, Ashok R.

2013-01-01

Most recent advances in fluorescence microscopy have focused on achieving spatial resolutions below the diffraction limit. However, the inherent capability of fluorescence microscopy to non-invasively resolve different biochemical or physical environments in biological samples has not yet been formally described, because an adequate and general theoretical framework is lacking. Here, we develop a mathematical characterization of the biochemical resolution in fluorescence detection with Fisher information analysis. To improve the precision and the resolution of quantitative imaging methods, we demonstrate strategies for the optimization of fluorescence lifetime, fluorescence anisotropy and hyperspectral detection, as well as different multi-dimensional techniques. We describe optimized imaging protocols, provide optimization algorithms and describe precision and resolving power in biochemical imaging thanks to the analysis of the general properties of Fisher information in fluorescence detection. These strategies enable the optimal use of the information content available within the limited photon-budget typically available in fluorescence microscopy. This theoretical foundation leads to a generalized strategy for the optimization of multi-dimensional optical detection, and demonstrates how the parallel detection of all properties of fluorescence can maximize the biochemical resolving power of fluorescence microscopy, an approach we term Hyper Dimensional Imaging Microscopy (HDIM). Our work provides a theoretical framework for the description of the biochemical resolution in fluorescence microscopy, irrespective of spatial resolution, and for the development of a new class of microscopes that exploit multi-parametric detection systems. PMID:24204821

McTwo: a two-step feature selection algorithm based on maximal information coefficient.

PubMed

Ge, Ruiquan; Zhou, Manli; Luo, Youxi; Meng, Qinghan; Mai, Guoqin; Ma, Dongli; Wang, Guoqing; Zhou, Fengfeng

2016-03-23

High-throughput bio-OMIC technologies are producing high-dimension data from bio-samples at an ever increasing rate, whereas the training sample number in a traditional experiment remains small due to various difficulties. This "large p, small n" paradigm in the area of biomedical "big data" may be at least partly solved by feature selection algorithms, which select only features significantly associated with phenotypes. Feature selection is an NP-hard problem. Due to the exponentially increased time requirement for finding the globally optimal solution, all the existing feature selection algorithms employ heuristic rules to find locally optimal solutions, and their solutions achieve different performances on different datasets. This work describes a feature selection algorithm based on a recently published correlation measurement, Maximal Information Coefficient (MIC). The proposed algorithm, McTwo, aims to select features associated with phenotypes, independently of each other, and achieving high classification performance of the nearest neighbor algorithm. Based on the comparative study of 17 datasets, McTwo performs about as well as or better than existing algorithms, with significantly reduced numbers of selected features. The features selected by McTwo also appear to have particular biomedical relevance to the phenotypes from the literature. McTwo selects a feature subset with very good classification performance, as well as a small feature number. So McTwo may represent a complementary feature selection algorithm for the high-dimensional biomedical datasets.

Mechanisms and therapeutic effectiveness of lactobacilli

PubMed Central

Di Cerbo, Alessandro; Palmieri, Beniamino; Aponte, Maria; Morales-Medina, Julio Cesar; Iannitti, Tommaso

2016-01-01

The gut microbiome is not a silent ecosystem but exerts several physiological and immunological functions. For many decades, lactobacilli have been used as an effective therapy for treatment of several pathological conditions displaying an overall positive safety profile. This review summarises the mechanisms and clinical evidence supporting therapeutic efficacy of lactobacilli. We searched Pubmed/Medline using the keyword ‘Lactobacillus’. Selected papers from 1950 to 2015 were chosen on the basis of their content. Relevant clinical and experimental articles using lactobacilli as therapeutic agents have been included. Applications of lactobacilli include kidney support for renal insufficiency, pancreas health, management of metabolic imbalance, and cancer treatment and prevention. In vitro and in vivo investigations have shown that prolonged lactobacilli administration induces qualitative and quantitative modifications in the human gastrointestinal microbial ecosystem with encouraging perspectives in counteracting pathology-associated physiological and immunological changes. Few studies have highlighted the risk of translocation with subsequent sepsis and bacteraemia following probiotic administration but there is still a lack of investigations on the dose effect of these compounds. Great care is thus required in the choice of the proper Lactobacillus species, their genetic stability and the translocation risk, mainly related to inflammatory disease-induced gut mucosa enhanced permeability. Finally, we need to determine the adequate amount of bacteria to be delivered in order to achieve the best clinical efficacy decreasing the risk of side effects. PMID:26578541

Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein.

PubMed

Kessler, P D; Podsakoff, G M; Chen, X; McQuiston, S A; Colosi, P C; Matelis, L A; Kurtzman, G J; Byrne, B J

1996-11-26

Somatic gene therapy has been proposed as a means to achieve systemic delivery of therapeutic proteins. However, there is limited evidence that current methods of gene delivery can practically achieve this goal. In this study, we demonstrate that, following a single intramuscular administration of a recombinant adeno-associated virus (rAAV) vector containing the beta-galactosidase (AAV-lacZ) gene into adult BALB/c mice, protein expression was detected in myofibers for at least 32 weeks. A single intramuscular administration of an AAV vector containing a gene for human erythropoietin (AAV-Epo) into mice resulted in dose-dependent secretion of erythropoietin and corresponding increases in red blood cell production that persisted for up to 40 weeks. Primary human myotubes transduced in vitro with the AAV-Epo vector also showed dose-dependent production of Epo. These results demonstrate that rAAV vectors are able to transduce skeletal muscle and are capable of achieving sustained expression and systemic delivery of a therapeutic protein following a single intramuscular administration. Gene therapy using AAV vectors may provide a practical strategy for the treatment of inherited and acquired protein deficiencies.

Dual delivery of biological therapeutics for multimodal and synergistic cancer therapies.

PubMed

Jang, Bora; Kwon, Hyokyoung; Katila, Pramila; Lee, Seung Jin; Lee, Hyukjin

2016-03-01

Cancer causes >8.2 million deaths annually worldwide; thus, various cancer treatments have been investigated over the past decades. Among them, combination drug therapy has become extremely popular, and treatment with more than one drug is often necessary to achieve appropriate anticancer efficacy. With the development of nanoformulations and nanoparticulate-based drug delivery, researchers have explored the feasibility of dual delivery of biological therapeutics to overcome the current drawbacks of cancer therapy. Compared with the conventional single drug therapy, dual delivery of therapeutics has provided various synergistic effects in addition to offering multimodality to cancer treatment. In this review, we highlight and summarize three aspects of dual-delivery systems for cancer therapy. These include (1) overcoming drug resistance by the dual delivery of chemical drugs with biological therapeutics for synergistic therapy, (2) targeted and controlled drug release by the dual delivery of drugs with stimuli-responsive nanomaterials, and (3) multimodal theranostics by the dual delivery of drugs and molecular imaging probes. Furthermore, recent developments, perspectives, and new challenges regarding dual-delivery systems for cancer therapy are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Therapeutic polymers for dental adhesives: Loading resins with bio-active components

PubMed Central

Imazato, Satoshi; Ma, Sai; Chen, Ji-hua; Xu, Hockin H.K.

2014-01-01

Objectives Many recent adhesives on the market exhibit reasonable clinical performance. Future innovations in adhesive materials should therefore seek out novel properties rather than simply modifying existing technologies. It is proposed that adhesive materials that are “bio-active” could contribute to better prognosis of restorative treatments. Methods This review examines the recent approaches used to achieve therapeutic polymers for dental adhesives by incorporating bio-active components. A strategy to maintain adhesive restorations is the focus of this paper. Results Major trials on therapeutic dental adhesives have looked at adding antibacterial activities or remineralization effects. Applications of antibacterial resin monomers based on quaternary ammonium compounds have received much research attention, and the loading of nano-sized bioactive particles or multiple ion-releasing glass fillers have been perceived as advantageous since they are not expected to influence the mechanical properties of the carrier polymer. Significance The therapeutic polymer approaches described here have the potential to provide clinical benefits. However, not many technological applications in this category have been successfully commercialized. Clinical evidence as well as further advancement of these technologies can be a driving force to make these new types of materials clinically available. PMID:23899387

M-wave, H- and V-reflex recruitment curves during maximal voluntary contraction.

PubMed

Racinais, Sebastien; Maffiuletti, Nicola A; Girard, Olivier

2013-08-01

To investigate whether the H reflex-M wave recruitment curves obtained during maximal voluntary contraction (MVC) differ from rest and to determine the stimulation intensities allowing to record stable reflex responses. Full recruitment curves (precision, 2 mA) were obtained from the soleus muscle in 14 volunteers at rest and during plantar flexion MVCs. Maximal M-wave reached significantly larger amplitude during MVC (+2.2 [0.4; 3.9] mV) for a higher stimulation intensity (+7.9 [-0.4; 16] mA). Similarly, maximal H-reflex reached significantly larger amplitude during MVC than at rest (+3.2 [0.9; 5.5] mV) for a much higher stimulation intensity (+17.7 [9.7; 25.7] mA). V-wave amplitude plateaued only when M-wave during MVC plateaued, that is, at higher intensity than M-wave at rest. V-wave was correlated to the maximal H-reflex during MVC (r = 0.79, P < 0.05). Electrically evoked potentials showed a specific recruitment curve during MVC with higher maximal values attained for higher stimulation intensities. Thus, recording reflex responses during MVC based on intensities determined at rest or as a percentage of M-wave may yield inaccurate results. V-wave presented a plateau for stimulation intensity of 1.5 times the onset of the resting M-wave plateau. Evoked potentials obtained during actual contractions should be normalized to M-waves obtained during contractions of the same force level.

Engineering of Fc Fragments with Optimized Physicochemical Properties Implying Improvement of Clinical Potentials for Fc-Based Therapeutics.

PubMed

Yang, Chunpeng; Gao, Xinyu; Gong, Rui

2017-01-01

Therapeutic monoclonal antibodies and Fc-fusion proteins are successfully used in treatment of various diseases mainly including cancer, immune disease, and viral infection, which belong to the Fc-based therapeutics. In recent years, engineered Fc-derived antibody domains have also shown potential for Fc-based therapeutics. To increase the druggability of Fc-based therapeutic candidates, many efforts have been made in optimizing physicochemical properties and functions mediated by Fc fragment. The desired result is that we can simultaneously obtain Fc variants with increased physicochemical properties in vitro and capacity of mediating appropriate functions in vivo . However, changes of physicochemical properties of Fc may result in alternation of Fc-mediated functions and vice versa , which leads to undesired outcomes for further development of Fc-based therapeutics. Therefore, whether modified Fc fragments are suitable for achievement of expected clinical results or not needs to be seriously considered. Now, this question comes to be noticed and should be figured out to make better translation from the results of laboratory into clinical applications. In this review, we summarize different strategies on engineering physicochemical properties of Fc, and preliminarily elucidate the relationships between modified Fc in vitro and the subsequent therapeutic influence in vivo .

Emotional Control and Instructional Effectiveness: Maximizing a Timeout

ERIC Educational Resources Information Center

Andrews, Staci R.

2015-01-01

This article provides recommendations for best practices for basketball coaches to maximize the instructional effectiveness of a timeout during competition. Practical applications are derived from research findings linking emotional intelligence to effective coaching behaviors. Additionally, recommendations are based on the implications of the…

Maximizing plant density affects broccoli yield and quality

USDA-ARS?s Scientific Manuscript database

Increased demand for fresh market bunch broccoli (Brassica oleracea L. var. italica) has led to increased production along the United States east coast. Maximizing broccoli yields is a primary concern for quickly expanding southeastern commercial markets. This broccoli plant density study was carr...

Possibility of Exosome-Based Therapeutics and Challenges in Production of Exosomes Eligible for Therapeutic Application.

PubMed

Yamashita, Takuma; Takahashi, Yuki; Takakura, Yoshinobu

2018-01-01

Exosomes are cell-derived vesicles with a diameter 30-120 nm. Exosomes contain endogenous proteins and nucleic acids; delivery of these molecules to exosome-recipient cells causes biological effects. Exosomes derived from some types of cells such as mesenchymal stem cells and dendritic cells have therapeutic potential and may be biocompatible and efficient agents against various disorders such as organ injury. However, there are many challenges for the development of exosome-based therapeutics. In particular, producing exosomal formulations is the major barrier for therapeutic application because of their heterogeneity and low productivity. Development and optimization of producing methods, including methods for isolation and storage of exosome formulations, are required for realizing exosome-based therapeutics. In addition, improvement of therapeutic potential and delivery efficiency of exosomes are important for their therapeutic application. In this review, we summarize current knowledge about therapeutic application of exosomes and discuss some challenges in their successful use.

Genetic engineering of cell lines using lentiviral vectors to achieve antibody secretion following encapsulated implantation.

PubMed

Lathuilière, Aurélien; Bohrmann, Bernd; Kopetzki, Erhard; Schweitzer, Christoph; Jacobsen, Helmut; Moniatte, Marc; Aebischer, Patrick; Schneider, Bernard L

2014-01-01

The controlled delivery of antibodies by immunoisolated bioimplants containing genetically engineered cells is an attractive and safe approach for chronic treatments. To reach therapeutic antibody levels there is a need to generate renewable cell lines, which can long-term survive in macroencapsulation devices while maintaining high antibody specific productivity. Here we have developed a dual lentiviral vector strategy for the genetic engineering of cell lines compatible with macroencapsulation, using separate vectors encoding IgG light and heavy chains. We show that IgG expression level can be maximized as a function of vector dose and transgene ratio. This approach allows for the generation of stable populations of IgG-expressing C2C12 mouse myoblasts, and for the subsequent isolation of clones stably secreting high IgG levels. Moreover, we demonstrate that cell transduction using this lentiviral system leads to the production of a functional glycosylated antibody by myogenic cells. Subsequent implantation of antibody-secreting cells in a high-capacity macroencapsulation device enables continuous delivery of recombinant antibodies in the mouse subcutaneous tissue, leading to substantial levels of therapeutic IgG detectable in the plasma.

Research-Based Unit and Lesson Planning: Maximizing Student Achievement

ERIC Educational Resources Information Center

Pagliaro, Marie

2012-01-01

By integrating the best of current research and practice in curriculum planning this book presents that comprehensive topic in a manageable form. Examples throughout are representative of different grade levels and subjects areas. It should be understood at the outset that the content offered for curriculum planning is not a rigid prescriptive…

Antiviral cationic peptides as a strategy for innovation in global health therapeutics for dengue virus: high yield production of the biologically active recombinant plectasin peptide.

PubMed

Rothan, Hussin A; Mohamed, Zulqarnain; Suhaeb, Abdulrazzaq M; Rahman, Noorsaadah Abd; Yusof, Rohana

2013-11-01

Dengue virus infects millions of people worldwide, and there is no vaccine or anti-dengue therapeutic available. Antimicrobial peptides have been shown to possess effective antiviral activity against various viruses. One of the main limitations of developing these peptides as potent antiviral drugs is the high cost of production. In this study, high yield production of biologically active plectasin peptide was inexpensively achieved by producing tandem plectasin peptides as inclusion bodies in E. coli. Antiviral activity of the recombinant peptide towards dengue serotype-2 NS2B-NS3 protease (DENV2 NS2B-NS3pro) was assessed as a target to inhibit dengue virus replication in Vero cells. Single units of recombinant plectasin were collected after applying consecutive steps of refolding, cleaving by Factor Xa, and nickel column purification to obtain recombinant proteins of high purity. The maximal nontoxic dose (MNTD) of the recombinant peptide against Vero cells was 20 μM (100 μg/mL). The reaction velocity of DENV2 NS2B-NS3pro decreased significantly after increasing concentrations of recombinant plectasin were applied to the reaction mixture. Plectasin peptide noncompetitively inhibited DENV2 NS2B-NS3pro at Ki value of 5.03 ± 0.98 μM. The percentage of viral inhibition was more than 80% at the MNTD value of plectasin. In this study, biologically active recombinant plectasin which was able to inhibit dengue protease and viral replication in Vero cells was successfully produced in E. coli in a time- and cost- effective method. These findings are potentially important in the development of potent therapeutics against dengue infection.

Antiviral Cationic Peptides as a Strategy for Innovation in Global Health Therapeutics for Dengue Virus: High Yield Production of the Biologically Active Recombinant Plectasin Peptide

PubMed Central

Mohamed, Zulqarnain; Suhaeb, Abdulrazzaq M.; Rahman, Noorsaadah Abd; Yusof, Rohana

2013-01-01

Abstract Dengue virus infects millions of people worldwide, and there is no vaccine or anti-dengue therapeutic available. Antimicrobial peptides have been shown to possess effective antiviral activity against various viruses. One of the main limitations of developing these peptides as potent antiviral drugs is the high cost of production. In this study, high yield production of biologically active plectasin peptide was inexpensively achieved by producing tandem plectasin peptides as inclusion bodies in E. coli. Antiviral activity of the recombinant peptide towards dengue serotype-2 NS2B-NS3 protease (DENV2 NS2B-NS3pro) was assessed as a target to inhibit dengue virus replication in Vero cells. Single units of recombinant plectasin were collected after applying consecutive steps of refolding, cleaving by Factor Xa, and nickel column purification to obtain recombinant proteins of high purity. The maximal nontoxic dose (MNTD) of the recombinant peptide against Vero cells was 20 μM (100 μg/mL). The reaction velocity of DENV2 NS2B-NS3pro decreased significantly after increasing concentrations of recombinant plectasin were applied to the reaction mixture. Plectasin peptide noncompetitively inhibited DENV2 NS2B-NS3pro at Ki value of 5.03±0.98 μM. The percentage of viral inhibition was more than 80% at the MNTD value of plectasin. In this study, biologically active recombinant plectasin which was able to inhibit dengue protease and viral replication in Vero cells was successfully produced in E. coli in a time- and cost- effective method. These findings are potentially important in the development of potent therapeutics against dengue infection. PMID:24044366

A Maximal Graded Exercise Test to Accurately Predict VO2max in 18-65-Year-Old Adults

ERIC Educational Resources Information Center

George, James D.; Bradshaw, Danielle I.; Hyde, Annette; Vehrs, Pat R.; Hager, Ronald L.; Yanowitz, Frank G.

2007-01-01

The purpose of this study was to develop an age-generalized regression model to predict maximal oxygen uptake (VO sub 2 max) based on a maximal treadmill graded exercise test (GXT; George, 1996). Participants (N = 100), ages 18-65 years, reached a maximal level of exertion (mean plus or minus standard deviation [SD]; maximal heart rate [HR sub…

MACROMOLECULAR THERAPEUTICS

PubMed Central

Yang, Jiyuan; Kopeček, Jindřich

2014-01-01

This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines – (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. PMID:24747162

Therapeutic potential of curcumin in digestive diseases

PubMed Central

Dulbecco, Pietro; Savarino, Vincenzo

2013-01-01

Curcumin is a low-molecular-weight hydrophobic polyphenol that is extracted from turmeric, which possesses a wide range of biological properties including anti-inflammatory, anti-oxidant, anti-proliferative and anti-microbial activities. Despite its diverse targets and substantial safety, clinical applications of this molecule for digestive disorders have been largely limited to case series or small clinical trials. The poor bioavailability of curcumin is likely the major hurdle for its more widespread use in humans. However, complexation of curcumin into phytosomes has recently helped to bypass this problem, as it has been demonstrated that this new lecithin formulation enables increased absorption to a level 29-fold higher than that of traditional curcuminoid products. This allows us to achieve much greater tissue substance delivery using significantly lower doses of curcumin than have been used in past clinical studies. As curcumin has already been shown to provide good therapeutic results in some small studies of both inflammatory and neoplastic bowel disorders, it is reasonable to anticipate an even greater efficacy with the advent of this new technology, which remarkably improves its bioavailability. These features are very promising and may represent a novel and effective therapeutic approach to both functional and organic digestive diseases. PMID:24409053

Therapeutic potential of gel-based injectables for vocal fold regeneration

PubMed Central

Bartlett, Rebecca S.; Thibeault, Susan L.; Prestwich, Glenn D.

2012-01-01

Vocal folds are anatomically and biomechanically unique, thus complicating the design and implementation of tissue engineering strategies for repair and regeneration. Integration of an enhanced understanding of tissue biomechanics, wound healing dynamics and innovative gel-based therapeutics has generated enthusiasm for the notion that an efficacious treatment for vocal fold scarring could be clinically attainable within several years. Fibroblast phenotype and gene expression are mediated by the three-dimensional mechanical and chemical microenvironment at an injury site. Thus, therapeutic approaches need to coordinate spatial and temporal aspects of the wound healing response in an injured vocal tissue to achieve an optimal clinical outcome. Successful gel-based injectables for vocal fold scarring will require a keen understanding of how the native inflammatory response sets into motion the later extracellular matrix remodeling, which in turn will determine the ultimate biomechanical properties of the tissue. We present an overview of the challenges associated with this translation as well as the proposed gel-based injectable solutions. PMID:22456756

Recognition-mediated activation of therapeutic gold nanoparticles inside living cells

NASA Astrophysics Data System (ADS)

Kim, Chaekyu; Agasti, Sarit S.; Zhu, Zhengjiang; Isaacs, Lyle; Rotello, Vincent M.

2010-11-01

Supramolecular chemistry provides a versatile tool for the organization of molecular systems into functional structures and the actuation of these assemblies for applications through the reversible association between complementary components. Use of this methodology in living systems, however, represents a significant challenge owing to the chemical complexity of cellular environments and lack of selectivity of conventional supramolecular interactions. Herein, we present a host-guest system featuring diaminohexane-terminated gold nanoparticles (AuNP-NH2) and complementary cucurbit[7]uril (CB[7]). In this system, threading of CB[7] on the particle surface reduces the cytotoxicity of AuNP-NH2 through sequestration of the particle in endosomes. Intracellular triggering of the therapeutic effect of AuNP-NH2 was then achieved through the administration of 1-adamantylamine (ADA), removing CB[7] from the nanoparticle surface, causing the endosomal release and concomitant in situ cytotoxicity of AuNP-NH2. This supramolecular strategy for intracellular activation provides a new tool for potential therapeutic applications.

Therapeutics incorporating blood constituents.

PubMed

Charoenphol, Phapanin; Oswalt, Katie; Bishop, Corey J

2018-04-05

Blood deficiency and dysfunctionality can result in adverse events, which can primarily be treated by transfusion of blood or the re-introduction of properly functioning sub-components. Blood constituents can be engineered on the sub-cellular (i.e., DNA recombinant technology) and cellular level (i.e., cellular hitchhiking for drug delivery) for supplementing and enhancing therapeutic efficacy, in addition to rectifying dysfunctioning mechanisms (i.e., clotting). Herein, we report the progress of blood-based therapeutics, with an emphasis on recent applications of blood transfusion, blood cell-based therapies and biomimetic carriers. Clinically translated technologies and commercial products of blood-based therapeutics are subsequently highlighted and perspectives on challenges and future prospects are discussed. Blood-based therapeutics is a burgeoning field and has advanced considerably in recent years. Blood and its constituents, with and without modification (i.e., combinatorial), have been utilized in a broad spectrum of pre-clinical and clinically-translated treatments. This review article summarizes the most up-to-date progress of blood-based therapeutics in the following contexts: synthetic blood substitutes, acellular/non-recombinant therapies, cell-based therapies, and therapeutic sub-components. The article subsequently discusses clinically-translated technologies and future prospects thereof. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Current Status of Dengue Therapeutics Research and Development.

PubMed

Low, Jenny G H; Ooi, Eng Eong; Vasudevan, Subhash G

2017-03-01

Dengue is a significant global health problem. Even though a vaccine against dengue is now available, which is a notable achievement, its long-term protective efficacy against each of the 4 dengue virus serotypes remains to be definitively determined. Consequently, drugs directed at the viral targets or critical host mechanisms that can be used safely as prophylaxis or treatment to effectively ameliorate disease or reduce disease severity and fatalities are still needed to reduce the burden of dengue. This review will provide a brief account of the status of therapeutics research and development for dengue. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Effect of questions used by psychiatrists on therapeutic alliance and adherence.

PubMed

Thompson, Laura; Howes, Christine; McCabe, Rose

2016-07-01

Psychiatrists' questions are the mechanism for achieving clinical objectives and managing the formation of a therapeutic alliance - consistently associated with patient adherence. No research has examined the nature of this relationship and the different practices used in psychiatry. Questions are typically defined in binary terms (e.g. 'open' v 'closed') that may have limited application in practice. To undertake a detailed examination of the types of questions psychiatrists ask patients and explore their association with the therapeutic alliance and patient adherence. A coding protocol was developed to classify questions from 134 out-patient consultations, predominantly by syntactic form. Bivariate correlations with measures of patient adherence and the therapeutic alliance (psychiatrist-rated) were examined and assessed using generalised estimating equations, adjusting for patient symptoms, psychiatrist identity and amount of speech. Psychiatrists used only four of ten question types regularly: yes/no auxiliary questions, 'wh-' questions, declarative questions and tag questions. Only declarative questions predicted better adherence and perceptions of the therapeutic relationship. Conversely, 'wh-' questions - associated with positive symptoms - predicted poorer perceptions of the therapeutic relationship. Declarative questions were frequently used to propose an understanding of patients' experiences, in particular their emotional salience for the patient. A refined defining of questioning practices is necessary to improve communication in psychiatry. The use of declarative questions may enhance alliance and adherence, or index their manifestation in talk, e.g. better mutual understanding. The function of 'so'-prefaced declaratives, also used in psychotherapy, is more nuanced than negatively connotated 'leading' questions. Hearable as displays of empathy, they attend closely to patient experience, while balancing the tasks of assessment and treatment. © The

WFH: closing the global gap--achieving optimal care.

PubMed

Skinner, Mark W

2012-07-01

For 50 years, the World Federation of Hemophilia (WFH) has been working globally to close the gap in care and to achieve Treatment for All patients, men and women, with haemophilia and other inherited bleeding disorders, regardless of where they might live. The WFH estimates that more than one in 1000 men and women has a bleeding disorder equating to 6,900,000 worldwide. To close the gap in care between developed and developing nations a continued focus on the successful strategies deployed heretofore will be required. However, in response to the rapid advances in treatment and emerging therapeutic advances on the horizon it will also require fresh approaches and renewed strategic thinking. It is difficult to predict what each therapeutic advance on the horizon will mean for the future, but there is no doubt that we are in a golden age of research and development, which has the prospect of revolutionizing treatment once again. An improved understanding of "optimal" treatment is fundamental to the continued evolution of global care. The challenges of answering government and payer demands for evidence-based medicine, and cost justification for the introduction and enhancement of treatment, are ever-present and growing. To sustain and improve care it is critical to build the body of outcome data for individual patients, within haemophilia treatment centers (HTCs), nationally, regionally and globally. Emerging therapeutic advances (longer half-life therapies and gene transfer) should not be justified or brought to market based only on the notion that they will be economically more affordable, although that may be the case, but rather more importantly that they will be therapeutically more advantageous. Improvements in treatment adherence, reductions in bleeding frequency (including microhemorrhages), better management of trough levels, and improved health outcomes (including quality of life) should be the foremost considerations. As part of a new WFH strategic plan

Profit Maximization Models for Exponential Decay Processes.

DTIC Science & Technology

1980-08-01

assumptions could easily be analyzed in similar fashion. References [1] Bensoussan, A., Hurst , E.G. and Nislund, B., Management Applications of Modern...TVIPe OF r 04PORNT A i M0 CiH O .V9RAE PROFIT MAXIMIZATION .ODELS FOR EXPONENT IAL Technical Report DECAY PROCESSES August 1990 ~~~I. PtA’OR~idNG ONqG

The effect of authentic leadership, organizational justice, and achievement motivation on teachers' performance in vocational high school seventeen Temanggung

NASA Astrophysics Data System (ADS)

Sugi, Slamet, Achmad; Martono, S.

2018-03-01

Teachers' performance in Temanggung in 2016 did not show maximal result. It was shown from many indicators. The low score of UN, UKG and PKB result. Individual performance was different. Achievement motivation could be seen through their attitude and behavior performances. The purpose of this research is to know the effect of authentic leadership, organizational justice, and achievement motivation on teachers' performance. The objects of this research are authentic leadership, organizational justice, achievement motivation and teachers' performance in Vocational High School Seventeen in Temanggung. The research method used is quantitative. Data collection was done by questioners. Then, the data were analyzed by using Path SPSS 16. The result of this research showed that authentic leadership, organizational justice, achievement motivation had significant effect on teachers' performance in Vocational High School Seventeen in Temanggung.

Teeth grinding, oral motor performance and maximal bite force in cerebral palsy children.

PubMed

Botti Rodrigues Santos, Maria Teresa; Duarte Ferreira, Maria Cristina; de Oliveira Guaré, Renata; Guimarães, Antonio Sergio; Lira Ortega, Adriana

2015-01-01

Identify whether the degree of oral motor performance is related to the presence of teeth grinding and maximal bite force values in children with spastic cerebral palsy. Ninety-five spastic cerebral palsy children with and without teeth grinding, according to caregivers' reports, were submitted to a comprehensive oral motor performance evaluation during the feeding process using the Oral Motor Assessment Scale. Maximal bite force was measured using an electronic gnathodynamometer. The teeth grinding group (n = 42) was younger, used anticonvulsant drugs, and was more frequently classified within the subfunctional oral motor performance category. Teeth grinding subfunctional spastic cerebral palsy children presented lower values of maximal bite force. The functional groups showing the presence or absence of teeth grinding presented higher values of maximal bite force compared with the subfunctional groups. In spastic cerebral palsy children, teeth grinding is associated with the worse oral motor performance. © 2015 Special Care Dentistry Association and Wiley Periodicals, Inc.

Effects of spine flexion and erector spinae maximal force on vertical squat jump height: a computational simulation study.

PubMed

Blache, Yoann; Monteil, Karine

2015-03-01

The purpose of this study was to evaluate the single and combined effects of initial spine flexion and maximal isometric force of the erector spinae on maximal vertical jump height during maximal squat jumping. Seven initial flexions of the 'thorax-head-arm' segment (between 20.1° and 71.6°) and five maximal isometric forces of the erector spinae (between 5600 and 8600 N) were tested. Thus, 35 squat jumps were simulated using a 2D simulation model of the musculoskeletal system. Vertical jump height varied at most about 0.094 and 0.021 m when the initial flexion of the 'thorax-head-arm' segment and the maximal force of the erector spinae were, respectively, maximal. These results were explained for the most part by the variation of total muscle work. The latter was mainly influenced by the work produced by the erector spinae which increased at most about 57 and 110 J when the initial flexion of the 'thorax-head-arm' segment and the maximal force of the erector spinae were, respectively, maximal. It was concluded that the increase in the initial flexion of the 'thorax-head-arm' segment and in the maximal isometric force of the erector spinae enables an increase in maximal vertical jump height during maximal squat jumping.

Power Maximization Control of Variable Speed Wind Generation System Using Permanent Magnet Synchronous Generator

NASA Astrophysics Data System (ADS)

Morimoto, Shigeo; Nakamura, Tomohiko; Takeda, Yoji

This paper proposes the sensorless output power maximization control of the wind generation system. A permanent magnet synchronous generator (PMSG) is used as a variable speed generator in the proposed system. The generator torque is suitably controlled according to the generator speed and thus the power from a wind turbine settles down on the maximum power point by the proposed MPPT control method, where the information of wind velocity is not required. Moreover, the maximum available generated power is obtained by the optimum current vector control. The current vector of PMSG is optimally controlled according to the generator speed and the required torque in order to minimize the losses of PMSG considering the voltage and current constraints. The proposed wind power generation system can be achieved without mechanical sensors such as a wind velocity detector and a position sensor. Several experimental results show the effectiveness of the proposed control method.

Therapeutic scrapbooking: a technique to promote positive coping and emotional strength in parents of pediatric oncology patients.

PubMed

McCarthy, Paula G; Sebaugh, Jill Genone

2011-01-01

Therapeutic scrapbooking is an intervention being used with parents and caregivers of children with cancer. The purpose of the group is to promote hopefulness, mobilize internal strengths, and thereby enhance the parents' and caregivers' coping abilities to benefit pediatric oncology patients. Facilitators, licensed in medical social work, provide a safe environment for participants to verbalize their stories and share their distress. Scrapbooking is a "normal" activity without the negative stigma that a "support group" may carry, minimizing the reluctance to attend this supportive group. Outcome measurements indicate this therapeutic intervention achieves positive results.

Therapeutic Nanodevices

NASA Astrophysics Data System (ADS)

Lee, Stephen C.; Ruegsegger, Mark; Barnes, Philip D.; Smith, Bryan R.; Ferrari, Mauro

Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'etre of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multi-step work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

Therapeutic Nanodevices

NASA Astrophysics Data System (ADS)

Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

[Plants as an alternative source of therapeutic proteins].

PubMed

Łucka, Marta; Kowalczyk, Tomasz; Szemraj, Janusz; Sakowicz, Tomasz

2015-03-22

In recent years, there has been an increased interest of researchers in developing efficient plant heterologous expression systems of proteins for a wide range of applications. It represents an alternative to the traditional strategy utilizing bacterial, yeast, insect or mammalian cells. New techniques of identification and characterization and effective methods of plant genetic transformation allow the range of recombinant protein products to be expanded. Great expectations are associated with the use of plants as bioreactors for the production of specific proteins of therapeutic interest. This strategy offers a number of advantages, the most important being: the possibility of a significant reduction in production costs, the safety of the products obtained and full eukaryotic post-translational modifications of proteins. A group of proteins of special interest is pharmaceuticals, and a number of successful experiments have confirmed the possibility of obtaining heterogeneous proteins with therapeutic potential: monoclonal antibodies, vaccine antigens, and a variety of cytokines. This work is focused on selected recombinant proteins belonging to those groups expression of which was achieved in plant cells. These proteins may be used in the future for therapy or prevention of viral, bacterial or cancer diseases.

Therapeutic mechanisms of high-frequency stimulation in Parkinson's disease and neural restoration via loop-based reinforcement.

PubMed

Santaniello, Sabato; McCarthy, Michelle M; Montgomery, Erwin B; Gale, John T; Kopell, Nancy; Sarma, Sridevi V

2015-02-10

High-frequency deep brain stimulation (HFS) is clinically recognized to treat parkinsonian movement disorders, but its mechanisms remain elusive. Current hypotheses suggest that the therapeutic merit of HFS stems from increasing the regularity of the firing patterns in the basal ganglia (BG). Although this is consistent with experiments in humans and animal models of Parkinsonism, it is unclear how the pattern regularization would originate from HFS. To address this question, we built a computational model of the cortico-BG-thalamo-cortical loop in normal and parkinsonian conditions. We simulated the effects of subthalamic deep brain stimulation both proximally to the stimulation site and distally through orthodromic and antidromic mechanisms for several stimulation frequencies (20-180 Hz) and, correspondingly, we studied the evolution of the firing patterns in the loop. The model closely reproduced experimental evidence for each structure in the loop and showed that neither the proximal effects nor the distal effects individually account for the observed pattern changes, whereas the combined impact of these effects increases with the stimulation frequency and becomes significant for HFS. Perturbations evoked proximally and distally propagate along the loop, rendezvous in the striatum, and, for HFS, positively overlap (reinforcement), thus causing larger poststimulus activation and more regular patterns in striatum. Reinforcement is maximal for the clinically relevant 130-Hz stimulation and restores a more normal activity in the nuclei downstream. These results suggest that reinforcement may be pivotal to achieve pattern regularization and restore the neural activity in the nuclei downstream and may stem from frequency-selective resonant properties of the loop.

Macromolecular therapeutics.

PubMed

Yang, Jiyuan; Kopeček, Jindřich

2014-09-28

This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines - (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. Copyright © 2014 Elsevier B.V. All rights reserved.

Influence of simulated microgravity on the maximal oxygen consumption of nontrained and trained rats

NASA Technical Reports Server (NTRS)

Woodman, Christopher R.; Monnin, Kimberly A.; Sebastian, Lisa A.; Tipton, Charles M.

1993-01-01

The effects of microgravity and endurance training (TR) on maximal O2 consumption was investigated in trained and nontrained (NT) rats subjected to head-down suspension (HDS) by comparing maximal O2 consumption, treadmill run time (RT), and mechanical efficiency (ME) of treadmill running in HDS rats, both NT and TR, and in respective cage controls. It was found that HDS for 28 days was associated with significant reduction in absolute maximal O2 consumption in both TR and NT rats. Relative maximal O2 consumption, however, was significantly reduced in TR but not NT rats. Reductions in RT and ME occurring in both TR and NT rats after 28 days of HDS were similar. The TR rats exhibited greater diuretic, natriuretic, and kaliuretic responses to HDS than the NT rats.

[Therapeutic cloning in debate].

PubMed

de Wert, G

2001-11-03

Human embryos can be conceived by cell nuclear transfer in order to isolate human embryonic stem cells (hES cells) for research into autologous cell therapy (therapeutic cloning). However, this technique broaches the major ethical problem concerning the instrumental use of human preimplantation embryos. From the viewpoint of subsidiarity, it is argued that various potential alternatives for therapeutic cloning should first be investigated further. The question as to whether therapeutic cloning should be allowed only becomes apparent when research with surplus embryos obtained in the course of in-vitro fertilization suggests that usable transplants can be obtained in vitro from hES cells, and when the potential alternatives for therapeutic cloning are either less promising or need more time for development than is currently expected.

Planning Routes Across Economic Terrains: Maximizing Utility, Following Heuristics

PubMed Central

Zhang, Hang; Maddula, Soumya V.; Maloney, Laurence T.

2010-01-01

We designed an economic task to investigate human planning of routes in landscapes where travel in different kinds of terrain incurs different costs. Participants moved their finger across a touch screen from a starting point to a destination. The screen was divided into distinct kinds of terrain and travel within each kind of terrain imposed a cost proportional to distance traveled. We varied costs and spatial configurations of terrains and participants received fixed bonuses minus the total cost of the routes they chose. We first compared performance to a model maximizing gain. All but one of 12 participants failed to adopt least-cost routes and their failure to do so reduced their winnings by about 30% (median value). We tested in detail whether participants’ choices of routes satisfied three necessary conditions (heuristics) for a route to maximize gain. We report failures of one heuristic for 7 out of 12 participants. Last of all, we modeled human performance with the assumption that participants assign subjective utilities to costs and maximize utility. For 7 out 12 participants, the fitted utility function was an accelerating power function of actual cost and for the remaining 5, a decelerating power function. We discuss connections between utility aggregation in route planning and decision under risk. Our task could be adapted to investigate human strategy and optimality of route planning in full-scale landscapes. PMID:21833269

Advances in refractory ulcerative colitis treatment: A new therapeutic target, Annexin A2

PubMed Central

Tanida, Satoshi; Mizoshita, Tsutomu; Ozeki, Keiji; Katano, Takahito; Kataoka, Hiromi; Kamiya, Takeshi; Joh, Takashi

2015-01-01

Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis (UC). Proposed mediators of inflammation in UC include pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-2, and the cell-surface adhesive molecule integrin α4β7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues (azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-α inhibitors infliximab or adalimumab, or a neutralizing antibody (vedolizumab) directed against integrin α4β7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-α shedding demonstrated that inhibition of annexin (ANX) A2 may be a new therapeutic strategy for the prevention of TNF-α shedding during inflammatory bowel disease (IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment. PMID:26269667

Mixed maximal and explosive strength training in recreational endurance runners.

PubMed

Taipale, Ritva S; Mikkola, Jussi; Salo, Tiina; Hokka, Laura; Vesterinen, Ville; Kraemer, William J; Nummela, Ari; Häkkinen, Keijo

2014-03-01

Supervised periodized mixed maximal and explosive strength training added to endurance training in recreational endurance runners was examined during an 8-week intervention preceded by an 8-week preparatory strength training period. Thirty-four subjects (21-45 years) were divided into experimental groups: men (M, n = 9), women (W, n = 9), and control groups: men (MC, n = 7), women (WC, n = 9). The experimental groups performed mixed maximal and explosive exercises, whereas control subjects performed circuit training with body weight. Endurance training included running at an intensity below lactate threshold. Strength, power, endurance performance characteristics, and hormones were monitored throughout the study. Significance was set at p ≤ 0.05. Increases were observed in both experimental groups that were more systematic than in the control groups in explosive strength (12 and 13% in men and women, respectively), muscle activation, maximal strength (6 and 13%), and peak running speed (14.9 ± 1.2 to 15.6 ± 1.2 and 12.9 ± 0.9 to 13.5 ± 0.8 km Ł h). The control groups showed significant improvements in maximal and explosive strength, but Speak increased only in MC. Submaximal running characteristics (blood lactate and heart rate) improved in all groups. Serum hormones fluctuated significantly in men (testosterone) and in women (thyroid stimulating hormone) but returned to baseline by the end of the study. Mixed strength training combined with endurance training may be more effective than circuit training in recreational endurance runners to benefit overall fitness that may be important for other adaptive processes and larger training loads associated with, e.g., marathon training.

Near Infrared Fluorescence Imaging in Nano-Therapeutics and Photo-Thermal Evaluation

PubMed Central

Vats, Mukti; Mishra, Sumit Kumar; Baghini, Mahdieh Shojaei; Chauhan, Deepak S.; Srivastava, Rohit; De, Abhijit

2017-01-01

The unresolved and paramount challenge in bio-imaging and targeted therapy is to clearly define and demarcate the physical margins of tumor tissue. The ability to outline the healthy vital tissues to be carefully navigated with transection while an intraoperative surgery procedure is performed sets up a necessary and under-researched goal. To achieve the aforementioned objectives, there is a need to optimize design considerations in order to not only obtain an effective imaging agent but to also achieve attributes like favorable water solubility, biocompatibility, high molecular brightness, and a tissue specific targeting approach. The emergence of near infra-red fluorescence (NIRF) light for tissue scale imaging owes to the provision of highly specific images of the target organ. The special characteristics of near infra-red window such as minimal auto-fluorescence, low light scattering, and absorption of biomolecules in tissue converge to form an attractive modality for cancer imaging. Imparting molecular fluorescence as an exogenous contrast agent is the most beneficial attribute of NIRF light as a clinical imaging technology. Additionally, many such agents also display therapeutic potentials as photo-thermal agents, thus meeting the dual purpose of imaging and therapy. Here, we primarily discuss molecular imaging and therapeutic potentials of two such classes of materials, i.e., inorganic NIR dyes and metallic gold nanoparticle based materials. PMID:28452928

Predicting seizure-free status for temporal lobe epilepsy patients undergoing surgery: prognostic value of quantifying maximal metabolic asymmetry extending over a specified proportion of the temporal lobe.

PubMed

Lin, Tina W; de Aburto, Michelle A Kung; Dahlbom, Magnus; Huang, Lynn L; Marvi, Michael M; Tang, Michael; Czernin, Johannes; Phelps, Michael E; Silverman, Daniel H S

2007-05-01

Conventional visual analysis of brain (18)F-FDG PET scans is useful for predicting postsurgical improvement for temporal lobe epilepsy (TLE) patients, but prognostic value for identifying patients who will achieve seizure-free status is considerably lower. We aimed to develop an approach with which to quantitatively assess prognostically pertinent aspects of metabolic asymmetry in presurgical PET scans for forecasting postsurgical seizure-free clinical outcomes. Presurgical brain PET scans of 75 TLE patients were examined using a display/analysis tool that quantified maximal metabolic asymmetry in a specified proportion (x%) of the temporal lobe pixels in the most asymmetric plane, generating a temporal lobe asymmetry index (T-AI(x)). Results of this analysis were compared with patients' actual postsurgical outcomes after an average of approximately 4 y of clinical follow-up. The investigation was divided into 2 main steps: The PET scans examined in the first step, selected by chronological order of scan acquisition dates, comprised just less than two thirds of the patient group studied (n=47) and were used to look for parameters predicting seizure-free postsurgical outcome; in the second step, the predictive value of the parameters suggested by the analysis in the first step was independently examined using the set of remaining PET scans (n=28) to check for wider applicability of the approach. Of the 75 patients studied, 42 became seizure free after surgery, whereas 33 continued to seize beyond the immediate postoperative period, during a mean 3.8-y follow-up interval. The specified proportion of temporal pixels with which to assess maximal asymmetry that provided the highest prognostic value with respect to achieving seizure-free status was 20%. Across the study population, those patients with scans having lower T-AI(20) values (corresponding to <40% difference in pixel intensities between left and right temporal lobes, among the 20% most asymmetric left

Quantum coherence generating power, maximally abelian subalgebras, and Grassmannian geometry

NASA Astrophysics Data System (ADS)

Zanardi, Paolo; Campos Venuti, Lorenzo

2018-01-01

We establish a direct connection between the power of a unitary map in d-dimensions (d < ∞) to generate quantum coherence and the geometry of the set Md of maximally abelian subalgebras (of the quantum system full operator algebra). This set can be seen as a topologically non-trivial subset of the Grassmannian over linear operators. The natural distance over the Grassmannian induces a metric structure on Md, which quantifies the lack of commutativity between the pairs of subalgebras. Given a maximally abelian subalgebra, one can define, on physical grounds, an associated measure of quantum coherence. We show that the average quantum coherence generated by a unitary map acting on a uniform ensemble of quantum states in the algebra (the so-called coherence generating power of the map) is proportional to the distance between a pair of maximally abelian subalgebras in Md connected by the unitary transformation itself. By embedding the Grassmannian into a projective space, one can pull-back the standard Fubini-Study metric on Md and define in this way novel geometrical measures of quantum coherence generating power. We also briefly discuss the associated differential metric structures.

Psychodynamic Perspective on Therapeutic Boundaries

PubMed Central

Bridges, Nancy A.

1999-01-01

Discussion of boundaries in therapeutic work most often focuses on boundary maintenance, risk management factors, and boundary violations. The psychodynamic meaning and clinical management of boundaries in therapeutic relationships remains a neglected area of discourse. Clinical vignettes will illustrate a psychodynamic, developmental-relational perspective using boundary dilemmas to deepen and advance the therapeutic process. This article contributes to the dialogue about the process of making meaning and constructing therapeutically useful and creative boundaries that further the psychotherapeutic process. PMID:10523432

The Relationship Between Maximal Aerobic Power and Recovery in Elite Ice Hockey Players During a Simulated Game.

PubMed

Steeves, Darren; Campagna, Phil

2018-02-14

This project investigated whether there was a relationship between maximal aerobic power and the recovery or performance in elite ice hockey players during a simulated hockey game. An on-ice protocol was used to simulate a game of ice hockey. Recovery values were determined by the differences in lactate and heart rate measures. Total distance traveled was also recorded as a performance measure. On two other days, subjects returned and completed a maximal aerobic power test on a treadmill and a maximal lactate test on ice. Statistical analysis showed no relationship between maximal aerobic power or maximal lactate values and recovery (heart rate, lactate) or the performance measure of distance traveled. It was concluded there was no relationship between maximal aerobic power and recovery during a simulated game in elite hockey players.

[Nuclear transfer and therapeutic cloning].

PubMed

Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

2005-03-01

Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

Controlling subcellular delivery to optimize therapeutic effect

PubMed Central

Mossalam, Mohanad; Dixon, Andrew S; Lim, Carol S

2010-01-01

This article focuses on drug targeting to specific cellular organelles for therapeutic purposes. Drugs can be delivered to all major organelles of the cell (cytosol, endosome/lysosome, nucleus, nucleolus, mitochondria, endoplasmic reticulum, Golgi apparatus, peroxisomes and proteasomes) where they exert specific effects in those particular subcellular compartments. Delivery can be achieved by chemical (e.g., polymeric) or biological (e.g., signal sequences) means. Unidirectional targeting to individual organelles has proven to be immensely successful for drug therapy. Newer technologies that accommodate multiple signals (e.g., protein switch and virus-like delivery systems) mimic nature and allow for a more sophisticated approach to drug delivery. Harnessing different methods of targeting multiple organelles in a cell will lead to better drug delivery and improvements in disease therapy. PMID:21113240

The efficacy of incorporating partial squats in maximal strength training.

PubMed

Bazyler, Caleb D; Sato, Kimitake; Wassinger, Craig A; Lamont, Hugh S; Stone, Michael H

2014-11-01

The purpose of our study was to examine the effects of 2 different training methods on dynamic and isometric measures of maximal strength. Seventeen recreationally trained men (1 repetition maximum [1RM] squat: 146.9 ± 22.4 kg) were assigned to 2 groups: full range of motion (ROM) squat (F) and full ROM with partial ROM squat (FP) for the 7-week training intervention. Repeated measures analysis of variance revealed that there was a statistically significant group-by-time interaction for impulse scaled at 50, 90, and 250 milliseconds at 90° of knee flexion and rate of force development at 200 milliseconds with 120° of knee flexion (p ≤ 0.05). There was also a statistically significant time effect (p ≤ 0.05) for the 1RM squat, 1RM partial squat, isometric squat peak force allometrically scaled (IPFa) 90°, IPFa 120°, and impulse allometrically scaled at 50, 90, 200, and 250 milliseconds at 90° and 120° of knee flexion. Additionally, the FP group achieved statistically larger relative training intensities (%1RM) during the final 3 weeks of training (p ≤ 0.05). There was a trend for FP to improve over F in 1RM squat (+3.1%, d = 0.53 vs. 0.32), 1RM partial squat (+4.7%, d = 0.95 vs. 0.69), IPFa 120° (+5.7%, d = 0.52 vs. 0.12), and impulse scaled at 50, 90, 200, and 250 milliseconds at 90° (+6.3 to 13.2%, d = 0.50-1.01 vs. 0.30-0.57) and 120° (+3.4 to 16.8%, d = 0.45-1.11 vs. 0.08-0.37). These larger effect sizes in the FP group can likely be explained their ability to train at larger relative training intensities during the final 3 weeks of training resulting in superior training adaptations. Our findings suggest that partial ROM squats in conjunction with full ROM squats may be an effective training method for improving maximal strength and early force-time curve characteristics in men with previous strength training experience. Practically, partial squats may be beneficial for strength and power athletes during a strength-speed mesocycle while peaking

Linear discriminant analysis based on L1-norm maximization.

PubMed

Zhong, Fujin; Zhang, Jiashu

2013-08-01

Linear discriminant analysis (LDA) is a well-known dimensionality reduction technique, which is widely used for many purposes. However, conventional LDA is sensitive to outliers because its objective function is based on the distance criterion using L2-norm. This paper proposes a simple but effective robust LDA version based on L1-norm maximization, which learns a set of local optimal projection vectors by maximizing the ratio of the L1-norm-based between-class dispersion and the L1-norm-based within-class dispersion. The proposed method is theoretically proved to be feasible and robust to outliers while overcoming the singular problem of the within-class scatter matrix for conventional LDA. Experiments on artificial datasets, standard classification datasets and three popular image databases demonstrate the efficacy of the proposed method.

Teacher Praise: Maximizing the Motivational Impact. Teaching Strategies.

ERIC Educational Resources Information Center

McVey, Mary D.

2001-01-01

Recognizes the influence of praise on human behavior, and provides specific suggestions on how to maximize the positive effects of praise when intended as positive reinforcement. Examines contingency, specificity, and selectivity aspects of praise. Cautions teachers to avoid the controlling effects of praise and the possibility that praise may…

Fertilizer placement to maximize nitrogen use by fescue

USDA-ARS?s Scientific Manuscript database

The method of fertilizer nitrogen(N) application can affect N uptake in tall fescue and therefore its yield and quality. Subsurface-banding (knife) of fertilizer maximizes fescue N uptake in the poorly-drained clay–pan soils of southeastern Kansas. This study was conducted to determine if knifed N r...

Fluid-electrolyte shifts and maximal oxygen uptake in man at simulated altitude /2,287 m/

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Bernauer, E. M.; Adams, W. C.; Juhos, L.

1978-01-01

Experiments were conducted on six trained distance runners (21-23 yr) subjected to an eight-day dietary control at sea level, followed by an eight-day stay in an altitude chamber (2287-m altitude) and a four-day recovery at sea level. Fluid and electrolyte shifts during exercise at altitude were evaluated to gain insight into the mechanism of reduction in working capacity. The results are discussed in terms of resting fluid volumes and blood constituents, maximal exercise variables, and maximal exercise fluid-electrolyte shifts. Since there are no significant changes in fluid balance or resting plasma volume (PV) at altitude, it is concluded that neither these nor the excessive PV shifts with exercise contribute to the reduction in maximal oxygen uptake at altitude. During altitude exposure the percent loss in PV is found to follow the percent reduction in maximal oxygen uptake; however, on the first day of recovery the percent change in PV remains depressed while maximal oxygen uptake returns to control levels.

Effect of Semirecumbent and Upright Body Position on Maximal and Submaximal Exercise Testing

ERIC Educational Resources Information Center

Scott, Alexander; Antonishen, Kevin; Johnston, Chris; Pearce, Terri; Ryan, Michael; Sheel, A. William; McKenzie, Don C.

2006-01-01

The study was designed to determine the effect of upright-posture (UP) versus semirecumbent (SR) cycling on commonly used measures of maximal and submaximal exercise capacity. Nine healthy, untrained men (M age = 27 years, SD = 4.8 years) underwent steady-state submaximal aerobic testing followed by a ramped test to determine maximal oxygen…

Navy Strategy for Achieving Information Dominance, 2013-2017. Optimizing Navy’s Primacy in the Maritime and Information Domains

DTIC Science & Technology

2013-01-01

and resources to optimize decision making and maximize warfighting effects, Navy Information Dominance has become a leading Service priority. In 2009...This Strategy for Achieving Information Dominance provides the framework through which the Navy s information capabilities will be mainstreamed into...the Navy s culture as a distinct warfighting discipline. The strategy focuses on the three fundamental Information Dominance capabilities of Assured

Therapeutic Inertia and Treatment Intensification.

PubMed

Josiah Willock, Robina; Miller, Joseph B; Mohyi, Michelle; Abuzaanona, Ahmed; Muminovic, Meri; Levy, Phillip D

2018-01-29

This review aims to emphasize how therapeutic inertia, the failure of clinicians to intensify treatment when blood pressure rises or remains above therapeutic goals, contributes to suboptimal blood pressure control in hypertensive populations. Studies reveal that the therapeutic inertia is quite common and contributes to suboptimal blood pressure control. Quality improvement programs and standardized approaches to support antihypertensive treatment intensification are ways to combat therapeutic inertia. Furthermore, programs that utilize non-physician medical professionals such as pharmacists and nurses demonstrate promise in mitigating the effects of this important problem. Therapeutic inertia impedes antihypertensive management and requires a broad effort to reduce its effects. There is an ongoing need for renewed focus and research in this area to improve hypertension control.

Milrinone in advanced heart failure: dose and therapeutic monitor outside intensive care unit.

PubMed

Charisopoulou, Dafni; Leaver, Neil; Banner, Nicholas R

2014-04-01

Advanced chronic heart failure (ACHF) patients often require inotropes before transplantation or ventricular assist device implantation. Milrinone, an inotrope and vasodilator, may accumulate in cardiorenal syndrome with serious adverse effects. We investigated the potential for therapeutic drug monitoring of milrinone levels using High Performance Liquid Chromatography Mass Spectrometry (HPLC-MS). 22 ACHF patients (15 males, 49±9 years) received milrinone 50 µg/kg intravenously (i.v.) during heart catheterization. Milrinone levels were 216±71 ng/ml (within the reported therapeutic range: 100-300 ng/ml), followed by improvements in cardiac index, pulmonary artery and wedge pressures (p < 0.005). 18 ACHF patients (17 males, 50±12 years, 13 had renal dysfunction) received continuous i.v. milrinone (5-26 days) at 0.1-0.2 µg/kg/min, titrated according to plasma milrinone levels. No adverse events occurred. Therapeutic levels were achieved with doses of 0.2±0.06 µg/Kg/min, below those recommended in Summary of Product Characteristics. Milrinone therapy can be noninvasively monitored by HPLC-MS, while avoiding toxicity in ACHF.

MULTI-STAGE DELIVERY NANO-PARTICLE SYSTEMS FOR THERAPEUTIC APPLICATIONS