Expansion/Facemask Treatment of an Adult Class III Malocclusion.

PubMed

Jackson, Gregory W; Kravitz, Neal D

2014-01-01

The orthodontic treatment of class III malocclusion with a maxillary deficiency is often treated with maxillary protraction with or without expansion. Skeletal and dental changes have been documented which have combined for the protraction of the maxilla and the correction of the class III malocclusion. Concerning the ideal time to treat a developing class III malocclusion, studies have reported that, although early treatment may be the most effective, face mask therapy can provide a viable option for older children as well. But what about young adults? Can the skeletal and dental changes seen in expansion/facemask therapy in children and adolescents be demonstrated in this age group as well, possibly eliminating the need for orthodontic dental camouflage treatment or orthognathic surgery? A case report is presented of an adult class III malocclusion with a Class III skeletal pattern and maxillary retrusion. Treatment was with nonextraction, comprehensive edgewise mechanics with slow maxillary expansion with a bonded expander and protraction facemask.

76 FR 16646 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-24

...-Settled Foreign Currency Option Fees, in Section III of the Fee Schedule, with Singly Listed Options \\3...\\. The Exchange currently assesses fees for sector index options and U.S. Dollar-Settled foreign currency... U.S. Dollar-Settled Foreign Currency Option Fees.'' \\4\\ BKX represents the KBW Bank Index. \\5\\ RUT...

17 CFR 3.33 - Withdrawal from registration.

Code of Federal Regulations, 2013 CFR

2013-04-01

... all customer, retail forex customer or option customer agreements, if any, have been terminated; (ii) That all customer, retail forex customer or option customer positions, if any, have been transferred on behalf of customers or option customers or closed; (iii) That all customer, retail forex customer or...

17 CFR 3.33 - Withdrawal from registration.

Code of Federal Regulations, 2014 CFR

2014-04-01

... all customer, retail forex customer or option customer agreements, if any, have been terminated; (ii) That all customer, retail forex customer or option customer positions, if any, have been transferred on behalf of customers or option customers or closed; (iii) That all customer, retail forex customer or...

A Kramers-Moyal approach to the analysis of third-order noise with applications in option valuation.

PubMed

Popescu, Dan M; Lipan, Ovidiu

2015-01-01

We propose the use of the Kramers-Moyal expansion in the analysis of third-order noise. In particular, we show how the approach can be applied in the theoretical study of option valuation. Despite Pawula's theorem, which states that a truncated model may exhibit poor statistical properties, we show that for a third-order Kramers-Moyal truncation model of an option's and its underlier's price, important properties emerge: (i) the option price can be written in a closed analytical form that involves the Airy function, (ii) the price is a positive function for positive skewness in the distribution, (iii) for negative skewness, the price becomes negative only for price values that are close to zero. Moreover, using third-order noise in option valuation reveals additional properties: (iv) the inconsistencies between two popular option pricing approaches (using a "delta-hedged" portfolio and using an option replicating portfolio) that are otherwise equivalent up to the second moment, (v) the ability to develop a measure R of how accurately an option can be replicated by a mixture of the underlying stocks and cash, (vi) further limitations of second-order models revealed by introducing third-order noise.

A Selected Annotated Bibliography on Work Time Options.

ERIC Educational Resources Information Center

Ivantcho, Barbara

This annotated bibliography is divided into three sections. Section I contains annotations of general publications on work time options. Section II presents resources on flexitime and the compressed work week. In Section III are found resources related to these reduced work time options: permanent part-time employment, job sharing, voluntary…

Treatment Options for Class III Malocclusion in Growing Patients with Emphasis on Maxillary Protraction

PubMed Central

Azamian, Zeinab; Shirban, Farinaz

2016-01-01

It is very difficult to diagnose and treat Class III malocclusion. This type of malocclusion involves a number of cranial base and maxillary and mandibular skeletal and dental compensation components. In Class III malocclusion originating from mandibular prognathism, orthodontic treatment in growing patients is not a good choice and in most cases orthognathic surgery is recommended after the end of growth. Approximately 30–40% of Class III patients exhibit some degree of maxillary deficiency; therefore, devices can be used for maxillary protraction for orthodontic treatment in early mixed dentition. In cases in which dental components are primarily responsible for Class III malocclusion, early therapeutic intervention is recommended. An electronic search was conducted using the Medline database (Entrez PubMed), the Cochrane Collaboration Oral Health Group Database of Clinical Trials, Science Direct, and Scopus. In this review article, we described the treatment options for Class III malocclusion in growing patient with an emphasis on maxillary protraction. It seems that the most important factor for treatment of Class III malocclusion in growing patient is case selection. PMID:27144056

The Strategic Design of Reward Systems.

DTIC Science & Technology

1982-10-01

AuTO1 , 8 CO NTRACT Ok .NANT NUMO lll , Edward E. Lawler III N-00014-81-K-0048 9 PERFORMING ORGANIZATION NAME AND ADORErS 10. PROGRAM ELEMENT...SUPPLEMENTARY NOTES .iL L:~ 19 KEY WORDS (Continue on reveres side It necessary and Identify by block number) A Pay, performance appraisal, motivation...retention, culture development:, and skill development are considered. The relationship between these object iwv and such design options as performance pay

Designing sustainable and economically attractive brownfield revitalization options using an integrated assessment model.

PubMed

Schädler, S; Morio, M; Bartke, S; Rohr-Zänker, R; Finkel, M

2011-03-01

We describe the development of an integrated assessment model which evaluates redevelopment options of large contaminated brownfields and we present the application of the model in a case study. Aiming to support efficient and sustainable revitalization and communication between stakeholders, the presented assessment model integrates three pinnacles of brownfield revitalization: (i) subsurface remediation and site preparation costs, (ii) market-oriented economic appraisal, and (iii) the expected contribution of planned future land use to sustainable community and regional development. For the assessment, focus is set on the early stage of the brownfield redevelopment process, which is characterized by limited data availability and by flexibility in land use planning and development scope. At this stage, revealing the consequences of adjustments and alterations in planning options can foster efficiency in communication between the involved parties and thereby facilitates the brownfield revitalization process. Results from the case-study application indicate that the integrated assessment provides help in the identification of land use options beneficial in both a sustainable and an economical sense. For the study site it is shown on one hand that brownfield redevelopment is not automatically in line with sustainable regional development, and on the other hand it is demonstrated that additional contributions to sustainability are not intrinsically tied to increased costs. Copyright © 2010 Elsevier Ltd. All rights reserved.

A Kramers-Moyal Approach to the Analysis of Third-Order Noise with Applications in Option Valuation

PubMed Central

Popescu, Dan M.; Lipan, Ovidiu

2015-01-01

We propose the use of the Kramers-Moyal expansion in the analysis of third-order noise. In particular, we show how the approach can be applied in the theoretical study of option valuation. Despite Pawula’s theorem, which states that a truncated model may exhibit poor statistical properties, we show that for a third-order Kramers-Moyal truncation model of an option’s and its underlier’s price, important properties emerge: (i) the option price can be written in a closed analytical form that involves the Airy function, (ii) the price is a positive function for positive skewness in the distribution, (iii) for negative skewness, the price becomes negative only for price values that are close to zero. Moreover, using third-order noise in option valuation reveals additional properties: (iv) the inconsistencies between two popular option pricing approaches (using a “delta-hedged” portfolio and using an option replicating portfolio) that are otherwise equivalent up to the second moment, (v) the ability to develop a measure R of how accurately an option can be replicated by a mixture of the underlying stocks and cash, (vi) further limitations of second-order models revealed by introducing third-order noise. PMID:25625856

76 FR 10735 - Medicaid Program; Community First Choice Option

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-25

... Vol. 76 Friday, No. 38 February 25, 2011 Part III Department of Health and Human Services Centers for Medicare & Medicaid Services 42 CFR Part 441 Medicaid Program; Community First Choice Option...; [[Page 10736

New Therapies Offer Valuable Options for Patients with Melanoma

Cancer.gov

Two phase III clinical trials of new therapies for patients with metastatic melanoma presented in June at the 2011 ASCO conference confirmed that vemurafenib and ipilimumab (Yervoy™) offer valuable new options for the disease.

Quantitative option analysis for implementation and management of landfills.

PubMed

Kerestecioğlu, Merih

2016-09-01

The selection of the most feasible strategy for implementation of landfills is a challenging step. Potential implementation options of landfills cover a wide range, from conventional construction contracts to the concessions. Montenegro, seeking to improve the efficiency of the public services while maintaining affordability, was considering privatisation as a way to reduce public spending on service provision. In this study, to determine the most feasible model for construction and operation of a regional landfill, a quantitative risk analysis was implemented with four steps: (i) development of a global risk matrix; (ii) assignment of qualitative probabilities of occurrences and magnitude of impacts; (iii) determination of the risks to be mitigated, monitored, controlled or ignored; (iv) reduction of the main risk elements; and (v) incorporation of quantitative estimates of probability of occurrence and expected impact for each risk element in the reduced risk matrix. The evaluated scenarios were: (i) construction and operation of the regional landfill by the public sector; (ii) construction and operation of the landfill by private sector and transfer of the ownership to the public sector after a pre-defined period; and (iii) operation of the landfill by the private sector, without ownership. The quantitative risk assessment concluded that introduction of a public private partnership is not the most feasible option, unlike the common belief in several public institutions in developing countries. A management contract for the first years of operation was advised to be implemented, after which, a long term operating contract may follow. © The Author(s) 2016.

Professionals' and laypersons' appreciation of various options for Class III surgical correction.

PubMed

Fabré, M; Mossaz, C; Christou, P; Kiliaridis, S

2010-08-01

The objectives of this study were to evaluate the assessments of maxillofacial surgeons, orthodontists, and laypersons on the predicted aesthetic outcome of various surgical options in Class III correction and the associations between certain initial cephalometric values and the judges' preferred option. Pre-surgical lateral headfilms and coloured profile photographs of 18 skeletal Class III Caucasian adult patients (10 males and 8 females) with a mean age of 24.5 years were used. The headfilms were hand traced and digitized. Conventional cephalometric analysis was performed. Computerized predictions of three surgical options, mandibular setback, Le Fort I advancement, and bimaxillary surgery, were made. For each case, the pre-surgical profile photograph with the three predictions was presented on a printed page. The questionnaire was sent to 51 maxillofacial surgeons (response rate 45.1 per cent), 78 orthodontists (response rate 71.8 per cent), and 61 laypersons (response rate 100 per cent) to aesthetically evaluate the pre-surgical photographs and the surgical predictions by placing a mark along a 10-graded visual analogue scale (VAS) using a standard profile for calibration. Confidence interval was calculated for each patient. An independent samples t-test was used to detect initial cephalometric values associated with the judges' preferred option and analysis of variance/Tukey's honestly significant differences to evaluate differences between judges. Intra-observer reliability was assessed with a paired t-test. All treatment predictions led to improved scoring of facial aesthetics with the exception of the setback option for three patients. For 14 patients, general agreement for the preferred option existed between the three groups of judges. Laypersons tended to give lower improvement scores than professionals. Overjet, nasofacial, and nasomental angles were important in decision making between the mandibular setback and Le Fort I options (the more negative the overjet, the larger the nasofacial angle, the smaller the nasomental angle, the greater the preference for the Le Fort I option). Wits appraisal seemed to be important in decision making between the mandibular setback and bimaxillary options (the more negative the Wits appraisal, the greater the preference for the latter option).

A Coordinated and Comprehensive School-Based Career Placement Model: Volume III of a Research Project to Develop a Coordinated Comprehensive Placement System.

ERIC Educational Resources Information Center

Wisconsin Univ., Madison. Center for Studies in Vocational and Technical Education.

Volume 3 presents a descriptive outline of the Wisconsin school-based career placement model. The two major objectives for the model are: (1) to maximize the individual student's competencies for independent career functioning and (2) to maximize the availability of career placement options. For orderly transition, each student must receive the…

Preliminary Results From the C-Pulse OPTIONS HF European Multicenter Post-Market Study.

PubMed

Schulz, Antonia; Krabatsch, Thomas; Schmitto, Jan D; Hetzer, Roland; Seidel, Mirko; Dohmen, Pascal M; Hotz, Holger

2016-02-18

BACKGROUND The C-Pulse System is an extra-aortic balloon counterpulsation device. It is used to treat patients with heart failure disease in NYHA functional class III or ambulatory class IV. MATERIAL AND METHODS We present preliminary site-reported 6-month data from 3 centers in Germany as part of the prospective observational post-market OPTIONS HF study. RESULTS Between May 2013 and March 2014, the C-Pulse System was implanted in 8 patients (7 male) with a mean age of 61.6±9.3 years. Four had ischemic and 4 had non-ischemic cardiomyopathy. No stroke, myocardial infarction, major bleeding, or major infection due to the device were reported. One patient developed non-device-related refractory tachycardia with worsening heart failure 12 h after surgery and underwent left ventricular assist device implantation. Within 6 months of observation, functional status improved from NYHA III to II in 5 patients, and 2 remained in NYHA III. Mean left ventricular ejection fraction increased from 24.3±7.9% to 44.5±4.5% (p<0.0001). Mean Kansas City Cardiomyopathy Questionnaire overall score improved from 28.6±19.1 to 59.1±22.5 (p=0.0183). Six-minute walk test was performed in 6 out of 7 patients at follow-up. The mean distance improved from 252.0±85.1 m to 279.2±87.5 m (p>0.05). One patient was weaned off the device after 6 months of support. CONCLUSIONS The C-Pulse System provides a therapeutic option for patients with moderate-to-severe heart failure and seems to improve quality of life and cardiac function over time.

Evolution of Class III treatment in orthodontics.

PubMed

Ngan, Peter; Moon, Won

2015-07-01

Angle, Tweed, and Moyers classified Class III malocclusions into 3 types: pseudo, dentoalveolar, and skeletal. Clinicians have been trying to identify the best timing to intercept a Class III malocclusion that develops as early as the deciduous dentition. With microimplants as skeletal anchorage, orthopedic growth modification became more effective, and it also increased the scope of camouflage orthodontic treatment for patients who were not eligible for orthognathic surgery. However, orthodontic treatment combined with orthognathic surgery remains the only option for patients with a severe skeletal Class III malocclusion or a craniofacial anomaly. Distraction osteogenesis can now be performed intraorally at an earlier age. The surgery-first approach can minimize the length of time that the malocclusion needs to worsen before orthognathic surgery. Finally, the use of computed tomography scans for 3-dimensional diagnosis and treatment planning together with advances in imaging technology can improve the accuracy of surgical movements and the esthetic outcomes for these patients. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Emerging pharmacological therapies in schizophrenia: what's new, what's different, what's next?

PubMed

Citrome, Leslie

2016-12-01

There are several new and emerging medication interventions for both the acute and maintenance treatment phases of schizophrenia. Recently approved are 2 new dopamine receptor partial agonists, brexpiprazole and cariprazine, as well as 2 new long-acting injectable antipsychotic formulations, aripiprazole lauroxil and 3-month paliperidone palmitate. Although differences in efficacy compared to other available choices are not expected, the new oral options offer different tolerability profiles that may be attractive for individual patients who have had difficulties with older medications. The new long-acting injectable options provide additional flexibility in terms of increasing the time interval between injections. In Phase III of clinical development is a novel antipsychotic, lumateperone (ITI-007), that appears to have little in the way of significant adverse effects. Deutetrabenazine and valbenazine are agents in Phase III for the treatment of tardive dyskinesia, a condition that can be found among persons receiving chronic antipsychotic therapy. On the horizon are additional injectable formulations of familiar antipsychotics, aripiprazole and risperidone, that may be more convenient than what is presently available.

CARE3MENU- A CARE III USER FRIENDLY INTERFACE

NASA Technical Reports Server (NTRS)

Pierce, J. L.

1994-01-01

CARE3MENU generates an input file for the CARE III program. CARE III is used for reliability prediction of complex, redundant, fault-tolerant systems including digital computers, aircraft, nuclear and chemical control systems. The CARE III input file often becomes complicated and is not easily formatted with a text editor. CARE3MENU provides an easy, interactive method of creating an input file by automatically formatting a set of user-supplied inputs for the CARE III system. CARE3MENU provides detailed on-line help for most of its screen formats. The reliability model input process is divided into sections using menu-driven screen displays. Each stage, or set of identical modules comprising the model, must be identified and described in terms of number of modules, minimum number of modules for stage operation, and critical fault threshold. The fault handling and fault occurence models are detailed in several screens by parameters such as transition rates, propagation and detection densities, Weibull or exponential characteristics, and model accuracy. The system fault tree and critical pairs fault tree screens are used to define the governing logic and to identify modules affected by component failures. Additional CARE3MENU screens prompt the user for output options and run time control values such as mission time and truncation values. There are fourteen major screens, many with default values and HELP options. The documentation includes: 1) a users guide with several examples of CARE III models, the dialog required to input them to CARE3MENU, and the output files created; and 2) a maintenance manual for assistance in changing the HELP files and modifying any of the menu formats or contents. CARE3MENU is written in FORTRAN 77 for interactive execution and has been implemented on a DEC VAX series computer operating under VMS. This program was developed in 1985.

Development document for final best conventional technology effluent limitations guidelines for the pharmaceutical manufacturing point source category. Final report

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

O'Farrell, T.; Hund, F.

1986-12-01

The document presents the technical rationale for best conventional technology (BCI) effluent limitations guidelines for the pharmaceutical manufacturing point-source category as required by the Clean Water Act of 1977 (P.L. 95-217, the Act). The document describes the technologies considered as the bases for BCT limitations. Section II of this document summarizes the rulemaking process. Sections III through V describe the technical data and engineering analyses used to develop the regulatory technology options. The costs and removals associated with each technology option for each plant and the application of the BCT cost test methodology are presented in Section VI. BCI limitationsmore » bases on the best conventional pollutant control technology are to be achieved by existing direct-discharging facilities.« less

Setting Priorities in Global Child Health Research Investments: Guidelines for Implementation of the CHNRI Method

PubMed Central

Rudan, Igor; Gibson, Jennifer L.; Ameratunga, Shanthi; El Arifeen, Shams; Bhutta, Zulfiqar A.; Black, Maureen; Black, Robert E.; Brown, Kenneth H.; Campbell, Harry; Carneiro, Ilona; Chan, Kit Yee; Chandramohan, Daniel; Chopra, Mickey; Cousens, Simon; Darmstadt, Gary L.; Gardner, Julie Meeks; Hess, Sonja Y.; Hyder, Adnan A.; Kapiriri, Lydia; Kosek, Margaret; Lanata, Claudio F.; Lansang, Mary Ann; Lawn, Joy; Tomlinson, Mark; Tsai, Alexander C.; Webster, Jayne

2008-01-01

This article provides detailed guidelines for the implementation of systematic method for setting priorities in health research investments that was recently developed by Child Health and Nutrition Research Initiative (CHNRI). The target audience for the proposed method are international agencies, large research funding donors, and national governments and policy-makers. The process has the following steps: (i) selecting the managers of the process; (ii) specifying the context and risk management preferences; (iii) discussing criteria for setting health research priorities; (iv) choosing a limited set of the most useful and important criteria; (v) developing means to assess the likelihood that proposed health research options will satisfy the selected criteria; (vi) systematic listing of a large number of proposed health research options; (vii) pre-scoring check of all competing health research options; (viii) scoring of health research options using the chosen set of criteria; (ix) calculating intermediate scores for each health research option; (x) obtaining further input from the stakeholders; (xi) adjusting intermediate scores taking into account the values of stakeholders; (xii) calculating overall priority scores and assigning ranks; (xiii) performing an analysis of agreement between the scorers; (xiv) linking computed research priority scores with investment decisions; (xv) feedback and revision. The CHNRI method is a flexible process that enables prioritizing health research investments at any level: institutional, regional, national, international, or global. PMID:19090596

OPTIM trial: a Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma.

PubMed

Kaufman, Howard L; Bines, Steven D

2010-06-01

There are few effective treatment options available for patients with advanced melanoma. An oncolytic herpes simplex virus type 1 encoding granulocyte macrophage colony-stimulating factor (GM-CSF; Oncovex(GM-CSF)) for direct injection into accessible melanoma lesions resulted in a 28% objective response rate in a Phase II clinical trial. Responding patients demonstrated regression of both injected and noninjected lesions highlighting the dual mechanism of action of Oncovex(GM-CSF) that includes both a direct oncolytic effect in injected tumors and a secondary immune-mediated anti-tumor effect on noninjected tumors. Based on these preliminary results a prospective, randomized Phase III clinical trial in patients with unresectable Stage IIIb or c and Stage IV melanoma has been initiated. The rationale, study design, end points and future development of the Oncovex(GM-CSF) Pivotal Trial in Melanoma (OPTIM) trial are discussed in this article.

Current Therapeutic Options for Esophageal Motor Disorders as Defined by the Chicago Classification.

PubMed

Zerbib, Frank; Roman, Sabine

2015-07-01

With the development of high-resolution manometry and specific metrics to characterize esophageal motility, the Chicago Classification has become the gold standard for the diagnosis of esophageal motor disorders. Major and significant disorders, that is, never observed in healthy subjects, are achalasia, esophagogastric junction outflow obstruction, distal esophageal spasm, absent peristalsis, and hypercontractile (Jackhammer) esophagus. Achalasia subtyping is relevant to predict the response to endoscopic and surgical therapies as several studies suggest that, pneumatic dilation is less effective than Heller myotomy, in type III achalasia. Peroral endoscopic myotomy, initially developed in expert centers, is a promising technique for the treatment of achalasia. The medical therapeutic options for distal esophageal spasm and hypercontractile esophagus are smooth muscle relaxants and pain modulators. Intraesophageal injection of botulinum toxin might be an interesting option for treatment of these disorders but further studies are required to determine the optimal injection protocol and the best candidates based on manometric patterns. The treatment of hypotensive motility disorders is disappointing and relies mainly on dietary and lifestyle changes as no effective esophageal prokinetic is currently available.

[Targeted therapies in hepatocellular carcinomas: recent results and future development].

PubMed

Marijon, H; Faivre, S; Raymond, E

2009-05-01

Hepatocellular carcinoma (HCC) is one of the 5th most common cancers around the world with a limited number of systemic therapeutic options. Cytotoxic agents, hormonotherapy and immunotherapy have failed to demonstrate benefit compared to best supportive care in patients with advanced HCC. The recent development of targeted therapies provided hope for the treatment of advanced HCC. We reviewed phases II-III trials presented in 2007 and 2008. Results are promising with a clinical benefit reported with molecular therapies targeting EGF/EGFR and VEGF/VEGFR pathways.

Bioremoval of trivalent chromium using Bacillus biofilms through continuous flow reactor.

PubMed

Sundar, K; Sadiq, I Mohammed; Mukherjee, Amitava; Chandrasekaran, N

2011-11-30

Present study deals with the applicability of bacterial biofilms for the bioremoval of trivalent chromium from tannery effluents. A continuous flow reactor was designed for the development of biofilms on different substrates like glass beads, pebbles and coarse sand. The parameters for the continuous flow reactor were 20 ml/min flow rate at 30°C, pH4. Biofilm biomass on the substrates was in the following sequence: coarse sand>pebbles>glass beads (4.8 × 10(7), 4.5 × 10(7) and 3.5 × 10(5)CFU/cm(2)), which was confirmed by CLSM. Biofilms developed using consortium of Bacillus subtilis and Bacillus cereus on coarse sand had more surface area and was able to remove 98% of Cr(III), SEM-EDX proved 92.60% Cr(III) adsorption on biofilms supported by coarse sand. Utilization of Bacillus biofilms for effective bioremoval of Cr(III) from chrome tanning effluent could be a better option for tannery industry, especially during post chrome tanning operation. Copyright © 2011 Elsevier B.V. All rights reserved.

75 FR 53366 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-31

... Rule Change Relating to Routing Fees, the Monthly Cap and Electronic Auctions August 25, 2010. Pursuant... Monthly Cap on equity option transaction fees; and (iii) clarify language relating to electronic auctions...-105. The Exchange also proposes to amend its Monthly Cap assessed on Registered Options Traders...

46 CFR 307.7 - Information required in report.

Code of Federal Regulations, 2010 CFR

2010-10-01

... information, and (viii) The keyword “MAREP”. If optional remarks are included, they must follow at the end of... (vi) The keyword “MAREP”. If optional remarks are included, they must follow at the end of the text... Radio Call Sign, (iii) Time at reported position, (iv) Latitude and longitude, and (v) The keyword...

Finishing occlusion in Class II or Class III molar relation: therapeutic Class II and III.

PubMed

Nangia, A; Darendeliler, M A

2001-11-01

The most frequent extraction regime consists of the removal of upper and lower premolars. Depending on anchorage requirements, camouflage treatment options, surgical intervention, or the absence of teeth in only one arch, it may become necessary to finalize the occlusion with a one-dental-unit discrepancy between the upper and lower dental arches. Guidelines are presented for finishing occlusions in Class II or Class III molar relation.

Neutron imaging systems utilizing lithium-containing semiconductor crystals

DOEpatents

Stowe, Ashley C.; Burger, Arnold

2017-04-25

A neutron imaging system, including: a plurality of Li-III-VI.sub.2 semiconductor crystals arranged in an array, wherein III represents a Group III element and VI represents a Group VI element; and electronics operable for detecting and a charge in each of the plurality of crystals in the presence of neutrons and for imaging the neutrons. Each of the crystals is formed by: melting the Group III element; adding the Li to the melted Group III element at a rate that allows the Li and Group III element to react, thereby providing a single phase Li-III compound; and adding the Group VI element to the single phase Li-III compound and heating. Optionally, each of the crystals is also formed by doping with a Group IV element activator.

Advanced Tactical Crew System (ATACS) Issues and Options: Impacts on Aircrew Selection and Training.

DTIC Science & Technology

1981-10-01

simulation-intensive aircrew training simulator comb1 al readiness tactics development fidelity training device Next Generation Training System 20. ABSTRACT...quest’ione~s. driv.ei iii large part b%’ thlie general reqeuiremuenits for initial and( ’oniiipaili training and for \\irFre iiev,, for achieviotg a...ni- cal In formationl Service. where if will he available to the general public. iicluding foreign nationals. •rhis paper has heen reviewed and is

FY16 ASME High Temperature Code Activities

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

Swindeman, M. J.; Jetter, R. I.; Sham, T. -L.

2016-09-01

One of the objectives of the ASME high temperature Code activities is to develop and validate both improvements and the basic features of Section III, Division 5, Subsection HB, Subpart B (HBB). The overall scope of this task is to develop a computer program to be used to assess whether or not a specific component under specified loading conditions will satisfy the elevated temperature design requirements for Class A components in Section III, Division 5, Subsection HB, Subpart B (HBB). There are many features and alternative paths of varying complexity in HBB. The initial focus of this task is amore » basic path through the various options for a single reference material, 316H stainless steel. However, the program will be structured for eventual incorporation all the features and permitted materials of HBB. Since this task has recently been initiated, this report focuses on the description of the initial path forward and an overall description of the approach to computer program development.« less

Mortality Probability Model III and Simplified Acute Physiology Score II

PubMed Central

Vasilevskis, Eduard E.; Kuzniewicz, Michael W.; Cason, Brian A.; Lane, Rondall K.; Dean, Mitzi L.; Clay, Ted; Rennie, Deborah J.; Vittinghoff, Eric; Dudley, R. Adams

2009-01-01

Background: To develop and compare ICU length-of-stay (LOS) risk-adjustment models using three commonly used mortality or LOS prediction models. Methods: Between 2001 and 2004, we performed a retrospective, observational study of 11,295 ICU patients from 35 hospitals in the California Intensive Care Outcomes Project. We compared the accuracy of the following three LOS models: a recalibrated acute physiology and chronic health evaluation (APACHE) IV-LOS model; and models developed using risk factors in the mortality probability model III at zero hours (MPM0) and the simplified acute physiology score (SAPS) II mortality prediction model. We evaluated models by calculating the following: (1) grouped coefficients of determination; (2) differences between observed and predicted LOS across subgroups; and (3) intraclass correlations of observed/expected LOS ratios between models. Results: The grouped coefficients of determination were APACHE IV with coefficients recalibrated to the LOS values of the study cohort (APACHE IVrecal) [R2 = 0.422], mortality probability model III at zero hours (MPM0 III) [R2 = 0.279], and simplified acute physiology score (SAPS II) [R2 = 0.008]. For each decile of predicted ICU LOS, the mean predicted LOS vs the observed LOS was significantly different (p ≤ 0.05) for three, two, and six deciles using APACHE IVrecal, MPM0 III, and SAPS II, respectively. Plots of the predicted vs the observed LOS ratios of the hospitals revealed a threefold variation in LOS among hospitals with high model correlations. Conclusions: APACHE IV and MPM0 III were more accurate than SAPS II for the prediction of ICU LOS. APACHE IV is the most accurate and best calibrated model. Although it is less accurate, MPM0 III may be a reasonable option if the data collection burden or the treatment effect bias is a consideration. PMID:19363210

Combining analytical frameworks to assess livelihood vulnerability to climate change and analyse adaptation options.

PubMed

Reed, M S; Podesta, G; Fazey, I; Geeson, N; Hessel, R; Hubacek, K; Letson, D; Nainggolan, D; Prell, C; Rickenbach, M G; Ritsema, C; Schwilch, G; Stringer, L C; Thomas, A D

2013-10-01

Experts working on behalf of international development organisations need better tools to assist land managers in developing countries maintain their livelihoods, as climate change puts pressure on the ecosystem services that they depend upon. However, current understanding of livelihood vulnerability to climate change is based on a fractured and disparate set of theories and methods. This review therefore combines theoretical insights from sustainable livelihoods analysis with other analytical frameworks (including the ecosystem services framework, diffusion theory, social learning, adaptive management and transitions management) to assess the vulnerability of rural livelihoods to climate change. This integrated analytical framework helps diagnose vulnerability to climate change, whilst identifying and comparing adaptation options that could reduce vulnerability, following four broad steps: i) determine likely level of exposure to climate change, and how climate change might interact with existing stresses and other future drivers of change; ii) determine the sensitivity of stocks of capital assets and flows of ecosystem services to climate change; iii) identify factors influencing decisions to develop and/or adopt different adaptation strategies, based on innovation or the use/substitution of existing assets; and iv) identify and evaluate potential trade-offs between adaptation options. The paper concludes by identifying interdisciplinary research needs for assessing the vulnerability of livelihoods to climate change.

New treatment options for lower respiratory tract infections.

PubMed

Kocsis, Bela; Szabo, Dora

2017-09-01

Community-acquired pneumonia (CAP) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are among the most frequent lower respiratory tract infections (LRTIs). They represent an increased morbidity and mortality rate in adults. Areas covered: This review describes recent advances regarding solithromycin, zabofloxacin and delafoxacin antibacterial agents that have been recently developed for treatment of CAP and in AECOPD. All of them have been introduced into phase III clinical trials. We will be summarising chemical structures, pharmacokinetics, antibacterial efficacy and toxicity of these agents. The manuscript has been prepared based on available scientific publications. Expert opinion: Novel agents of known antimicrobial classes have been developed that demonstrate treatment options in CAP and in AECOPD. Antimicrobials discussed in this review showed bactericide effect against major respiratory tract pathogens. Each has multiple targets in bacteria, thus enabling them for more potency, even against strains exhibiting resistance to commonly used antibiotics. Solithromycin, delafloxacin and zabofloxcian demonstrate broad-spectrum antibacterial activity together with other beneficial features like intracellular accumulation, anti-inflammatory effect and inhibition of biofilm production. These agents showed moderately severe or mild adverse events and demonstrated favourable tissue penetration. These features can make solithromycin, zabofloxacin and delafloxacin treatment options in LRTIs.

Probing the Natural World, Level III, Student Guide: Investigating Variation. Intermediate Science Curriculum Study.

ERIC Educational Resources Information Center

Bonar, John R., Ed.; Hathway, James A., Ed.

This is the student's text of one unit of the Intermediate Science Curriculum Study (ISCS) for level III students (grade 9). This unit focuses on diversity in human populations, measurement, and data collection. Numerous activities are given and optional excursions encourage students to pursue a topic in greater depth. Data tables within the…

32 CFR 199.5 - TRICARE Extended Care Health Option (ECHO).

Code of Federal Regulations, 2010 CFR

2010-07-01

...-eligible dependents: (i) A spouse, child, or unmarried person (as described in § 199.3(b)(2)(i), (b)(2)(ii.... (ii) An abused dependent as described in § 199.3(b)(2)(iii). (iii) A spouse, child, or unmarried... member for over one-half of such dependent's support. (iv) A spouse, child, or unmarried person (as...

General Military Training: Standardization and Reduction Options

DTIC Science & Technology

2012-01-01

pregnancy prevention (navy) n Y n Y n Y III SGLI (Marine Corps) n n n Y n Y III Table A.1—Continued Our Assessment of Topics That Meet the Approved...sensitive issues promotes trust and unit esprit de corps. The Army chooses to uti - lize time for CMT as an opportunity for a unit leader to mentor

77 FR 49035 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-15

...; and (iii) establish a fee of $0.10 per contract for NYSE Amex Options Market Maker executions of SPY... than SPY would continue to pay the existing transaction charges, as provided in the Fee Schedule. 2... for SPY options are currently $0.25 per contract, which, when coupled with the proposed $0.10 per...

26 CFR 1.417(a)(3)-1 - Required explanation of qualified joint and survivor annuity and qualified preretirement survivor...

Code of Federal Regulations, 2010 CFR

2010-04-01

... grouping rules of paragraph (c)(2)(iii) of this section. Separate charts are provided for ages 55, 60, and...) Simplified presentations permitted—(A) Grouping of certain optional forms. Two or more optional forms of... starting date, a reasonable assumption for the age of the participant's spouse, or, in the case of a...

Generalized worry disorder: a review of DSM-IV generalized anxiety disorder and options for DSM-V.

PubMed

Andrews, Gavin; Hobbs, Megan J; Borkovec, Thomas D; Beesdo, Katja; Craske, Michelle G; Heimberg, Richard G; Rapee, Ronald M; Ruscio, Ayelet Meron; Stanley, Melinda A

2010-02-01

Generalized anxiety disorder (GAD) has undergone a series of substantial classificatory changes since its first inclusion in DSM-III. The majority of these revisions have been in response to its poor inter-rater reliability and concerns that it may lack diagnostic validity. This article provides options for the revision of the DSM-IV GAD criteria for DSM-V. First, searches were conducted to identify the evidence that previous DSM Work Groups relied upon when revising the DSM-III-R GAD and the overanxious disorder classifications. Second, the literature pertaining to the DSM-IV criteria for GAD was examined. The review presents a number of options to be considered for DSM-V. One option is for GAD to be re-labeled in DSM-V as generalized worry disorder. This would reflect its hallmark feature. Proposed revisions would result in a disorder that is characterized by excessive anxiety and worry generalized to a number of events or activities for 3 months or more. Worry acts as a cognitive coping strategy that manifests in avoidant behaviors. The reliability and validity of the proposed changes could be investigated in DSM-V validity tests and field trials.

Role of indigenous arsenate and iron(III) respiring microorganisms in controlling the mobilization of arsenic in a contaminated soil sample.

PubMed

Vaxevanidou, K; Christou, C; Kremmydas, G F; Georgakopoulos, D G; Papassiopi, N

2015-03-01

In this study two different treatment options were investigated for the release of arsenic from a contaminated soil sample. The first option was based on the "bioaugmentation" principle and involved addition of a pure Fe(III)-reducing culture, i.e. Desulfuromonas palmitatis. The second option consisted in the "biostimulation" of indigenous bacteria and involved simple addition of nutrients. Due to the strong association of As with soil ferric oxides, the reductive dissolution of soil oxides by D. palmitatis lead to 45 % arsenic release in solution (2.15 mM). When only nutrients were supplied to the soil, the same amounts of Fe and As were dissolved with slower rates and most aqueous As was found to be in the trivalent state, indicating the presence of arsenate reducing species. The arsenate reducing microorganisms were enriched with successive cultures, using Na2HAsO4 as electron acceptor. The phylogenetic analysis revealed that the enriched microbial consortium contained Desulfosporosinus species, which are known arsenate reducers.

Dialysis shunt-associated steal syndrome (DASS) following brachial accesses: the value of fistula banding under blood flow control.

PubMed

Thermann, Florian; Ukkat, Jörg; Wollert, Ulrich; Dralle, Henning; Brauckhoff, Michael

2007-11-01

Dialysis shunt-associated steal syndrome (DASS) is a rare complication of hemodialysis access (HA) which preferably occurs in brachial fistulas. Treatment options are discussed controversially. Aim of this study was to evaluate flow-controlled fistula banding. Patients treated between 2002 and 2006 were included in this prospective survey. According to a classification we established, patients were typed DASS I-III (I: short history, no dermal lesions; II: long history, skin lesions; III: long history, gangrene). Surgical therapy was HA banding including controlled reduction (about 50% of initial flow) of HA blood flow (patients type I and II). Patients with type III underwent closure of the HA. In 15 patients with relevant DASS, blood-flow-controlled banding was performed. In ten patients (all type I), banding led to restitution of the hand function while preserving the HA. In five patients (all type II), banding was not successful; in two patients, closure of the HA was performed eventually. In five patients (type III), primary closure of the HA was performed. Four patients with DASS type II but only two with DASS type I had diabetes mellitus (p = 0.006). Banding under blood flow control resulting in an approximately 50% reduction in the initial blood flow is an adequate therapeutic option in patients with brachial HA and type I-DASS. In type II-DASS, banding does not lead to satisfying results, more complex surgical options might be more successful. Diabetes is associated with poor HA outcome in case of DASS.

Review of phase III trial data on IL-23 inhibitors tildrakizumab and guselkumab for psoriasis.

PubMed

Amin, M; Darji, K; No, D J; Wu, J J

2017-10-01

The development of monoclonal antibodies targeting IL-12 and IL-23 has enhanced the therapeutic options available for psoriasis patients. Recent research suggests that IL-23 alone plays a role in the pathogenesis of psoriasis. The objective was to review the phase III clinical trial data for the anti-IL-23 agents to evaluate the safety and efficacy profile of each agent. We reviewed the results of the phase III clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab. The results of phase III trials on risankizumab have not yet been reported. By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was >60% among the most efficacious dose of each agent. The percentage of patients achieving PASI 90 at week 16 was the primary endpoint for the phase III trials for guselkumab, which was above 70%. The safety profiles of the agents were comparable, with the most commonly reported adverse events of nasopharyngitis and upper respiratory tract infections. The anti-IL-23 agents demonstrated a rapid clinical improvement that is similar or superior to the improvement seen with currently marketed IL-17 inhibitors with a favourable short-term safety profile. The results of the phase III trials support the notion that IL-23 is a potential target in psoriasis treatment. © 2017 European Academy of Dermatology and Venereology.

Issues for Active State Management of the JTPA Title III Grant: A Guide for State Planners and Managers.

ERIC Educational Resources Information Center

Reesman, Cilla J.

This technical assistance guide presents the various options available to state planners and managers in considering five elements of active grant management. Each element is treated in a separate chapter. Chapter 1 addresses issues surrounding the setting of policies that ensure that Title III grants complement state agendas. Chapter 2 concerns…

Non-extraction treatment of a Class III skeletal case.

PubMed

Gonzalez, Bulmario

2009-01-01

Adult Class III Skeletal treatment options have generally included some form of surgery (Maxillary advancement in midface deficient cases and/or Mandibular set-back). This article discusses non-surgical treatment of an adult patient using the combined concepts of mandibular molar distalization enhanced with TADs and non-extraction camouflage dental correction through maxillary incisor protraction and mandibular incisor lingualization.

Probing the Natural World, Level III, Teacher's Edition: Investigating Variation. Intermediate Science Curriculum Study.

ERIC Educational Resources Information Center

Bonar, John R., Ed.; Hathway, James A., Ed.

This is the teacher's edition of one of the eight units of the Intermediate Science Curriculum Study (ISCS) for level III students (grade 9). This unit focuses on diversity in human populations, measurement, and data collection. Optional excursions are described for students who wish to study a topic in greater depth. An introduction describes…

Probing the Natural World, Level III, Student Guide: What's Up? Intermediate Science Curriculum Study.

ERIC Educational Resources Information Center

Bonar, John R., Ed.; Hathway, James A., Ed.

This is the student's text of one unit of the Intermediate Science Curriculum Study (ISCS) for level III students (grade 9). The chapters contain basic information about rockets, space, and principles of physics, as well as activities related to the subject and optional excursions. A section of introductory notes to the student discusses how the…

Probing the Natural World, Level III, Teacher's Edition: Environmental Science. Intermediate Science Curriculum Study.

ERIC Educational Resources Information Center

Bonar, John R., Ed.; Hathway, James A., Ed.

This is the teacher's edition of one of the eight units of the Intermediate Science Curriculum Study (ISCS) for level III students (grade 9). This unit and its activities focuses on environmental pollution and hazards. Optional excursions are suggested for students who wish to study an area in greater depth. An introduction describes the problem…

Intravenous Vancomycin Associated With the Development of Nephrotoxicity in Patients With Class III Obesity.

PubMed

Choi, Yookyung Christy; Saw, Stephen; Soliman, Daniel; Bingham, Angela L; Pontiggia, Laura; Hunter, Krystal; Chuang, Linda; Siemianowski, Laura A; Ereshefsky, Benjamin; Hollands, James M

2017-11-01

A consensus statement recommends initial intravenous (IV) vancomycin dosing of 15-20 mg/kg every 8- 24 hours, with an optional 25- to 30-mg/kg loading dose. Although some studies have shown an association between weight and the development of vancomycin-associated nephrotoxicity, results have been inconsistent. To evaluate the correlation between incidence of nephrotoxicity associated with weight-based IV vancomycin dosing strategies in nonobese and obese patients. This retrospective cohort study evaluated hospitalized adult patients admitted who received IV vancomycin. Patients were stratified into nonobese (body mass index [BMI] <25 kg/m 2 ), obesity class I and II (BMI 30-39.9kg/m 2 ), and obesity class III (BMI≥40 kg/m 2 ) groups; patients who were overweight but not obese were excluded. Incidence of nephrotoxicity and serum vancomycin trough concentrations were evaluated. Of a total of 62 documented cases of nephrotoxicity (15.1%), 13 (8.7%), 23 (14.3%), and 26 (26.3%) cases were observed in nonobese, obesity class I and II, and obesity class III groups, respectively ( P=0.002). Longer durations of therapy ( P<0.0001), higher initial maintenance doses in both total milligrams/day ( P=0.0137) and milligrams/kilogram ( P=0.0307), and any trough level >20 mg/L ( P<0.0001) were identified as predictors of development of nephrotoxicity. Concomitant administration of piperacillin/tazobactam, diuretics, and IV contrast were associated with development of nephrotoxicity ( P<0.005, all). Patients with class III obesity were 3-times as likely to develop nephrotoxicity when compared with nonobese patients (odds ratio [OR]=2.99; CI=1.12-7.94) and obesity class I and II patients (OR=3.14; CI=1.27-7.75). Obesity and other factors are associated with a higher risk of vancomycin-associated nephrotoxicity.

The early management of Class III malocclusions using protraction headgear.

PubMed

Macey-Dare, L V

2000-12-01

Class III malocclusions affect approximately 3% of Caucasians. Treatment options include; growth modification, dental camouflage and, once growth has ceased, orthognathic surgery. Originally, Class III malocclusions were thought to arise primarily from an overdevelopment of the mandible, but it is now known that maxillary retrusion contributes in up to 60% of cases. Maxillary retrusion is best treated with a combination of protraction headgear and rapid maxillary expansion, preferably before the age of 9 years. This article provides an overview of the management of skeletal Class III cases using protraction headgear with particular guidance for the general dental practitioner on when and how to treat.

76 FR 62118 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Approving a Proposed Rule Change Amending...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-06

... the Text of NYSE Arca Options Rule 6.96(b)(1)(B) to More Accurately Reflect the Regulatory Services... conditions), and to clarify the text of NYSE Arca Options Rule 6.96(b)(1)(B) to more accurately reflect the... Release''). See also Notice, 76 FR at 53515, n.5 and accompanying text. \\7\\ See Notice. III. Discussion...

17 CFR 240.15c3-1a - Options (Appendix A to 17 CFR 240.15c3-1).

Code of Federal Regulations, 2012 CFR

2012-04-01

... terms theoretical gains and losses shall mean the gain and loss in the value of individual option series... paragraph (a)(1)(iii) of this section). Theoretical gains and losses shall be calculated using a theoretical... models. Any such model shall calculate theoretical gains and losses as described in paragraph (a)(1)(i)(A...

Development of a Humanized Monoclonal Antibody with Therapeutic Potential against West Nile Virus

PubMed Central

Oliphant, Theodore; Engle, Michael; Nybakken, Grant E.; Doane, Chris; Johnson, Syd; Huang, Ling; Gorlatov, Sergey; Mehlhop, Erin; Marri, Anantha; Chung, Kyung Min; Ebel, Gregory D.; Kramer, Laura D.; Fremont, Daved H.; Diamond, Michael S.

2006-01-01

Neutralization of West Nile virus (WNV) in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Using random mutagenesis and yeast surface display, we defined individual contact residues of 14 newly generated mAbs against domain III of the WNV E protein. MAbs that strongly neutralized WNV localized to a surface patch on the lateral face of domain III. Convalescent antibodies from human patients who had recovered from WNV infection also detected this epitope. One mAb, E16, neutralized 10 different strains in vitro, and demonstrated therapeutic efficacy in mice, even when administered as a single dose 5 d after infection. A humanized version of E16 was generated that retained antigen specificity, avidity, and neutralizing activity. In post-exposure therapeutic trials in mice, a single dose of humanized E16 protected mice against WNV-induced mortality, and thus, may be a viable treatment option against WNV infection in humans. PMID:15852016

The development and application of multi-criteria decision-making tool with consideration of uncertainty: the selection of a management strategy for the bio-degradable fraction in the municipal solid waste.

PubMed

El Hanandeh, Ali; El-Zein, Abbas

2010-01-01

A modified version of the multi-criteria decision aid, ELECTRE III has been developed to account for uncertainty in criteria weightings and threshold values. The new procedure, called ELECTRE-SS, modifies the exploitation phase in ELECTRE III, through a new definition of the pre-order and the introduction of a ranking index (RI). The new approach accommodates cases where incomplete or uncertain preference data are present. The method is applied to a case of selecting a management strategy for the bio-degradable fraction in the municipal solid waste of Sydney. Ten alternatives are compared against 11 criteria. The results show that anaerobic digestion (AD) and composting of paper are less environmentally sound options than recycling. AD is likely to out-perform incineration where a market for heating does not exist. Moreover, landfilling can be a sound alternative, when considering overall performance and conditions of uncertainty.

Site Development, Operations, and Closure Plan Topical Report 5 An Assessment of Geologic Carbon Sequestration Options in the Illinois Basin. Phase III

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

Finley, Robert; Payne, William; Kirksey, Jim

2015-06-01

The Midwest Geological Sequestration Consortium (MGSC) has partnered with Archer Daniels Midland Company (ADM) and Schlumberger Carbon Services to conduct a large-volume, saline reservoir storage project at ADM’s agricultural products processing complex in Decatur, Illinois. The Development Phase project, named the Illinois Basin Decatur Project (IBDP) involves the injection of 1 million tonnes of carbon dioxide (CO 2) into a deep saline formation of the Illinois Basin over a three-year period. This report focuses on objectives, execution, and lessons learned/unanticipated results from the site development (relating specifically to surface equipment), operations, and the site closure plan.

Probing the Natural World, Level III, Record Book, Student Guide: What's Up? Intermediate Science Curriculum Study.

ERIC Educational Resources Information Center

Bonar, John R., Ed.; Hathway, James A., Ed.

This is the student's edition of the Record Book for the unit "What's Up" of the Intermediate Science Curriculum Study (ISCS) for level III students (grade 9). Space is provided for answers to the questions from the student text as well as for the optional excursions and the self evaluation. An introductory note to the student explains…

Probing the Natural World, Level III, Teacher's Edition: Well-Being. Intermediate Science Curriculum Study.

ERIC Educational Resources Information Center

Bonar, John R., Ed.; Hathway, James A., Ed.

This is the teacher's edition of one of the eight units of the Intermediate Science Curriculum Study (ISCS) for level III students (grade 9). This unit focuses on hazards to the body from drug use. Activities are given that relate to the topic. Optional excursions are suggested for students who wish to study an area in greater depth. An…

Methods for synthesizing semiconductor quality chalcopyrite crystals for nonlinear optical and radiation detection applications and the like

DOEpatents

Stowe, Ashley; Burger, Arnold

2016-05-10

A method for synthesizing I-III-VI.sub.2 compounds, including: melting a Group III element; adding a Group I element to the melted Group III element at a rate that allows the Group I and Group III elements to react thereby providing a single phase I-III compound; and adding a Group VI element to the single phase I-III compound under heat, with mixing, and/or via vapor transport. The Group III element is melted at a temperature of between about 200 degrees C. and about 700 degrees C. Preferably, the Group I element consists of a neutron absorber and the group III element consists of In or Ga. The Group VI element and the single phase I-III compound are heated to a temperature of between about 700 degrees C. and about 1000 degrees C. Preferably, the Group VI element consists of S, Se, or Te. Optionally, the method also includes doping with a Group IV element activator.

Pawnee Nation Energy Option Analyses

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

Matlock, M.; Kersey, K.; Riding In, C.

2009-07-31

In 2003, the Pawnee Nation leadership identified the need for the tribe to comprehensively address its energy issues. During a strategic energy planning workshop a general framework was laid out and the Pawnee Nation Energy Task Force was created to work toward further development of the tribe’s energy vision. The overarching goals of the “first steps” project were to identify the most appropriate focus for its strategic energy initiatives going forward, and to provide information necessary to take the next steps in pursuit of the “best fit” energy options. Based on the request of Pawnee Nation’s Energy Task Force themore » research team, consisting Tribal personnel and Summit Blue Consulting, focused on a review of renewable energy resource development potential, funding sources and utility organizational along with energy savings options. Elements of the energy demand forecasting and characterization and demand side options review remained in the scope of work, but were only addressed at a high level. Description of Activities Performed Renewable Energy Resource Development Potential The research team reviewed existing data pertaining to the availability of biomass (focusing on woody biomass, agricultural biomass/bio-energy crops, and methane capture), solar, wind and hydropower resources on the Pawnee-owned lands. Using these data, combined with assumptions about costs and revenue streams, the research team performed preliminary feasibility assessments for each resource category. The research team also reviewed available funding resources and made recommendations to Pawnee Nation highlighting those resources with the greatest potential for financially-viable development, both in the near-term and over a longer time horizon. Energy Efficiency Options While this was not a major focus of the project, the research team highlighted common strategies for reducing energy use in buildings. The team also discussed the benefits of adopting a building energy code and introduced two model energy codes Pawnee Nation should consider for adoption. Summary of Current and Expected Future Electricity Usage The research team provided a summary overview of electricity usage patterns in current buildings and included discussion of known plans for new construction. Utility Options Review Pawnee Nation electric utility options were analyzed through a four-phase process, which included: 1) summarizing the relevant utility background information; 2) gathering relevant utility assessment data; 3) developing a set of realistic Pawnee electric utility service options, and 4) analyzing the various Pawnee electric utility service options for the Pawnee Energy Team’s consideration. III. Findings and Recommendations Due to a lack of financial incentives for renewable energy, particularly at the state level, combined mediocre renewable energy resources, renewable energy development opportunities are limited for Pawnee Nation. However, near-term potential exists for development of solar hot water at the gym, and an exterior wood-fired boiler system at the tribe’s main administrative building. Pawnee Nation should also explore options for developing LFGTE resources in collaboration with the City of Pawnee. Significant potential may also exist for development of bio-energy resources within the next decade. Pawnee Nation representatives should closely monitor market developments in the bio-energy industry, establish contacts with research institutions with which the tribe could potentially partner in grant-funded research initiatives. In addition, a substantial effort by the Kaw and Cherokee tribes is underway to pursue wind development at the Chilocco School Site in northern Oklahoma where Pawnee is a joint landowner. Pawnee Nation representatives should become actively involved in these development discussions and should explore the potential for joint investment in wind development at the Chilocco site.« less

Full-scale simulation of seawater reverse osmosis desalination processes for boron removal: Effect of membrane fouling.

PubMed

Park, Pyung-Kyu; Lee, Sangho; Cho, Jae-Seok; Kim, Jae-Hong

2012-08-01

The objective of this study is to further develop previously reported mechanistic predictive model that simulates boron removal in full-scale seawater reverse osmosis (RO) desalination processes to take into account the effect of membrane fouling. Decrease of boron removal and reduction in water production rate by membrane fouling due to enhanced concentration polarization were simulated as a decrease in solute mass transfer coefficient in boundary layer on membrane surface. Various design and operating options under fouling condition were examined including single- versus double-pass configurations, different number of RO elements per vessel, use of RO membranes with enhanced boron rejection, and pH adjustment. These options were quantitatively compared by normalizing the performance of the system in terms of E(min), the minimum energy costs per product water. Simulation results suggested that most viable options to enhance boron rejection among those tested in this study include: i) minimizing fouling, ii) exchanging the existing SWRO elements to boron-specific ones, and iii) increasing pH in the second pass. The model developed in this study is expected to help design and optimization of the RO processes to achieve the target boron removal at target water recovery under realistic conditions where membrane fouling occurs during operation. Copyright © 2012 Elsevier Ltd. All rights reserved.

78 FR 19552 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-01

...\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on March 20, 2013, the Chicago Board Options... (the ``Commission'') the proposed rule change as described in Items I and II below, which Items have... rule change pursuant to Section 19(b)(3)(A)(iii) of the Act \\3\\ and Rule 19b-4(f)(6) thereunder.\\4\\ The...

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

Oberije, Cary, E-mail: cary.oberije@maastro.nl; De Ruysscher, Dirk; Universitaire Ziekenhuizen Leuven, KU Leuven

Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing andmore » validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and Materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability ( (www.predictcancer.org)). The data set can be downloaded at (https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048). Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.« less

A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients.

PubMed

Oberije, Cary; De Ruysscher, Dirk; Houben, Ruud; van de Heuvel, Michel; Uyterlinde, Wilma; Deasy, Joseph O; Belderbos, Jose; Dingemans, Anne-Marie C; Rimner, Andreas; Din, Shaun; Lambin, Philippe

2015-07-15

Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability (www.predictcancer.org). The data set can be downloaded at https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048. The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome.

PubMed

Saturveithan, C; Premganesh, G; Fakhrizzaki, S; Mahathir, M; Karuna, K; Rauf, K; William, H; Akmal, H; Sivapathasundaram, N; Jaspreet, K

2016-07-01

Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option.

Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome

PubMed Central

Premganesh, G; Fakhrizzaki, S; Mahathir, M; Karuna, K; Rauf, K; William, H; Akmal, H; Sivapathasundaram, N; Jaspreet, K

2016-01-01

Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option. PMID:28435559

Solar Design Workbook

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

Franta, G.; Baylin, F.; Crowther, R.

1981-06-01

This Solar Design Workbook presents solar building design applications for commercial buildir^s. The book is divided into four sections. The first section describes the variety of solar applications in buildings including conservation aspects, solar fundamentals, passive systems, active systems, daylighting, and other solar options. Solar system design evaluation techniques including considerations for building energy requirements, passive systems, active systems, and economics are presented in Section II. The third section attempts to assist the designer in the building design process for energy conservation and solar applications including options and considerations for pre-design, design, and post-design phases. The information required for themore » solar design proee^ has not been fully developed at this time. Therefore, Section III is incomplete, but an overview of the considerations with some of the design proces elements is presented. Section IV illustrates ease studies that utilize solar applications in the building design.« less

26 CFR 1.752-1 - Treatment of partnership liabilities.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., obligations under a short sale, and obligations under derivative financial instruments such as options, forward contracts, futures contracts, and swaps. (iii) Other liabilities. For obligations that are not § 1...

12 CFR 552.5 - Bylaws.

Code of Federal Regulations, 2014 CFR

2014-01-01

... chapter. (iii) Bylaw provisions that adopt the language of the model or optional bylaws in OTS's... body or bodies of law selected for its corporate governance procedures, and shall file a copy of such...

12 CFR 552.5 - Bylaws.

Code of Federal Regulations, 2012 CFR

2012-01-01

... chapter. (iii) Bylaw provisions that adopt the language of the model or optional bylaws in OTS's... body or bodies of law selected for its corporate governance procedures, and shall file a copy of such...

12 CFR 552.5 - Bylaws.

Code of Federal Regulations, 2013 CFR

2013-01-01

... chapter. (iii) Bylaw provisions that adopt the language of the model or optional bylaws in OTS's... body or bodies of law selected for its corporate governance procedures, and shall file a copy of such...

Foldit Biology

DTIC Science & Technology

2015-07-31

vicinity of the enzyme , searching for the active site; (iii) find the active site and position the substrate at it, triggering the catalysis . As the...visualization options. The Lysozyme example is used to introduce the concepts of how enzymes work, and use a view option to visualize the surface of the... enzyme , its active site and its substrate. It is also in this example that we introduce the Foldit Biology notion of a ‘protein state’. Each protein

Stage III nasopharyngeal angiofibroma: Improving results with endoscopic-assisted midfacial degloving and modification to the Fisch staging system.

PubMed

Shah, Saurin R; Keshri, Amit; Patadia, Simple; Sahu, Rabi Narayan; Srivastava, Arun Kumar; Behari, Sanjay

2015-10-01

To study outcomes with endoscopic-assisted midfacial degloving for Fisch stage III nasopharyngeal angiofibroma and propose a new staging system. Retrospective study of patients with Fisch stage III juvenile nasopharyngeal angiofibroma (JNA) including preoperative angiography, intraoperative blood loss and residue/recurrence following surgery. Tertiary care superspecialty referral center. Fifteen consecutive patients with Fisch stage III JNA undergoing operations over a period of 18 months. Preoperative angiography details, intraoperative blood loss, residue/recurrence, complications of surgery. Transarterial embolization with particulate agents followed by endoscopic-assisted midfacial degloving provides excellent outcomes with Fisch stage III JNAs. The modified Fisch staging system proposed would allow better preoperative evaluation and comparison of outcomes with different treatment options for stage III JNAs. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

48 CFR 43.301 - Use of forms.

Code of Federal Regulations, 2010 CFR

2010-10-01

... result of economic price adjustment, (ii) termination notices, and (iii) purchase order modifications as... Optional Form 336 (OF 336), Continuation Sheet, or a blank sheet of paper, may be used as a continuation...

7 CFR 1468.4 - Establishing Conservation Farm Option (CFO) pilot project areas.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) Conservation of soil, water, and related natural resources, (ii) Water quality protection or improvement, (iii... that can be geographically described and has specific environmental sensitivities or significant soil...

48 CFR 570.105-2 - Two-phase design-build selection procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... lease construction projects with options to purchase the real property leased. Use the procedures in.... (iii) The capability and experience of potential contractors. (iv) The suitability of the project for...

Cost-effectiveness analysis of apatinib treatment for chemotherapy-refractory advanced gastric cancer.

PubMed

Chen, Hong-Dou; Zhou, Jing; Wen, Feng; Zhang, Peng-Fei; Zhou, Ke-Xun; Zheng, Han-Rui; Yang, Yu; Li, Qiu

2017-02-01

Apatinib, a third-line or later treatment for advanced gastric cancer (aGC), was shown to improve overall survival and progression-free survival (PFS) compared with placebo in the phase III trial. Given the modest benefit with high costs, we further evaluated the cost-effectiveness of apatinib for patients with chemotherapy-refractory aGC. A Markov model was developed to simulate the disease process of aGC (PFS, progressive disease, and death) and estimate the incremental cost-effectiveness ratio (ICER) of apatinib to placebo. The health outcomes and utility scores were derived from the phase III trial and previously published sources, respectively. Total costs were calculated from the perspective of the Chinese health-care payer. Sensitivity analysis was used to explore model uncertainties. Treatment with apatinib was estimated to provide an incremental 0.09 quality-adjusted life years (QALYs) at an incremental cost of $8113.86 compared with placebo, which resulted in an ICER of $90,154.00 per QALY. Sensitivity analysis showed that across the wide variation of parameters, the ICER exceeded the willingness-to-pay threshold of $23,700.00 per QALY which was three times the Gross Domestic Product per Capita in China. Apatinib is not a cost-effective option for patients with aGC who experienced failure of at least two lines chemotherapy in China. However, for its positive clinical value and subliminal demand, apatinib can provide a new therapeutic option.

Recent advances in management and treatment of hereditary angioedema.

PubMed

Sardana, Niti; Craig, Timothy J

2011-12-01

Hereditary angioedema (HAE) is a rare autosomal-dominant disease characterized by recurrent self-limiting episodes of skin and mucosal edema. Morbidity and mortality are significant, and new and pending therapies are now available to reduce the risk associated with the disease. To update the reader on new advances in HAE to improve patient care. We performed a literature search of Ovid, PubMed, and Google to develop this review. Articles that are necessary for the understanding and use of the new therapeutic options for HAE were chosen, and studies of high quality were used to support the use of therapies, and in most cases, results from phase III studies were used. Until recently, therapy for HAE attacks in the United States consisted of symptom relief with narcotics, hydration, and fresh-frozen plasma, which contains active C1 inhibitor. Therapy to prevent HAE attacks has been confined to androgens and, occasionally, antifibrinolytic agents; however, both drug groups have significant adverse effects. The approval of C1-inhibitor concentrate for prevention and acute therapy has improved efficacy and safety. Ecallantide has also been approved for therapy of attacks, and icatibant is expected to be approved in the next few months for attacks. Recombinant C1 inhibitor is presently in phase III studies and should be available for attacks in the near future. In this article we review the changing therapeutic options available for patients in 2011 and beyond.

33 CFR 105.257 - Security measures for newly-hired employees.

Code of Federal Regulations, 2011 CFR

2011-07-01

... or the FSO enters the following information on the new hire into the Coast Guard's Homeport website...; (iii) Social security number (optional); (iv) Employer name and 24 hour contact information; and (v...

33 CFR 105.257 - Security measures for newly-hired employees.

Code of Federal Regulations, 2012 CFR

2012-07-01

... or the FSO enters the following information on the new hire into the Coast Guard's Homeport website...; (iii) Social security number (optional); (iv) Employer name and 24 hour contact information; and (v...

33 CFR 105.257 - Security measures for newly-hired employees.

Code of Federal Regulations, 2010 CFR

2010-07-01

... or the FSO enters the following information on the new hire into the Coast Guard's Homeport website...; (iii) Social security number (optional); (iv) Employer name and 24 hour contact information; and (v...

33 CFR 105.257 - Security measures for newly-hired employees.

Code of Federal Regulations, 2014 CFR

2014-07-01

... or the FSO enters the following information on the new hire into the Coast Guard's Homeport website...; (iii) Social security number (optional); (iv) Employer name and 24 hour contact information; and (v...

33 CFR 105.257 - Security measures for newly-hired employees.

Code of Federal Regulations, 2013 CFR

2013-07-01

... or the VSO enters the following information on the new hire into the Coast Guard's Homeport website...; (iii) Social security number (optional); (iv) Employer name and 24 hour contact information; and (v...

Real options and asset valuation in competitive energy markets

NASA Astrophysics Data System (ADS)

Oduntan, Adekunle Richard

The focus of this work is to develop a robust valuation framework for physical power assets operating in competitive markets such as peaking or mid-merit thermal power plants and baseload power plants. The goal is to develop a modeling framework that can be adapted to different energy assets with different types of operating flexibilities and technical constraints and which can be employed for various purposes such as capital budgeting, business planning, risk management and strategic bidding planning among others. The valuation framework must also be able to capture the reality of power market rules and opportunities, as well as technical constraints of different assets. The modeling framework developed conceptualizes operating flexibilities of power assets as "switching options' whereby the asset operator decides at every decision point whether to switch from one operating mode to another mutually exclusive mode, within the limits of the equipment constraints of the asset. As a current decision to switch operating modes may affect future operating flexibilities of the asset and hence cash flows, a dynamic optimization framework is employed. The developed framework accounts for the uncertain nature of key value drivers by representing them with appropriate stochastic processes. Specifically, the framework developed conceptualizes the operation of a power asset as a multi-stage decision making problem where the operator has to make a decision at every stage to alter operating mode given currently available information about key value drivers. The problem is then solved dynamically by decomposing it into a series of two-stage sub-problems according to Bellman's optimality principle. The solution algorithm employed is the Least Squares Monte Carlo (LSM) method. The developed valuation framework was adapted for a gas-fired thermal power plant, a peaking hydroelectric power plant and a baseload power plant. This work built on previously published real options valuation methodologies for gas-fired thermal power plants by factoring in uncertainty from gas supply/consumption imbalance which is usually faced by gas-fired power generators. This source of uncertainty arises because of mismatch between natural gas and electricity wholesale markets. Natural gas markets in North America operate on a day-ahead basis while power plants are dispatched in real time. Inability of a power generator to match its gas supply and consumption in real time, leading to unauthorized gas over-run or under-run, attracts penalty charges from the gas supplier to the extent that the generator can not manage the imbalance through other means. By considering an illustrative power plant operating in Ontario, we show effects of gas-imbalance on dispatch strategies on a daily cycling operation basis and the resulting impact on net revenue. Similarly, we employ the developed valuation framework to value a peaking hydroelectric power plant. This application also builds on previous real options valuation work for peaking hydroelectric power plants by considering their operations in a joint energy and ancillary services market. Specifically, the valuation model is developed to capture the value of a peaking power plant whose owner has the flexibility to participate in a joint operating reserve market and an energy market, which is currently the case in the Ontario wholesale power market. The model factors in water inflow uncertainty into the reservoir forebay of a hydroelectric facility and also considers uncertain energy and operating reserve prices. The switching options considered include (i) a joint energy and operating reserve bid (ii) an energy only bid and (iii) a do nothing (idle) strategy. Being an energy limited power plant, by doing nothing at a decision interval, the power asset operator is able to timeshift scarce water for use at a future period when market situations are expected to be better. Finally, the developed valuation framework was employed to optimize life-cycle management decisions of a baseload power plant, such as a nuclear power plant. Given uncertainty of long-term value drivers, including power prices, equipment performance and the relationship between current life cycle spending and future equipment degradation, optimization is carried out with the objective of minimizing overall life-cycle related costs. These life-cycle costs include (i) lost revenue during planned and unplanned outages, (ii) potential costs of future equipment degradation due to inadequate preventative maintenance, and (iii) the direct costs of implementing the life-cycle projects. The switching options in this context include the option to shutdown the power plant in order to execute a given preventative maintenance and inspection project and the option to keep the option "alive" by choosing to delay a planned life-cycle activity.

Therapy for Clostridium difficile infection - any news beyond Metronidazole and Vancomycin?

PubMed

Manthey, C F; Eckmann, L; Fuhrmann, V

2017-11-01

Infections with Clostridium difficile (CDI) represent a major burden for the health care system. Treatment is generally by antibiotic therapy with metronidazole and vancomycin, but efficacy remains suboptimal. Areas covered: This review discusses established and emerging treatment options for CDI, and current therapeutic guidelines, taking into account disease severity and risk of relapse. Expert commentary: New therapeutic approaches, including antibodies and new classes of antibiotics, and new measures for preventing infection with vaccines are under development in phase II/III clinical trials. We performed a systematic literature review using the search terms 'Clostridium difficile' and 'treatment'.

26 CFR 1.401(a)-4 - Optional forms of benefit (before 1994).

Code of Federal Regulations, 2012 CFR

2012-04-01

... nondiscriminatory group of employees. (iii) Special rule for certain governmental or church plans. Plans described... income taxation under section 501(a), including plans subject to section 403(b)(12)(A)(i) (nonelective...

26 CFR 1.401(a)-4 - Optional forms of benefit (before 1994).

Code of Federal Regulations, 2014 CFR

2014-04-01

... nondiscriminatory group of employees. (iii) Special rule for certain governmental or church plans. Plans described... income taxation under section 501(a), including plans subject to section 403(b)(12)(A)(i) (nonelective...

26 CFR 1.401(a)-4 - Optional forms of benefit (before 1994).

Code of Federal Regulations, 2013 CFR

2013-04-01

... nondiscriminatory group of employees. (iii) Special rule for certain governmental or church plans. Plans described... income taxation under section 501(a), including plans subject to section 403(b)(12)(A)(i) (nonelective...

State of the art and perspectives in the treatment of glioblastoma.

PubMed

Grimm, Sean A; Chamberlain, Marc C

2012-09-01

Glioblastoma is the most common malignant primary brain tumor. Cures are rare and median survival varies from several to 22 months. Standard treatment for good performance patients consists of maximal safe surgical resection followed by radiotherapy with concurrent temozolomide (TMZ) chemotherapy and six cycles of postradiotherapy TMZ. At recurrence, treatment options include repeat surgery (with or without Gliadel wafer placement), reirradiation or systemic therapy. Most patients with good performance status are treated with cytotoxic chemotherapy or targeted biologic therapy following or in lieu of repeat surgery. Cytotoxic chemotherapy options include nitrosoureas, rechallenge with TMZ, platins, phophoramides and topoisomerase inhibitors, although efficacy is limited. Despite the intense effort of developing biologic agents that target angiogenesis and growth and proliferative pathways, bevacizumab is the only agent that has shown efficacy in clinical trials. It was awarded accelerated approval in the USA after demonstrating an impressive radiographic response in two open-label, prospective Phase II studies. Two randomized, Phase III trials of upfront bevacizumab have completed and may demonstrate survival benefit; however, results are pending at this time. Given the limited treatment options at tumor recurrence, consideration for enrollment on a clinical trial is encouraged.

An Update on the Current Management of Perforated Diverticulitis.

PubMed

Zoog, Evon; Giles, W Heath; Maxwell, Robert A

2017-12-01

The management of perforated diverticulitis is a challenging aspect of general surgery. The prevalence of colonic diverticular disease has increased over the last decade and will continue to increase as the baby boomers add to the elderly population. Improvements in diagnostic imaging modalities, efforts to maintain intestinal continuity, and percutaneous drainage procedures now result in several alternatives when selecting a management strategy for complicated presentations. Specifically, laparoscopic lavage and resection with primary anastomosis have emerged as options for treatment of Hinchey III and IV diverticulitis in place of diversion in the appropriately selected patient. Percutaneous drainage of Hinchey II diverticulitis in centers equipped with interventional radiology provides another minimally invasive adjunct. The objective of this paper is to provide an update on the current management of perforated diverticulitis, with a focus on the advantages and disadvantages of the surgical options for the treatment of Hinchey III and IV diverticulitis.

New treatments for the motor symptoms of Parkinson's disease.

PubMed

Vijverman, Anne-Catherine; Fox, Susan H

2014-11-01

Levodopa remains the most potent drug to treat motor symptoms in Parkinson's disease (PD); however, motor fluctuations and levodopa-induced dyskinesia that occur with long-term use restrict some of its therapeutic value. Despite these limitations, the medical treatment of PD strives for continuous relief of symptoms using different strategies throughout the course of the illness: increasing the half-life of levodopa, using 'levodopa-sparing agents' and adding non-dopaminergic drugs. New options to 'improve' delivery of levodopa are under investigation, including long-acting levodopa, nasal inhalation and continuous subcutaneous or intrajejunal administration of levodopa. Long-acting dopamine agonists were recently developed and are undergoing further comparative studies to investigate potential superiority over the immediate-release formulations. Non-dopaminergic drugs acting on adenosine receptors, cholinergic, adrenergic, serotoninergic and glutamatergic pathways are newly developed and many are being evaluated in Phase II and Phase III trials. This article focuses on promising novel therapeutic approaches for the management of PD motor symptoms and motor complications. We will provide an update since 2011 on new formulations of current drugs, new drugs with promising results in Phase II and Phase III clinical trials, old drugs with new possibilities and some new potential strategies that are currently in Phase I and II of development (study start date may precede 2011 but are included as study is still ongoing or full data have not yet been published). Negative Phase II and Phase III clinical trials published since 2011 will also be briefly mentioned.

Electrochemotherapy efficacy evaluation for treatment of locally advanced stage III cutaneous squamous cell carcinoma: a 22-cases retrospective analysis.

PubMed

Di Monta, Gianluca; Caracò, Corrado; Simeone, Ester; Grimaldi, Antonio Maria; Marone, Ugo; Di Marzo, Massimiliano; Vanella, Vito; Festino, Lucia; Palla, Marco; Mori, Stefano; Mozzillo, Nicola; Ascierto, Paolo Antonio

2017-04-26

Extensive squamous cell carcinoma has few therapeutic options. In such cases, electrochemotherapy involving electroporation combined with antineoplastic drug appears to be a new potential option and may be considered as an alternative treatment. The aim of this retrospective single-center study was to evaluate electrochemotherapy efficacy in treatment of locally advanced stage III squamous cell carcinoma, in which surgical procedures would have entailed wide tissue sacrifice. Clinical features, treatment response, and adverse effects were evaluated in 22 patients treated with electrochemotherapy with intravenous injection of bleomycin for extensive stage III cutaneous squamous cell carcinoma. Treatment of cutaneous lesions were performed according to the European Standard Operating Procedures of Electrochemotherapy. Overall response to electrochemotherapy treatment was observed in 18 (81.8%) patients. Clinical response with necrosis of tumor mass was observed from the first session and lasted for all follow up period that ranged between 5 and 48 months with a median of 34 months. Overall the treatment was well tolerated with a very low complication rate. Electrochemotherapy represents a safe and effective therapeutic approach, associated with a good tolerability.

75 FR 15760 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-30

... schedule to execution charges for inbound ``Linkage Orders'' which only applied to the execution of linkage... in footnote (6) regarding the marketing fee; (iii) delete references to the old linkage in footnote...

Routine Treatment of Cervical Cytological Cell Changes

PubMed Central

Huber, J.; Pötsch, B.; Gantschacher, M.; Templ, M.

2016-01-01

Introduction: Diagnosis and treatment of vaginal and cervical cytological cell changes are described in European and national guidelines. The aim of this data collection was to evaluate the remission rates of PAP III and PAP III D cytological findings in patients over a period of 3–4 months. Method: The current state of affairs in managing suspicious and cytological findings (PAP III, and III D) in gynecological practice was assessed in the context of a data collection survey. An evaluation over a period of 24 months was conducted on preventative measures, the occurrence and changes to normal/suspect/pathological findings and therapy management (for suspicious or pathological findings). Results: 307 female patients were included in the analysis. At the time of the survey 186 patients (60.6 %) had PAP III and 119 (38.8 %) had PAP III D findings. The spontaneous remission rate of untreated PAP III patients was 6 % and that of untreated PAP III D patients was 11 %. The remission rates of patients treated with a vaginal gel were 77 % for PAP III and 71 % for PAP III D. Conclusion: A new treatment option was used in gynecological practice on patients with PAP III and PAP III D findings between confirmation and the next follow-up with excellent success. PMID:27761030

Report on the FY17 Development of Computer Program for ASME Section III, Division 5, Subsection HB, Subpart B Rules

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

Swindeman, M. J.; Jetter, R. I.; Sham, T. -L.

One of the objectives of the high temperature design methodology activities is to develop and validate both improvements and the basic features of ASME Boiler and Pressure Vessel Code, Section III, Rules for Construction of Nuclear Facility Components, Division 5, High Temperature Reactors, Subsection HB, Subpart B (HBB). The overall scope of this task is to develop a computer program to aid assessment procedures of components under specified loading conditions in accordance with the elevated temperature design requirements for Division 5 Class A components. There are many features and alternative paths of varying complexity in HBB. The initial focus ofmore » this computer program is a basic path through the various options for a single reference material, 316H stainless steel. However, the computer program is being structured for eventual incorporation all of the features and permitted materials of HBB. This report will first provide a description of the overall computer program, particular challenges in developing numerical procedures for the assessment, and an overall approach to computer program development. This is followed by a more comprehensive appendix, which is the draft computer program manual for the program development. The strain limits rules have been implemented in the computer program. The evaluation of creep-fatigue damage will be implemented in future work scope.« less

Understanding your capital options.

PubMed

Payne, Christopher T

2012-05-01

When planning capital expenditures, hospitals and health systems should understand the following financing considerations: Traditional fixed-rate tax-exempt bonds; Variable-rate financing alternatives; Basel III Accord requirements; Direct tax-exempt bank loans; Total return swaps Taxable financings; Interest-rate swaps and collateral requirements

[Techniques for Preventing Postoperative Complication in Esophageal Salvage Surgery].

PubMed

Iwama, Mitsuru; Yasuda, Takushi; Shiraishi, Osamu; Kato, Hiroaki; Hiraki, Yoko; Tanaka, Yumiko; Yasuda, Atsushi; Shinkai, Masayuki; Imano, Motohiro; Kimura, Yutaka; Imamoto, Haruhiko

2017-07-01

Patients with esophageal cancer are often treated with definitive chemoradiotherapy (dCRT). Regardless of arrival at dCRT, the risk of local/regional recurrence during follow-up is significant. Many patient are faced with limited options for therapy once dCRT has failed. Salvage surgery is the only way for complete cure of patients with local/regional recurrent esophageal cancer after dCRT. However, salvage surgery has a significant high risk of fatal complications. We examine our preventive measures to reduce the incidence of postoperative complications after salvage surgery for thoracic esophageal cancer. The points of our preventive measures are them; I. the ingenuity of surgery, II. the securement of blood supply for the respiratory tract, III. standard lymphadenectomy, IV. countermeasures of anastomotic failure, V. countermeasures of dead space, VI. countermeasures of respiratory complications, VII. perioperative managements. Salvage surgery is a reasonable option to treat patients with local/regional recurrence after failed dCRT. Our preventive mesures are effective, therefore, we have to make the further technological developments and the safety of salvage surgery.

Biodiversity Hotspots, Climate Change, and Agricultural Development: Global Limits of Adaptation

NASA Astrophysics Data System (ADS)

Schneider, U. A.; Rasche, L.; Schmid, E.; Habel, J. C.

2017-12-01

Terrestrial ecosystems are threatened by climate and land management change. These changes result from complex and heterogeneous interactions of human activities and natural processes. Here, we study the potential change in pristine area in 33 global biodiversity hotspots within this century under four climate projections (representative concentration pathways) and associated population and income developments (shared socio-economic pathways). A coupled modelling framework computes the regional net expansion of crop and pasture lands as result of changes in food production and consumption. We use a biophysical crop simulation model to quantify climate change impacts on agricultural productivity, water, and nutrient emissions for alternative crop management systems in more than 100 thousand agricultural land polygons (homogeneous response units) and for each climate projection. The crop simulation model depicts detailed soil, weather, and management information and operates with a daily time step. We use time series of livestock statistics to link livestock production to feed and pasture requirements. On the food consumption side, we estimate national demand shifts in all countries by processing population and income growth projections through econometrically estimated Engel curves. Finally, we use a global agricultural sector optimization model to quantify the net change in pristine area in all biodiversity hotspots under different adaptation options. These options include full-scale global implementation of i) crop yield maximizing management without additional irrigation, ii) crop yield maximizing management with additional irrigation, iii) food yield maximizing crop mix adjustments, iv) food supply maximizing trade flow adjustments, v) healthy diets, and vi) combinations of the individual options above. Results quantify the regional potentials and limits of major agricultural producer and consumer adaptation options for the preservation of pristine areas in biodiversity hotspots. Results also quantify the conflicts between food and water security, biodiversity protection, and climate change mitigation.

Using computer technology for HIV prevention among African-Americans: development of a tailored information program for safer sex (TIPSS)

PubMed Central

Noar, Seth M.; Webb, Elizabeth M.; Van Stee, Stephanie K.; Redding, Colleen A.; Feist-Price, Sonja; Crosby, Richard; Troutman, Adewale

2011-01-01

New prevention options are urgently needed for African-Americans in the United States given the disproportionate impact of HIV/AIDS on this group. This combined with recent evidence supporting the efficacy of computer technology-based interventions in HIV prevention led our research group to pursue the development of a computer-delivered individually tailored intervention for heterosexually active African-Americans—the tailored information program for safer sex (TIPSS). In the current article, we discuss the development of the TIPSS program, including (i) the targeted population and behavior, (ii) theoretical basis for the intervention, (iii) design of the intervention, (iv) formative research, (v) technical development and testing and (vi) intervention delivery and ongoing randomized controlled trial. Given the many advantages of computer-based interventions, including low-cost delivery once developed, they offer much promise for the future of HIV prevention among African-Americans and other at-risk groups. PMID:21257676

MarsSedEx III: linking Computational Fluid Dynamics (CFD) and reduced gravity experiments

NASA Astrophysics Data System (ADS)

Kuhn, N. J.; Kuhn, B.; Gartmann, A.

2015-12-01

Nikolaus J. Kuhn (1), Brigitte Kuhn (1), and Andres Gartmann (2) (1) University of Basel, Physical Geography, Environmental Sciences, Basel, Switzerland (nikolaus.kuhn@unibas.ch), (2) Meteorology, Climatology, Remote Sensing, Environmental Sciences, University of Basel, Switzerland Experiments conducted during the MarsSedEx I and II reduced gravity experiments showed that using empirical models for sediment transport on Mars developed for Earth violates fluid dynamics. The error is caused by the interaction between runing water and sediment particles, which affect each other in a positive feedback loop. As a consequence, the actual flow conditions around a particle cannot be represented by drag coefficients derived on Earth. This study exmines the implications of such gravity effects on sediment movement on Mars, with special emphasis on the limits of sandstones and conglomerates formed on Earth as analogues for sedimentation on Mars. Furthermore, options for correctiong the errors using a combination of CFD and recent experiments conducted during the MarsSedEx III campaign are presented.

18 CFR 806.23 - Standards for water withdrawals.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of groundwater or stream flow levels; rendering competing supplies unreliable; affecting other water..., at its own expense, an alternate water supply or other mitigating measures. (iii) Require the project... deficiencies, identify alternative water supply options, and support existing and proposed future withdrawals. ...

40 CFR 98.3 - What are the general monitoring, reporting, recordkeeping and verification requirements of this...

Code of Federal Regulations, 2012 CFR

2012-07-01

... (c)(12)(iii) of this section. If the latter reporting option is chosen, you must report: (i) Annual... flow meter's primary element (e.g., the orifice plate), or when there is only a differential pressure...

46 CFR 308.546 - Standard optional endorsement No. 1-A, Form MA-316-A.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... 308.546 Section 308.546 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Iii-Facultative War Risk Cargo Insurance § 308.546... from the American War Risk Agency or MARAD. ...

46 CFR 308.546 - Standard optional endorsement No. 1-A, Form MA-316-A.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... 308.546 Section 308.546 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Iii-Facultative War Risk Cargo Insurance § 308.546... from the American War Risk Agency or MARAD. ...

46 CFR 308.546 - Standard optional endorsement No. 1-A, Form MA-316-A.

Code of Federal Regulations, 2013 CFR

2013-10-01

.... 308.546 Section 308.546 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Iii-Facultative War Risk Cargo Insurance § 308.546... from the American War Risk Agency or MARAD. ...

46 CFR 308.546 - Standard optional endorsement No. 1-A, Form MA-316-A.

Code of Federal Regulations, 2012 CFR

2012-10-01

.... 308.546 Section 308.546 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Iii-Facultative War Risk Cargo Insurance § 308.546... from the American War Risk Agency or MARAD. ...

[Necessary and unnecessary treatment options for hemorrhoids].

PubMed

Zindel, Joel; Inglin, Roman; Brügger, Lukas

2014-12-01

Up to one third of the general population suffers from symptoms caused by hemorrhoids. Conservative treatment comes first unless the patient presents with an acute hemorrhoidal prolapse or a thrombosis. A fiber enriched diet is the primary treatment option, recommended in the perioperative period as well as a long-term prophylaxis. A timely limited application of topical ointments or suppositories and/or flavonoids are further treatment options. When symptoms persist interventional procedures for grade I-II hemorrhoids, and surgery for grade III-IV hemorrhoids should be considered. Rubber band ligation is the interventional treatment of choice. A comparable efficacy using sclerosing or infrared therapy has not yet been demonstrated. We therefore do not recommend these treatment options for the cure of hemorrhoids. Self-treatment by anal insertion of bougies is of lowrisk and may be successful, particularly in the setting of an elevated sphincter pressure. Anal dilation, sphincterotomy, cryosurgery, bipolar diathermy, galvanic electrotherapy, and heat therapy should be regarded as obsolete given the poor or missing data reported for these methods. For a long time, the classic excisional hemorrhoidectomy was considered to be the gold standard as far as surgical procedures are concerned. Primary closure (Ferguson) seems to be superior compared to the "open" version (Milligan Morgan) with respect to postoperative pain and wound healing. The more recently proposed stapled hemorrhoidopexy (Longo) is particularly advisable for circular hemorrhoids. Compared to excisional hemorrhoidectomy the Longo-operation is associated with reduced postoperative pain, shorter operation time and hospital stay as well as a faster recovery, with the disadvantage though of a higher recurrence rate. Data from Hemorrhoidal Artery Ligation (HAL)-, if appropriate in combination with a Recto-Anal Repair (HAL/RAR)-, demonstrates a similar trend towards a better tolerance of the procedure at the expense of a higher recurrence rate. These relatively "new" procedures equally qualify for the treatment of grade III and IV hemorrhoids, and, in the case of stapled hemorrhoidopexy, may even be employed in the emergency situation of an acute anal prolapse. While under certain circumstances different treatment options are equivalent, there is a clear specificity with respect to the application of those procedures in other situations. The respective pros and cons need to be discussed separately with every patient. According to their own requirements a treatment strategy has to be defined according to their individual requirements.

Fast fluorescence techniques for crystallography beamlines

PubMed Central

Stepanov, Sergey; Hilgart, Mark; Yoder, Derek W.; Makarov, Oleg; Becker, Michael; Sanishvili, Ruslan; Ogata, Craig M.; Venugopalan, Nagarajan; Aragão, David; Caffrey, Martin; Smith, Janet L.; Fischetti, Robert F.

2011-01-01

This paper reports on several developments of X-ray fluorescence techniques for macromolecular crystallography recently implemented at the National Institute of General Medical Sciences and National Cancer Institute beamlines at the Advanced Photon Source. These include (i) three-band on-the-fly energy scanning around absorption edges with adaptive positioning of the fine-step band calculated from a coarse pass; (ii) on-the-fly X-ray fluorescence rastering over rectangular domains for locating small and invisible crystals with a shuttle-scanning option for increased speed; (iii) fluorescence rastering over user-specified multi-segmented polygons; and (iv) automatic signal optimization for reduced radiation damage of samples. PMID:21808424

Combining analytical frameworks to assess livelihood vulnerability to climate change and analyse adaptation options☆

PubMed Central

Reed, M.S.; Podesta, G.; Fazey, I.; Geeson, N.; Hessel, R.; Hubacek, K.; Letson, D.; Nainggolan, D.; Prell, C.; Rickenbach, M.G.; Ritsema, C.; Schwilch, G.; Stringer, L.C.; Thomas, A.D.

2013-01-01

Experts working on behalf of international development organisations need better tools to assist land managers in developing countries maintain their livelihoods, as climate change puts pressure on the ecosystem services that they depend upon. However, current understanding of livelihood vulnerability to climate change is based on a fractured and disparate set of theories and methods. This review therefore combines theoretical insights from sustainable livelihoods analysis with other analytical frameworks (including the ecosystem services framework, diffusion theory, social learning, adaptive management and transitions management) to assess the vulnerability of rural livelihoods to climate change. This integrated analytical framework helps diagnose vulnerability to climate change, whilst identifying and comparing adaptation options that could reduce vulnerability, following four broad steps: i) determine likely level of exposure to climate change, and how climate change might interact with existing stresses and other future drivers of change; ii) determine the sensitivity of stocks of capital assets and flows of ecosystem services to climate change; iii) identify factors influencing decisions to develop and/or adopt different adaptation strategies, based on innovation or the use/substitution of existing assets; and iv) identify and evaluate potential trade-offs between adaptation options. The paper concludes by identifying interdisciplinary research needs for assessing the vulnerability of livelihoods to climate change. PMID:25844020

Tyk2 as a target for immune regulation in human viral/bacterial pneumonia.

PubMed

Berg, Johanna; Zscheppang, Katja; Fatykhova, Diana; Tönnies, Mario; Bauer, Torsten T; Schneider, Paul; Neudecker, Jens; Rückert, Jens C; Eggeling, Stephan; Schimek, Maria; Gruber, Achim D; Suttorp, Norbert; Hippenstiel, Stefan; Hocke, Andreas C

2017-07-01

The severity and lethality of influenza A virus (IAV) infections is frequently aggravated by secondary bacterial pneumonia. However, the mechanisms in human lung tissue that provoke this increase in fatality are unknown and therapeutic immune modulatory options are lacking.We established a human lung ex vivo co-infection model to investigate innate immune related mechanisms contributing to the susceptibility of secondary pneumococcal pneumonia.We revealed that type I and III interferon (IFN) inhibits Streptococcus pneumoniae -induced interleukin (IL)-1β release. The lack of IL-1β resulted in the repression of bacterially induced granulocyte-macrophage colony-stimulating factor (GM-CSF) liberation. Specific inhibition of IFN receptor I and III-associated tyrosine kinase 2 (Tyk2) completely restored the S. pneumoniae -induced IL-1β-GM-CSF axis, leading to a reduction of bacterial growth. A preceding IAV infection of the human alveolus leads to a type I and III IFN-dependent blockade of the early cytokines IL-1β and GM-CSF, which are key for orchestrating an adequate innate immune response against bacteria. Their virally induced suppression may result in impaired bacterial clearance and alveolar repair.Pharmacological inhibition of Tyk2 might be a new treatment option to sustain beneficial endogenous GM-CSF levels in IAV-associated secondary bacterial pneumonia. Copyright ©ERS 2017.

Cetuximab in locally advanced head-and-neck cancer: defining the population

PubMed Central

Ho, C.

2010-01-01

Encouraging data for targeted therapy in head-and-neck squamous cell carcinoma are opening new options for treatment. Phase III trials of cetuximab, an antibody directed against the epidermal growth factor receptor (egfr) have demonstrated benefit in the locally advanced and metastatic settings. Recognizing the importance of emerging therapies, Cancer Care Ontario published guideline recommendations for egfr-targeted therapy in stage iii and iv head-and-neck cancer. The present paper takes a further look at the population for whom an offer of cetuximab therapy may be appropriate. PMID:20697514

DSN command system Mark III-78. [data processing

NASA Technical Reports Server (NTRS)

Stinnett, W. G.

1978-01-01

The Deep Space Network command Mark III-78 data processing system includes a capability for a store-and-forward handling method. The functions of (1) storing the command files at a Deep Space station; (2) attaching the files to a queue; and (3) radiating the commands to the spacecraft are straightforward. However, the total data processing capability is a result of assuming worst case, failure-recovery, or nonnominal operating conditions. Optional data processing functions include: file erase, clearing the queue, suspend radiation, command abort, resume command radiation, and close window time override.

Moving granular-bed filter development program, Option III: Development of moving granular-bed filter technology for multi-contaminant control. Task 14: Test plan; Topical report

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

Haas, J.C.; Olivo, C.A.; Wilson, K.B.

1994-04-01

An experimental test plan has been prepared for DOE/METC review and approval to develop a filter media suitable for multi-contaminant control in granular-bed filter (GBF) applications. The plan includes identification, development, and demonstration of methods for enhanced media morphology, chemical reactivity, and mechanical strength. The test plan includes media preparation methods, physical and chemical characterization methods for fresh and reacted media, media evaluation criteria, details of test and analytical equipment, and test matrix of the proposed media testing. A filter media composed of agglomerated limestone and clay was determined to be the best candidate for multi-contaminate control in GBF operation.more » The combined limestone/clay agglomerate has the potential to remove sulfur and alkali species, in addition to particulate, and possibly halogens and trace heavy metals from coal process streams.« less

Magnetic levitation assisted aircraft take-off and landing (feasibility study - GABRIEL concept)

NASA Astrophysics Data System (ADS)

Rohacs, Daniel; Rohacs, Jozsef

2016-08-01

The Technology Roadmap 2013 developed by the International Air Transport Association envisions the option of flying without an undercarriage to be in operation by 2032. Preliminary investigations clearly indicate that magnetic levitation technology (MagLev) might be an appealing solution to assist the aircraft take-off and landing. The EU supported research project, abbreviated as GABRIEL, was dealing with (i) the concept development, (ii) the identification, evaluation and selection of the deployable magnetic levitation technology, (iii) the definition of the core system elements (including the required aircraft modifications, the ground-based system and airport elements, and the rendezvous control system), (iv) the analysis of the safety and security aspects, (v) the concept validation and (vi) the estimation of the proposed concept impact in terms of aircraft weight, noise, emission, cost-benefit). All results introduced here are compared to a medium size hypothetic passenger aircraft (identical with an Airbus A320). This paper gives a systematic overview of (i) the applied methods, (ii) the investigation of the possible use of magnetic levitation technology to assist the commercial aircraft take-off and landing processes and (iii) the demonstrations, validations showing the feasibility of the radically new concept. All major results are outlined.

GBM heterogeneity as a function of variable epidermal growth factor receptor variant III activity.

PubMed

Lindberg, Olle R; McKinney, Andrew; Engler, Jane R; Koshkakaryan, Gayane; Gong, Henry; Robinson, Aaron E; Ewald, Andrew J; Huillard, Emmanuelle; David James, C; Molinaro, Annette M; Shieh, Joseph T; Phillips, Joanna J

2016-11-29

Abnormal activation of the epidermal growth factor receptor (EGFR) due to a deletion of exons 2-7 of EGFR (EGFRvIII) is a common alteration in glioblastoma (GBM). While this alteration can drive gliomagenesis, tumors harboring EGFRvIII are heterogeneous. To investigate the role for EGFRvIII activation in tumor phenotype we used a neural progenitor cell-based murine model of GBM driven by EGFR signaling and generated tumor progenitor cells with high and low EGFRvIII activation, pEGFRHi and pEGFRLo. In vivo, ex vivo, and in vitro studies suggested a direct association between EGFRvIII activity and increased tumor cell proliferation, decreased tumor cell adhesion to the extracellular matrix, and altered progenitor cell phenotype. Time-lapse confocal imaging of tumor cells in brain slice cultures demonstrated blood vessel co-option by tumor cells and highlighted differences in invasive pattern. Inhibition of EGFR signaling in pEGFRHi promoted cell differentiation and increased cell-matrix adhesion. Conversely, increased EGFRvIII activation in pEGFRLo reduced cell-matrix adhesion. Our study using a murine model for GBM driven by a single genetic driver, suggests differences in EGFR activation contribute to tumor heterogeneity and aggressiveness.

76 FR 9820 - Notice of Information Collection

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-22

... . SUPPLEMENTARY INFORMATION: I. Abstract LaRC leadership desires to seek out customer feedback across all mission..., customers will have the option to provide their feedback via e-mail, Web-based survey, or phone conversation in accordance with their preference. III. Data Title: LaRC Customer Satisfaction Assessment OMB...

75 FR 71648 - Federal Motor Vehicle Safety Standards, Child Restraint Systems; Hybrid III 10-Year-Old Child...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-24

...This document proposes to amend Federal Motor Vehicle Safety Standard (FMVSS) No. 213, Child Restraint Systems, regarding a Hybrid III 10-year-old child test dummy that the agency seeks to use in the compliance test procedures of the standard. This document supplements a 2005 notice of proposed rulemaking (NPRM) and a 2008 SNPRM previously published in this rulemaking (RIN 2127-AJ44) regarding this test dummy. In the 2005 NPRM, in response to Anton's Law, NHTSA proposed to adopt the 10-year-old child test dummy into FMVSS No. 213 to test child restraints for older children. Subsequently, to address variation that was found in dummy readings due to chin-to-chest contact, NHTSA published the 2008 SNPRM to propose a NHTSA-developed procedure for positioning the test dummy in belt-positioning seats. Comments on the SNPRM objected to the positioning procedure, and some suggested an alternative procedure developed by the University of Michigan Transportation Research Institute (UMTRI). Today's SNPRM proposes to use the UMTRI procedure to position the test dummy rather than the NHTSA-developed procedure. We note that the 10-year-old child dummy may sometimes experience stiff contact between its chin and upper sternal bib region which may result in an unrealistically high value of the head injury criterion (HIC) \\1\\ referenced in the standard. Accordingly, NHTSA proposes that the dummy's HIC measurement will not be used to assess the compliance of the tested child restraint. This SNPRM also proposes other amendments to FMVSS No. 213, including a proposal to permit NHTSA to use, at the manufacturer's option, the Hybrid II or Hybrid III versions of the 6-year-old test dummy, and a proposal to use the UMTRI procedure to position the Hybrid III 6-year- old and 10-year-old dummies when testing belt-positioning seats. ---------------------------------------------------------------------------

Molecular Genetics Information System (MOLGENIS): alternatives in developing local experimental genomics databases.

PubMed

Swertz, Morris A; De Brock, E O; Van Hijum, Sacha A F T; De Jong, Anne; Buist, Girbe; Baerends, Richard J S; Kok, Jan; Kuipers, Oscar P; Jansen, Ritsert C

2004-09-01

Genomic research laboratories need adequate infrastructure to support management of their data production and research workflow. But what makes infrastructure adequate? A lack of appropriate criteria makes any decision on buying or developing a system difficult. Here, we report on the decision process for the case of a molecular genetics group establishing a microarray laboratory. Five typical requirements for experimental genomics database systems were identified: (i) evolution ability to keep up with the fast developing genomics field; (ii) a suitable data model to deal with local diversity; (iii) suitable storage of data files in the system; (iv) easy exchange with other software; and (v) low maintenance costs. The computer scientists and the researchers of the local microarray laboratory considered alternative solutions for these five requirements and chose the following options: (i) use of automatic code generation; (ii) a customized data model based on standards; (iii) storage of datasets as black boxes instead of decomposing them in database tables; (iv) loosely linking to other programs for improved flexibility; and (v) a low-maintenance web-based user interface. Our team evaluated existing microarray databases and then decided to build a new system, Molecular Genetics Information System (MOLGENIS), implemented using code generation in a period of three months. This case can provide valuable insights and lessons to both software developers and a user community embarking on large-scale genomic projects. http://www.molgenis.nl

Expression of short hairpin RNAs using the compact architecture of retroviral microRNA genes.

PubMed

Burke, James M; Kincaid, Rodney P; Aloisio, Francesca; Welch, Nicole; Sullivan, Christopher S

2017-09-29

Short hairpin RNAs (shRNAs) are effective in generating stable repression of gene expression. RNA polymerase III (RNAP III) type III promoters (U6 or H1) are typically used to drive shRNA expression. While useful for some knockdown applications, the robust expression of U6/H1-driven shRNAs can induce toxicity and generate heterogeneous small RNAs with undesirable off-target effects. Additionally, typical U6/H1 promoters encompass the majority of the ∼270 base pairs (bp) of vector space required for shRNA expression. This can limit the efficacy and/or number of delivery vector options, particularly when delivery of multiple gene/shRNA combinations is required. Here, we develop a compact shRNA (cshRNA) expression system based on retroviral microRNA (miRNA) gene architecture that uses RNAP III type II promoters. We demonstrate that cshRNAs coded from as little as 100 bps of total coding space can precisely generate small interfering RNAs (siRNAs) that are active in the RNA-induced silencing complex (RISC). We provide an algorithm with a user-friendly interface to design cshRNAs for desired target genes. This cshRNA expression system reduces the coding space required for shRNA expression by >2-fold as compared to the typical U6/H1 promoters, which may facilitate therapeutic RNAi applications where delivery vector space is limiting. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

21 CFR 145.175 - Canned pears.

Code of Federal Regulations, 2010 CFR

2010-04-01

... optional ingredients. (i) Natural and artificial flavors. (ii) Spice. (iii) Vinegar, lemon juice, or... characterizes the product as specified in § 101.22 of this chapter and a declaration of any spice or seasoning that characterizes the product; for example, “Spice added”, or in lieu of the word “Spice”, the common...

40 CFR 89.102 - Effective dates, optional inclusion, flexibility for equipment manufacturers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... exemptions for technical or engineering hardship. You may request additional engine allowances under... technical or engineering problems that prevent you from meeting the requirements of this part. You must show... your engine supplier to design products. (iii) Describe the engineering or technical problems causing...

42 CFR 447.52 - Cost sharing.

Code of Federal Regulations, 2014 CFR

2014-10-01

... agency imposes cost sharing under § 447.54, the process by which hospital emergency room services are... State option, cost sharing imposed for any service (other than for drugs and non-emergency services... group under § 447.56(a), and (iii) For cost sharing imposed for non-emergency services furnished in an...

40 CFR 89.102 - Effective dates, optional inclusion, flexibility for equipment manufacturers.

Code of Federal Regulations, 2013 CFR

2013-07-01

... exemptions for technical or engineering hardship. You may request additional engine allowances under... technical or engineering problems that prevent you from meeting the requirements of this part. You must show... your engine supplier to design products. (iii) Describe the engineering or technical problems causing...

40 CFR 89.102 - Effective dates, optional inclusion, flexibility for equipment manufacturers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... exemptions for technical or engineering hardship. You may request additional engine allowances under... technical or engineering problems that prevent you from meeting the requirements of this part. You must show... your engine supplier to design products. (iii) Describe the engineering or technical problems causing...

Reframing Reality: Christmas at the Mall.

ERIC Educational Resources Information Center

Long, Nicholas J.; Daniels, Doug

1993-01-01

Presents Life Space Interview (LSI), effective intervention strategy for use during crisis work with troubled students, as it was applied to case of eight-year-old boy attending Option III class for emotionally handicapped students when he accompanied class to mall for holiday shopping trip. Following interview are instructional comments on the…

77 FR 67269 - Voluntary Licensing of Amateur Rocket Operations; Withdrawal

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-09

...-0318; Amdt. No. 400-4] RIN 2120-AK16 Voluntary Licensing of Amateur Rocket Operations; Withdrawal... that conduct certain amateur rocket launches to voluntarily apply for a commercial space transportation... give operators of Class 3 advanced high-power rockets the option of applying for a chapter III launch...

75 FR 3941 - Notice of Information Collection

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-25

... collection and analysis of worldwide safety issues. II. Method of Collection Aviation stakeholders will be... option of printing it and filling it out manually and then returning it via traditional mail, filling it.... III. Data Title: Biennial NextGen Safety Issue Survey. OMB Number: 2700-XXXX. Type of Review: New...

Routine Treatment of Cervical Cytological Cell Changes: Diagnostic Standard, Prevention and Routine Treatment of Cervical Cytological Cell Changes - An Assessment of Primary and Secondary Prevention and Routine Treatment Data in the Context of an Anonymous Data Collection from Practicing Gynaecologists; an Academic, Non-Interventional Study.

PubMed

Huber, J; Pötsch, B; Gantschacher, M; Templ, M

2016-10-01

Introduction: Diagnosis and treatment of vaginal and cervical cytological cell changes are described in European and national guidelines. The aim of this data collection was to evaluate the remission rates of PAP III and PAP III D cytological findings in patients over a period of 3-4 months. Method: The current state of affairs in managing suspicious and cytological findings (PAP III, and III D) in gynecological practice was assessed in the context of a data collection survey. An evaluation over a period of 24 months was conducted on preventative measures, the occurrence and changes to normal/suspect/pathological findings and therapy management (for suspicious or pathological findings). Results: 307 female patients were included in the analysis. At the time of the survey 186 patients (60.6 %) had PAP III and 119 (38.8 %) had PAP III D findings. The spontaneous remission rate of untreated PAP III patients was 6 % and that of untreated PAP III D patients was 11 %. The remission rates of patients treated with a vaginal gel were 77 % for PAP III and 71 % for PAP III D. Conclusion: A new treatment option was used in gynecological practice on patients with PAP III and PAP III D findings between confirmation and the next follow-up with excellent success.

Hepatocellular Cancer: New Kids on the Block.

PubMed

Hoffmann, Andreas-Claudiu; Gerken, Guido G H

2014-05-01

With over 600,000 newly diagnosed hepatocellular cancer (HCC) patients worldwide every year and ongoing clinical research, it is surprising that many of the new molecular entities have not yet resulted in significant prolongation of progression-free or overall survival. Nevertheless, there are a number of promising agents currently under investigation. Given the unique tumor biology and heterogeneous clinical manifestations of HCC, the application of molecular and cellular markers could also benefit patient selection, disease prognosis and trial design. This paper provides an overview of the current therapeutic strategies for HCC in the curative and palliative settings. Furthermore, we introduce some of the promising small molecules and antibodies that may find their way into clinical practice, with a focus on substances that are currently in phase III testing. Finally, we summarize the role of promising biomarkers, such as circulating tumor or cancer stem cells. Despite the rising prevalence of HCC and active clinical research, few therapeutic options besides sorafenib have been established. This review discusses the new therapeutic agents in the pipeline. Although many promising preclinical studies have resulted in phase I-II trials on HCC, so far only the tyrosine and Raf kinase inhibitor sorafenib has made its way into the hands of physicians. This multikinase inhibitor is the only approved option for systemic treatment of advanced HCC. Currently, the development of promising approaches for disease management is guided by biomarkers such as molecular markers or cellular characteristics. The use of biomarkers may facilitate early diagnosis in high-risk groups and therefore enhance outcomes by detecting patients whose disease is still curable.

Advances in the management of follicular lymphoma.

PubMed

Seiler, Till M; Hiddemann, Wolfgang

2012-11-01

Antibody-based therapy has revolutionized treatment strategies in follicular lymphoma. This review focuses on current standards and recent innovations in the management of the disease. Understanding the mechanism of action of antibodies led to the development of next generation CD20 antibodies, antibodies targeting other molecules and bispecific antibodies. With obinutuzumab, a promising next generation of CD20 antibodies has entered phase III of clinical trials. The bispecific T-cell engager blinatumomab combines targeted therapy with immunologic activation of T cells exerting cytotoxic activity on the target cells. Apart from antibodies, small molecules targeting key pathways in lymphoma have shown promising activity in vitro and are currently in clinical development. A wealth of new substances has entered various stages of clinical trials and has yet to show superiority over rituximab-based immunochemotherapy. Intelligent therapeutic regimens containing these drugs have to be developed. Large randomized trials comparing promising treatment options are urgently needed.

A Neural Circuit Mechanism for the Involvements of Dopamine in Effort-Related Choices: Decay of Learned Values, Secondary Effects of Depletion, and Calculation of Temporal Difference Error

PubMed Central

2018-01-01

Abstract Dopamine has been suggested to be crucially involved in effort-related choices. Key findings are that dopamine depletion (i) changed preference for a high-cost, large-reward option to a low-cost, small-reward option, (ii) but not when the large-reward option was also low-cost or the small-reward option gave no reward, (iii) while increasing the latency in all the cases but only transiently, and (iv) that antagonism of either dopamine D1 or D2 receptors also specifically impaired selection of the high-cost, large-reward option. The underlying neural circuit mechanisms remain unclear. Here we show that findings i–iii can be explained by the dopaminergic representation of temporal-difference reward-prediction error (TD-RPE), whose mechanisms have now become clarified, if (1) the synaptic strengths storing the values of actions mildly decay in time and (2) the obtained-reward-representing excitatory input to dopamine neurons increases after dopamine depletion. The former is potentially caused by background neural activity–induced weak synaptic plasticity, and the latter is assumed to occur through post-depletion increase of neural activity in the pedunculopontine nucleus, where neurons representing obtained reward exist and presumably send excitatory projections to dopamine neurons. We further show that finding iv, which is nontrivial given the suggested distinct functions of the D1 and D2 corticostriatal pathways, can also be explained if we additionally assume a proposed mechanism of TD-RPE calculation, in which the D1 and D2 pathways encode the values of actions with a temporal difference. These results suggest a possible circuit mechanism for the involvements of dopamine in effort-related choices and, simultaneously, provide implications for the mechanisms of TD-RPE calculation. PMID:29468191

Ongoing developments in RSV prophylaxis: a clinician's analysis.

PubMed

Rezaee, Fariba; Linfield, Debra T; Harford, Terri J; Piedimonte, Giovanni

2017-06-01

Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children worldwide. Lower respiratory tract infection due to RSV is one of the most common causes of hospitalization for infants, especially those born premature or with chronic lung or heart disease. Furthermore, RSV infection is an important cause of morbidity in adults, particularly in the elderly and immunocompromised individuals. The acute phase of this infection is often followed by episodes of wheezing that recur for months or years and usually lead to a physician diagnosis of asthma. RSV was discovered more than 50 years ago, and despite extensive research to identify pharmacological therapies, the most effective management of this infection remains supportive care. The trial of a formalin-inactivated RSV vaccine in the 1960s resulted in priming the severe illness upon natural infection. Currently, Palivizumab is the only available option for RSV prophylaxis, and because of restricted clinical benefits and high costs, it has been limited to a group of high-risk infants. There are several ongoing trials in preclinical, Phase-I, Phase-II, or Phase-III clinical stages for RSV vaccine development based on various strategies. Here we review the existing available prophylactic options, the current stages of RSV vaccine clinical trials, different strategies, and major hurdles in the development of an effective RSV vaccine. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Revisiting policy on chronic HCV treatment under the Thai Universal Health Coverage: An economic evaluation and budget impact analysis.

PubMed

Rattanavipapong, Waranya; Anothaisintawee, Thunyarat; Teerawattananon, Yot

2018-01-01

Thailand is encountering challenges to introduce the high-cost sofosbuvir for chronic hepatitis C treatment as part of the Universal Health Care's benefit package. This study was conducted in respond to policy demand from the Thai government to assess the value for money and budget impact of introducing sofosbuvir-based regimens in the tax-based health insurance scheme. The Markov model was constructed to assess costs and benefits of the four treatment options that include: (i) current practice-peginterferon alfa (PEG) and ribavirin (RBV) for 24 weeks in genotype 3 and 48 weeks for other genotypes; (ii) Sofosbuvir plus peginterferon alfa and ribavirin (SOF+PEG-RBV) for 12 weeks; (iii) Sofosbuvir and daclatasvir (SOF+DCV) for 12 weeks; (iv) Sofosbuvir and ledipasvir (SOF+LDV) for 12 weeks for non-3 genotypes and SOF+PEG-RBV for 12 weeks for genotype 3 infection. Given that policy options (ii) and (iii) are for pan-genotypic infection, the cost of genotype testing was applied only for policy options (i) and (iv). Results reveal that all sofosbuvir-based regimens had greater quality adjusted life years (QALY) gains compared with the current treatment, therefore associated with lower lifetime costs and more favourable health outcomes. Additionally, among the three regimens of sofosbuvir, SOF+PEG-RBV for genotype 3 and SOF+LDV for non-3 genotype are the most cost-effective treatment option with the threshold of 160,000 THB per QALY gained. The results of this study had been used in policy discussion which resulted in the recent inclusion of SOF+PEG-RBV for genotype 3 and SOF+LDV for non-3 genotype in the Thailand's benefit package.

Process mining in oncology using the MIMIC-III dataset

NASA Astrophysics Data System (ADS)

Prima Kurniati, Angelina; Hall, Geoff; Hogg, David; Johnson, Owen

2018-03-01

Process mining is a data analytics approach to discover and analyse process models based on the real activities captured in information systems. There is a growing body of literature on process mining in healthcare, including oncology, the study of cancer. In earlier work we found 37 peer-reviewed papers describing process mining research in oncology with a regular complaint being the limited availability and accessibility of datasets with suitable information for process mining. Publicly available datasets are one option and this paper describes the potential to use MIMIC-III, for process mining in oncology. MIMIC-III is a large open access dataset of de-identified patient records. There are 134 publications listed as using the MIMIC dataset, but none of them have used process mining. The MIMIC-III dataset has 16 event tables which are potentially useful for process mining and this paper demonstrates the opportunities to use MIMIC-III for process mining in oncology. Our research applied the L* lifecycle method to provide a worked example showing how process mining can be used to analyse cancer pathways. The results and data quality limitations are discussed along with opportunities for further work and reflection on the value of MIMIC-III for reproducible process mining research.

The role of integrated scientific approach facing the changing ocean policy. The case of the Mediterranean

NASA Astrophysics Data System (ADS)

Vallega, Adalberto

1999-08-01

In the mid-1980s the debate about the role of oceanography vis-à-vis the evolving demand for ocean research was initiated in the framework of the Intergovernmental Oceanographic Commission (IOC) of UNESCO. That discussion was basically triggered by the need to meet the demand for research generated by the United Nations Conference on the Human Environment (1972). More recently, also as a consequence of the inputs from the United Nations Conference on Environment and Development (UNCED, 1992), the discussion of the role of oceanography in the framework of the co-operation between physical and social disciplines was initiated focusing on the prospect of building up the ocean science. The prospect of the ocean science as designed by IOC (1984) was finalised only to integrate the branches of oceanography. To discuss how that design could be implemented on the basis of progress in epistemology and ocean policy, the subject is focused on considering three levels: i) the epistemological level, where the option between positivism- and constructivism- based epistemologies has arisen; ii) the logical level, where the option is concerned with disjunctive and conjunctive logic; and iii) the methodological level, where the option regards the analytical-deductive and the inductive-axiomatic methods. The thesis is sustained that, to meet the demand for management-oriented research, the pathway including constructivist epistemology, conjunctive logic and inductive-axiomatic methods could be usefully adopted as the cement of inter-disciplinarity. The second part of the paper is concerned with the Mediterranean, and how holism-referred and management-aimed investigations might be conducted by applying the above conceptual approach is considered: i) presenting the individual emerging subject areas on which the demand for management patterns is expected to focus in the mid- and long-run; ii) illustrating the major aspects of the individual subject areas to be investigated; iii) deducing what leading role might be assigned to oceanography in building up inter-disciplinary approaches; iv) which disciplines might be stimulated to co-operate. The subject areas considered with reference to the Mediterranean include: i) integrated coastal management; ii) the deep-ocean coastal uses with special consideration of living resources management; iii) the protection of biodiversity. Ocean Geographical Information Systems (OGIS), data management, and education and training are presented as intersecting research areas calling for inter-disciplinary approaches. As a conclusion, a breakdown of questions on which discussion might be concentrated is considered.

Development and 10-year history of a biosimilar: the example of Binocrit®

PubMed Central

Aapro, Matti; Krendyukov, Andriy; Höbel, Nadja; Seidl, Andreas; Gascón, Pere

2018-01-01

Patent expirations for several biological products have prompted the development of alternative versions, termed ‘biosimilars’, which have comparable quality, safety and efficacy to a licensed biological medicine (also referred to as the ‘reference’ medicine). The first biosimilars developed in oncology were the supportive-care agents filgrastim and epoetin. Binocrit® (HX575) is a biosimilar version of epoetin alfa, indicated in the oncology setting for the treatment of chemotherapy-induced anemia (CIA). The process for development and approval of Binocrit® as a biosimilar included extensive analytical characterization and comparison with the reference epoetin alfa. This was followed by a clinical development program comprising phase I pharmacokinetic/pharmacodynamic studies to show bioequivalence to the reference medicine and a confirmatory phase III study to confirm therapeutic effectiveness in CIA. Since its approval, Binocrit® has been extensively used and studied in real-world clinical practice. The accumulated data confirm that Binocrit® is an effective and well-tolerated option for the treatment of CIA in patients with cancer.

Dental ceramics: a review of new materials and processing methods.

PubMed

Silva, Lucas Hian da; Lima, Erick de; Miranda, Ranulfo Benedito de Paula; Favero, Stéphanie Soares; Lohbauer, Ulrich; Cesar, Paulo Francisco

2017-08-28

The evolution of computerized systems for the production of dental restorations associated to the development of novel microstructures for ceramic materials has caused an important change in the clinical workflow for dentists and technicians, as well as in the treatment options offered to patients. New microstructures have also been developed by the industry in order to offer ceramic and composite materials with optimized properties, i.e., good mechanical properties, appropriate wear behavior and acceptable aesthetic characteristics. The objective of this literature review is to discuss the main advantages and disadvantages of the new ceramic systems and processing methods. The manuscript is divided in five parts: I) monolithic zirconia restorations; II) multilayered dental prostheses; III) new glass-ceramics; IV) polymer infiltrated ceramics; and V) novel processing technologies. Dental ceramics and processing technologies have evolved significantly in the past ten years, with most of the evolution being related to new microstructures and CAD-CAM methods. In addition, a trend towards the use of monolithic restorations has changed the way clinicians produce all-ceramic dental prostheses, since the more aesthetic multilayered restorations unfortunately are more prone to chipping or delamination. Composite materials processed via CAD-CAM have become an interesting option, as they have intermediate properties between ceramics and polymers and are more easily milled and polished.

16 CFR 610.2 - Centralized source for requesting annual file disclosures from nationwide consumer reporting...

Code of Federal Regulations, 2011 CFR

2011-01-01

... FEDERAL TRADE COMMISSION THE FAIR CREDIT REPORTING ACT FREE ANNUAL FILE DISCLOSURES § 610.2 Centralized... request methods, at the consumers' option: (i) A single, dedicated Internet website, (ii) A single, dedicated toll-free telephone number; and (iii) Mail directed to a single address; (2) Be designed, funded...

16 CFR 610.2 - Centralized source for requesting annual file disclosures from nationwide consumer reporting...

Code of Federal Regulations, 2012 CFR

2012-01-01

... FEDERAL TRADE COMMISSION THE FAIR CREDIT REPORTING ACT FREE ANNUAL FILE DISCLOSURES § 610.2 Centralized... request methods, at the consumers' option: (i) A single, dedicated Internet website, (ii) A single, dedicated toll-free telephone number; and (iii) Mail directed to a single address; (2) Be designed, funded...

Study of Default Options in Advance Directives

ClinicalTrials.gov

2015-06-29

COPD; Severe or Very Severe Airflow Obstruction and/or Receiving or Eligible to Receive Long-term Oxygen Therapy; Idiopathic Pulmonary Fibrosis; Other Interstitial Lung Disease Without Curative Therapy; Congestive Heart Failure; NYHA Class IV or NYHA Class III Plus 1 Hospitalization in the Past Year; Malignancy; Any Stage 3B or 4 Solid Tumor

21 CFR 145.180 - Canned pineapple.

Code of Federal Regulations, 2010 CFR

2010-04-01

... optional ingredients: (i) Natural fruit flavors. (ii) Mint flavor. (iii) Spices, spice oils. (iv) Vinegar... declaration of any spice or seasoning that characterizes the product; for example, “Spice added”, or, in lieu of the word “Spice”, the common name of the spice; or “Seasoned with vinegar” or, in lieu of the word...

5 CFR 870.506 - Optional insurance: Cancelling a waiver.

Code of Federal Regulations, 2010 CFR

2010-01-01

... can increase the number of multiples, upon his/her marriage or divorce, upon a spouse's death, or upon... children, the number of eligible children acquired; and (iii) For divorce or death of a spouse, the total... coverage upon divorce or death of a spouse, if the employee has any eligible children. (ii) An employee...

34 CFR 200.37 - Notice of identification for improvement, corrective action, or restructuring.

Code of Federal Regulations, 2013 CFR

2013-07-01

... of each child enrolled in the school of this identification. (b) The notice referred to in paragraph... explanation of the parents' option to transfer their child to another public school, including the provision... schools to which the child may transfer. (iii) The explanation may include other information on the school...

34 CFR 200.37 - Notice of identification for improvement, corrective action, or restructuring.

Code of Federal Regulations, 2010 CFR

2010-07-01

... of each child enrolled in the school of this identification. (b) The notice referred to in paragraph... explanation of the parents' option to transfer their child to another public school, including the provision... schools to which the child may transfer. (iii) The explanation may include other information on the school...

34 CFR 200.37 - Notice of identification for improvement, corrective action, or restructuring.

Code of Federal Regulations, 2014 CFR

2014-07-01

... of each child enrolled in the school of this identification. (b) The notice referred to in paragraph... explanation of the parents' option to transfer their child to another public school, including the provision... schools to which the child may transfer. (iii) The explanation may include other information on the school...

34 CFR 200.37 - Notice of identification for improvement, corrective action, or restructuring.

Code of Federal Regulations, 2011 CFR

2011-07-01

... of each child enrolled in the school of this identification. (b) The notice referred to in paragraph... explanation of the parents' option to transfer their child to another public school, including the provision... schools to which the child may transfer. (iii) The explanation may include other information on the school...

34 CFR 200.37 - Notice of identification for improvement, corrective action, or restructuring.

Code of Federal Regulations, 2012 CFR

2012-07-01

... of each child enrolled in the school of this identification. (b) The notice referred to in paragraph... explanation of the parents' option to transfer their child to another public school, including the provision... schools to which the child may transfer. (iii) The explanation may include other information on the school...

76 FR 57745 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-16

... Information Collection: Standardized Pharmacy Notice: Your Prescription Cannot be Filled (f/k/a Medicare... eliminate the previously available option of posting the standardized notice at the pharmacy. Revised 423.562(a)(3) and an associated regulatory provision at Sec. 423.128(b)(7)(iii) require the pharmacy to...

21 CFR 155.130 - Canned corn.

Code of Federal Regulations, 2010 CFR

2010-04-01

... a high vacuum in the container. (iii) The color type used only when the product consists of white... manner, before or after being sealed in a container, so as to prevent spoilage. (2) Styles. The optional... liquid in the container, as determined by the method prescribed in paragraph (b)(2)(i) of this section...

42 CFR 447.52 - Minimum and maximum income-related charges.

Code of Federal Regulations, 2013 CFR

2013-10-01

... agency imposes cost sharing under § 447.54, the process by which hospital emergency room services are... option, cost sharing imposed for any service (other than for drugs and non-emergency services furnished... group under § 447.56(a), and (iii) For cost sharing imposed for non-emergency services furnished in an...

40 CFR 80.164 - Certification test fuels.

Code of Federal Regulations, 2014 CFR

2014-07-01

... certification option in § 80.163(a)(1)(iii) are contained in § 80.177. (1) Quantitative specifications for the... compositional data must be collected only from samples of premium gasoline. (ii) The fuel composition survey... and that all survey data must have been collected within three years of the date the certification...

Near-Term Options for Improving Security at Los Angeles International Airport

DTIC Science & Technology

2004-09-26

the Transportation Security Administration (TSA), the Los Angeles Police Department ( LAPD ), and LAX to make sure the list was reasonable...World Airports; the Transportation Security Agency; the Los Angeles International Airport Police Department ; the Los Angeles Police Department ; the Los ...Airports. iii PREFACE This document assesses near-term security

21 CFR 312.305 - Requirements for all expanded access uses.

Code of Federal Regulations, 2010 CFR

2010-04-01

... options; (iii) The criteria for patient selection or, for an individual patient, a description of the... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Requirements for all expanded access uses. 312.305 Section 312.305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

Successful and stable orthodontic camouflage of a mandibular asymmetry with sliding jigs.

PubMed

Oliveira, Dauro Douglas; Oliveira, Bruno Franco de; Mordente, Carolina Morsani; Godoy, Gabriela Martins; Soares, Rodrigo Villamarim; Seraidarian, Paulo Isaías

2018-03-12

The purpose of this paper is to present and discuss a simple and low-cost clinical approach to correct an asymmetric skeletal Class III combined to an extensive dental open bite that significantly compromised the occlusal function and smile aesthetics of an adult male patient. The patient did not accept the idealistic surgical-orthodontic treatment option, neither the use of temporary anchorage devices to facilitate the camouflage of the asymmetrical skeletal Class III/open bite. Therefore, a very simple and inexpensive biomechanical approach using sliding jigs in the mandibular arch was implemented as the compensatory treatment of the malocclusion. Although minor enhancements in facial aesthetics were obtained, the occlusal function and dental aesthetics were significantly improved. Furthermore, the patient was very satisfied with his new smile appearance. Some advantages of this treatment option included the small invasiveness and the remarkably low financial costs involved. Moreover, the final results fulfilled all realistic treatment objectives and the patient's expectations. Results remained stable 5 years post-treatment demonstrating that excellent results can be obtained when simple and low cost, but well-controlled mechanics are conducted.

The Discriminant Analysis Flare Forecasting System (DAFFS)

NASA Astrophysics Data System (ADS)

Leka, K. D.; Barnes, Graham; Wagner, Eric; Hill, Frank; Marble, Andrew R.

2016-05-01

The Discriminant Analysis Flare Forecasting System (DAFFS) has been developed under NOAA/Small Business Innovative Research funds to quantitatively improve upon the NOAA/SWPC flare prediction. In the Phase-I of this project, it was demonstrated that DAFFS could indeed improve by the requested 25% most of the standard flare prediction data products from NOAA/SWPC. In the Phase-II of this project, a prototype has been developed and is presently running autonomously at NWRA.DAFFS uses near-real-time data from NOAA/GOES, SDO/HMI, and the NSO/GONG network to issue both region- and full-disk forecasts of solar flares, based on multi-variable non-parametric Discriminant Analysis. Presently, DAFFS provides forecasts which match those provided by NOAA/SWPC in terms of thresholds and validity periods (including 1-, 2-, and 3- day forecasts), although issued twice daily. Of particular note regarding DAFFS capabilities are the redundant system design, automatically-generated validation statistics and the large range of customizable options available. As part of this poster, a description of the data used, algorithm, performance and customizable options will be presented, as well as a demonstration of the DAFFS prototype.DAFFS development at NWRA is supported by NOAA/SBIR contracts WC-133R-13-CN-0079 and WC-133R-14-CN-0103, with additional support from NASA contract NNH12CG10C, plus acknowledgment to the SDO/HMI and NSO/GONG facilities and NOAA/SWPC personnel for data products, support, and feedback. DAFFS is presently ready for Phase-III development.

Engineering assessment of inactive uranium mill tailings, Durango site, Durango, Colorado. A summary of the Phase II, Title I

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

Not Available

1977-11-01

Ford, Bacon and Davis Utah Inc. has performed an engineering assessment of the problems resulting from the existence of radioactive uranium mill tailings at Durango, Colorado. The Phase II, Title I services include the preparation of topographic maps, the performance of core drillings and radiometric measurements sufficient to determine areas and volumes of tailings and other radium-contaminated materials, the evaluation of resulting radiation exposures of individuals and nearby populations, the investigation of site hydrology and meteorology and the evaluation and costing of alternative corrective actions. Radon gas release from the 1.555 million tons of tailings at the Durango site constitutesmore » the most significant environmental impact, although windblown tailings and external gamma radiation are also factors. The eight alternative actions presented range from vegetative stabilization (Option I), to contouring and stabilizing in-place with varying depths of cover material (Options II and III), to removal to an isolated long-term disposal site (Options V to VIII). All options include remedial action costs for offsite locations where tailings have been placed. Costs estimated for the eight options range from $4,340,000 to $13,590,000. Reprocessing the tailings for uranium is sufficiently economically attractive to justify reprocessing in conjunction with each of the options.« less

Engineering assessment of inactive uranium mill tailings, Durango site, Durango, Colorado. Phase II, Title I

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

Not Available

1977-11-01

Ford, Bacon and Davis Utah Inc. has performed an engineering assessment of the problems resulting from the existence of radioactive uranium mill tailings at Durango, Colorado. The Phase II, Title I services include the preparation of topographic maps, the performance of core drillings and radiometric measurements sufficient to determine areas and volumes of tailings and other radium-contaminated materials, the evaluation of resulting radiation exposures of individuals and nearby populations, the investigation of site hydrology and meteorology and the evaluation and costing of alternative corrective actions. Radon gas release from the 1.555 million tons of tailings at the Durango site constitutesmore » the most significant environmental impact, although windblown tailings and external gamma radiation are also factors. The eight alternative actions presented range from vegetative stabilization (Option I), to contouring and stabilizing in-place with varying depths of cover material (Options II and III), to removal to an isolated long-term disposal site (Options V to VIII). All options include remedial action costs for offsite locations where tailings have been placed. Costs estimated for the eight options range from $4,340,000 to $13,590,000. Reprocessing the tailings for uranium is sufficiently economically attractive to justify reprocessing in conjunction with each of the options.« less

Appropriate customization of radiation therapy for stage II and III rectal cancer: Executive summary of an ASTRO Clinical Practice Statement using the RAND/UCLA Appropriateness Method.

PubMed

Goodman, Karyn A; Patton, Caroline E; Fisher, George A; Hoffe, Sarah E; Haddock, Michael G; Parikh, Parag J; Kim, John; Baxter, Nancy N; Czito, Brian G; Hong, Theodore S; Herman, Joseph M; Crane, Christopher H; Hoffman, Karen E

2016-01-01

To summarize results of a Clinical Practice Statement on radiation therapy for stage II-III rectal cancer, which addressed appropriate customization of (neo)adjuvant radiation therapy and use of non-surgical therapy for patients who are inoperable or refuse abdominoperineal resection. The RAND/University of California, Los Angeles, Appropriateness Method was applied to combine current evidence with multidisciplinary expert opinion. A systematic literature review was conducted and used by the expert panel to rate appropriateness of radiation therapy options for different clinical scenarios. Treatments were categorized by median rating as Appropriate, May Be Appropriate, or Rarely Appropriate. In the neoadjuvant setting, chemoradiation was rated Appropriate and the ratings indicated short-course radiation therapy, chemotherapy alone, and no neoadjuvant therapy are potential options in selected patients. However, neoadjuvant endorectal brachytherapy was rated Rarely Appropriate. For adjuvant therapy, chemoradiation (plus ≥4 months of chemotherapy) was rated Appropriate and chemotherapy alone May Be Appropriate for most scenarios. For medically inoperable patients, definitive external beam radiation therapy and chemotherapy alone were rated May Be Appropriate, whereas endorectal brachytherapy and chemoradiation plus endorectal brachytherapy were possible approaches for some scenarios. The last option, definitive chemoradiation, was rated Appropriate to May Be Appropriate based on performance status. Finally, for patients with low-lying tumors refusing abdominoperineal resection, definitive chemoradiation alone, chemoradiation plus endorectal brachytherapy, and chemoradiation plus external beam radiation therapy were all rated Appropriate. This Clinical Practice Statement demonstrated the central role of radiation therapy in stage II-III rectal cancer management and evaluated ways to better individualize its use in the neoadjuvant, adjuvant, and definitive settings. Ongoing trials may clarify areas of continuing uncertainty and allow further customization. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Treatment of skeletal Class III malocclusions: orthognathic surgery or orthodontic camouflage? How to decide.

PubMed

Benyahia, Hicham; Azaroual, Mohamed Faouzi; Garcia, Claude; Hamou, Edith; Abouqal, Redouane; Zaoui, Fatima

2011-06-01

The choice of treatment in adult skeletal Class III occlusions often poses a particularly tricky problem for the orthodontist. Faced with the option of either orthodontic camouflage or orthognathic surgery, the clinician's clinical experience is of paramount importance, especially in borderline cases. The aim of our study was to uncover a guide model enabling the practitioner to distinguish between skeletal Class III cases which can be suitably treated with orthodontics and those requiring orthognathic surgery. The lateral headfilms of 47 adult patients exhibiting skeletal Class III occlusions were analyzed. The orthodontic group comprised 22 patients and the surgical group 25. Twenty-seven linear, proportional and angular measurements were scrutinized. Stepwise discriminant analysis was used to identify the dentoskeletal and esthetic variables which most distinguished the two groups. The Holdaway angle was chosen to differentiate between patients prior to treatment. This model enables us to classify 87.2% of patients correctly. Copyright © 2011 CEO. Published by Elsevier Masson SAS. All rights reserved.

Quantum Finance

NASA Astrophysics Data System (ADS)

Baaquie, Belal E.

2007-09-01

Foreword; Preface; Acknowledgements; 1. Synopsis; Part I. Fundamental Concepts of Finance: 2. Introduction to finance; 3. Derivative securities; Part II. Systems with Finite Number of Degrees of Freedom: 4. Hamiltonians and stock options; 5. Path integrals and stock options; 6. Stochastic interest rates' Hamiltonians and path integrals; Part III. Quantum Field Theory of Interest Rates Models: 7. Quantum field theory of forward interest rates; 8. Empirical forward interest rates and field theory models; 9. Field theory of Treasury Bonds' derivatives and hedging; 10. Field theory Hamiltonian of forward interest rates; 11. Conclusions; Appendix A: mathematical background; Brief glossary of financial terms; Brief glossary of physics terms; List of main symbols; References; Index.

Sigma Team for Advanced Actinide Recycle FY2015 Accomplishments and Directions

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

Moyer, Bruce A.

The Sigma Team for Minor Actinide Recycle (STAAR) has made notable progress in FY 2015 toward the overarching goal to develop more efficient separation methods for actinides in support of the United States Department of Energy (USDOE) objective of sustainable fuel cycles. Research in STAAR has been emphasizing the separation of americium and other minor actinides (MAs) to enable closed nuclear fuel recycle options, mainly within the paradigm of aqueous reprocessing of used oxide nuclear fuel dissolved in nitric acid. Its major scientific challenge concerns achieving selectivity for trivalent actinides vs lanthanides. Not only is this challenge yielding to researchmore » advances, but technology concepts such as ALSEP (Actinide Lanthanide Separation) are maturing toward demonstration readiness. Efforts are organized in five task areas: 1) combining bifunctional neutral extractants with an acidic extractant to form a single process solvent, developing a process flowsheet, and demonstrating it at bench scale; 2) oxidation of Am(III) to Am(VI) and subsequent separation with other multivalent actinides; 3) developing an effective soft-donor solvent system for An(III) selective extraction using mixed N,O-donor or all-N donor extractants such as triazinyl pyridine compounds; 4) testing of inorganic and hybrid-type ion exchange materials for MA separations; and 5) computer-aided molecular design to identify altogether new extractants and complexants and theory-based experimental data interpretation. Within these tasks, two strategies are employed, one involving oxidation of americium to its pentavalent or hexavalent state and one that seeks to selectively complex trivalent americium either in the aqueous phase or the solvent phase. Solvent extraction represents the primary separation method employed, though ion exchange and crystallization play an important role. Highlights of accomplishments include: Confirmation of the first-ever electrolytic oxidation of Am(III) in a noncomplexing aqueous solution and submission of this scientific breakthrough as a paper in Science; The first-ever co-crystallization of Am(VI) with UO 2(NO 3) 2 ∙ 6H 2O, opening the door to a new approach for separating hexavalent actinides as a group; Results showing that three potentially problematic metals will not present risk in ALSEP; Improvement in ALSEP contactor stripping kinetics to acceptable performance; A comparison of centrifugal contactors vs mixer-settlers showing the former performs better in ALSEP stripping; Synthesis of new mixed N,O-donor extractants with enhanced solubility and strength for selective trivalent actinide extraction; Development of computational methods showing promise in prediction of the selectivity of new extractants for trivalent actinides vs lanthanides; An order-of-magnitude improvement in aqueous Am/Eu complexation selectivity of an alternative macrocyclic stripping agent for ALSEP, potentially enabling an option for an Am product stream free from both Ln and Cm. An alternative aqueous combination of dipicolinate complexant and malonate buffer that may present options for ALSEP and TALSPEAK (Trivalent Actinide-Lanthanide Separations by Phosphorus-reagent Extraction from Aqueous Komplexes) type separations. The ALSEP concept is advancing toward a benchtop flowsheet demonstration planned for FY 2016, and a bench-scale test bed at Idaho National Laboratory (INL) will be employed to demonstrate at least one tandem Am oxidation and separation concept. This report outlines the goals of the STAAR, significance of achieving these goals, STAAR organization around the above aims and questions, recent highlights, and future directions. The report also includes a listing of publications, reports, patents, and dissertations.« less

77 FR 7640 - Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... 30 days after the date of the filing, or such shorter time as the Commission may designate, it has...-4(f)(6)(iii) \\8\\ permits the Commission to designate a shorter time if such action is consistent... without further delay. The Exchange notes that the introduction of the additional optional variation of...

77 FR 7642 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... 30 days after the date of the filing, or such shorter time as the Commission may designate, it has...-4(f)(6)(iii) \\8\\ permits the Commission to designate a shorter time if such action is consistent... trading costs without further delay. The Exchange notes that the introduction of the additional optional...

75 FR 10873 - Energy Conservation Program: Energy Conservation Standards for Small Electric Motors

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-09

... design option to be technologically feasible if it is in use by the respective industry or if research.... Baseline Motor Performance 3. Higher Efficiency Motor Designs a. Electrical Steel b. Thermal Analysis c... a variety of provisions designed to improve energy efficiency. Part A of Title III (42 U.S.C. 6291...

38 CFR 36.4253 - Title and lien requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., which right by the terms thereof is exercisable only if: (i) An owner elects to sell, (ii) The option price is not less than the price at which the then owner is willing to sell to another, and (iii... the then owner of the then owner's election to sell, stating the price and the identity of the...

38 CFR 36.4253 - Title and lien requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., which right by the terms thereof is exercisable only if: (i) An owner elects to sell, (ii) The option price is not less than the price at which the then owner is willing to sell to another, and (iii... the then owner of the then owner's election to sell, stating the price and the identity of the...

38 CFR 36.4253 - Title and lien requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., which right by the terms thereof is exercisable only if: (i) An owner elects to sell, (ii) The option price is not less than the price at which the then owner is willing to sell to another, and (iii... the then owner of the then owner's election to sell, stating the price and the identity of the...

38 CFR 36.4253 - Title and lien requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., which right by the terms thereof is exercisable only if: (i) An owner elects to sell, (ii) The option price is not less than the price at which the then owner is willing to sell to another, and (iii... the then owner of the then owner's election to sell, stating the price and the identity of the...

38 CFR 36.4253 - Title and lien requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., which right by the terms thereof is exercisable only if: (i) An owner elects to sell, (ii) The option price is not less than the price at which the then owner is willing to sell to another, and (iii... the then owner of the then owner's election to sell, stating the price and the identity of the...

Weed management, training, and irrigation practices for organic production of trailing blackberry: III. Accumulation and removal of aboveground biomass, carbon, and nutrients

USDA-ARS?s Scientific Manuscript database

The effects of various production practices on biomass, C, and nutrient content, accumulation, and loss were assessed over 2 years in a mature organic trailing blackberry (Rubus L. subgenus Rubus, Watson) production system. Treatments included two irrigation options (no irrigation after harvest and ...

24 CFR 291.415 - Lease with option to purchase properties for use by the homeless.

Code of Federal Regulations, 2013 CFR

2013-04-01

... child care expenses); (ii) Ten percent of the family's monthly income; or (iii) If the family is.... (d) Damage to leased properties. Any damage to leased property caused by the intentional or negligent... not make the necessary repairs within a reasonable time after the damage occurs, HUD may, at its...

24 CFR 291.415 - Lease with option to purchase properties for use by the homeless.

Code of Federal Regulations, 2012 CFR

2012-04-01

... child care expenses); (ii) Ten percent of the family's monthly income; or (iii) If the family is.... (d) Damage to leased properties. Any damage to leased property caused by the intentional or negligent... not make the necessary repairs within a reasonable time after the damage occurs, HUD may, at its...

24 CFR 291.415 - Lease with option to purchase properties for use by the homeless.

Code of Federal Regulations, 2014 CFR

2014-04-01

... child care expenses); (ii) Ten percent of the family's monthly income; or (iii) If the family is.... (d) Damage to leased properties. Any damage to leased property caused by the intentional or negligent... not make the necessary repairs within a reasonable time after the damage occurs, HUD may, at its...

24 CFR 291.415 - Lease with option to purchase properties for use by the homeless.

Code of Federal Regulations, 2011 CFR

2011-04-01

... child care expenses); (ii) Ten percent of the family's monthly income; or (iii) If the family is.... (d) Damage to leased properties. Any damage to leased property caused by the intentional or negligent... not make the necessary repairs within a reasonable time after the damage occurs, HUD may, at its...

24 CFR 291.415 - Lease with option to purchase properties for use by the homeless.

Code of Federal Regulations, 2010 CFR

2010-04-01

... child care expenses); (ii) Ten percent of the family's monthly income; or (iii) If the family is.... (d) Damage to leased properties. Any damage to leased property caused by the intentional or negligent... not make the necessary repairs within a reasonable time after the damage occurs, HUD may, at its...

75 FR 39597 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-09

... $1 Strike Program such that these options are now among some of the most popular products traded on... interested parties. III. Date of Effectiveness of the Proposed Rule Change and Timing for Commission Action... action is necessary or appropriate in the public interest, for the protection of investors, or otherwise...

34 CFR 200.48 - Funding for choice-related transportation and supplemental educational services.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Agencies Lea and School Improvement § 200.48 Funding for choice-related transportation and supplemental... all requests for supplemental educational services under § 200.45; or (iii) Pay for both paragraph (a... school choice options under § 200.44, in the amounts required under paragraph (a)(2) of this section; and...

34 CFR 200.48 - Funding for choice-related transportation and supplemental educational services.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Agencies Lea and School Improvement § 200.48 Funding for choice-related transportation and supplemental... all requests for supplemental educational services under § 200.45; or (iii) Pay for both paragraph (a... school choice options under § 200.44, in the amounts required under paragraph (a)(2) of this section; and...

40 CFR 63.1571 - How and when do I conduct a performance test or other initial compliance demonstration?

Code of Federal Regulations, 2011 CFR

2011-07-01

... the option in paragraph (a)(1)(iii) in § 63.1564 (Ni lb/hr), and you use continuous parameter monitoring systems, you must establish an operating limit for the equilibrium catalyst Ni concentration based on the laboratory analysis of the equilibrium catalyst Ni concentration from the initial performance...

The Job Training Partnership Act and Computer-Assisted Instruction. Research Report 88-13.

ERIC Educational Resources Information Center

Education Turnkey Systems, Inc., Falls Church, VA.

A study sought to (1) determine the current and potential instructional application of computers in Job Training Partnership Act (JTPA) Titles II, III, and IV programs; and (2) present policy options that would increase the effective use of this technology in employment and training programs. Research methodology involved conducting an assessment…

The Effect of an End-of-Clerkship Review Session on NBME Psychiatry Subject Exam Scores

ERIC Educational Resources Information Center

Sidhu, Shawn S.; Chandra, Rohit M.; Wang, Lei; Gollan, Jacqueline K.; Rasminsky, Sonya; Brar, Simerjeet K.; Anzia, Joan M.

2012-01-01

Objective: The NBME Psychiatry Subject Examination (PSE) is used throughout North America to test MS-III end-of-clerkship knowledge; yet, literature on PSE preparatory methods remains sparse. This study assesses the effect of a curriculum intervention on NBME PSE scores. Method: An optional 1.5-hour review session and accompanying…

75 FR 67258 - Position Reports for Physical Commodity Swaps

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-02

... Cattle. CME Milk Class III. Comex (``CMX'') Copper Grade 1. CMX Gold. CMX Silver. ICE Futures US (``ICUS... Oats. CME Butter. CME Cheese. CME Dry Whey. CME Hardwood Pulp. CME Lean Hogs. CME Non Fat Dry Milk. CME... contract--The ICE WTI Average Price Option is indirectly linked to a 20.2 listed futures contract because...

76 FR 3184 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-19

...); (ii) establish a VIX Tier Appointment; (iii) amend the monthly fee for Floor Broker Trading Permits... demutualization, CBOE amended its Fees Schedule to establish Trading Permit, tier appointment and bandwidth packet... permit ($) 1 permit 10 permits 6,000 Tier 1 11 permits 20 permits 4,800 Tier 2 21 or more permits...

40 CFR 53.23 - Test procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... up and stabilize. Determine measurement noise at each of two fixed concentrations, first using zero.... Note to § 53.23(b)(2): Use of a chart recorder in addition to the DM is optional. (iii) Measure zero... atmosphere concentration of 80 ±5 percent of the URL instead of zero air, and let S at 80 percent of the URL...

40 CFR 53.23 - Test procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... up and stabilize. Determine measurement noise at each of two fixed concentrations, first using zero.... Note to § 53.23(b)(2): Use of a chart recorder in addition to the DM is optional. (iii) Measure zero... atmosphere concentration of 80 ±5 percent of the URL instead of zero air, and let S at 80 percent of the URL...

40 CFR 53.23 - Test procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... up and stabilize. Determine measurement noise at each of two fixed concentrations, first using zero.... Note to § 53.23(b)(2): Use of a chart recorder in addition to the DM is optional. (iii) Measure zero... atmosphere concentration of 80 ±5 percent of the URL instead of zero air, and let S at 80 percent of the URL...

78 FR 22926 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-17

... System (a) Definition: No change. (b) Types of Complex Orders: No change. (c) Complex Order Book (i)-(iii..., the System will evaluate the COB when a complex order enters the COB, when the Exchange BBO changes... System may generate leg orders for the remaining size of the complex order in accordance with...

26 CFR 1.743-1 - Optional adjustment to basis of partnership property.

Code of Federal Regulations, 2012 CFR

2012-04-01

... acquired partnership interest); and decreased by (iii) The amount of tax gain (including any remedial.... See § 1.460-4(k)(3)(v)(B) for a rule relating to the computation of income or loss that would be... immediately after the hypothetical transaction, decreased by $7,000, the amount of tax gain allocated to T...

26 CFR 1.743-1 - Optional adjustment to basis of partnership property.

Code of Federal Regulations, 2011 CFR

2011-04-01

... acquired partnership interest); and decreased by (iii) The amount of tax gain (including any remedial.... See § 1.460-4(k)(3)(v)(B) for a rule relating to the computation of income or loss that would be... immediately after the hypothetical transaction, decreased by $7,000, the amount of tax gain allocated to T...

26 CFR 1.743-1 - Optional adjustment to basis of partnership property.

Code of Federal Regulations, 2013 CFR

2013-04-01

... acquired partnership interest); and decreased by (iii) The amount of tax gain (including any remedial.... See § 1.460-4(k)(3)(v)(B) for a rule relating to the computation of income or loss that would be... immediately after the hypothetical transaction, decreased by $7,000, the amount of tax gain allocated to T...

26 CFR 1.743-1 - Optional adjustment to basis of partnership property.

Code of Federal Regulations, 2010 CFR

2010-04-01

... acquired partnership interest); and decreased by (iii) The amount of tax gain (including any remedial.... See § 1.460-4(k)(3)(v)(B) for a rule relating to the computation of income or loss that would be... immediately after the hypothetical transaction, decreased by $7,000, the amount of tax gain allocated to T...

26 CFR 1.743-1 - Optional adjustment to basis of partnership property.

Code of Federal Regulations, 2014 CFR

2014-04-01

... acquired partnership interest); and decreased by (iii) The amount of tax gain (including any remedial.... See § 1.460-4(k)(3)(v)(B) for a rule relating to the computation of income or loss that would be... immediately after the hypothetical transaction, decreased by $7,000, the amount of tax gain allocated to T...

Manufacturing Methods for Cutting, Machining and Drilling Composites. Volume 1. Composites Machining Handbook

DTIC Science & Technology

1978-08-01

12°±30’ 1180±2° OPTIONAL .0005 IN./IN. BACK TAPER 015 RAD LIPS TO BE WITHIN .002 OF TRUE ANGULAR POSITION NOTES: 1. LAND WIDTH: 28% ± .005... horoscope and dye-penetrant requirements. 79 PHASE 1 PHASE II PHASE III PHASE IV CUTTING DRILLING MACHINING NONDESTRUCTIVE EVALUATION METHOD MATERIAL

50 CFR 680.41 - Transfer of QS, PQS, IFQ and IPQ.

Code of Federal Regulations, 2013 CFR

2013-10-01

...://alaskafisheries.noaa.gov, or by contacting NMFS at: 800-304-4846, Option 2. (c) Eligibility to receive QS, PQS... to any person on request or on the Internet at http://www.fakr.noaa.gov/. (ii) Contents. A complete... permit is issued and the QS holder must re-apply for any subsequent transfers. (iii) NMFS will not...

50 CFR 680.41 - Transfer of QS, PQS, IFQ and IPQ.

Code of Federal Regulations, 2012 CFR

2012-10-01

...://alaskafisheries.noaa.gov, or by contacting NMFS at: 800-304-4846, Option 2. (c) Eligibility to receive QS, PQS... to any person on request or on the Internet at http://www.fakr.noaa.gov/. (ii) Contents. A complete... permit is issued and the QS holder must re-apply for any subsequent transfers. (iii) NMFS will not...

Sulfur mustard skin lesions: A systematic review on pathomechanisms, treatment options and future research directions.

PubMed

Rose, Dorothee; Schmidt, Annette; Brandenburger, Matthias; Sturmheit, Tabea; Zille, Marietta; Boltze, Johannes

2018-09-01

Sulfur mustard (SM) is a chemical warfare, which has been used for one hundred years. However, its exact pathomechanisms are still incompletely understood and there is no specific therapy available so far. In this systematic review, studies published between January 2000 and July 2017 involving pathomechanisms and experimental treatments of SM-induced skin lesions were analyzed to summarize current knowledge on SM pathology, to provide an overview on novel treatment options, and to identify promising targets for future research to more effectively counter SM effects. We suggest that future studies should focus on (I) systemic effects of SM intoxication due to its distribution throughout the body, (II) removal of SM depots that continuously release active compound contributing to chronic skin damage, and (III) therapeutic options that counteract the pleiotropic effects of SM. Copyright © 2017 Elsevier B.V. All rights reserved.

Treatment of achalasia in the era of high-resolution manometry

PubMed Central

Torresan, Francesco; Ioannou, Alexandros; Azzaroli, Francesco; Bazzoli, Franco

2015-01-01

Esophageal achalasia is a primary motility disorder characterized by impaired lower esophageal sphincter relaxation and absence of esophageal peristalsis leading to impaired bolus transit, manifested with symptoms such as dysphagia, regurgitation, retrosternal pain, and weight loss. The standard diagnostic tool is esophageal manometry which demonstrates incomplete relaxation of the lower esophageal sphincter and impaired esophageal peristalsis. Recently, a new advanced technique, high-resolution manometry (HRM) with the addition of pressure topography plotting, using multiple sensors to capture the manometric data as a spatial continuum, allows a detailed pressure recording of the esophageal motility. This technique, currently the gold standard for the diagnosis of achalasia, has led to a subclassification of three manometric types that seem to have different responsiveness to treatment. Because its pathogenesis is as yet unknown, achalasia treatment options are not curative. Type II achalasia patients respond better to treatment compared to those with types I and III. Low-risk patients with type I or II achalasia have good outcome with both graded pneumatic dilatations and laparoscopic Heller myotomy, while type III achalasia patients respond better to laparoscopic Heller myotomy. Although, type III achalasia patients responds less in comparison to types I and II to laparoscopic Heller myotomy. Peroral endoscopic myotomy is a promising new technique but long-term follow-up studies for its safety and efficacy must be performed. This article reviews the current therapeutic options, highlighting the impact of HRM to predict the outcome and the new insights for the treatment of achalasia. PMID:26130022

Postoperative surgical complications of lymphadenohysterocolpectomy

PubMed Central

Marin, F; Pleşca, M; Bordea, CI; Voinea, SC; Burlănescu, I; Ichim, E; Jianu, CG; Nicolăescu, RR; Teodosie, MP; Maher, K; Blidaru, A

2014-01-01

Rationale The current standard surgical treatment for the cervix and uterine cancer is the radical hysterectomy (lymphadenohysterocolpectomy). This has the risk of intraoperative accidents and postoperative associated morbidity. Objective The purpose of this article is the evaluation and quantification of the associated complications in comparison to the postoperative morbidity which resulted after different types of radical hysterectomy. Methods and results Patients were divided according to the type of surgery performed as follows: for cervical cancer – group A- 37 classic radical hysterectomies Class III Piver - Rutledge -Smith ( PRS ), group B -208 modified radical hysterectomies Class II PRS and for uterine cancer- group C -79 extended hysterectomies with pelvic lymphadenectomy from which 17 patients with paraaortic lymphnode biopsy . All patients performed preoperative radiotherapy and 88 of them associated radiosensitization. Discussion Early complications were intra-abdominal bleeding ( 2.7% Class III PRS vs 0.48% Class II PRS), supra-aponeurotic hematoma ( 5.4% III vs 2.4% II) , dynamic ileus (2.7% III vs 0.96% II) and uro - genital fistulas (5.4% III vs 0.96% II).The late complications were the bladder dysfunction (21.6% III vs 16.35% II) , lower limb lymphedema (13.5% III vs 11.5% II), urethral strictures (10.8% III vs 4.8% II) , incisional hernias ( 8.1% III vs 7.2% II), persistent pelvic pain (18.91% III vs 7.7% II), bowel obstruction (5.4% III vs 1.4% II) and deterioration of sexual function (83.3% III vs 53.8% II). PRS class II radical hysterectomy is associated with fewer complications than PRS class III radical hysterectomy , except for the complications of lymphadenectomy . A new method that might reduce these complications is a selective lymphadenectomy represented by sentinel node biopsy . In conclusion PRS class II radical hysterectomy associated with neoadjuvant radiotherapy is a therapeutic option for the incipient stages of cervical cancer. Abbreviations: PRS- Piver Rutledge-Smith, II- class II, III- class III PMID:24653760

Endocrine therapy for postmenopausal women with hormone receptor-positive her2-negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement.

PubMed

Pritchard, K I; Gelmon, K A; Rayson, D; Provencher, L; Webster, M; McLeod, D; Verma, S

2013-02-01

Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2-) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients-efect, sofea, confirm, and bolero-2-have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2- advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient's age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged.

Endocrine therapy for postmenopausal women with hormone receptor–positive her2–negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement

PubMed Central

Pritchard, K.I.; Gelmon, K.A.; Rayson, D.; Provencher, L.; Webster, M.; McLeod, D.; Verma, S.

2013-01-01

Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2–) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients—efect, sofea, confirm, and bolero-2—have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2– advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient’s age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged. PMID:23443928

Research, Development, and Field Testing of Thermochemical Recuperation for High Temperature Furnace

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

Kurek, Harry; Kozlov, Aleksandr

Gas Technology Institute (GTI) evaluated the technical and economic feasibility of utilizing a non-catalytic ThermoChemical Recuperation System (TCRS) to recover a significant amount of energy from the waste gases of natural gas fired steel reheat furnaces. The project was related to DOE-AMO’s (formerly known as ITP) one of the technical areas of interest: Technologies to improve energy efficiency and reduce the carbon footprint of equipment currently used in energy-intensive industries such as iron and steel, and reduce by at least 30% energy consumption and carbon dioxide emission compared to the conventional technologies. ThermoChemical Recuperation (TCR) is a technique that recoversmore » sensible heat in the exhaust gas from an industrial process, furnace, engine etc., when a hydrocarbon fuel is used for combustion. TCR enables waste heat recovery by both combustion air preheat and hydrocarbon fuel (natural gas, for example) reforming into a higher calorific fuel. The reforming process uses hot flue gas components (H2O and CO2) or steam to convert the fuel into a combustible mixture of hydrogen (H2), carbon monoxide (CO), and some unreformed hydrocarbons (CnHm). Reforming of natural gas with recycled exhaust gas or steam can significantly reduce fuel consumption, CO2 emissions and cost as well as increase process thermal efficiency. The calorific content of the fuel can be increased by up to ~28% with the TCR process if the original source fuel is natural gas. In addition, the fuel is preheated during the TCR process adding sensible heat to the fuel. The Research and Development work by GTI was proposed to be carried out in three Phases (Project Objectives). • Phase I: Develop a feasibility study consisting of a benefits-derived economic evaluation of a ThermoChemical Recuperation (TCR) concept with respect to high temperature reheat furnace applications within the steel industry (and cross-cutting industries). This will establish the design parameters and potential performance of TCR. • Phase II: Conduct research and development to take the validated technology concept from Phase I to a developmental state for a Phase 3, prototype field test. • Phase III: Design, fabricate, and prototype field testing of the TCR unit close coupled to an existing high temperature reheat furnace at a steel company for evaluation under industrial conditions The project was initiated on September 30, 2008. The report of Phase I results and conclusions was issued on October 30, 2009. The findings were reviewed by the project partners and the collective recommendation was to proceed with Phase II. Upon the work-conclusion, the Phase II report was issued on March 5, 2012. The scope of work involved the physical testing of a laboratory scale Recuperative Reformer (RR) to validate predicted performances from the feasibility study in Phase I (26% fuel reduction). Although the testing was a successful validation (21% fuel reduction mode), a technical issue 5 arose, namely a Methane Reforming Rate (MRR) roll off or non-sustaining of the methane reforming rate. GTI’s preliminary conclusions were that mechanism(s) producing the methane reforming rate reduction were not entirely known or understood and the chemical kinetics that triggered the roll off mechanism and/or other mechanisms needed to be further evaluated. GTI developed a plan to uncover the reason(s) for not sustaining a satisfactory Methane Reforming Rate (MRR) of the laboratory scale recuperator reformer (RR). The extended testing program consisted primarily of four tasks based on expected outcomes at that time. The project partners reviewed the proposal and recommended the proposed work extension to proceed and suspension of Phase III pending further review of the results of this work identified as Task 2.5. Additional Temperature Threshold Testing was undertaken by GTI and simultaneously independent analysis was carried out by the University of California Davis. Upon completion of the work, the Phase II - Task 2.5 - Extended TCR Testing Report was issued on July 10, 2013. As a result of the work performed in Phase II, Task 2.5, the end conclusion was that temperature dependency has been affirmed, but with temperatures within the recuperative reformer with higher criticality than the flue gas temperature entering into the recuperative reformer. GTI’s further conclusion is that adjustments to the lab recuperative reformer design, given the three-heat exchanger-configuration, remains a valid constraint, and therefore, it would be necessary to scale up to a field experiment capacity level. Design modifications to the recuperative reformer would likely be necessary requiring re-examining space velocity (residence time), heat transfer surface area, plus other considerations, so that a target “temperature profile envelope” within the recuperative reformer would be broad enough to perform satisfactorily in the field with varying flue gas exit temperatures from the majority of the reheat furnace population. A project review meeting was held with the project partners July 17, 2013. Task 2.5 results were reviewed along with the conclusions and recommendations. GTI proposed three field experiment options for Phase III. On the basis of successful sets of Temperature Threshold Tests (TTT), measured results demonstrated that the current design can capably be scaled up and GTI recommended consideration of these three options for a Phase III field experiment. Option 1: Production furnace ~250 MMBtu/h Option 2: Production furnace ~100 - 200 MMBtu/h Option 3: Production furnace ~50 - 100 MMBtu/h The project partners’ resulting unanimous recommendation was to provisionally proceed with Phase 3 – Option 3. Subsequently, after further deliberation, review and analysis of their respective field experiment sites, the three steel industry partners determined not to continue to Phase III of the project for both technical reasons and reasons of process economics, i.e., limited applicability of TCR technology due to higher exhaust gas temperature ranges and sensitivity to natural gas prices. As of this report, the current natural gas price is lower than the $6.03 per 6 MMBtu projected to return positive NPVs for implementing TCR technology. Accordingly, the project work was terminated effective December 31, 2013.« less

Vedolizumab for the treatment of ulcerative colitis and Crohn’s disease

PubMed Central

McLean, Leon P; Shea-Donohue, Terez; Cross, Raymond K

2013-01-01

Crohn’s disease and ulcerative colitis are chronic, relapsing inflammatory disorders of the GI tract. In both Crohn’s disease and ulcerative colitis, leukocytic infiltration of the mucosa is associated with epithelial damage. Recently, monoclonal antibodies directed against cell adhesion molecules (CAMs) involved in leukocyte extravasation have been developed. Natalizumab, the first drug brought to market targeting CAMs, is clinically effective but is associated with serious adverse effects including the uncommon, but often fatal, neurological disease progressive multifocal leukoencephalopathy. Vedolizumab targets a subset of the CAMs blocked by natalizumab and is currently in Phase III trials to study its efficacy and safety in patients with inflammatory bowel disease. Here, we discuss the current treatment options available for patients with Crohn’s disease or ulcerative colitis, the history of CAM inhibitors, the current state of development of vedolizumab and its future role in inflammatory bowel disease, if approved by regulatory agencies. PMID:23046232

Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin

PubMed Central

Righi, Elda; Carnelutti, Alessia; Vena, Antonio; Bassetti, Matteo

2018-01-01

The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care. PMID:29670380

Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin.

PubMed

Righi, Elda; Carnelutti, Alessia; Vena, Antonio; Bassetti, Matteo

2018-01-01

The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care.

Investment in hydrogen tri-generation for wastewater treatment plants under uncertainties

NASA Astrophysics Data System (ADS)

Gharieh, Kaveh; Jafari, Mohsen A.; Guo, Qizhong

2015-11-01

In this article, we present a compound real option model for investment in hydrogen tri-generation and onsite hydrogen dispensing systems for a wastewater treatment plant under price and market uncertainties. The ultimate objective is to determine optimal timing and investment thresholds to exercise initial and subsequent options such that the total savings are maximized. Initial option includes investment in a 1.4 (MW) Molten Carbonate Fuel Cell (MCFC) fed by mixture of waste biogas from anaerobic digestion and natural gas, along with auxiliary equipment. Produced hydrogen in MCFC via internal reforming, is recovered from the exhaust gas stream using Pressure Swing Adsorption (PSA) purification technology. Therefore the expansion option includes investment in hydrogen compression, storage and dispensing (CSD) systems which creates additional revenue by selling hydrogen onsite in retail price. This work extends current state of investment modeling within the context of hydrogen tri-generation by considering: (i) Modular investment plan for hydrogen tri-generation and dispensing systems, (ii) Multiple sources of uncertainties along with more realistic probability distributions, (iii) Optimal operation of hydrogen tri-generation is considered, which results in realistic saving estimation.

Orthodontic Camouflage: A Treatment Option - A Clinical Case Report.

PubMed

Mazzini, William Ubilla; Torres, Fátima Mazzini

2017-01-01

Orthodontic camouflage provides an alternative treatment for angle III malocclusion since patients with limited economic resources cannot opt for orthognathic surgery, it being clear that correction will be achieved at the dental level and not at the bone complex. To determine an alternative treatment for patients who do not have the possibility of having orthognathic surgery. A 13-year-old female patient, dolico facial biotype with slightly concave profile, with Class III Skeletal by mandibular prognathism, anterior crossbite, anterior diastema, and large mandibular body, molar class, and canine III. Alexander technique brackets were placed; premolar extraction was not planned. Once the case was completed, the correction of the anterior crossbite was achieved, thanks to the use of the spaces that existed at the beginning of the treatment and also that a correct distalization of canines and retraction of the lower anterior segment were performed.

Orthodontic Camouflage: A Treatment Option – A Clinical Case Report

PubMed Central

Mazzini, William Ubilla; Torres, Fátima Mazzini

2017-01-01

Orthodontic camouflage provides an alternative treatment for angle III malocclusion since patients with limited economic resources cannot opt for orthognathic surgery, it being clear that correction will be achieved at the dental level and not at the bone complex. Objective: To determine an alternative treatment for patients who do not have the possibility of having orthognathic surgery. Clinical case: A 13-year-old female patient, dolico facial biotype with slightly concave profile, with Class III Skeletal by mandibular prognathism, anterior crossbite, anterior diastema, and large mandibular body, molar class, and canine III. Alexander technique brackets were placed; premolar extraction was not planned. Once the case was completed, the correction of the anterior crossbite was achieved, thanks to the use of the spaces that existed at the beginning of the treatment and also that a correct distalization of canines and retraction of the lower anterior segment were performed. PMID:29326524

Bronchial and bronchovascular sleeve resection for treatment of central lung tumors.

PubMed

Lausberg, H F; Graeter, T P; Wendler, O; Demertzis, S; Ukena, D; Schäfers, H J

2000-08-01

To improve postoperative pulmonary reserve, we have employed parenchyma-sparing resections for central lung tumors irrespective of pulmonary function. The results of lobectomy, pneumonectomy, and sleeve resection were analyzed retrospectively. From October 1995 to June 1999, 422 typical lung resections were performed for lung cancer. Of these, 301 were lobectomies (group I), 81 were sleeve resections (group II), and 40 were pneumonectomies (group III). Operative mortality was 2% in group I, 1.2% in group II, and 7.5% in group III (group I and II vs. group III, p<0.03). Mean time of intubation was 1.0+/-4.1 days in group I, 0.9+/-1.3 days in group II, and 3.6+/-11.2 days in group III (groups I and II vs. group III, p<0.01). The incidence of bronchial complications was 1.3% in group I, none in group II, and 7.5% in group III (group I and II vs group III, p<0.001). After 2 years, survival was 64% in group I, 61.9% in group II, and 56.1% in group III (p = NS). Freedom from local disease recurrence was 92.1% in group I, 95.7% in group II, and 90.9% in group III after 2 years (p = NS). Sleeve resection is a useful surgical option for the treatment of central lung tumors, thus avoiding pneumonectomy with its associated risks. Morbidity, early mortality, long-term survival, and recurrence of disease after sleeve resection are similar to those seen after lobectomy.

Evidence basis for management of spine and chest wall deformities in children.

PubMed

Sponseller, Paul D; Yazici, Muharrem; Demetracopoulos, Constantine; Emans, John B

2007-09-01

: Review of relevant studies, including levels of evidence. : To review research on growth of the spine and chest wall and treatment of deformities. To place this knowledge in context of evidence-based assessment. : Knowledge of the growth of the spine, chest wall, and lung in the normal and deformity states has evolved among independent specialties over the past 60 years. Interest in the interrelationship has blossomed as more tools for assessment and treatment have developed. Spine-based and chest wall-based treatment options now exist, as well as options of resection versus gradual distraction. : Peer-reviewed research published on the growth of the spine, lung, chest wall, and treatment of their deformities was reviewed. Treatment methods and outcomes were compared. Ranking of the levels of evidence was performed where possible. : Most studies of these topics are Level III and IV studies, consisting of case-control studies and case series. This limitation arises because of the rarity and heterogeneity of the disorders affecting the growing spine and chest wall. The natural history of most types of spinal/chest wall deformities is not known with accuracy. Some experimental evidence informs the treatments which involve modulation of the growth of the spine. However, accurate models of the deformities themselves are lacking. Improvements in imaging and measurement offer options for more accurate patient comparison. : The natural history and results of treatment of deformities of the spine and chest wall offer much opportunity for further evidence-based research.

Runway Independent Aircraft Extremely Short Takeoff and Landing Regional Airliner: The Model 110

NASA Technical Reports Server (NTRS)

Hall, David W.

2003-01-01

Airports throughout the United States are plagued with growing congestion. With the increase in air traffic predicted in the next few years, congestion will worsen. The accepted solution of building larger airplanes to carry more travelers is no longer a viable option, as airports are unable to accommodate larger aircraft without expensive infrastructure changes. Past NASA research has pointed to the need for a new approach, which can economically and safely utilize smaller airports. To study this option further, NASA requested the California Polytechnic State University at San Luis Obispo (Cal Poly/SLO) to design a baseline aircraft to be used for system studies. The requirements put forth by NASA are summarized. The design team was requested to create a demonstrator vehicle, which could be built without requiring enabling technology development. To this end, NASA requested that the tested and proven high-lift system of the Boeing C-17 Globemaster III be combined with the fuselage of the BAe-146. NASA also requested that Cal Poly determine the availability and usability of underutilized airports starting with California, then expanding if time and funds permitted to the U.S.

26 CFR 1.936-6 - Intangible property income when an election out is made: Cost sharing and profit split options...

Code of Federal Regulations, 2010 CFR

2010-04-01

... answer 12. (iii) The principles contained in questions and answers 11, 12, 13, and 14 are illustrated by... treated as the owner, for purposes of obtaining a return thereon, of any marketing intangibles except... corporation. Q. 6: How is income attributable to marketing intangibles treated under the cost sharing method...

75 FR 6762 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-10

... Effectiveness of Proposed Rule Change Relating to the Penny Pilot Program February 3, 2010. Pursuant to Section... Exchange filed the proposal as a ``non- controversial'' proposed rule change pursuant to Section 19(b)(3)(A)(iii) of the Act \\3\\ and Rule 19b-4(f)(6) thereunder.\\4\\ The Commission is publishing this notice to...

77 FR 39779 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-05

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-67302; File No. SR-CBOE-2012-061] Self... Effectiveness of a Proposed Rule Change Relating to the Exchange's Automated Improvement Mechanism June 28, 2012...\\ 15 U.S.C. 78s(b)(3)(A)(iii). \\4\\ 17 CFR 240.19b-4(f)(6). I. Self-Regulatory Organization's Statement...

77 FR 39777 - Self-Regulatory Organizations; C2 Options Exchange, Incorporated; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-05

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-67303; File No. SR-C2-2012-021] Self-Regulatory... Rule Change Relating to the Exchange's Automated Improvement Mechanism June 28, 2012. Pursuant to.... 78s(b)(3)(A)(iii). \\4\\ 17 CFR 240.19b-4(f)(6). I. Self-Regulatory Organization's Statement of the...

College Today, Part III: College Closings. Options in Education Transcript: Program No. 121.

ERIC Educational Resources Information Center

George Washington Univ., Washington, DC. Inst. for Educational Leadership.

The closing of a college is the topic of the third in a series of four transcripts of radio programs on college today. The dialogue includes: a press conference at Lone Mountain College, with a discussion of financial problems by the president and comments by Lone Mountain's student body president, college vice president, art department chairman,…

A role for two-stage pharmacoeconomic appraisal? Is there a role for interim approval of a drug for reimbursement based on modelling studies with subsequent full approval using phase III data?

PubMed

Hill, Suzanne; Freemantle, Nick

2003-01-01

Healthcare decision makers and pharmaceutical companies are increasingly using techniques of economic evaluation, particularly modelling, to assist them in their decisions about drug purchasing and drug development. The use of models in other types of policy decisions is also well established. One option, to shorten the time to a purchasing decision, would be for an interim decision for approval for reimbursement to be based on an economic model. Such a system would mainly benefit the drug development process and thus the pharmaceutical industry; however the approach could also lead to poor decision making, unethical marketing and withdrawal of drugs from the consumer. In this article, we consider the option of a two-stage economic appraisal process from the point of view of the seller, the purchaser and the patient and public. Although a two-stage process may offer some advantages in terms of early return on investment and access, there are significant disadvantages in terms of certainty about effects and public policy and expenditure. Until there are better methods of predicting the effectiveness of a new product, it is unlikely that interim decisions can be seen as a reasonable health policy alternative, although it seems likely that industry may continue to lobby for such an approach.

Differential neurobiological effects of expert advice on risky choice in adolescents and adults.

PubMed

Engelmann, Jan B; Moore, Sara; Monica Capra, C; Berns, Gregory S

2012-06-01

We investigated behavioral and neurobiological mechanisms by which risk-averse advice, provided by an expert, affected risky decisions across three developmental groups [early adolescents (12-14 years), late adolescents (15-17 years), adults (18+ years)]. Using cumulative prospect theory, we modeled choice behavior during a risky-choice task. Results indicate that advice had a significantly greater impact on risky choice in both adolescent groups than in adults. Using functional magnetic resonance imaging, we investigated the neural correlates of this behavioral effect. Developmental effects on correlations between brain activity and valuation parameters were obtained in regions that can be classified into (i) cognitive control regions, such as dorsolateral prefrontal cortex (DLPFC) and ventrolateral PFC; (ii) social cognition regions, such as posterior temporoparietal junction; and (iii) reward-related regions, such as ventromedial PFC (vmPFC) and ventral striatum. Within these regions, differential effects of advice on neural correlates of valuation were observed across development. Specifically, advice increased the correlation strength between brain activity and parameters reflective of safe choice options in adolescent DLPFC and decreased correlation strength between activity and parameters reflective of risky choice options in adult vmPFC. Taken together, results indicate that, across development, distinct brain systems involved in cognitive control and valuation mediate the risk-reducing effect of advice during decision making under risk via specific enhancements and reductions of the correlation strength between brain activity and valuation parameters.

Potential role for mammalian target of rapamycin inhibitors as first-line therapy in hormone receptor–positive advanced breast cancer

PubMed Central

Beck, J Thaddeus

2015-01-01

Despite advances in cytotoxic chemotherapy and targeted therapies, 5-year survival rates remain low for patients with advanced breast cancer at diagnosis. This highlights the limited effectiveness of current treatment options. An improved understanding of cellular functions associated with the development and progression of breast cancer has resulted in the creation of a number of novel targeted molecular therapies. However, more work is needed to improve outcomes, particularly in the first-line recurrent or metastatic hormone receptor–positive breast cancer setting. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) pathway is a major intracellular signaling pathway that is often upregulated in breast cancer, and overactivation of this pathway has been associated with primary or developed resistance to endocrine treatment. Clinical data from the Phase III Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study of the mTOR inhibitor everolimus combined with exemestane in hormone receptor–positive advanced breast cancer were very promising, highlighting the potential role of mTOR inhibitors in combination with endocrine therapies as a first-line treatment option for these patients. It is hoped that the use of mTOR inhibitors combined with current standard-of-care endocrine therapies, such as aromatase inhibitors, in the first-line advanced breast cancer setting may result in greater antitumor effects and also delay or reverse treatment resistance. PMID:26675495

Immunotherapy in head and neck cancer - scientific rationale, current treatment options and future directions.

PubMed

Rothschild, Uta; Muller, Laurent; Lechner, Axel; Schlösser, Hans A; Beutner, Dirk; Läubli, Heinz; Zippelius, Alfred; Rothschild, Sacha I

2018-05-14

Head and neck squamous cell carcinoma (HNSCC) is a frequent tumour arising from multiple anatomical subsites in the head and neck region. The treatment for early-stage disease is generally single modality, either surgery or radiotherapy. The treatment for locally advanced tumours is multimodal. For recurrent/metastatic HNSCC palliative chemotherapy is standard of care. The prognosis is limited and novel treatment approaches are urgently needed. HNSCC evades immune responses through multiple resistance mechanisms. HNSCC is particularly characterised by an immunosuppressive environment which includes the release of immunosuppressive factors, activation, expansion of immune cells with inhibitory activity and decreased tumour immunogenicity. An in-depth understanding of these mechanisms led to rational design of immunotherapeutic approaches and clinical trials. Currently, only immune checkpoint inhibitors, namely monoclonal antibodies targeting the immune inhibitory receptor programmed cell death 1 (PD-1) and its ligand PD-L1 have proven clinical efficacy in randomised phase III trials. The PD-1 inhibitor nivolumab is the only drug approved for platinum-refractory recurrent/metastatic HNSCC. However, many more immunotherapeutic treatment options are currently under investigation. Ongoing trials are investigating immunotherapeutic approaches also in the curative setting and combination therapies using different immunotherapeutic approaches. This review article summarises current knowledge of the role of the immune system in the development and progression of HNSCC, and provides a comprehensive overview on the development of immunotherapeutic approaches.

New treatment options for ALK+ advanced non-small-cell lung cancer: critical appraisal of ceritinib

PubMed Central

Rothschild, Sacha I

2016-01-01

Rearrangements in ALK gene and EML4 gene were first described in 2007. This genomic aberration is found in about 2%–8% of non-small-cell lung cancer (NSCLC) patients. Crizotinib was the first ALK tyrosine kinase inhibitor licensed for the treatment of metastatic ALK-positive NSCLC based on a randomized Phase III trial. Despite the initial treatment response of crizotinib, disease progression inevitably develops after approximately 10 months of therapy. Different resistance mechanisms have recently been described. One relevant mechanism of resistance is the development of mutations in ALK. Novel ALK tyrosine kinase inhibitors have been developed to overcome these mutations. Ceritinib is an oral second-generation ALK inhibitor showing clinical activity not only in crizotinib-resistant ALK-positive NSCLC but also in treatment-naïve ALK-positive disease. In this paper, preclinical and clinical data of ceritinib are reviewed, and its role in the clinical setting is put into perspective. PMID:27217763

New treatment options for ALK+ advanced non-small-cell lung cancer: critical appraisal of ceritinib.

PubMed

Rothschild, Sacha I

2016-01-01

Rearrangements in ALK gene and EML4 gene were first described in 2007. This genomic aberration is found in about 2%-8% of non-small-cell lung cancer (NSCLC) patients. Crizotinib was the first ALK tyrosine kinase inhibitor licensed for the treatment of metastatic ALK-positive NSCLC based on a randomized Phase III trial. Despite the initial treatment response of crizotinib, disease progression inevitably develops after approximately 10 months of therapy. Different resistance mechanisms have recently been described. One relevant mechanism of resistance is the development of mutations in ALK. Novel ALK tyrosine kinase inhibitors have been developed to overcome these mutations. Ceritinib is an oral second-generation ALK inhibitor showing clinical activity not only in crizotinib-resistant ALK-positive NSCLC but also in treatment-naïve ALK-positive disease. In this paper, preclinical and clinical data of ceritinib are reviewed, and its role in the clinical setting is put into perspective.

Chinese expert consensus on multidisciplinary diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus: 2016 edition.

PubMed

Cheng, Shuqun; Chen, Minshan; Cai, Jianqiang

2017-01-31

Hepatocellular carcinoma is the fourth leading cause of cancer-related morbidity and mortality in China. Portal vein tumor thrombus (PVTT) is common and it worsens prognosis of hepatocellular carcinoma (HCC). There is no internationally accepted consensus or guideline for diagnosis and treatment of HCC with PVTT. Based on existing evidences and common current practices, Chinese Experts on Multidisciplinary Diagnosis and Treatment of HCC with portal vein tumor thrombus met to develop a national consensus on diagnosis and treatment of HCC with PVTT. The meeting concluded with the First Edition (version 2016) of consensus statements with grades of evidence given as grades Ia, Ib, IIa, IIb, III and IV, and ranking as Classes A, B, C, D and I for quality of evidence and strength of recommendation by the United State Preventive Service Task Force, respectively. The consensus suggests recommended treatment to be based on patients' PVTT type and ECOG functional status; surgery being the preferred treatment for Child-Pugh A, PVTT type I/II, and ECOG PS 0-1; transcatheter arterial chemoembolization (TACE) for non-resectable PVTT I/II and Child-Pugh A; and radiotherapy for non-resectable PVTT I/II/III and Child-Pugh A. Symptomatic treatment is recommended for Child-Pugh C, with massive ascites or gastrointestinal bleeding. By updating clinicians with treatment options for HCC with PVTT, the consensus statement aimed to prolong overall survival and to improve quality of life of patients with minimal treatment complication. Future treatment strategies for HCC with PVTT in China would depend on new evidences from more future clinical trials, especially studies defining the role of traditional Chinese medicine and clarifying molecular aspects of HCC.

A System Dynamics Approach for the Selection of Contaminated Land Management Options

NASA Astrophysics Data System (ADS)

McKnight, U. S.; Kuebert, M.; Finkel, M.; Bieg, M.

2006-12-01

Large-scale contaminated land and groundwater is a widespread problem that can severely impact human health, the environment and the economy at many urban sites all over the world. Usually a considerable number of potential management solutions exist at each of these sites. A detailed investigation of all these options, however, is not economically feasible which makes streamlining of the planning and decision process a mandatory requirement. Decisions to be taken should be made as early as possible in order to reduce expenditures on site investigation. Therefore, a tiered decision-making procedure is required, including (i) identification and prioritization of focal areas of risks, (ii) feasibility screening of remediation targets and available management alternatives to narrow the range of possible options for (iii) subsequent detailed investigations of only a select group of preferable options. For each of these elements, tailored decision and investigation concepts are required. These concepts and applied methods should be specifically adapted to the type and scale of the particular decision to be taken- more target-oriented, cost-efficient investigation programs, as well as model-based assessment methods are needed (Ruegner et al. 2006). A gap exists within this framework with respect to preliminary assessment methodologies representing the first decision level. To fill this gap, a new system dynamics approach has been developed that represents the system of source- pathway-receptor sequences by means of a mass flux model. The dynamics are governed by the effects of possible remedial actions, which are described as mass flux change over time (Serapiglia et al. 2005). This approach has been implemented in the preliminary evaluation tool CARO-plus (Cost-efficiency Assessment of Remediation Options) that models the effects of potential remedial actions, including tackling the contaminant source and managing the groundwater plume. The model represents the causal relationships that exist between the state of the system, the effects of the technologies and their costs, and may considerably impact the outcome to be predicted. The tool enables a fast and effective "screening" of management scenarios using simplified approaches (analytical models). Replacing the concept of total cleanup of sites based on concentration standards, the evaluation tool contains risk modules that describe exposure pathways, i.e. transfer of contaminants from groundwater to the receptor "human being", in accordance to MEPAS (Strenge & Chamberlain 1995). As multiple lines of evidence may apply, the effects of remediation options can be analyzed on the basis of contaminant mass flux, concentrations, and/or risk indices (carcinogenic/noncarcinogenic). Costs are calculated in terms of net present values. Uncertainty is taken into account using Monte-Carlo sensitivity analyses. In the presentation, examples will be shown for how the proposed approach helps to pre-select compatible remediation options by giving an overview to the following set of questions: (i) what is the time scale for risks expected at a particular site, (ii) does the scenario reduce/control risk at the receptor, (iii) is the scenario compatible with cleanup objectives (e.g. in the case that concentration standards are still required for specific compounds present at a site), (iv) does the scenario satisfy cost objectives and can therefore be considered financially viable, (v) is the scenario acceptable to regulators and the community, and (vi) what factors are most critical to the decision-making process.

Surgical-orthodontic treatment of a skeletal class III malocclusion.

PubMed

Katiyar, Radha; Singh, G K; Mehrotra, Divya; Singh, Alka

2010-07-01

For patients whose orthodontic problems are so severe that neither growth modification nor camouflage offers a solution, surgery to realign the jaws or reposition dentoalveolar segments is the only possible treatment option left. One indication for surgery obviously is a malocclusion too severe for orthodontics alone. It is possible now to be at least semiquantitative about the limits of orthodontic treatment, in the context of producing normal occlusion as the diagrams of the "envelope of discrepancy" indicate. In this case report we present orthognathic treatment plan of an adult female patient with skeletal class III malocclusion. Patient's malocclusion was decompensated by orthodontic treatment just before the surgery and then normal jaw relationship achieved by bilateral sagittal split osteotomy.

Treatment in Borderline Class III Malocclusion: Orthodontic Camouflage (Extraction) Versus Orthognathic Surgery.

PubMed

Rabie, A-Bakr M; Wong, Ricky W K; Min, G U

2008-01-01

To investigate the differences in morphological characteristics of borderline class III patients who had undergone camouflage orthodontic treatment or orthognathic surgery, and to compare the treatment effects between these two modalities. Cephalograms of 25 patients (13 orthodontic, 12 surgical) with class III malocclusion were analyzed. All had a pretreatment ANB angle greater than -5 masculine. Using discriminant analysis, only Holdaway angle was selected to differentiate patients in the pretreatment stage. Seventy-two per cent patients were correctly classified. In the orthodontic group, reverse overjet was corrected by retraction of the lower incisors and downward and backward rotation of the mandible. The surgical group was corrected by setback of the lower anterior dentoalveolus and uprighting of the lower incisors. No difference was found in posttreatment soft tissue measurements between the two groups. Twelve degree for the Holdaway angle can be a guideline in determining the treatment modalities for borderline class III patients, but the preferences of operators and patients are also important. (2) Both therapeutic options should highlight changes in the lower dentoalveolus and lower incisors. (3) Both treatment modalities can achieve satisfactory improvements to the people.

Development of Internet algorithms and some calculations of power plant COP

NASA Astrophysics Data System (ADS)

Ustjuzhanin, E. E.; Ochkov, V. F.; Znamensky, V. E.

2017-11-01

The authors have analyzed Internet resources containing information on some thermodynamic properties of technically important substances (the water, the air etc.). There are considered databases those possess such resources and are hosted in organizations (Joint Institute for High Temperatures (Russian Academy of Sciences), Standartinform (Russia), National Institute of Standards and Technology (USA), Institute for Thermal Physics (Siberian Branch of the Russian Academy of Sciences), etc.). Currently, a typical form is an Internet resource that includes a text file, for example, it is a file containing tabulated properties, R = (ρ, s, h…), here ρ - the density, s - the entropy, h - the enthalpy of a substance. It is known a small number of Internet resources those have the following characteristic. The resource allows a customer to realize a number of options, for example: i) to enter the input data, Y = (p, T), here p - the pressure, T - the temperature, ii) to calculate R property using “an exe-file” program, iii) to copy the result X = (p, T, ρ, h, s, …). Recently, some researchers (including the authors of this report) have requested a software (SW) that is designed for R property calculations and has a form of an open interactive (OI) Internet resource (“a client function”, “template”). A computing part of OI resource is linked: 1) with a formula, which is applied to calculate R property, 2) with a Mathcad program, Code_1(R,Y). An interactive part of OI resource is based on Informatics and Internet technologies. We have proposed some methods and tools those are related to this part and let us: a) to post OI resource on a remote server, b) to link a client PC with the remote server, c) to implement a number of options to clients. Among these options, there are: i) to calculate R property at given Y arguments, ii) to copy mathematical formulas, iii) to copy Code_1(R,Y) as a whole. We have developed some OI - resources those are focused on sharing: a) SW that is used to design power plants, for an example, Code - GTP_1(Z,R,Y) and b) client functions those are aimed to determine R properties of the working fluid at fixed points of the thermodynamic cycle. The program let us calculate energy criteria, Z, including the internal coefficient of performance (COP) for a power plant. We have discussed OI resources, among them OI resource that includes Code - GTP_1(Z,R,Y) and connected with a complex power plant included: i) several gas turbines, i) several compressors etc.

UAVSAR - A New Airborne L-Band Radar for Repeat Pass Interferometry

NASA Technical Reports Server (NTRS)

Mace, Thomas H.; Lou, Yunling

2009-01-01

NASA/JPL has developed a new airborne Synthetic Aperture Radar (SAR) which has become available for use by the scientific community in January, 2009. Pod mounted, the UAVSAR was designed to be portable among a variety of aircraft, including unmanned aerial systems (UAS). The instrument operates in the L-Band, has a resolution under 2m from a GPS altitude of 12Km and a swath width of approximately 20Km. UAVSAR currently flies on a modified Gulfstream-III aircraft, operated by NASA s Dryden Flight Research Center at Edwards, California. The G-III platform enables repeat-pass interferometric measurements, by using a modified autopilot and precise kinematic differential GPS to repeatedly fly the aircraft within a specified 10m tube. The antenna is electronically steered along track to assure that the antenna beam can be directed independently, regardless of speed and wind direction. The instrument can be controlled remotely, AS AN OPTION, using the Research Environment for Vehicle Embedded Analysis on Linux (REVEAL). This allows simulation of the telepresence environment necessary for flight on UAS. Potential earth science research and applications include surface deformation, volcano studies, ice sheet dynamics, and vegetation structure.

Treatments for achalasia in 2017: how to choose among them.

PubMed

Kahrilas, Peter J; Pandolfino, John E

2017-07-01

To review recent advances in achalasia diagnostics and therapeutics. The cardinal feature of achalasia, impaired lower esophageal sphincter (LES) relaxation, can occur in association with varied patterns of esophageal contractility. The Chicago Classification distinguishes among these as follows: without contractility (type I), with panesophageal pressurization (type II), with premature (spastic) distal esophageal contractions (type III), or even with preserved peristalsis [esophagogastric junction (EGJ) outlet obstruction]. Physiological testing also reveals achalasia-like syndromes that also benefit from achalasia therapies. Coincident with this has been the development of peroral endoscopic myotomy (POEM), an endoscopic technique for performing an esophageal myotomy. Hence, the option now exists to either selectively ablate the LES (pneumatic dilation, laparoscopic Heller myotomy, or POEM) or to ablate the sphincter and create a myotomy along some or the entire adjacent smooth muscle esophagus (POEM). Each achalasia syndrome has unique treatment considerations; type II achalasia responds well to all therapies, whereas type III responds best to POEM. Emerging data support the concept that optimal management of achalasia is phenotype-specific, guided by high-resolution manometry, and, in some instance, functional luminal imaging probe studies. This opinion article reviews the varied characteristic and treatment considerations of achalasia syndromes as currently understood.

Update on options for treatment of metastatic castration-resistant prostate cancer.

PubMed

Vishnu, Prakash; Tan, Winston W

2010-06-24

Prostate cancer is one of the most common cancers in men in US and European countries. Despite having a favorable prognosis, the incidence of incurable metastatic disease and mortality in the US is about 28,000 per year. Although hormone-based androgen deprivation therapies typically result in rapid responses, nearly all patients eventually develop progressive castration-resistant disease state. With readily available prostate-specific antigen (PSA) testing, most of these patients are asymptomatic and manifest progression simply as a rising PSA. In patients with castration-resistant prostate cancer (CRPC), the median survival is about 1-2 years, with improvements in survival seen mostly with docetaxel-based regimens. The purpose of this article is to review the recent developments in the treatment of advanced CRPC. Since the two landmark trials (TAX-327 and Southwest Oncology Group 99-16) in CRPC, several newer cytotoxic drugs (epothilones, satraplatin), targeted agents (abiraterone, MDV3100) and vaccines have been tested in phase II and III setting with promising results. The role of newer agents in the treatment of CRPC still needs to be validated by phase III trials, which are currently ongoing. Whilst the novel biomarkers, 'circulating tumor cells', have been shown to provide important prognostic information and are anticipated to be incorporated in future clinical decision-making, their exact utility and relevance calls for a larger prospective validation.

Emerging therapies for the management of chronic hyperkalemia in the ambulatory care setting.

PubMed

Henneman, Amy; Guirguis, Erenie; Grace, Yasmin; Patel, Dimple; Shah, Bhoomi

2016-01-15

Emerging treatment options for the management of chronic hyperkalemia in the outpatient setting are reviewed. Current treatment options for the management of hyperkalemia are limited and often accompanied by serious adverse effects. Two investigational drugs for the treatment of hyperkalemia are being evaluated in Phase III trials: sodium zirconium cyclosilicate and patiromer. Both of these drugs are administered orally and act by enhancing potassium's removal, predominantly through the gastrointestinal tract. The safety and efficacy of sodium zirconium cyclosilicate and patiromer were evaluated in Phase II and III trials. Both agents were studied in patients with chronic mild-to-severe hyperkalemia, chronic kidney disease (CKD), or heart failure as well as those taking a renin-angiotensin system (RAS) inhibitor, an aldosterone antagonist, or both therapies. These clinical trials found that sodium zirconium cyclosilicate and patiromer normalized serum potassium levels quickly and maintained normalized serum potassium levels over several weeks. Both medications caused a rapid decrease in serum potassium, with two studies examining efficacy endpoints for 12 weeks or longer. The overall frequency of adverse effects in these clinical trials was low, with gastrointestinal adverse events being the most commonly observed. Options for the management of hyperkalemia, particularly chronic hyperkalemia in the outpatient setting, are limited. Both sodium zirconium cyclosilicate and patiromer are emerging therapies that may provide long-term management of hyperkalemia, particularly in patients with underlying heart failure or CKD as well as those taking an RAS inhibitor, an aldosterone antagonist, or both. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Investigation of e-beam sensitive negative-tone chemically amplified resists for binary mask making

NASA Astrophysics Data System (ADS)

Irmscher, Mathias; Berger, Lothar; Beyer, Dirk; Butschke, Joerg; Dress, Peter; Hoffmann, Thomas; Hudek, Peter; Koepernik, Corinna; Tschinkl, Martin; Voehringer, Peter

2003-08-01

Negative-tone chemically amplified resists MES-EN1G (JSR), FEN-270 (Fujifilm ARCH), EN-024M (TOK) and NEB-22 (Sumitomo) were evaluated for binary mask making. The investigations were performed on an advanced tool set comprising a 50kV e-beam writer Leica SB350, a Steag Hamatech hot/cool plate module APB5000, a Steag Hamatech developer ASP5000, an UNAXIS MASK ETCHER III and a SEM LEO1560 with integrated CD measurement option. We investigated and compared the evaluated resists in terms of resolution, e-beam sensitivity, resist profile, post exposure bake sensitivity, CD-uniformity, line edge roughness, pattern fidelity and etch resistance. Furthermore, the influence of post coating delay and post exposure delay in vacuum and air was determined.

Treating advanced non-small-cell lung cancer in Chinese patients: focus on icotinib

PubMed Central

Liang, Jun-Li; Ren, Xiao-Cang; Lin, Qiang

2014-01-01

Icotinib hydrochloride is an orally administered small-molecule reversible tyrosine kinase inhibitor that has been independently researched and developed and has independent intellectual property rights in the People’s Republic of China. Clinical trials have demonstrated that the response to icotinib among advanced non-small-cell lung cancer (NSCLC) patients who received at least one platinum-based chemotherapy regimen was not inferior to gefitinib. Since being launched August 2011 in the People’s Republic of China, icotinib has been widely used in clinics, and has become an important treatment option for Chinese patients with advanced NSCLC. The present study presents the Phase I, II, and III clinical trials of icotinib and discusses current clinical applications in the People’s Republic of China and future research directions. PMID:24876785

Radiofrequency facial rejuvenation: evidence-based effect.

PubMed

el-Domyati, Moetaz; el-Ammawi, Tarek S; Medhat, Walid; Moawad, Osama; Brennan, Donna; Mahoney, My G; Uitto, Jouni

2011-03-01

Multiple therapies involving ablative and nonablative techniques have been developed for rejuvenation of photodamaged skin. Monopolar radiofrequency (RF) is emerging as a gentler, nonablative skin-tightening device that delivers uniform heat to the dermis at a controlled depth. We evaluated the clinical effects and objectively quantified the histologic changes of the nonablative RF device in the treatment of photoaging. Six individuals of Fitzpatrick skin type III to IV and Glogau class I to II wrinkles were subjected to 3 months of treatment (6 sessions at 2-week intervals). Standard photographs and skin biopsy specimens were obtained at baseline, and at 3 and 6 months after the start of treatment. We performed quantitative evaluation of total elastin, collagen types I and III, and newly synthesized collagen using computerized histometric and immunohistochemical techniques. Blinded photographs were independently scored for wrinkle improvement. RF produced noticeable clinical results, with high satisfaction and corresponding facial skin improvement. Compared with the baseline, there was a statistically significant increase in the mean of collagen types I and III, and newly synthesized collagen, while the mean of total elastin was significantly decreased, at the end of treatment and 3 months posttreatment. A limitation of this study is the small number of patients, yet the results show a significant improvement. Although the results may not be as impressive as those obtained by ablative treatments, RF is a promising treatment option for photoaging with fewer side effects and downtime. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Organ donation after controlled cardiac death under Maastricht category iii: Ethical implications and end of life care.

PubMed

González-Méndez, M Isabel; López-Rodríguez, Luís

2017-12-11

The decrease in potential donation after brain death has resulted in a need to evaluate alternative sources. Donation after cardiac death is a good option. The objectives of this article are to describe the Maastricht type iii controlled organ donation characteristics and to determine end-of-life care and the role of nurses in the donation process. In this type of donation, cardiocirculatory arrest is predictable after the limitation of life sustaining treatments. These are patients for whom there are no effective therapy options and, in the context of an organised and planned practice involving all the professionals involved in the care of the patient, the decision is made, in consultation with the family, to withdraw life support measures. This limitation of life sustaining treatments is never carried out with the aim of making a Maastricht iii donation, but to avoid prolonging the dying process through useless and possibly degrading interventions. The obligation of the health team is to provide a dignified death and this not only includes the absence of pain, but the patient and their family must be guaranteed a feeling of calmness and serenity. Once the decision has been taken to withhold or withdraw measures, the nurse has an important role in the implementation of a palliative care plan in where physicians, nurses and patients/families should be involved and whose focus should be on patients' dignity and comfort, considering their physical, psychological and spiritual needs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Arsenic removal with iron(II) and iron(III) in waters with high silicate and phosphate concentrations.

PubMed

Roberts, Linda C; Hug, Stephan J; Ruettimann, Thomas; Billah, Morsaline; Khan, Abdul Wahab; Rahman, Mohammad Tariqur

2004-01-01

Arsenic removal by passive treatment, in which naturally present Fe(II) is oxidized by aeration and the forming iron(III) (hydr)oxides precipitate with adsorbed arsenic, is the simplest conceivable water treatment option. However, competing anions and low iron concentrations often require additional iron. Application of Fe(II) instead of the usually applied Fe(III) is shown to be advantageous, as oxidation of Fe(II) by dissolved oxygen causes partial oxidation of As(III) and iron(III) (hydr)oxides formed from Fe(II) have higher sorption capacities. In simulated groundwater (8.2 mM HCO3(-), 2.5 mM Ca2+, 1.6 mM Mg2+, 30 mg/L Si, 3 mg/L P, 500 ppb As(III), or As(V), pH 7.0 +/- 0.1), addition of Fe(II) clearly leads to better As removal than Fe(III). Multiple additions of Fe(II) further improved the removal of As(II). A competitive coprecipitation model that considers As(III) oxidation explains the observed results and allows the estimation of arsenic removal under different conditions. Lowering 500 microg/L As(III) to below 50 microg/L As(tot) in filtered water required > 80 mg/L Fe(III), 50-55 mg/L Fe(II) in one single addition, and 20-25 mg/L in multiple additions. With As(V), 10-12 mg/L Fe(II) and 15-18 mg/L Fe(III) was required. In the absence of Si and P, removal efficiencies for Fe(II) and Fe(III) were similar: 30-40 mg/L was required for As(II), and 2.0-2.5 mg/L was required for As(V). In a field study with 22 tubewells in Bangladesh, passive treatment efficiently removed phosphate, but iron contents were generally too low for efficient arsenic removal.

5 CFR 410.203 - Options for developing employees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Options for developing employees. 410.203... Planning and Evaluating Training § 410.203 Options for developing employees. Agencies may use a full range of options to meet their mission-related organizational and employee development needs, such as...

RETROFIT COSTS FOR SO2 AND NOX CONTROL OPTIONS AT 200 COAL-FIRED PLANTS, VOLUME III - SITE SPECIFIC STUDIES FOR IN, KY, MA, MD, MI, MN

EPA Science Inventory

The report gives results of a study, the objective of which was to significantly improve engineering cost estimates currently being used to evaluate the economic effects of applying SO2 and NOx controls at 200 large SO2-emitting coal-fired utility plants. To accomplish the object...

25 CFR 547.8 - What are the minimum technical software standards applicable to Class II gaming systems?

Code of Federal Regulations, 2014 CFR

2014-04-01

... display the following: (i) The purchase or wager amount; (ii) Game results; and (iii) Any player credit balance. (2) Between plays of any game and until the start of the next play, or until the player selects a new game option such as purchase or wager amount or card selection, whichever is earlier, if not...

25 CFR 547.8 - What are the minimum technical software standards applicable to Class II gaming systems?

Code of Federal Regulations, 2013 CFR

2013-04-01

... display the following: (i) The purchase or wager amount; (ii) Game results; and (iii) Any player credit balance. (2) Between plays of any game and until the start of the next play, or until the player selects a new game option such as purchase or wager amount or card selection, whichever is earlier, if not...

40 CFR Table 3 to Subpart Qqqq of... - Operating Limits if Using the Emission Rate With Add-On Controls Option

Code of Federal Regulations, 2011 CFR

2011-07-01

... combustion temperature in any 3-hour period must not fall below the combustion temperature limit established according to § 63.4767(a) i. Collecting the combustion temperature data according to § 63.4768(c);ii. Reducing the data to 3-hour block averages; and iii. Maintaining the 3-hour block average combustion...

40 CFR Table 1 to Subpart Rrrr of... - Operating Limits if Using the Emission Rate With Add-on Controls Option

Code of Federal Regulations, 2010 CFR

2010-07-01

... combustion temperature in any 3-hour period must not fall below the combustion temperature limit established according to § 63.4966(a) i. collecting the combustion temperature data according to § 63.4967(c);ii. reducing the data to 3-hour block averages; and iii. maintaining the 3-hour average combustion temperature...

40 CFR Table 1 to Subpart Nnnn of... - Operating Limits if Using the Emission Rate With Add-On Controls Option

Code of Federal Regulations, 2012 CFR

2012-07-01

... combustion temperature in any 3-hour period must not fall below the combustion temperature limit established according to § 63.4167(a) i. collecting the combustion temperature data according to § 63.4168(c);ii. reducing the data to 3-hour block averages; and iii. maintaining the 3-hour average combustion temperature...

40 CFR Table 1 to Subpart Nnnn of... - Operating Limits if Using the Emission Rate With Add-On Controls Option

Code of Federal Regulations, 2014 CFR

2014-07-01

... combustion temperature in any 3-hour period must not fall below the combustion temperature limit established according to § 63.4167(a) i. collecting the combustion temperature data according to § 63.4168(c);ii. reducing the data to 3-hour block averages; and iii. maintaining the 3-hour average combustion temperature...

40 CFR Table 3 to Subpart Qqqq of... - Operating Limits if Using the Emission Rate With Add-On Controls Option

Code of Federal Regulations, 2010 CFR

2010-07-01

... combustion temperature in any 3-hour period must not fall below the combustion temperature limit established according to § 63.4767(a) i. Collecting the combustion temperature data according to § 63.4768(c);ii. Reducing the data to 3-hour block averages; and iii. Maintaining the 3-hour block average combustion...

40 CFR Table 1 to Subpart Rrrr of... - Operating Limits if Using the Emission Rate With Add-on Controls Option

Code of Federal Regulations, 2013 CFR

2013-07-01

... average combustion temperature in any 3-hour period must not fall below the combustion temperature limit established according to § 63.4966(a) i. collecting the combustion temperature data according to § 63.4967(c);ii. reducing the data to 3-hour block averages; and iii. maintaining the 3-hour average combustion...

40 CFR Table 1 to Subpart Rrrr of... - Operating Limits if Using the Emission Rate With Add-on Controls Option

Code of Federal Regulations, 2014 CFR

2014-07-01

... average combustion temperature in any 3-hour period must not fall below the combustion temperature limit established according to § 63.4966(a) i. collecting the combustion temperature data according to § 63.4967(c);ii. reducing the data to 3-hour block averages; and iii. maintaining the 3-hour average combustion...

40 CFR Table 1 to Subpart Nnnn of... - Operating Limits if Using the Emission Rate With Add-On Controls Option

Code of Federal Regulations, 2013 CFR

2013-07-01

... combustion temperature in any 3-hour period must not fall below the combustion temperature limit established according to § 63.4167(a) i. collecting the combustion temperature data according to § 63.4168(c);ii. reducing the data to 3-hour block averages; and iii. maintaining the 3-hour average combustion temperature...

40 CFR Table 1 to Subpart Rrrr of... - Operating Limits if Using the Emission Rate With Add-on Controls Option

Code of Federal Regulations, 2012 CFR

2012-07-01

... average combustion temperature in any 3-hour period must not fall below the combustion temperature limit established according to § 63.4966(a) i. collecting the combustion temperature data according to § 63.4967(c);ii. reducing the data to 3-hour block averages; and iii. maintaining the 3-hour average combustion...

40 CFR Table 1 to Subpart Rrrr of... - Operating Limits if Using the Emission Rate With Add-on Controls Option

Code of Federal Regulations, 2011 CFR

2011-07-01

... combustion temperature in any 3-hour period must not fall below the combustion temperature limit established according to § 63.4966(a) i. collecting the combustion temperature data according to § 63.4967(c);ii. reducing the data to 3-hour block averages; and iii. maintaining the 3-hour average combustion temperature...

75 FR 68015 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-04

... change is reasonable in light of the planned introduction of a multi-platform feature to SPX (discussed... SPX is reasonable in light of the introduction of the multi-platform feature to SPX. \\8\\ 15 U.S.C. 78f... competition; and (iii) become operative prior to 30 days from the date on which it was filed, or such shorter...

78 FR 59994 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-30

... to avoid any erroneous inference that those are the only provisions of OCC's By-Laws and Rules that... its By-Laws and Rules as well. III. Discussion Section 19(b)(2)(C) of the Act \\5\\ directs the... of participants or among participants in the use of the clearing agency. \\5\\ 15 U.S.C. 78s(b)(2)(C...

17 CFR 240.15c3-1f - Optional market and credit risk requirements for OTC derivatives dealers (Appendix F to 17 CFR...

Code of Federal Regulations, 2011 CFR

2011-04-01

... would be determined. (iii) Internal risk management control systems. An OTC derivatives dealer shall provide a comprehensive description of its internal risk management control systems and how those systems... internal risk management control systems that meet the requirements set forth in § 240.15c3-4; and (ii) Has...

17 CFR 240.15c3-1f - Optional market and credit risk requirements for OTC derivatives dealers (Appendix F to 17 CFR...

Code of Federal Regulations, 2012 CFR

2012-04-01

... would be determined. (iii) Internal risk management control systems. An OTC derivatives dealer shall provide a comprehensive description of its internal risk management control systems and how those systems... internal risk management control systems that meet the requirements set forth in § 240.15c3-4; and (ii) Has...

78 FR 14386 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

... Effectiveness of a Proposed Rule Change To Amend the CBOE Stock Exchange Fees Schedule February 27, 2013. Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934 (the ``Act''),\\1\\ and Rule 19b-4...'') the proposed rule change as described in Items I, II, and III below, which Items have been prepared by...

78 FR 3065 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-15

... Effectiveness of a Proposed Rule Change Amending Rule 5.5.04 To Permit the Exchange To List Additional Strike... Exchange Commission (the ``Commission'') the proposed rule change as described in Items I and II below...- controversial'' proposed rule change pursuant to Section 19(b)(3)(A)(iii) of the Act \\3\\ and Rule 19b-4(f)(6...

Radiopharmaceuticals for imaging the heart

DOEpatents

Green, Mark A.; Tsang, Brenda W.

1994-01-01

Radiopharmaceuticals for imaging myocardial tissues are prepared by forming lipophilic, cationic complexes of radioactive metal ions with metal chelating ligands comprising the Schiff base adducts of triamines and tetraamines with optionally substituted salicylaldehydes. The lipophilic, cationic, radioactive complexes of the invention exhibit high uptake and retention in myocardial tissues. Preferred gallium-68(III) complexes in accordance with this invention can be used to image the heart using positron emission tomography.

76 FR 42163 - East Penn Railroad, L.L.C.; Lease and Operation Exemption; Norfolk Southern Railway Company

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-18

... Railroad, L.L.C. (ESPN), a Class III rail carrier, has filed a verified notice of exemption under 49 CFR... the rent, but ESPN requested a lease credit option to give it an opportunity to earn a lower rental... annual revenues resulting from the proposed transaction will not result in ESPN becoming a Class II or...

An emerging treatment option for glaucoma: Rho kinase inhibitors

PubMed Central

Wang, Sean K; Chang, Robert T

2014-01-01

Rho kinase (ROCK) inhibitors are a novel potential class of glaucoma therapeutics with multiple compounds currently in Phase II and III US Food and Drug Administration trials in the United States. These selective agents work by relaxing the trabecular meshwork through inhibition of the actin cytoskeleton contractile tone of smooth muscle. This results in increased aqueous outflow directly through the trabecular meshwork, achieving lower intraocular pressures in a range similar to prostaglandins. There are also animal studies indicating that ROCK inhibitors may improve blood flow to the optic nerve, increase ganglion cell survival, and reduce bleb scarring in glaucoma surgery. Given the multiple beneficial effects for glaucoma patients, ROCK inhibitors are certainly a highly anticipated emerging treatment option for glaucoma. PMID:24872673

To create a cleanroom controlled environment using a mobile air decontamination unit for the preparation of antineoplastic drugs.

PubMed

Lecordier, Julien; Plivard, Claire; Gardeux, Michel; Daouadi, Karim; Lahet, Jean-Jacques

2016-02-01

To use a mobile air decontamination unit (MADU) for a microbial destruction and decreased particle burden making a cleanroom controlled environment in a Centralized Chemotherapy Preparation Unit (CCPU). Good manufacturing practices (GMP) in France specify that the ambient air in the vicinity of a class III biosafety cabinet (isolator) complies with air cleanliness ISO 8 level in CCPU. This guideline has a significant impact because implementing a dedicated air handling unit (AHU) brings some engineering constraints and generates substantial additional costs. Authors have previously studied some technical and economical aspects to evaluate the feasibility of the MADU option. Using a MADU was the chosen option. Qualification of the CCPU showed that results were in compliance with the French GMP. After one year of use, the efficiency of the MADU was confirmed. According to these results, using a MADU constitutes a beneficial option for CCPU previously equipped with an isolator when compared to renovation work involving a standard built-in AHU. © The Author(s) 2014.

Surgical options in benign parotid tumors: a proposal for classification.

PubMed

Quer, Miquel; Vander Poorten, Vincent; Takes, Robert P; Silver, Carl E; Boedeker, Carsten C; de Bree, Remco; Rinaldo, Alessandra; Sanabria, Alvaro; Shaha, Ashok R; Pujol, Albert; Zbären, Peter; Ferlito, Alfio

2017-11-01

Different surgical options are currently available for treating benign tumors of the parotid gland, and the discussion on optimal treatment continues despite several meta-analyses. These options include more limited resections (extracapsular dissection, partial lateral parotidectomy) versus more extensive and traditional options (lateral parotid lobectomy, total parotidectomy). Different schools favor one option or another based on their experience, skills and tradition. This review provides a critical analysis of the literature regarding these options. The main limitation of all the studies is the bias of selection for different surgical approaches. For this reason, we propose a staging system that could facilitate clinical decision making and the comparison of results. We propose four categories based on the size of the tumor and its location within the parotid gland. Category I includes tumors up to 3 cm, which are mobile, close to the outer surface and close to the parotid borders. Category II includes deeper tumors up to 3 cm. Category III comprises tumors greater than 3 cm involving two levels of the parotid gland, and category IV tumors are greater than 3 cm and involve more than 2 levels. For each category and for the various pathologic types, a guideline of surgical extent is proposed. The objective of this classification is to facilitate prospective multicentric studies on surgical techniques in the treatment of benign parotid tumors and to enable the comparison of results of different clinical studies.

Engineering assessment of inactive uranium mill tailings, Gunnison Site, Gunnison, Colorado. Phase II, Title I

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

None

1977-11-01

Ford, Bacon and Davis Utah Inc. has performed an engineering assessment of the problems resulting from the existence of radioactive uranium mill tailings at Gunnison, Colorado. The Phase II - Title I services include the preparation of topographic measurements sufficient to determine areas and volumes of tailings and other radium-contaminated materials, the evaluation of resulting radiation exposures of individuals and nearby populations, the investigation of site hydrology and meteorology, and the evaluation and costing of alternative corrective actions. Radon gas release from the 0.5 million tons of tailings at the Gunnison site constitutes the most significant environmental impact, although windblownmore » tailings and external gamma radiation are also factors. The nine alternative actions presented range from millsite decontamination (Option I), to adding various depths of stabilization cover material (Options II and III), to removal of the tailings to long-term storage sites and decontamination of the present site (Options IV through IX). Cost estimates for the nine options range from $480,000 to $5,890,000. Reprocessing the tailings for uranium does not appear to be economically attractive at present.« less

Molecular Preadaptation to Antimony Resistance in Leishmania donovani on the Indian Subcontinent

PubMed Central

Imamura, H.; Zander, D.; D’Haenens, E.; Maes, I.; Domagalska, M. A.; Clos, J.

2018-01-01

ABSTRACT Antimonials (Sb) were used for decades for chemotherapy of visceral leishmaniasis (VL). Now abandoned in the Indian subcontinent (ISC) because of Leishmania donovani resistance, this drug offers a unique model for understanding drug resistance dynamics. In a previous phylogenomic study, we found two distinct populations of L. donovani: the core group (CG) in the Gangetic plains and ISC1 in the Nepalese highlands. Sb resistance was only encountered within the CG, and a series of potential markers were identified. Here, we analyzed the development of resistance to trivalent antimonials (SbIII) upon experimental selection in ISC1 and CG strains. We observed that (i) baseline SbIII susceptibility of parasites was higher in ISC1 than in the CG, (ii) time to SbIII resistance was higher for ISC1 parasites than for CG strains, and (iii) untargeted genomic and metabolomic analyses revealed molecular changes along the selection process: these were more numerous in ISC1 than in the CG. Altogether these observations led to the hypothesis that CG parasites are preadapted to SbIII resistance. This hypothesis was experimentally confirmed by showing that only wild-type CG strains could survive a direct exposure to the maximal concentration of SbIII. The main driver of this preadaptation was shown to be MRPA, a gene involved in SbIII sequestration and amplified in an intrachromosomal amplicon in all CG strains characterized so far. This amplicon emerged around 1850 in the CG, well before the implementation of antimonials for VL chemotherapy, and we discuss here several hypotheses of selective pressure that could have accompanied its emergence. IMPORTANCE The “antibiotic resistance crisis” is a major challenge for scientists and medical professionals. This steady rise in drug-resistant pathogens also extends to parasitic diseases, with antimony being the first anti-Leishmania drug that fell in the Indian subcontinent (ISC). Leishmaniasis is a major but neglected infectious disease with limited therapeutic options. Therefore, understanding how parasites became resistant to antimonials is of commanding importance. In this study, we experimentally characterized the dynamics of this resistance acquisition and show for the first time that some Leishmania populations of the ISC were preadapted to antimony resistance, likely driven by environmental factors or by drugs used in the 19th century. PMID:29669889

Surgical–orthodontic treatment of a skeletal class III malocclusion

PubMed Central

Katiyar, Radha; Singh, G. K.; Mehrotra, Divya; Singh, Alka

2010-01-01

For patients whose orthodontic problems are so severe that neither growth modification nor camouflage offers a solution, surgery to realign the jaws or reposition dentoalveolar segments is the only possible treatment option left. One indication for surgery obviously is a malocclusion too severe for orthodontics alone. It is possible now to be at least semiquantitative about the limits of orthodontic treatment, in the context of producing normal occlusion as the diagrams of the “envelope of discrepancy” indicate. In this case report we present orthognathic treatment plan of an adult female patient with skeletal class III malocclusion. Patient's malocclusion was decompensated by orthodontic treatment just before the surgery and then normal jaw relationship achieved by bilateral sagittal split osteotomy. PMID:22442586

Assessment of DOE radioactive scrap metal disposition options

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

Butler, C.R.; Kasper, K.M.; Bossart, S.J.

1997-02-01

The DOE has amassed a large amount of radioactively-contaminated scrap metal (RSM) as a result of past operations and decontamination and decommissioning (D&D) projects. The volume of RSM will continue to increase as a result of the D&D of more than 6,000 surplus facilities and many of the 14,000 operating facilities in the DOE complex. RSM can be either surface contaminated or volumetrically contaminated, or both, with varying amounts of radioactivity. Several options exist for the disposition of this RSM, including disposal as radioactive waste, recycling by decontamination and free-release for unrestricted use, or recycling for restricted reuse inside amore » DOE controlled area. The DOE Office of Science and Technology (EM-50) has been actively investing in technology and strategy development in support of restricted-reuse RSM recycling for the past several years. This paper will assess the nature of the RSM recycling issue, review past investment by DOE to develop technologies and strategies to recycle RSM, and then discuss some recommendations concerning future investments in support of RSM management. Available information on the supply of RSM will be presented in Section II. The regulatory and policy framework concerning recycling RSM will be presented in Section III. A review of DOE investment in RSM recycling technology and current programs will be presented in Section IV. The current and projected industrial capacity will be described in Section V. And, finally, a discussion of issues and recommendations regarding DOE technology development interests in RSM recycling will be presented in Section VI and VII, respectively.« less

Long-Term Results of Mandibular Distraction Osteogenesis with a Resorbable Device in Infants with Robin Sequence: Effects on Developing Molars and Mandibular Growth.

PubMed

Paes, Emma C; Bittermann, Gerhard K P; Bittermann, Dirk; Muradin, Marvick M; van Hogezand, Rose; Etty, Erika; Mink van der Molen, Aebele B; Kon, Moshe; Breugem, Corstiaan C

2016-02-01

Mandibular distraction osteogenesis with a unidirectional resorbable device is an effective treatment option for severe upper airway obstruction in infants with Robin sequence. Long-term effects, especially with regard to tooth development and mandibular outgrowth, are not known. Robin sequence infants with a follow-up of greater than or equal to 5 years were included. Baseline characteristics were extracted from medical records. Panoramic and lateral cephalometric radiographs were analyzed and patients were recalled for physical examination. Ten infants underwent mandibular distraction osteogenesis at a mean age of 3.7 months (median, 19 months; range, 11 days to 27 months). Mean length of follow-up was 6.8 years (range, 5.0 to 7.9 years). Ten Robin sequence infants without mandibular distraction osteogenesis (mean length of follow-up, 7.4 years; range, 6.7 to 8.9 years) were the controls. Shape anomalies, positional changes, and root malformations of molars were seen significantly more often than in the control group (p = 0.007, p = 0.009, and p = 0.043, respectively). Mandibular length was shorter (p = 0.030), but mandibular ramus height was comparable (p = 0.838) with that of the non-mandibular distraction osteogenesis group. Compared with healthy controls, all Robin sequence infants had a significantly shorter mandible. Mandibular distraction osteogenesis with a resorbable system reveals overall good short- and long-term results, but the effects on developing molars and mandibular outgrowth likely necessitate secondary procedures. This factor should be considered when deciding on treatment options and counseling of parents. Therapeutic, III.

The management of uterine fibroids in women with otherwise unexplained infertility.

PubMed

Carranza-Mamane, Belina; Havelock, Jon; Hemmings, Robert

2015-03-01

To provide recommendations regarding the best management of fibroids in couples who present with infertility. Usual and novel treatment options for fibroids will be reviewed with emphasis on their applicability in women who wish to conceive. Management of fibroids in women wishing to conceive first involves documentation of the presence of the fibroid and determination of likelihood of the fibroid impacting on the ability to conceive. Treatment of fibroids in this instance is primarily surgical, but must be weighed against the evidence of surgical management improving clinical outcomes, and risks specific to surgical management and approach. The outcomes of primary concern are the improvement in pregnancy rates and outcomes with management of fibroids in women with infertility. Published literature was retrieved through searches of PubMed, MEDLINE, the Cochrane Library in November 2013 using appropriate controlled vocabulary (e.g., leiomyoma, infertility, uterine artery embolization, fertilization in vitro) and key words (e.g., fibroid, myomectomy). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English and French. There were no date restrictions. Searches were updated on a regular basis and incorporated in the guideline to November 2013. Grey (unpublished literature) was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described by the Canadian Task Force on Preventive Health Care (Table). These recommendations are expected to allow adequate management of women with fibroids and infertility, maximizing their chances of pregnancy by minimizing risks introduced by unnecessary myomectomies. Reducing complications and eliminating unnecessary interventions are also expected to decrease costs to the health care system. Summary Statements 1. Subserosal fibroids do not appear to have an impact on fertility; the effect of intramural fibroids remains unclear. If intramural fibroids do have an impact on fertility, it appears to be small and to be even less significant when the endometrium is not involved. (II-3) 2. Because current medical therapy for fibroids is associated with suppression of ovulation, reduction of estrogen production, or disruption of the target action of estrogen or progesterone at the receptor level, and it has the potential to interfere in endometrial development and implantation, there is no role for medical therapy as a stand-alone treatment for fibroids in the infertile population. (III) 3. Preoperative assessment of submucosal fibroids is essential to the decision on the best approach for treatment. (III) 4. There is little evidence on the use of Foley catheters, estrogen, or intrauterine devices for the prevention of intrauterine adhesions following hysteroscopic myomectomy. (II-3) 5. In the infertile population, cumulative pregnancy rates by the laparoscopic and the minilaparotomy approaches are similar, but the laparoscopic approach is associated with a quicker recovery, less postoperative pain, and less febrile morbidity. (II-2) 6. There are lower pregnancy rates, higher miscarriage rates, and more adverse pregnancy outcomes following uterine artery embolization than after myomectomy. (II-3) Studies also suggest that uterine artery embolization is associated with loss of ovarian reserve, especially in older patients. (III) Recommendations 1. In women with infertility, an effort should be made to adequately evaluate and classify fibroids, particularly those impinging on the endometrial cavity, using transvaginal ultrasound, hysteroscopy, hysterosonography, or magnetic resonance imaging. (III-A) 2. Preoperative assessment of submucosal fibroids should include, in addition to an assessment of fibroid size and location within the uterine cavity, evaluation of the degree of invasion of the cavity and thickness of residual myometrium to the serosa. A combination of hysteroscopy and transvaginal ultrasound or hysterosonography are the modalities of choice. (III-B) 3. Submucosal fibroids are managed hysteroscopically. The fibroid size should be < 5 cm, although larger fibroids have been managed hysteroscopically, but repeat procedures are often necessary. (III-B) 4. A hysterosalpingogram is not an appropriate exam to evaluate and classify fibroids. (III-D)  5. In women with otherwise unexplained infertility, submucosal fibroids should be removed in order to improve conception and pregnancy rates. (II-2A) 6. Removal of subserosal fibroids is not recommended. (III-D) 7. There is fair evidence to recommend against myomectomy in women with intramural fibroids (hysteroscopically confirmed intact endometrium) and otherwise unexplained infertility, regardless of their size. (II-2D) If the patient has no other options, the benefits of myomectomy should be weighed against the risks, and management of intramural fibroids should be individualized. (III-C) 8. If fibroids are removed abdominally, efforts should be made to use an anterior uterine incision to minimize the formation of postoperative adhesions. (II-2A) 9. Widespread use of the laparoscopic approach to myomectomy may be limited by the technical difficulty of this procedure. Patient selection should be individualized based on the number, size, and location of uterine fibroids and the skill of the surgeon. (III-A) 10. Women, fertile or infertile, seeking future pregnancy should not generally be offered uterine artery embolization as a treatment option for uterine fibroids. (II-3E).

24 CFR 221.775 - Option period.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Option period. 221.775 Section 221.775 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued... § 221.775 Option period. The mortgagee may exercise its option to assign within one year following the...

Orthodontic decompensation in class III patients by means of distalization of upper molars.

PubMed

Carlos, Villegas B; Giovanni, Oberti; Diego, Rey; Angela, Sierra; Baccetti, Tiziano

2009-01-01

Pre-surgical orthodontic treatments have the objective of establishing harmony between the dental arches by moving the teeth to ideal positions in relation to their bony bases, in order to achieve adequate antero-posterior occlusal and transverse relationships at the moment of surgery. Among the typical requirements in terms of dental compensations presented by Class III patients that require surgery, the inclination of anterior teeth must be changed in most cases by proclination of the lower incisors and retroclination of upper incisors. To achieve the inclination of the upper incisors, many different alternatives have been proposed, such as inter-proximal reduction, extractions, or distalization of upper molars, which has not been widely reported in the literature as a means to decompensate Class III malocclusion prior to surgery. This article describes the Bone Supported Pendulum (BSP) as an efficient therapeutic option to distalize molars through the use of an appliance stabilized to the palate by mini-implants, thus avoiding extractions and providing good interdigitation and coordination of the dental arches.

Development and clinical applications of novel antibodies for prevention and treatment of respiratory syncytial virus infection.

PubMed

Mejias, Asuncion; Garcia-Maurino, Cristina; Rodriguez-Fernandez, Rosa; Peeples, Mark E; Ramilo, Octavio

2017-01-11

Respiratory syncytial virus (RSV) remains a significant cause of morbidity and mortality in infants and young children, immunocompromised patients and the elderly. Despite the high disease burden, an effective and safe vaccine is lacking, although several candidates are currently in development. Current treatment for RSV infection remains largely supportive and RSV-specific options for prophylaxis are limited to palivizumab. In the past few years, novel therapeutic options including nanobodies, polyclonal and monoclonal antibodies have emerged and there are several products in preclinical and Phase-I, -II or -III clinical trials. The major target for antiviral drug development is the surface fusion (F) glycoprotein, which is crucial for the infectivity and pathogenesis of the virus. Solving the structures of the two conformations of the RSV F protein, the prefusion and postfusion forms, has revolutionized RSV research. It is now known that prefusion F is highly superior in inducing neutralizing antibodies. In this section we will review the stages of development and availability of different antibodies directed against RSV for the prevention and also for treatment of acute RSV infections. Some of these newer anti-RSV agents have shown enhanced potency, are being explored through alternative routes of administration, have improved pharmacokinetic profiles with an extended half-life, and may reduce design and manufacturing costs. Management strategies will require targeting not only high-risk populations (including adults or immunocompromised patients), but also previously healthy children who, in fact, represent the majority of children hospitalized with RSV infection. Following treated patients longitudinally is essential for determining the impact of these strategies on the acute disease as well as their possible long-term benefits on lung morbidity. Copyright © 2016 Elsevier Ltd. All rights reserved.

RIGScan CR: RIGScan CR49.

PubMed

2004-01-01

RIGScan CR49, a 125I-labelled CR monoclonal antibody directed against the tumour-associated antigen TAG-72, is undergoing development with Neoprobe for the intraoperative detection of metastatic colorectal cancer. The Neoprobe's proprietary RIGS (radioimmunoguided surgery) technology combines an injectable radiolabelled cancer-targeting agent and hand-held radiation detection probe that emits an audible tone when located tissue has accumulated a significant amount of the radioactive agent. Neoprobe's RIGS technology also includes a patented surgical method providing surgeons with real-time information to locate tumour deposits that can not be detected by other conventional methods. The RIGS technology has been evaluated in late clinical studies for the detection of adenocarcinomas including primary colorectal, gastrointestinal, breast, ovarian, pancreatic, prostate and neuroendocrine/endocrine. Neoprobe signed an option agreement for its first-generation RIGScan compound, RIGScan CR, with OncoSurg Inc. (formerly NuRigs Ltd). The second-generation humanised RIGScan CR agent was also optionally licensed to OncoSurg Inc. In 1997, Neoprobe filed for approval with the US FDA and the EMEA for RIGScan CR for the intraoperative detection of metastatic colorectal cancer. Both regulatory agencies have requested additional clinical data. On 19 April 2004, Neoprobe announced that it had met with the US FDA to discuss its position on submitting additional clinical information in response to the FDA's questions regarding the Biologic Licence Application (BLA) for RIGScan CR49. The company provided the FDA with new information related to a survival differential for patients whose colorectal cancer was evaluated with RIGScan CR49. The information was not available at the time of the BLA's submission in 1997. The agency indicated that it would consider accepting survival data from one of the two phase III trials, NEO2-14, but not from another trial NEO2-13, as supportive data for a prognostic indication for colorectal cancer. The FDA also clarified that two well controlled studies were required for approval, and indicated that Neoprobe needed to complete an additional confirmatory phase III study for a prognostic indication in colorectal cancer. In its Annual Report 2002, Neoprobe stated that it had been working to secure a partner for further development of its proprietary RIGS technology. The company intends either to find a development partner or sell or licence out their RIGS assets if the partner is not found.

AVIATION SECURITY: Transportation Security Administration Faces Immediate and Long-Term Challenges

DTIC Science & Technology

2002-07-25

circumvent airport security , and provide whistleblower protection for air carrier and airport security workers. (See app. III for a summary of pending...GAO-01-1171T. Washington, D.C.: September 25, 2001. Aviation Security: Weaknesses in Airport Security and Options for Assigning Screening...125. Washington, D.C.: March 16, 2000. Aviation Security: FAA’s Actions to Study Responsibilities and Funding for Airport Security and to Certify

Applications of GIFTS III to Structural Engineering Problems.

DTIC Science & Technology

The paper describes the latest version of the GIFTS SYSTEM (Graphics Oriented Interactive Finite Element Package for Time-Sharing), due for release...at the end of March 1976. The paper gives a description of the program modules available in the GIFTS library and the options available within its...framework. Examples are given to demonstrate the use of GIFTS in design-oriented applications. Some performance measurements are included. Amongst the

Scalability of Robotic Controllers: An Evaluation of Controller Options-Experiment III

DTIC Science & Technology

2012-04-01

NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) U.S. Army Research Laboratory ATTN: RDRL- HRM -DW Aberdeen Proving Ground, MD 21005-5425...In this condition, the operator manually controlled all the robotic functions using a COTS Microsoft Xbox* 360 game controller (figure 3). The...Xbox is a trademark of Microsoft Corporation. 5 Figure 3. Game controller (GC/MC). 2.2.3.2 Virtual

Radiopharmaceuticals for imaging the heart

DOEpatents

Green, M.A.; Tsang, B.W.

1994-06-28

Radiopharmaceuticals for imaging myocardial tissues are prepared by forming lipophilic, cationic complexes of radioactive metal ions with metal chelating ligands comprising the Schiff base adducts of triamines and tetraamines with optionally substituted salicylaldehydes. The lipophilic, cationic, radioactive complexes of the invention exhibit high uptake and retention in myocardial tissues. Preferred gallium-68(III) complexes in accordance with this invention can be used to image the heart using positron emission tomography. 6 figures.

[Standards, options, and recommendations for initial management of patients with malignant ovarian epithelial tumors].

PubMed

Kerbrat, P; Lhommé, C; Fervers, B; Guastalla, J P; Thomas, L; Basuyau, J P; Duvillard, P; Cohen-Solal, C; Dauplat, J; Tournemaine, N

2000-12-09

Suprapubic and transvaginal pelvic ultrasound exploration is indicated for suspected ovarian tumor (standard). Diagnosis and search for extension require surgery and pathology examination. Systematic preoperative computed tomography is not recommended (standard). Surgery for cancer of the ovary is a specialized procedure requiring skill in cancer, gynecology, visceral surgery and laparoscopic surgery. If the patient is referred to a specialized center after a primary procedure considered to be inadequate, a new procedure is recommended for staging. Residual tumor volume after the primary procedure has prognostic value. Systematic second look procedures are not recommended for routine practice (standard). For patients with grade IA G1 tumors, there is no indication for complementary treatment (standard). For patients with grade IA G2-3 or clear cell tumors, IB, IC, IIA, there is no standard. no complementary treatment, complementary chemotherapy using platinum, complementary external abdominopelvic radiotherapy. A complementary treatment is recommended for grades IC and IIA. Complementary treatment for grades IIB (no residual tissue), IIC (with residual tissue), III (no residual tissue), is based on: complementary chemotherapy with platinium, complementary external abdominopelvic radiotherapy (options). Complementary treatment for advanced forms (IIB (with residual tissue), IIC (with residual tissue), III (with residual tissue) and IV) is based on polychemotherapy with platinium (standard). platinium combined with paclitaxel (intravenous), platinium combined with cyclophosphamide and/or doxorubicin (intravenous) or intraperitoneal cisplatin combined with cyclophosphamide (intravenous). The chemotherapy work-up includes physical examination, assay of serum markers (particularly CA125) and abdominopelvic computed tomography (proof level B) (standard). Physical examination is recommended for monitoring patients in complete remission with no sign of suspected recurrence (standard). This document was reviewed in April 1977. The working group again validated the Standards, OPTIONS and Recommendations, without modifications in June 1999.

Treatment in Borderline Class III Malocclusion: Orthodontic Camouflage (Extraction) Versus Orthognathic Surgery

PubMed Central

Rabie, A-Bakr M.; Wong, Ricky W.K.; Min, G.U.

2008-01-01

Aims: To investigate the differences in morphological characteristics of borderline class III patients who had undergone camouflage orthodontic treatment or orthognathic surgery, and to compare the treatment effects between these two modalities. Materials and Methods: Cephalograms of 25 patients (13 orthodontic, 12 surgical) with class III malocclusion were analyzed. All had a pretreatment ANB angle greater than -5º. Results: Using discriminant analysis, only Holdaway angle was selected to differentiate patients in the pretreatment stage. Seventy-two per cent patients were correctly classified. In the orthodontic group, reverse overjet was corrected by retraction of the lower incisors and downward and backward rotation of the mandible. The surgical group was corrected by setback of the lower anterior dentoalveolus and uprighting of the lower incisors. No difference was found in posttreatment soft tissue measurements between the two groups. Conclusions: Twelve degree for the Holdaway angle can be a guideline in determining the treatment modalities for borderline class III patients, but the preferences of operators and patients are also important. (2) Both therapeutic options should highlight changes in the lower dentoalveolus and lower incisors. (3) Both treatment modalities can achieve satisfactory improvements to the people. PMID:19088881

Avanafil for the treatment of erectile dysfunction: initial data and clinical key properties.

PubMed

Kedia, George T; Uckert, Stefan; Assadi-Pour, Farhang; Kuczyk, Markus A; Albrecht, Knut

2013-02-01

Orally active, selective inhibitors of phosphodiesterase type 5 (PDE 5, cyclic GMP PDE), such as sildenafil, tadalafil and vardenafil, are currently the first-choice treatment options for the clinical management of erectile dysfunction (ED) of various etiologies and severities. However, a significant number of patients remain dissatisfied with the available therapies due a lack of efficacy or discomfort arising from adverse events. Several new PDE5 inhibitors, among which are avanafil (TA-1790), lodenafil, mirodenafil, udenafil, SLX-2101, JNJ-10280205 and JNJ-10287069, have recently been approved and introduced into the market or are in the final stages of their clinical development. Avanafil (marketed in the US under the brand name STENDRA(™)) has been developed by VIVUS Inc. (Mountain View, CA, USA) and has recently received approval from the US Food and Drug Administration (FDA) for use in the treatment of male ED. The drug has demonstrated improved selectivity for PDE5, is rapidly absorbed after oral administration with a fast onset of action and a plasma half-life that is comparable to sildenfil and vardenafil. In phase II and phase III clinical trials that included a large number of patients, avanafil has been shown to be effective and well tolerated. Owing to its favorable pharmacodynamic and pharmacokinetic profile, avanafil is considered as a promising new option in the treatment of ED. The present article summarizes the initial data and clinical key properties of avanafil.

Avanafil for the treatment of erectile dysfunction: initial data and clinical key properties

PubMed Central

Ückert, Stefan; Assadi-Pour, Farhang; Kuczyk, Markus A.; Albrecht, Knut

2013-01-01

Orally active, selective inhibitors of phosphodiesterase type 5 (PDE 5, cyclic GMP PDE), such as sildenafil, tadalafil and vardenafil, are currently the first-choice treatment options for the clinical management of erectile dysfunction (ED) of various etiologies and severities. However, a significant number of patients remain dissatisfied with the available therapies due a lack of efficacy or discomfort arising from adverse events. Several new PDE5 inhibitors, among which are avanafil (TA-1790), lodenafil, mirodenafil, udenafil, SLX-2101, JNJ-10280205 and JNJ-10287069, have recently been approved and introduced into the market or are in the final stages of their clinical development. Avanafil (marketed in the US under the brand name STENDRA™) has been developed by VIVUS Inc. (Mountain View, CA, USA) and has recently received approval from the US Food and Drug Administration (FDA) for use in the treatment of male ED. The drug has demonstrated improved selectivity for PDE5, is rapidly absorbed after oral administration with a fast onset of action and a plasma half-life that is comparable to sildenfil and vardenafil. In phase II and phase III clinical trials that included a large number of patients, avanafil has been shown to be effective and well tolerated. Owing to its favorable pharmacodynamic and pharmacokinetic profile, avanafil is considered as a promising new option in the treatment of ED. The present article summarizes the initial data and clinical key properties of avanafil. PMID:23372609

The New Era of Interferon-Free Treatment of Chronic Hepatitis C

PubMed Central

Solbach, Philipp; Wedemeyer, Heiner

2015-01-01

Summary Background Within the development and approval of several new direct-acting antivirals (DAA) against hepatitis C virus (HCV), a new era of hepatitis C therapy has begun. Even more treatment options are likely to become available during the next 1-2 years. Methods A summary of the current phase II and III trials investigating DAA and a review of the recent HCV guidelines was conducted. Results With the development of new potent DAA and the approval of different DAA combinations, cure rates of HCV infection of >90% are achievable for almost all HCV genotypes and stages of liver disease. Currently available DAA target different steps in the HCV replication cycle, in particular the NS3/4A protease, the NS5B polymerase, and the NS5A replication complex. Treatment duration varies between 8 and 24 weeks depending on the stage of fibrosis, prior treatment, HCV viral load, and HCV genotype. Ribavirin is required only for some treatment regimens and may be particularly beneficial in patients with cirrhosis. DAA resistance influences treatment outcome only marginally; thus, drug resistance testing is not routinely recommended before treatment. In the case of treatment failure, however, resistance testing should be performed before re-treatment with other DAA is initiated. Conclusion With the new, almost side effect-free DAA treatment options chronic HCV infection became a curable disease. The clinical benefit of DAA combination therapies in patients with advanced cirrhosis and the effects on incidence rates of hepatocellular carcinoma remain to be determined. PMID:26557839

The Role of New Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia

PubMed Central

Pophali, Priyanka A.; Patnaik, Mrinal M.

2015-01-01

Imatinib mesylate was the first tyrosine kinase inhibitor (TKI) approved for the management of chronic myeloid leukemia (CML). Imatinib produces acceptable responses in ~ 60% of patients; with ~20% discontinuing therapy due to intolerance and ~20% developing drug resistance. The advent of newer TKIs’ such as, nilotinib, dasatinib, bosutinib and ponatinib have provided multiple options for patients. These agents are more potent, have unique side effect profiles and are more likely to achieve relevant milestones such as, early molecular responses (3-6 months) and optimal molecular responses (12 months). The acquisition of BCR-ABL kinase domain mutations is also reportedly lower with these drugs. Thus far, none of the randomized phase III clinical trials have shown a clinically significant survival difference between frontline imatinib versus newer TKIs’. Cost and safety issues with the newer TKIs’ such as, vascular disease with nilotinib and ponatinib and pulmonary hypertension with dasatinib have dampened the enthusiasm of using these drugs as frontline options. While the utility of new TKIs’ in the setting of imatinib failure or intolerance is clear, their use as frontline agents should factor in the age of the patient, additional comorbidities, risk stratification (Sokal score) and cost. Combination therapies and newer agents with potential to eradicate quiescent CML stem cells offer future hope. PMID:26841016

Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011)

PubMed Central

Averbuch, Diana; Cordonnier, Catherine; Livermore, David M.; Mikulska, Małgorzata; Orasch, Christina; Viscoli, Claudio; Gyssens, Inge C.; Kern, Winfried V.; Klyasova, Galina; Marchetti, Oscar; Engelhard, Dan; Akova, Murat

2013-01-01

The detection of multi-resistant bacterial pathogens, particularly those to carbapenemases, in leukemic and stem cell transplant patients forces the use of old or non-conventional agents as the only remaining treatment options. These include colistin/polymyxin B, tigecycline, fosfomycin and various anti-gram-positive agents. Data on the use of these agents in leukemic patients are scanty, with only linezolid subjected to formal trials. The Expert Group of the 4th European Conference on Infections in Leukemia has developed guidelines for their use in these patient populations. Targeted therapy should be based on (i) in vitro susceptibility data, (ii) knowledge of the best treatment option against the particular species or phenotype of bacteria, (iii) pharmacokinetic/pharmacodynamic data, and (iv) careful assessment of the risk-benefit balance. For infections due to resistant Gram-negative bacteria, these agents should be preferably used in combination with other agents that remain active in vitro, because of suboptimal efficacy (e.g., tigecycline) and the risk of emergent resistance (e.g., fosfomycin). The paucity of new antibacterial drugs in the near future should lead us to limit the use of these drugs to situations where no alternative exists. PMID:24323984

Clinical trials as treatment option: bioethics and health care disparities in substance dependency.

PubMed

Timmermans, Stefan; McKay, Tara

2009-12-01

Bioethicists have warned against the dangers of mixing research with treatment. They are concerned that research priorities may take precedence over individual patient needs and that research subjects tend to misunderstand the purpose of research or overestimate the direct medical benefits of participating in studies. Yet, other work has questioned whether clinical research can always be separated from therapeutic benefit for participants. Using in-depth interviews with participants in two phase III randomized U.S. clinical trials for methamphetamine dependency, we examine the treatment options available to participants, their experiences with participating in the trials, and potential problems of trial participation. We find that while participants have experience with four alternative treatment modalities - quitting alone, support groups, in-patient treatment facilities, and consulting primary care physicians - the randomized clinical trials compare favorably to alternatives because they provide access to evidence-based behavioral treatments, specialized medical professionals, non-judgmental staff, and the possibility of receiving an experimental drug. We conclude that while randomized clinical trials are imperfect substitutes for clinical care, they constitute a fragile and sporadic therapeutic niche in a country with fundamental problems in access to health care, a mixed punitive-therapeutic drug addiction policy, and a profit-driven pharmaceutical development and approval process.

Antiangiogenic treatment in hepatocellular carcinoma: the balance of efficacy and safety

PubMed Central

Welker, Martin-Walter; Trojan, Joerg

2013-01-01

Hepatocellular carcinoma (HCC) is a severe complication of advanced liver disease with a worldwide incidence of more than 600,000 patients per year. Liver function, clinical performance status, and tumor size are considered in the Barcelona Clinic Liver Cancer (BCLC) system. While curative treatment options are available for early stages, most patients present with intermediate- or advanced-stage HCC, burdened with a poor prognosis, substantially influenced by the degree of liver-function impairment. Hypervascularization is a major characteristic of HCC, and antiangiogenic treatments are the basis of treatment in noncurative stages, including interventional and pharmacological treatments. Currently, the tyrosine-kinase inhibitor sorafenib is still the only approved drug for HCC. Further improvements in survival in patients with intermediate- and advanced-stage HCC may be anticipated by both multimodal approaches, such as combination of interventional and systemic treatments, and new systemic treatment options. Until now, the Phase III development of other tyrosine-kinase inhibitors in patients with advanced HCC has failed due to minor efficacy and/or increased toxicity compared to sorafenib. However, promising Phase II data have been reported with MET inhibitors in this hard-to-treat population. This review gives a critical overview of antiangiogenic drugs and strategies in intermediate- and advanced-stage HCC, with a special focus on safety. PMID:24204170

Soluble Mesothelin Related Peptide (SMRP) and Osteopontin (OPN) as Early Detection Markers for Malignant Mesothelioma (MM) — EDRN Public Portal

Cancer.gov

Phase I: - Identification and assemblage of representative cohorts of individuals with MM, no malignancies but increased risk for MM due to asbestos exposure, and (optionally) lung malignancies other than MM Phase II (A) - Determine the sensitivity and specificity of SMRP and OPN in distinguishing individuals with a clinical diagnosis of malignant mesothelioma from individuals who are asbestos-exposed but without a clinical diagnosis of malignant mesothelioma. Phase II (B) – Determine the comparability of analyte values across contributing centers and determine covariates that influence analyte levels Phase II (C) – Determine the sensitivity and specificity of SMRP and OPN, alone and in combination, in distinguishing individuals with MM from those without. Phase III. Determine the sensitivity and specificity of SMRP and OPN in distinguishing individuals who would subsequently develop malignant mesothelioma from matched individuals who did not subsequently develop malignant mesothelioma. Phase IV. Determine the sensitivity and specificity of SMRP and OPN in other populations of interest.

Design, synthesis and evaluation of MCH receptor 1 antagonists--Part III: Discovery of pre-clinical development candidate BI 186908.

PubMed

Oost, Thorsten; Heckel, Armin; Kley, Jörg T; Lehmann, Thorsten; Müller, Stephan; Roth, Gerald J; Rudolf, Klaus; Arndt, Kirsten; Budzinski, Ralph; Lenter, Martin; Lotz, Ralf R H; Maier, Gerd-Michael; Markert, Michael; Thomas, Leo; Stenkamp, Dirk

2015-08-15

Although overweight and obesity are highly prevalent conditions, options to treat them are still very limited. As part of our search for safe and effective MCH-R1 antagonists for the treatment of obesity, two series of pyridones and pyridazinones were evaluated. Optimization was aimed at improving DMPK properties by increasing metabolic stability and improving the safety profile by reducing inhibition of the hERG channel and reducing the potential to induce phospholipidosis. Steric shielding of a labile keto moiety with an ortho-methyl group and fine-tuning of the polarity in several parts of the molecule resulted in BI 186908 (11 g), a potent and selective MCH-R1 antagonist with favorable DMPK and CMC properties. Chronic administration of BI 186908 resulted in significant body weight reduction comparable to sibutramine in a 4 week diet-induced obesity model in rats. Based on its favorable safety profile, BI 186908 was advanced to pre-clinical development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Safety and clinical efficacy of everolimus in the treatment of advanced renal cell carcinoma (RCC)

PubMed Central

Shahani, Rohan; Kwan, Kevin G; Kapoor, Anil

2010-01-01

Renal cell carcinoma (RCC) is one of the most lethal genitourinary malignancies. Recently, there has been a paradigm shift in the management of advanced RCC. New targeted therapies including vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors have been developed which have shown promising results in a patient population who otherwise had very few options for treatment. The first mTOR inhibitor, temsirolimus, an intravenous prodrug, has shown improved overall survival in poor prognosis patients. More recently, an oral mTOR inhibitor, everolimus (RAD 001), has been developed which has been shown to delay disease progression in patients with metastatic RCC who have progressed on other targeted therapies. Although a survival advantage in phase III trials is seen with everolimus, associated systemic toxicities, while generally well tolerated, are not insignificant. These include mucositis, hyperglycemia, hyperlipidemia, and pneumonitis. Despite the side effects, emerging evidence points to everolimus as the optimal second-line treatment for patients with advanced renal cell carcinoma. PMID:21701620

New Aspects in the Differential Diagnosis and Therapy of Bladder Pain Syndrome/Interstitial Cystitis

PubMed Central

Neuhaus, Jochen; Schwalenberg, Thilo; Horn, Lars-Christian; Alexander, Henry; Stolzenburg, Jens-Uwe

2011-01-01

Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical “columns”: (i) clinical diagnostics, (ii) histopathology, and (iii) molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC. PMID:22028706

New aspects in the differential diagnosis and therapy of bladder pain syndrome/interstitial cystitis.

PubMed

Neuhaus, Jochen; Schwalenberg, Thilo; Horn, Lars-Christian; Alexander, Henry; Stolzenburg, Jens-Uwe

2011-01-01

Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical "columns": (i) clinical diagnostics, (ii) histopathology, and (iii) molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC.

A combined model to assess technical and economic consequences of changing conditions and management options for wastewater utilities.

PubMed

Giessler, Mathias; Tränckner, Jens

2018-02-01

The paper presents a simplified model that quantifies economic and technical consequences of changing conditions in wastewater systems on utility level. It has been developed based on data from stakeholders and ministries, collected by a survey that determined resulting effects and adapted measures. The model comprises all substantial cost relevant assets and activities of a typical German wastewater utility. It consists of three modules: i) Sewer for describing the state development of sewer systems, ii) WWTP for process parameter consideration of waste water treatment plants (WWTP) and iii) Cost Accounting for calculation of expenses in the cost categories and resulting charges. Validity and accuracy of this model was verified by using historical data from an exemplary wastewater utility. Calculated process as well as economic parameters shows a high accuracy compared to measured parameters and given expenses. Thus, the model is proposed to support strategic, process oriented decision making on utility level. Copyright © 2017 Elsevier Ltd. All rights reserved.

Thermodynamic database for proteins: features and applications.

PubMed

Gromiha, M Michael; Sarai, Akinori

2010-01-01

We have developed a thermodynamic database for proteins and mutants, ProTherm, which is a collection of a large number of thermodynamic data on protein stability along with the sequence and structure information, experimental methods and conditions, and literature information. This is a valuable resource for understanding/predicting the stability of proteins, and it can be accessible at http://www.gibk26.bse.kyutech.ac.jp/jouhou/Protherm/protherm.html . ProTherm has several features including various search, display, and sorting options and visualization tools. We have analyzed the data in ProTherm to examine the relationship among thermodynamics, structure, and function of proteins. We describe the progress on the development of methods for understanding/predicting protein stability, such as (i) relationship between the stability of protein mutants and amino acid properties, (ii) average assignment method, (iii) empirical energy functions, (iv) torsion, distance, and contact potentials, and (v) machine learning techniques. The list of online resources for predicting protein stability has also been provided.

Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 3: Endoscopic computer-assisted electromagnetic navigation and ultrasonography as technical adjuvants for shunt placement.

PubMed

Flannery, Ann Marie; Duhaime, Ann-Christine; Tamber, Mandeep S; Kemp, Joanna

2014-11-01

This systematic review was undertaken to answer the following question: Do technical adjuvants such as ventricular endoscopic placement, computer-assisted electromagnetic guidance, or ultrasound guidance improve ventricular shunt function and survival? The US National Library of Medicine PubMed/MEDLINE database and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words specifically chosen to identify published articles detailing the use of cerebrospinal fluid shunts for the treatment of pediatric hydrocephalus. Articles meeting specific criteria that had been delineated a priori were then examined, and data were abstracted and compiled in evidentiary tables. These data were then analyzed by the Pediatric Hydrocephalus Systematic Review and Evidence-Based Guidelines Task Force to consider evidence-based treatment recommendations. The search yielded 163 abstracts, which were screened for potential relevance to the application of technical adjuvants in shunt placement. Fourteen articles were selected for full-text review. One additional article was selected during a review of literature citations. Eight of these articles were included in the final recommendations concerning the use of endoscopy, ultrasonography, and electromagnetic image guidance during shunt placement, whereas the remaining articles were excluded due to poor evidence or lack of relevance. The evidence included 1 Class I, 1 Class II, and 6 Class III papers. An evidentiary table of relevant articles was created. CONCLUSIONS/RECOMMENDATION: There is insufficient evidence to recommend the use of endoscopic guidance for routine ventricular catheter placement. Level I, high degree of clinical certainty. The routine use of ultrasound-assisted catheter placement is an option. Level III, unclear clinical certainty. The routine use of computer-assisted electromagnetic (EM) navigation is an option. Level III, unclear clinical certainty.

The management of patients with limited-stage classical Hodgkin lymphoma.

PubMed

Gospodarowicz, Mary K; Meyer, Ralph M

2006-01-01

The term limited-stage Hodgkin lymphoma refers to those patients with stage I-II disease and an absence of bulky disease. Among those patients with classical Hodgkin lymphoma, approximately one-third of patients will fall into this category. As long-term disease control can now be anticipated in more than 90% of these patients, management strategies must increasingly address the need to reduce the long-term treatment-related risks. Current treatment options include use of combined modality therapy that includes an abbreviated course of chemotherapy and involved-field radiation or treatment with chemotherapy, currently consisting of ABVD, as a single modality. The choice of treatment between these two options involves specific trade-offs that must balance issues of disease control against long-term risk of late effects.

A real options approach to biotechnology investment policy-the case of developing a Campylobacter vaccine to poultry.

PubMed

Lund, Mogens; Jensen, Jørgen Dejgård

2016-06-01

The aim of the article is to identify and analyse public-private incentives for the development and marketing of new animal vaccines within a real options methodological framework, and to investigate how real options methodology can be utilized to support economic incentives for vaccine development in a cost-effective way. The development of a vaccine against Campylobacter jejuni in poultry is applied as a case study. Employing the real options methodology, the net present value of the vaccine R&D project becomes larger than a purely probabilistic expected present value throughout the different stages of the project - and the net present value becomes larger, when more types of real options are taken into consideration. The insight from the real options analysis reveals opportunities for new policies to promote the development of animal vaccines. One such approach might be to develop schemes combining stage-by-stage optimized subsidies in the individual development stages, with proper account taken of investors'/developers' economic incentives to proceed, sell or cancel the project in the respective stages. Another way of using the real options approach to support the development of desirable animal vaccines could be to issue put options for the vaccine candidate, enabling vaccine developers to hedge against the economic risk from market volatility. Copyright © 2016 Elsevier B.V. All rights reserved.

Intra-tumoral gene delivery of feIL-2, feIFN-gamma and feGM-CSF using magnetofection as a neoadjuvant treatment option for feline fibrosarcomas: a phase-I study.

PubMed

Jahnke, A; Hirschberger, J; Fischer, C; Brill, T; Köstlin, R; Plank, C; Küchenhoff, H; Krieger, S; Kamenica, K; Schillinger, U

2007-12-01

Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have a high relapse rate. In this study, a new treatment option based on immune stimulation by intra-tumoral delivery of three feline cytokine genes was performed. The objective of this phase-I dose-escalation study was to determine a safe dose for further evaluation in a subsequent phase-II trial. Twenty-five client-owned cats with clinical diagnosis of fibrosarcoma - primary tumours as well as recurrences - entered the study. Four increasing doses of plasmids coding for feIL-2, feIFN-gamma or feGM-CSF, respectively, were previously defined. In groups I, II, III and IV these doses were 15, 50, 150 and 450 microg per plasmid and a corresponding amount of magnetic nanoparticles. Two preoperative intra-tumoral injections of the magnetic DNA solution were followed by magnetofection. A group of four control cats received only surgical treatment. Side effects were registered and graded according to the VCOG-CTCAE scale and correlated to treatment. Statistical analyses included one-way anova, post hoc and Kruskal-Wallis tests. ELISA tests detecting plasma feIFN-gamma and plasma feGM-CSF were performed. One cat out of group IV (450 microg per plasmid) showed adverse events probably related to gene delivery. As these side effects were self-limiting and occurred only in one of eight cats in group IV, this dose was determined to be well tolerable. Altogether six cats developed local recurrences during a 1-year observation period. Four of these cats had been treated with dose IV. Regarding these observations, a subsequent phase-II trial including a representative amount of cats should be tested for the efficacy of dose IV as well as dose III.

Utility of the AAOS Appropriate Use Criteria (AUC) for Pediatric Supracondylar Humerus Fractures in Clinical Practice.

PubMed

Ibrahim, Talal; Hegazy, Abdelsalam; Abulhail, Safa I S; Ghomrawi, Hassan M K

2017-01-01

The American Academy of Orthopaedic Surgeons (AAOS) recently developed an Appropriate Use Criteria (AUC) for pediatric supracondylar humerus fractures (PSHF). The AUC is intended to improve quality of care by informing surgeon decision making. The aim of our study was to cross-reference the management of operatively treated PSHF with the AAOS-published AUC. The AUC for PSHF include 220 patient scenarios, based on different combinations of 6 factors. For each patient scenario, 8 treatment options are evaluated as "appropriate," "maybe appropriate," and "rarely appropriate." We retrospectively reviewed the medical charts and radiographs of all operatively treated PSHF at our hospital from January 2013 to December 2014 and determined the appropriateness of the treatment. Over the study period, 94 children (mean age: 5.2 y; 51 male, 43 female) were admitted with PSHF and underwent a surgical procedure (type IIA: 7, type IIB: 14, type III: 70, flexion type: 3). Only 8 of the 220 scenarios were observed in our patient cohort. The most frequent scenario was represented by a type III fracture, palpable distal pulse, no nerve injury, closed soft-tissue envelope, no radius/ulna fracture, and typical swelling. Of the 94 fractures, the AUC was "appropriate" for 84 cases and "maybe appropriate" for 9 cases. There was only 1 case of "rarely appropriate" management. Closed reduction with lateral pinning and immobilization was the most prevalent treatment option (58.5%). The rate of appropriateness was not affected by the operating surgeon. However, the definition of a case as emergent had a significant impact on the rate of appropriateness. Application of the AUC to actual clinical data was relatively simple. The majority of operatively treated PSHF (89.4%) were managed appropriately. With the introduction of electronic medical charts, an AUC application becomes attractive and easy for orthopaedic surgeons to utilize in clinical practice. However, validity studies of the AUC in different clinical settings are still required. Level IV.

DRUMS: Disk Repository with Update Management and Select option for high throughput sequencing data.

PubMed

Nettling, Martin; Thieme, Nils; Both, Andreas; Grosse, Ivo

2014-02-04

New technologies for analyzing biological samples, like next generation sequencing, are producing a growing amount of data together with quality scores. Moreover, software tools (e.g., for mapping sequence reads), calculating transcription factor binding probabilities, estimating epigenetic modification enriched regions or determining single nucleotide polymorphism increase this amount of position-specific DNA-related data even further. Hence, requesting data becomes challenging and expensive and is often implemented using specialised hardware. In addition, picking specific data as fast as possible becomes increasingly important in many fields of science. The general problem of handling big data sets was addressed by developing specialized databases like HBase, HyperTable or Cassandra. However, these database solutions require also specialized or distributed hardware leading to expensive investments. To the best of our knowledge, there is no database capable of (i) storing billions of position-specific DNA-related records, (ii) performing fast and resource saving requests, and (iii) running on a single standard computer hardware. Here, we present DRUMS (Disk Repository with Update Management and Select option), satisfying demands (i)-(iii). It tackles the weaknesses of traditional databases while handling position-specific DNA-related data in an efficient manner. DRUMS is capable of storing up to billions of records. Moreover, it focuses on optimizing relating single lookups as range request, which are needed permanently for computations in bioinformatics. To validate the power of DRUMS, we compare it to the widely used MySQL database. The test setting considers two biological data sets. We use standard desktop hardware as test environment. DRUMS outperforms MySQL in writing and reading records by a factor of two up to a factor of 10000. Furthermore, it can work with significantly larger data sets. Our work focuses on mid-sized data sets up to several billion records without requiring cluster technology. Storing position-specific data is a general problem and the concept we present here is a generalized approach. Hence, it can be easily applied to other fields of bioinformatics.

Agricultural waste utilisation strategies and demand for urban waste compost: Evidence from smallholder farmers in Ethiopia.

PubMed

Nigussie, Abebe; Kuyper, Thomas W; de Neergaard, Andreas

2015-10-01

The use of agricultural waste for soil amendment is limited in developing countries. Competition between fuel and feed is the major cause for the insufficient application of agricultural waste on cropland. The aims of this study were therefore (i) to investigate variation in agricultural waste allocation between groups of farmers with different livelihood strategies and link this allocation with the nutrient balances of their production systems, (ii) to identify farm characteristics that influence utilisation of agricultural waste for soil amendment, and (iii) to assess demand for urban waste compost. A total of 220 farmers were selected randomly and interviewed using standardised semi-structured questionnaires. Four groups of farmers, namely (i) field crop farmers, (ii) vegetable producers, (iii) ornamental-plant growers, and (iv) farmers practising mixed farming, were identified using categorical principal component and two-step cluster analyses. Field crop farmers produced the largest quantity of agricultural waste, but they allocated 80% of manure to fuel and 85% of crop residues to feed. Only <10% of manure and crop residues were applied on soils. Farmers also sold manure and crop residues, and this generated 5-10% of their annual income. Vegetable and ornamental-plant growers allocated over 40% of manure and crop residues to soil amendment. Hence, nutrient balances were less negative in vegetable production systems. Education, farm size, land tenure and access to extension services were the variables that impeded allocation of agricultural waste to soil amendment. Replacement of fuel and feed through sustainable means is a viable option for soil fertility management. Urban waste compost should also be used as alternative option for soil amendment. Our results showed variation in compost demand between farmers. Education, landownership, experience with compost and access to extension services explained variation in compost demand. We also demonstrated that labour availability should be used to estimate compost demand beside cash. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enobosarm (GTx-024, S-22): a potential treatment for cachexia.

PubMed

Srinath, Reshmi; Dobs, Adrian

2014-02-01

Muscle loss and wasting occurs with aging and in multiple disease states including cancer, heart failure, chronic obstructive pulmonary disease, end-stage liver disease, end-stage renal disease and HIV. Cachexia is defined as a multifactorial syndrome that is associated with anorexia, weight loss and increased catabolism, with increased morbidity and mortality. Currently no therapy is approved for the treatment or prevention of cachexia. Different treatment options have been suggested but many have proven to be ineffective or associated with adverse events. Nonsteroidal selective androgen receptor modulators (SARMs) are a new class of anabolic agents that bind the androgen receptor and exhibit tissue selectivity. Enobosarm (GTx-024, S-22) is a recently developed SARM, developed by GTx, Inc. (TN, USA), which has been tested in Phase I, II and III trials with promising results in terms of improving lean body mass and measurements of physical function and power. Enobosarm has received fast track designation by the US FDA and results from the Phase III trials POWER1 and POWER2 will help determine approval for use in the prevention and treatment of muscle wasting in patients with non-small-cell lung cancer. This article provides an introduction to enobosarm as a new therapeutic strategy for the prevention and treatment of cachexia. A review of the literature was performed using search terms 'cachexia', 'sarcopenia', 'SARM', 'enobosarm' and 'GTx-024' in September 2013 using multiple databases as well as online resources.

Class III HD-Zip activity coordinates leaf development in Physcomitrella patens.

PubMed

Yip, Hoichong Karen; Floyd, Sandra K; Sakakibara, Keiko; Bowman, John L

2016-11-01

Land plant bodies develop from meristems, groups of pluripotent stem cells, which may persist throughout the life of a plant or, alternatively, have a transitory existence. Early diverging land plants exhibit indeterminate (persistent) growth in their haploid gametophytic generation, whereas later diverging lineages exhibit indeterminate growth in their diploid sporophytic generation, raising the question of whether genetic machinery directing meristematic functions was co-opted between generations. Class III HD-Zip (C3HDZ) genes are required for the establishment and maintenance of shoot apical meristems in flowering plants. We demonstrate that in the moss Physcomitrella patens, C3HDZ genes are expressed in transitory meristems in both the gametophytic and sporophytic generations, but not in the persistent shoot meristem of the gametyphyte. Loss-of-function of P. patens C3HDZ was engineered using ectopic expression of miR166, an endogenous regulator of C3HDZ gene activity. Loss of C3HDZ gene function impaired the function of gametophytic transitory meristematic activity but did not compromise the functioning of the persistent shoot apical meristem during the gametophyte generation. These results argue against a wholesale co-option of meristematic gene regulatory networks from the gametophyte to the sporophyte during land plant evolution, instead suggesting that persistent meristems with a single apical cell in P. patens and persistent complex meristems in flowering plants are regulated by different genetic programs. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma

PubMed Central

Trojan, Jörg; Waidmann, Oliver

2016-01-01

Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC. PMID:27703962

Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma.

PubMed

Trojan, Jörg; Waidmann, Oliver

2016-01-01

Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC.

A Future Vision for Remotely Piloted Aircraft: Leveraging Interoperability and Networked Operations

DTIC Science & Technology

2013-06-21

over the next 25 years  Balances the effects envisioned in the USAF UAS Flight Plan with the reality of constrained resources and ambitious...theater-level unmanned systems must detect, avoid, or counter threats – operating from permissive to highly contested access in all weather...Rapid Reaction Group II/III SUAS Unit  Light Footprint, Low Cost ISR Option  Networked Autonomous C2 System  Air-Launched SUAS  Common

76 FR 44636 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-26

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-64930; File No. SR-CBOE-2011-066] Self... Improvement Mechanism July 20, 2011. Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934 (the...(b)(1). \\2\\ 17 CFR 240.19b-4. \\3\\ 15 U.S.C. 78s(b)(3)(A)(iii). \\4\\ 17 CFR 240.19b-4(f)(6). I. Self...

76 FR 44635 - Self-Regulatory Organizations; C2 Options Exchange, Incorporated; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-26

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-64929; File No. SR-C2-2011-015] Self-Regulatory... Rule Change To Extend a Pilot Program Related to the Exchange's Automated Improvement Mechanism July 20...(b)(1). \\2\\ 17 CFR 240.19b-4. \\3\\ 15 U.S.C. 78s(b)(3)(A)(iii). \\4\\ 17 CFR 240.19b-4(f)(6). I. Self...

I-III-VI.sub.2 based solar cell utilizing the structure CuInGaSe.sub.2 CdZnS/ZnO

DOEpatents

Chen, Wen S.; Stewart, John M.

1992-01-07

A thin film I-III-VI.sub.2 based solar cell having a first layer of copper indium gallium selenide, a second layer of cadmium zinc sulfide, a double layer of zinc oxide, and a metallization structure comprised of a layer of nickel covered by a layer of aluminum. An optional antireflective coating may be placed on said metallization structure. The cadmium zinc sulfide layer is deposited by means of an aqueous solution growth deposition process and may actually consist of two layers: a low zinc content layer and a high zinc content layer. Photovoltaic efficiencies of 12.5% at Air Mass 1.5 illumination conditions and 10.4% under AMO illumination can be achieved.

Alectinib for treatment of ALK-positive non-small-cell lung cancer.

PubMed

Avrillon, Virginie; Pérol, Maurice

2017-02-01

Alectinib is a highly selective second-generation ALK inhibitor that is active against most crizotinib ALK resistance mutations, with a good penetration in CNS and a good safety profile. Thanks to the positive results of Phase II trials, alectinib was approved in Japan and by the US FDA for ALK-positive non-small-cell lung cancer (NSCLC) patients pretreated with crizotinib. Recently, the Phase III J-ALEX study demonstrated superiority of alectinib over crizotinib in crizotinib naive ALK-positive NSCLC, with an impressive improvement of progression-free survival. From the results and those expected of Phase III ALEX study, alectinib might become the frontline treatment of ALK-positive NSCLC. This article summarizes the therapeutic options in ALK-positive advanced NSCLC, and the chemical, pharmacodynamics, pharmacokinetics, metabolism and clinical efficacy of alectinib.

24 CFR 982.639 - Homeownership option: Administrative fees.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Homeownership option: Administrative fees. 982.639 Section 982.639 Housing and Urban Development Regulations Relating to Housing and... Housing Types Homeownership Option § 982.639 Homeownership option: Administrative fees. The ongoing...

24 CFR 982.628 - Homeownership option: Eligible units.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Homeownership option: Eligible units. 982.628 Section 982.628 Housing and Urban Development Regulations Relating to Housing and Urban... Types Homeownership Option § 982.628 Homeownership option: Eligible units. (a) Initial requirements...

Exposure assessment of carcass disposal options in the event of a notifiable exotic animal disease: application to avian influenza virus.

PubMed

Pollard, Simon J T; Hickman, Gordon A W; Irving, Phil; Hough, Rupert L; Gauntlett, Daniel M; Howson, Simon F; Hart, Alwyn; Gayford, Paul; Gent, Nick

2008-05-01

We present a generalized exposure assessment of 28 disposal options for poultry carcasses in the event of a highly pathogenic avian influenza (HPAI) outbreak. The analysis supports a hereto unverified disposal hierarchy for animal carcasses, placing waste processing (e.g., incineration and rendering) above controlled disposal (e.g., landfill), above uncontrolled disposal (e.g., burial on-farm). We illustrate that early stages of the disposal chain (on-farm) pose greater opportunities for exposure to hazardous agents than later stages, where agents are generally contained, wastes are treated, and residues are managed by regulated processes. In selecting carcass disposal options, practitioners are advised to consider the full range of hazards rather than focusing solely on the HPAI agent, and to give preference to technologies that (i) offer high destruction efficiencies for target pathogens; (ii) do not give rise to significant releases of other pathogenic organisms; and (iii) do not release unacceptable concentrations of toxic chemicals. The approach offers an exposure assessment perspective for carcass disposal, thus providing a risk-informed basis for contingency planning and operational intervention. The authors recognize that relevant legislation, public perception, available capacity, and cost also need to be considered when selecting disposal options in the event of HPAI.

24 CFR 982.626 - Homeownership option: Initial requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Homeownership option: Initial requirements. 982.626 Section 982.626 Housing and Urban Development Regulations Relating to Housing and Urban... Types Homeownership Option § 982.626 Homeownership option: Initial requirements. (a) List of initial...

24 CFR 982.643 - Homeownership option: Downpayment assistance grants.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Homeownership option: Downpayment assistance grants. 982.643 Section 982.643 Housing and Urban Development Regulations Relating to Housing and... Housing Types Homeownership Option § 982.643 Homeownership option: Downpayment assistance grants. (a...

Reducing the ecological consequences of night-time light pollution: options and developments

PubMed Central

Gaston, Kevin J; Davies, Thomas W; Bennie, Jonathan; Hopkins, John

2012-01-01

1. Much concern has been expressed about the ecological consequences of night-time light pollution. This concern is most often focused on the encroachment of artificial light into previously unlit areas of the night-time environment, but changes in the spectral composition, duration and spatial pattern of light are also recognized as having ecological effects. 2. Here, we examine the potential consequences for organisms of five management options to reduce night-time light pollution. These are to (i) prevent areas from being artificially lit; (ii) limit the duration of lighting; (iii) reduce the ‘trespass’ of lighting into areas that are not intended to be lit (including the night sky); (iv) change the intensity of lighting; and (v) change the spectral composition of lighting. 3. Maintaining and increasing natural unlit areas is likely to be the most effective option for reducing the ecological effects of lighting. However, this will often conflict with other social and economic objectives. Decreasing the duration of lighting will reduce energy costs and carbon emissions, but is unlikely to alleviate many impacts on nocturnal and crepuscular animals, as peak times of demand for lighting frequently coincide with those in the activities of these species. Reducing the trespass of lighting will maintain heterogeneity even in otherwise well-lit areas, providing dark refuges that mobile animals can exploit. Decreasing the intensity of lighting will reduce energy consumption and limit both skyglow and the area impacted by high-intensity direct light. Shifts towards ‘whiter’ light are likely to increase the potential range of environmental impacts as light is emitted across a broader range of wavelengths. 4. Synthesis and applications. The artificial lightscape will change considerably over coming decades with the drive for more cost-effective low-carbon street lighting solutions and growth in the artificially lit area. Developing lighting strategies that minimize adverse ecological impacts while balancing the often conflicting requirements of light for human utility, comfort and safety, aesthetic concerns, energy consumption and carbon emission reduction constitute significant future challenges. However, as both lighting technology and understanding of its ecological effects develop, there is potential to identify adaptive solutions that resolve these conflicts. PMID:23335816

Reducing the ecological consequences of night-time light pollution: options and developments.

PubMed

Gaston, Kevin J; Davies, Thomas W; Bennie, Jonathan; Hopkins, John

2012-12-01

1. Much concern has been expressed about the ecological consequences of night-time light pollution. This concern is most often focused on the encroachment of artificial light into previously unlit areas of the night-time environment, but changes in the spectral composition, duration and spatial pattern of light are also recognized as having ecological effects.2. Here, we examine the potential consequences for organisms of five management options to reduce night-time light pollution. These are to (i) prevent areas from being artificially lit; (ii) limit the duration of lighting; (iii) reduce the 'trespass' of lighting into areas that are not intended to be lit (including the night sky); (iv) change the intensity of lighting; and (v) change the spectral composition of lighting.3. Maintaining and increasing natural unlit areas is likely to be the most effective option for reducing the ecological effects of lighting. However, this will often conflict with other social and economic objectives. Decreasing the duration of lighting will reduce energy costs and carbon emissions, but is unlikely to alleviate many impacts on nocturnal and crepuscular animals, as peak times of demand for lighting frequently coincide with those in the activities of these species. Reducing the trespass of lighting will maintain heterogeneity even in otherwise well-lit areas, providing dark refuges that mobile animals can exploit. Decreasing the intensity of lighting will reduce energy consumption and limit both skyglow and the area impacted by high-intensity direct light. Shifts towards 'whiter' light are likely to increase the potential range of environmental impacts as light is emitted across a broader range of wavelengths.4.Synthesis and applications. The artificial lightscape will change considerably over coming decades with the drive for more cost-effective low-carbon street lighting solutions and growth in the artificially lit area. Developing lighting strategies that minimize adverse ecological impacts while balancing the often conflicting requirements of light for human utility, comfort and safety, aesthetic concerns, energy consumption and carbon emission reduction constitute significant future challenges. However, as both lighting technology and understanding of its ecological effects develop, there is potential to identify adaptive solutions that resolve these conflicts.

Q-BIC3 - A Québec-Bavarian international collaboration for adapting regional watershed management to climate change

NASA Astrophysics Data System (ADS)

Ludwig, Ralf

2010-05-01

Adapting to the impacts of climate change is certainly one of the major challenges in water resources management over the next decades. Adaptation to climate change risks is most crucial in this domain, since projected increase in mean air temperature in combination with an expected increase in the temporal variability of precipitation patterns will contribute to pressure on current water availability, allocation and management practices. The latter often involve the utilization of valuable infrastructure, such as dams, reservoirs and water intakes, for which adaptation options must by developed over long-term and often dynamic planning horizons. Research to establish novel methodologies for improved adaptation to climate change is thus very important and only beginning to emerge in regional watershed management. The presented project Q-BIC³, funded by the Bavarian Minstry for the Environment and the Québec Ministère du Développement économique, de l'Innovation et de l'Exportation, aims to develop and apply a newly designed spectrum of tools to support the improved assessment of adaptation options to climate change in regional watershed management. It addresses in particular selected study sites in Québec and Bavaria. The following key issues have been prioritized within Q-BIC³: i) The definition of potential adaptation options in the context of climate change for pre-targeted water management key issues using a subsequent and logical chain of modelling tools (climate, hydrological and water management modeling tools) ii) The definition of an approach that accounts for hydrological projection uncertainties in the search for potential adaptation options in the context of climate change iii) The investigation of the required complexity in hydrological models to estimate climate change impacts and to develop specific adaptation options for Québec and Bavaria watersheds. iv) The development and prototyping of a regionally transferable and modular modelling system for integrated watershed management under climate change conditions. The study sites under investigation, namely the Haut-Saint Francois and Gatineau watersheds in Québec and the Isar and Regnitz catchments in Bavaria, are under heavy anthropogenic use. Intense dam and reservoir operations and even water transfer systems are in place to satisfy multi-purpose demands on available water resources. These are imposing extreme modifications to the natural flow regimes. In the first phase of the project, climatic forcing, stemming from an ensemble of selected GCM and RCM runs, is applied to a variety of hydrological models with different complexity. The derived projections of future hydrological conditions serve to investigate, whether current operation rules and/or existing infrastructure needs to be adapted to a changing environment. First findings demonstrate the large uncertainties associated to the model chain outputs, but also indicate that related adaptation is indispensable to meet the challenges of the rapidly changing man-environment systems.

Safety, Efficacy, and Patient Acceptability of Everolimus in the Treatment of Breast Cancer.

PubMed

Lousberg, Laurence; Jerusalem, Guy

2016-01-01

Everolimus combined with exemestane is an important treatment option for patients suffering from estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (ABC) who have been previously treated with a nonsteroidal aromatase inhibitor (NSAI). After presentation of phase III registration trial BOLERO-2, several phase IIIb trials have been started to evaluate this regimen in a more real-world setting. Here, we review the efficacy and safety data published or presented at selected international meetings. These studies confirmed the outcome observed in the BOLERO-2 trial. Patient acceptance rate is also discussed by focusing on the permanent everolimus discontinuation rate in these trials. Factors influencing the safety profile are also reported, including the impact of age. The optimal sequence of combined therapy approaches associating targeted and endocrine therapy (ET) has yet to be determined as new treatment options such as cyclin-dependent kinase inhibitors become available. However, everolimus-exemestane remains an important treatment option with a major impact on progression-free survival (PFS) and an acceptable safety profile.

Safety, Efficacy, and Patient Acceptability of Everolimus in the Treatment of Breast Cancer

PubMed Central

Lousberg, Laurence; Jerusalem, Guy

2016-01-01

Everolimus combined with exemestane is an important treatment option for patients suffering from estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (ABC) who have been previously treated with a nonsteroidal aromatase inhibitor (NSAI). After presentation of phase III registration trial BOLERO-2, several phase IIIb trials have been started to evaluate this regimen in a more real-world setting. Here, we review the efficacy and safety data published or presented at selected international meetings. These studies confirmed the outcome observed in the BOLERO-2 trial. Patient acceptance rate is also discussed by focusing on the permanent everolimus discontinuation rate in these trials. Factors influencing the safety profile are also reported, including the impact of age. The optimal sequence of combined therapy approaches associating targeted and endocrine therapy (ET) has yet to be determined as new treatment options such as cyclin-dependent kinase inhibitors become available. However, everolimus–exemestane remains an important treatment option with a major impact on progression-free survival (PFS) and an acceptable safety profile. PMID:28096680

Modulation of hexavalent chromium toxicity on Οriganum vulgare in an acidic soil amended with peat, lime, and zeolite.

PubMed

Antoniadis, Vasileios; Zanni, Anna A; Levizou, Efi; Shaheen, Sabry M; Dimirkou, Anthoula; Bolan, Nanthi; Rinklebe, Jörg

2018-03-01

Dynamics of chromate (Cr(VI)) in contaminated soils may be modulated by decreasing its phytoavailability via the addition of organic matter-rich amendments, which might accelerate Cr(VI) reduction to inert chromite (Cr(III)) or high-cation exchange capacity amendments. We studied Cr(VI) phytoavailability of oregano in a Cr(VI)-spiked acidic soil non-treated (S) and treated with peat (SP), lime (SL), and zeolite (SZ). The addition of Cr(VI) increased the concentrations of Cr(VI) and Cr(III) in soils and plants, especially in the lime-amended soil. The plant biomass decreased in the lime-amended soil compared to the un-spiked soil (control) due to decreased plant phosphorus concentrations and high Cr(VI) concentrations in root at that treatment. Oregano in the peat-amended soil exhibited significantly less toxic effects, due to the role of organic matter in reducing toxic Cr(VI) to Cr(III) and boosted plant vigour in this treatment. In the lime-amended soil, the parameters of soil Cr(VI), soil Cr(III), and root Cr(III) increased significantly compared to the non-amended soil, indicating that Cr(VI) reduction to Cr(III) was accelerated at high pH. Added zeolite failed to decreased Cr(VI) level to soil and plant. Oregano achieved a total uptake of Cr(III) and Cr(VI) of 0.275 mg in plant kg -1 soil in a pot in the non-amended soil. We conclude that peat as soil amendment might be considered as a suitable option for decreasing Cr(VI) toxicity in soil and plant, and that oregano as tolerant plant species has a certain potential to be used as a Cr accumulator. Copyright © 2017 Elsevier Ltd. All rights reserved.

SOGC–GOC–SCC Joint Policy Statement. No. 255, March 2011. Cervical cancer prevention in low-resource settings.

PubMed

Elit, Laurie; Jimenez, Waldo; McAlpine, Jessica; Ghatage, Prafull; Miller, Dianne; Plante, Marie

2011-03-01

To help care providers understand the current status of cervical cancer in low-resource countries. The most effective and practical options for cervical screening and treatment in low-resource countries are evaluated. Improvement in rates of prevention and early detection of cervical cancer in low-resource countries. PubMed or Medline, CINAHL, and The Cochrane Library were searched for studies published in English between January 2006 and December 2009. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table). RECOMMENDATIONS 1. All girls 9 years old or over should have access to the cervical cancer vaccine before they become sexually active. (I-A) 2. Cervical cancer screening by visual inspection with acetic acid is suggested for low-resource settings acceptable. Cervical cytology or human papillomavirus testing may also be used when practical. (II-2B) 3. Cryotherapy is a safe, effective, and low-cost therapy that should be included in pre-invasive cervical cancer treatment. (III-B) 4. All countries should have a documented cervical cancer prevention strategy that includes public education built on existing outreach programs. (III-C) 5. Countries should define a centre or centres of excellence for the management of cervical cancer. (III-C) Because these units would serve a larger population, they would be able to identify leaders and develop their skills, and would be able to invest in costly radiation equipment. 6. All women with cervical cancer should have access to pain management. (III-C).

Early dialogue with health technology assessment bodies: a European perspective.

PubMed

Cuche, Matthieu; Beckerman, Rachel; Chowdhury, Cyrus A; van Weelden, Marije A

2014-12-01

Evidence requirements may differ across HTA bodies, and so pharmaceutical companies must plan to synergize their evidence generation strategy, across global regulatory and HTA bodies. Until recently, companies had no official platform to discuss the clinical development of a drug with HTA bodies; however, this is changing. To achieve broad usage in the EU, products must achieve both regulatory and reimbursement approval, the latter of which is based on HTA appraisal in many markets. The objective of this study is to present and evaluate the different options available for early HTA consultation (during drug development/Phase III) in the major European markets from the industry perspective. An exploratory (nonsystematic) literature review was performed to identify the European markets offering early HTA consultations, and each process was analyzed using a set of predefined metrics that are relevant to industry (the ability to consult with the regulatory body in parallel, consultation fees, length of consultation meeting, language of consultation meeting, maximum number of pharmaceutical company employees attending, procedural timelines, nature of data for which consultative advice can be sought, the output of the process, and the ability to involve external experts). Four different types of early HTA consultation processes were identified across the major European HTA markets. The nature of these processes varied in terms of the types and number of questions that can be addressed, the length of the meeting, the reporting output, and the ability to involve external experts. The availability of various options for early HTA consultation may help to avoid a mismatch between the evidence generated by means of a product's clinical development program, and the evidence expected by HTA bodies and payers, which can facilitate the pricing and reimbursement process upon a product's market authorization.

Cost-effectiveness of New Surgical Treatments for Hemorrhoidal Disease: A Multicentre Randomized Controlled Trial Comparing Transanal Doppler-guided Hemorrhoidal Artery Ligation With Mucopexy and Circular Stapled Hemorrhoidopexy.

PubMed

Lehur, Paul A; Didnée, Anne S; Faucheron, Jean-Luc; Meurette, Guillaume; Zerbib, Philippe; Siproudhis, Laurent; Vinson-Bonnet, Béatrice; Dubois, Anne; Casa, Christine; Hardouin, Jean-Benoit; Durand-Zaleski, Isabelle

2016-11-01

To compare Doppler-guided hemorrhoidal artery ligation (DGHAL) with circular stapled hemorrhoidopexy (SH) in the treatment of grade II/III hemorrhoidal disease (HD). DGHAL is a treatment option for symptomatic HD; existing studies report limited risk and satisfactory outcomes. DGHAL has never before been compared with SH in a large-scale multi-institutional randomized clinical trial. Three hundred ninety-three grade II/III HD patients recruited in 22 centers from 2010 to 2013 were randomized to DGHAL (n = 197) or SH (n = 196). The primary endpoint was operative-related morbidity at 3 months (D.90) based on the Clavien-Dindo surgical complications grading. Total cost, cost-effectiveness, and clinical outcome were assessed at 1 year. At D.90, operative-related adverse events occurred after DGHAL and SH, respectively, in 47 (24%) and 50 (26%) patients (P = 0.70). DGHAL resulted in longer mean operating time (44±16 vs 30±14 min; P < 0.001), less pain (postoperative and at 2 wks visual analogic scale: 2.2 vs 2.8; 1.3 vs 1.9; P = 0.03; P = 0.013) and shorter sick leave (12.3 vs 14.8 d; P = 0.045). At 1 year, DGHAL led to more residual grade III HD (15% vs 5%) and a higher reoperation rate (8% vs 4%). Patient satisfaction was >90% for both procedures. Total cost at 1 year was greater for DGHAL [&OV0556;2806 (&OV0556;2670; 2967) vs &OV0556;2538 (&OV0556;2386; 2737)]. The D.90, incremental cost-effectiveness ratio (ICER) was &OV0556;7192 per averted complication. At 1 year DGHAL strategy was dominated. DGHAL and SH are viable options in grade II/III HD with no significant difference in operative-related risk. Although resulting in less postoperative pain and shorter sick leave, DGHAL was more expensive, took longer, and provided a possible inferior anatomical correction suggesting an increased risk of recurrence.

Support for HLW Direct Feed - Phase 2, VSL-15R3440-1

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

Matlack, K. S.; Pegg, I.; Joseph, I.

This report describes work performed to develop and test new glass and feed formulations originating from a potential flow-sheet for the direct vitrification of High Level Waste (HLW) with minimal or no pretreatment. In the HLW direct feed option that is under consideration for early operations at the Hanford Tank Waste Treatment and Immobilization Plant (WTP), the pretreatment facility would be bypassed in order to support an earlier start-up of the vitrification facility. For HLW, this would mean that the ultrafiltration and caustic leaching operations that would otherwise have been performed in the pretreatment facility would either not be performedmore » or would be replaced by an interim pretreatment function (in-tank leaching and settling, for example). These changes would likely affect glass formulations and waste loadings and have impacts on the downstream vitrification operations. Modification of the pretreatment process may result in: (i) Higher aluminum contents if caustic leaching is not performed; (ii) Higher chromium contents if oxidative leaching is not performed; (iii) A higher fraction of supernate in the HLW feed resulting from the lower efficiency of in-tank washing; and (iv) A higher water content due to the likely lower effectiveness of in-tank settling compared to ultrafiltration. The HLW direct feed option has also been proposed as a potential route for treating HLW streams that contain the highest concentrations of fast-settling plutoniumcontaining particles, thereby avoiding some of the potential issues associated with such particles in the WTP Pretreatment facility [1]. In response, the work presented herein focuses on the impacts of increased supernate and water content on wastes from one of the candidate source tanks for the direct feed option that is high in plutonium.« less

Methods and systems for utilizing carbide lime or slag

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

Devenney, Martin; Fernandez, Miguel; Chen, Irvin

Provided herein are methods comprising a) treating a slag solid or carbide lime suspension with an ammonium salt in water to produce an aqueous solution comprising calcium salt, ammonium salt, and solids; b) contacting the aqueous solution with carbon dioxide from an industrial process under one or more precipitation conditions to produce a precipitation material comprising calcium carbonate and a supernatant aqueous solution wherein the precipitation material and the supernatant aqueous solution comprise residual ammonium salt; and c) removing and optionally recovering ammonia and/or ammonium salt using one or more steps of (i) recovering a gas exhaust stream comprising ammoniamore » during the treating and/or the contacting step; (ii) recovering the residual ammonium salt from the supernatant aqueous solution; and (iii) removing and optionally recovering the residual ammonium salt from the precipitation material.« less

Communicating scientific uncertainty

PubMed Central

Fischhoff, Baruch; Davis, Alex L.

2014-01-01

All science has uncertainty. Unless that uncertainty is communicated effectively, decision makers may put too much or too little faith in it. The information that needs to be communicated depends on the decisions that people face. Are they (i) looking for a signal (e.g., whether to evacuate before a hurricane), (ii) choosing among fixed options (e.g., which medical treatment is best), or (iii) learning to create options (e.g., how to regulate nanotechnology)? We examine these three classes of decisions in terms of how to characterize, assess, and convey the uncertainties relevant to each. We then offer a protocol for summarizing the many possible sources of uncertainty in standard terms, designed to impose a minimal burden on scientists, while gradually educating those whose decisions depend on their work. Its goals are better decisions, better science, and better support for science. PMID:25225390

UAVSAR Program: Initial Results from New Instrument Capabilities

NASA Technical Reports Server (NTRS)

Lou, Yunling; Hensley, Scott; Moghaddam, Mahta; Moller, Delwyn; Chapin, Elaine; Chau, Alexandra; Clark, Duane; Hawkins, Brian; Jones, Cathleen; Marks, Phillip;

Dornase alfa: a new option in the management of cystic fibrosis.

PubMed

Witt, D M; Anderson, L

1996-01-01

Recombinant human DNase I, or dornase alfa, is the first new therapy developed specifically for cystic fibrosis in almost 30 years. It selectively digests extracellular DNA and reduces the viscosity of purulent sputum. In clinical trials dornase alfa modestly improved pulmonary function, slightly decreasing the number of respiratory exacerbations requiring parenteral antibiotics compared with placebo. Phase III studies suggest that patients receiving dornase alfa also spend slightly fewer days in the hospital than those treated with placebo. The aerosolized preparation is safe and generally well tolerated. Voice alteration and sore throat are the most commonly reported adverse effects. Further research is necessary to determine the optimum time to initiate therapy and to evaluate the agent's pharmacoeconomic impact on the treatment of cystic fibrosis. Aerosolized dornase alfa should always be given in conjunction with standard cystic fibrosis therapies including antibiotics, chest physiotherapy, and pancreatic enzyme supplementation.

Vision for the Future of the US National Strong-Motion Program

USGS Publications Warehouse

,

1997-01-01

This document provides the requested vision for the future of the National Strong-Motion Program operated by the US Geological Survey. Options for operation of the program are presented in a companion document. Each of the three major charges of the EHRP, program council pertaining to the vision document is addressed here. The 'Vision Summary' through a series of answers to specific questions is intended to provide a complete synopsis of the committees response to program council charges. The Vision for the Future of the NSMP is presented as section III of the Summary. Analysis and detailed discussion supporting the answers in the summary are presented as sections organized according to the charges of the program council. The mission for the program is adopted from that developed at the national workshop entitled 'Research Needs for Strong Motion Data to Support Earthquake Engineering' sponsored by the National Science Foundation.

Health Security and Risk Aversion.

PubMed

Herington, Jonathan

2016-09-01

Health security has become a popular way of justifying efforts to control catastrophic threats to public health. Unfortunately, there has been little analysis of the concept of health security, nor the relationship between health security and other potential aims of public health policy. In this paper I develop an account of health security as an aversion to risky policy options. I explore three reasons for thinking risk avoidance is a distinctly worthwhile aim of public health policy: (i) that security is intrinsically valuable, (ii) that it is necessary for social planning and (iii) that it is an appropriate response to decision-making in contexts of very limited information. Striking the right balance between securing and maximizing population health thus requires a substantive, and hitherto unrecognized, value judgment. Finally, I critically evaluate the current health security agenda in light of this new account of the concept and its relationship to the other aims of public health policy. © 2016 John Wiley & Sons Ltd.

Functional abdominal pain and irritable bowel syndrome in children and adolescents

PubMed Central

Chiou, Eric; Nurko, Samuel

2011-01-01

Functional abdominal pain (FAP) and irritable bowel syndrome (IBS) are both associated with recurrent abdominal pain and are among the most commonly diagnosed medical problems in pediatrics. The majority of patients with mild complaints improve with reassurance and time. For a distinct subset of patients with more severe and disabling illness, finding effective treatment for these disorders remains a challenge. Based on the biopsychosocial model of functional disease, the Rome III criteria have helped frame FAP and IBS in terms of being a positive diagnosis and not a diagnosis of exclusion. However, the lack of a single, proven intervention highlights the complex interplay of pathologic mechanisms likely involved in the development of childhood FAP and IBS and the need for a multidisciplinary, integrated approach. This article discusses the epidemiology, proposed mechanisms, clinical approach and therapeutic options for the management of FAP and IBS in children and adolescents. PMID:21731470

Development of WAIS-III General Ability Index Minus WMS-III memory discrepancy scores.

PubMed

Lange, Rael T; Chelune, Gordon J; Tulsky, David S

2006-09-01

Analysis of the discrepancy between intellectual functioning and memory ability has received some support as a useful means for evaluating memory impairment. In recent additions to Wechlser scale interpretation, the WAIS-III General Ability Index (GAI) and the WMS-III Delayed Memory Index (DMI) were developed. The purpose of this investigation is to develop base rate data for GAI-IMI, GAI-GMI, and GAI-DMI discrepancy scores using data from the WAIS-III/WMS-III standardization sample (weighted N = 1250). Base rate tables were developed using the predicted-difference method and two simple-difference methods (i.e., stratified and non-stratified). These tables provide valuable data for clinical reference purposes to determine the frequency of GAI-IMI, GAI-GMI, and GAI-DMI discrepancy scores in the WAIS-III/WMS-III standardization sample.

Youth with cerebral palsy with differing upper limb abilities: how do they access computers?

PubMed

Davies, T Claire; Chau, Tom; Fehlings, Darcy L; Ameratunga, Shanthi; Stott, N Susan

2010-12-01

To identify the current level of awareness of different computer access technologies and the choices made regarding mode of access by youth with cerebral palsy (CP) and their families. Survey. Two tertiary-level rehabilitation centers in New Zealand and Canada. Youth (N=60) with CP, Manual Ability Classification Scale (MACS) levels I to V, age 13 to 25 years. Not applicable. Questionnaire. Fifty (83%) of the 60 youth were aware of at least 1 available assistive technology (AT), such as touch screens and joysticks. However, only 34 youth (57%) were familiar with the accessibility options currently available in the most common operating systems. Thirty-three (94%) of 35 youth who were MACS I and II used a standard mouse and keyboard, while few chose to use assistive technology or accessibility options. In contrast, 10 (40%) of 25 youth who were MACS III to V used a variety of assistive technologies such as touch screens, joysticks, trackballs, and scanning technologies. This group also had the highest use of accessibility options, although only 15 (60%) of the 25 were aware of them. Most youth with CP were aware of, and used, assistive technologies to enhance their computer access but were less knowledgeable about accessibility options. Accessibility options allow users to modify their own computer interface and can thus enhance computer access for youth with CP. Clinicians should be knowledgeable enough to give informed advice in this area of computer access, thus ensuring that all youth with CP can benefit from both AT and accessibility options, as required. Copyright © 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Healthy food and beverages in senior community football club canteens in New South Wales, Australia.

PubMed

Young, Kylie; Kennedy, Vanessa; Kingsland, Melanie; Sawyer, Amy; Rowland, Bosco; Wiggers, John; Wolfenden, Luke

2012-08-01

Little is known of the extent to which senior sports clubs support the consumption of healthy food and beverages. This study of senior community football clubs aimed to describe: i) the food and beverages available in club canteens; ii) the perceived acceptability of club representatives (e.g. club president or secretary) to selling healthy food and beverages in club canteens; iii) the perceived barriers of club representatives to providing healthy food and beverage options in their club canteen; iv) the associations between the availability of healthy options in canteens, perceived barriers to healthy food and drink availability, and club characteristics; and (v) the food and beverages usually purchased from canteens by club members. The study involved 70 senior community football clubs (Australian Rules Football, Soccer, Rugby League and Rugby Union) across New South Wales, Australia. Club representatives and club members took part in cross-sectional telephone surveys. The most frequently available items at club canteens were regular soft drinks and potato chips or other salty snacks (available at 99% of clubs). Approximately two-thirds (66%) of club representatives agreed or strongly agreed that clubs should provide a greater variety of healthy food options. Perishability and lack of demand were the most frequently cited barriers to healthy food provision. Healthy food options were more available at AFL clubs compared with other football codes. Overall, 6% of club members reported purchasing a healthy food option. Senior community football clubs primarily stock and sell unhealthy food and beverage items. There is support within clubs for providing more healthy options; however, clubs face a number of barriers to the inclusion of healthy foods in club canteens.

Reorienting programme budgeting and marginal analysis (PBMA) towards disinvestment.

PubMed

Mortimer, Duncan

2010-10-14

Remarkable progress has been made over the past 40 years in developing rational, evidence-based mechanisms for the allocation of health resources. Much of this progress has centred on mechanisms for commissioning new medical devices and pharmaceuticals. The attention of fund-managers and policy-makers is only now turning towards development of mechanisms for decommissioning, disinvesting or redeploying resources from currently funded interventions. While Programme Budgeting and Marginal Analysis would seem well-suited to this purpose, past applications include both successes and failures in achieving disinvestment and resource release. Drawing on recent successes/failures in achieving disinvestment and resource release via PBMA, this paper identifies four barriers/enablers to disinvestment via PBMA: (i) specification of the budget constraint, (ii) scope of the programme budget, (iii) composition and role of the advisory group, and (iv) incentives for/against contributing to a 'shift list' of options for disinvestment and resource release. A number of modifications to the PBMA process are then proposed with the aim of reorienting PBMA towards disinvestment. The reoriented model is differentiated by four features: (i) hard budget constraint with budgetary pressure; (ii) programme budgets with broad scope but specific investment proposals linked to disinvestment proposals with similar input requirements; (iii) advisory/working groups that include equal representation of sectional interests plus additional members with responsibility for advocating in favour of disinvestment, (iv) 'shift lists' populated and developed prior to 'wish lists' and investment proposals linked to disinvestment proposals within a relatively narrow budget area. While the argument and evidence presented here suggest that the reoriented model will facilitate disinvestment and resource release, this remains an empirical question. Likewise, further research will be required to determine whether or not the re-oriented model sacrifices feasibility and acceptability to obtain its hypothesised greater emphasis on disinvestment.

Reorienting programme budgeting and marginal analysis (PBMA) towards disinvestment

PubMed Central

2010-01-01

Background Remarkable progress has been made over the past 40 years in developing rational, evidence-based mechanisms for the allocation of health resources. Much of this progress has centred on mechanisms for commissioning new medical devices and pharmaceuticals. The attention of fund-managers and policy-makers is only now turning towards development of mechanisms for decommissioning, disinvesting or redeploying resources from currently funded interventions. While Programme Budgeting and Marginal Analysis would seem well-suited to this purpose, past applications include both successes and failures in achieving disinvestment and resource release. Discussion Drawing on recent successes/failures in achieving disinvestment and resource release via PBMA, this paper identifies four barriers/enablers to disinvestment via PBMA: (i) specification of the budget constraint, (ii) scope of the programme budget, (iii) composition and role of the advisory group, and (iv) incentives for/against contributing to a 'shift list' of options for disinvestment and resource release. A number of modifications to the PBMA process are then proposed with the aim of reorienting PBMA towards disinvestment. Summary The reoriented model is differentiated by four features: (i) hard budget constraint with budgetary pressure; (ii) programme budgets with broad scope but specific investment proposals linked to disinvestment proposals with similar input requirements; (iii) advisory/working groups that include equal representation of sectional interests plus additional members with responsibility for advocating in favour of disinvestment, (iv) 'shift lists' populated and developed prior to 'wish lists' and investment proposals linked to disinvestment proposals within a relatively narrow budget area. While the argument and evidence presented here suggest that the reoriented model will facilitate disinvestment and resource release, this remains an empirical question. Likewise, further research will be required to determine whether or not the re-oriented model sacrifices feasibility and acceptability to obtain its hypothesised greater emphasis on disinvestment. PMID:20942972

24 CFR 982.625 - Homeownership option: General.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Homeownership option: General. 982... Types Homeownership Option § 982.625 Homeownership option: General. (a) The homeownership option is used... family assisted under the homeownership option may be a newly admitted or existing participant in the...

Apatinib for the treatment of gastric cancer.

PubMed

Geng, Ruixuan; Li, Jin

2015-01-01

Antiangiogenesis therapy plays an important role in cancer treatment. Apatinib mesylate, a small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, has been recommended as third-line treatment for metastatic gastric cancer patients. The current review summarizes the publications and conference reports relating to apatinib from preclinical and clinical research in gastric cancer. Apatinib showed good safety, tolerance and treatment efficacy in Phase I/II studies. In a Phase III study, apatinib prolonged the median overall survival of patients with chemotherapy-refractory metastatic gastric cancer by 55 days and the median progression-free survival by 25 days compared with placebo. Apatinib is a new treatment option for advanced gastric cancer. Apatinib is expected to have a broader application when it has been evaluated worldwide. The key issues are to find biomarkers and overcome drug resistance.

A “Fork-to-Farm” Multi-Scale Approach to Promote Sustainable Food Systems for Nutrition and Health: A Perspective for the Mediterranean Region

PubMed Central

Verger, Eric O.; Perignon, Marlene; El Ati, Jalila; Darmon, Nicole; Dop, Marie-Claude; Drogué, Sophie; Dury, Sandrine; Gaillard, Cédric; Sinfort, Carole; Amiot, Marie-Josèphe; Amiot, Marie-Josèphe

2018-01-01

Mediterranean countries are undergoing dietary and nutritional changes that affect their inhabitants' health, while facing massive environmental challenges. The increasing demand of water in agriculture, the capacity to maintain local food production, and the growing dependence on food imports are interconnected issues that must be addressed to ensure food security and nutrition in the Mediterranean region. Here, we present the conceptual framework and methodologies developed by the MEDINA-Study Group for rethinking food systems toward sustainable consumption and production modes. Based on its multidisciplinary expertise, the MEDINA-Study Group designed a “fork-to-farm” multi-scale approach, stemming from current dietary habits and examining how some options to nutritionally improve these habits might affect the food systems. This approach was developed for research activities in the South of France and Tunisia, two areas with very different diet-agriculture-environment nexus. The conceptual framework is based on the analysis of elements of the food systems (from consumption to production) at different levels (individual, household, regional and national levels). The methods include: (i) modeling options of dietary changes at different scales, in order to nutritionally optimize food consumption-production without increasing the environmental impact, (ii) translating the best-choice changes into possible policy actions, (iii) testing the acceptability and feasibility of these actions with several stakeholders, and (iv) producing guidelines for sustainable food choices and production. The MEDINA-Study Group identified additional issues that could be included in a future framework to help designing ambitious agricultural, food and health policies in the Mediterranean region. PMID:29872660

Surgical repair of propagating condylar fractures of the third metacarpal/metatarsal bones with cortical screws placed in lag fashion in 26 racehorses (2007-2015).

PubMed

Moulin, N; François, I; Coté, N; Alford, C; Cleary, O; Desjardins, M R

2018-01-19

Despite the recommendation of plate fixation for propagating condylar fractures of the third metacarpal (McIII) or third metatarsal bone (MtIII), lag screw fixation can be a viable surgical option. To evaluate short-term outcome and long-term racing performance of horses that underwent lag screw fixation of long condylar fractures of the McIII/MtIII. Retrospective case series. Medical records, post-surgical racing performance and outcome of 26 horses with propagating fractures of the medial and/or lateral condyle of McIII/MtIII were reviewed. Medical information included were age, breed, sex, physical examination at admission, circumstances of fracture, radiographic evaluation, anaesthesia and recovery records, surgical and post-operative management, as well as complications. Outcome included racing data and information from telephone interviews. Twenty-six horses (9 Standardbreds and 17 Thoroughbreds) were admitted with a long condylar fracture of the McIII/MtIII. Fore- and hindlimbs were equally represented with the left hindlimb being more frequently involved. Most of the fractures had a spiralling component (76%) and four (15%) were comminuted. Fifteen (58%) horses raced post-surgery including nine Standardbreds (100%) and six Thoroughbreds (35%). Twelve of them were placed in at least one race and 11 won at least once. One horse sustained a severe complication in recovery. No significant difference was observed in the racing performances before and after surgery. Follow-up method and duration were not standardised and there is a low number of cases with six surgeons. Long condylar fractures can be repaired using lag fashion technique combined with a half-limb or full-limb tight cast for recovery as a good surgical alternative. Similar results to plate fixation can be expected, with a return to racing of more than 50%, and the prognosis being even better for pacers. © 2018 EVJ Ltd.

Space station data system analysis/architecture study. Task 2: Options development, DR-5. Volume 2: Design options

NASA Technical Reports Server (NTRS)

1985-01-01

The primary objective of Task 2 is the development of an information base that will support the conduct of trade studies and provide sufficient data to make key design/programmatic decisions. This includes: (1) the establishment of option categories that are most likely to influence Space Station Data System (SSDS) definition; (2) the identification of preferred options in each category; and (3) the characterization of these options with respect to performance attributes, constraints, cost and risk. This volume contains the options development for the design category. This category comprises alternative structures, configurations and techniques that can be used to develop designs that are responsive to the SSDS requirements. The specific areas discussed are software, including data base management and distributed operating systems; system architecture, including fault tolerance and system growth/automation/autonomy and system interfaces; time management; and system security/privacy. Also discussed are space communications and local area networking.

DOE/NNSA perspective safeguard by design: GEN III/III+ light water reactors and beyond

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

Pan, Paul Y

2010-12-10

An overview of key issues relevant to safeguards by design (SBD) for GEN III/IV nuclear reactors is provided. Lessons learned from construction of typical GEN III+ water reactors with respect to SBD are highlighted. Details of SBD for safeguards guidance development for GEN III/III+ light water reactors are developed and reported. This paper also identifies technical challenges to extend SBD including proliferation resistance methodologies to other GEN III/III+ reactors (except HWRs) and GEN IV reactors because of their immaturity in designs.

Conflicts between Public Car Insurance and Public Medical Insurance in Japan: International Comparison Survey

PubMed Central

SAKAGUCHI, Kazuki; MORI, Koichiro

2014-01-01

This paper clarifies essential issues regarding conflicts between public car insurance and public medical insurance in Japan, presenting the findings of an international survey to detect similar problems in other countries and discussing possible options for the resolution of these problems. Three essential issues are important to note: (i) Different prices between the two systems of public insurance provide stakeholders with the irrelevant incentive to apply public medical insurance in the case of car accidents; (ii) Public medical insurance sometimes covers medical expenses due to car accidents, although it should not cover them in principle; and (iii) The costs are imposed on tax payers unconsciously when people use public medical insurance for car accidents. Five findings were obtained from the international survey: (1) Most countries have compulsory car insurance; (2) Private insurance companies manage the financial affairs of compulsory car insurance in most developed countries; (3) Fault for casualties is not considered in the compensation of medical expenses in most countries; (4) Japan is unique in that people can choose between the two systems of public insurance; and (5) Prices for the same medical services differ between the two systems of public insurance in only a few countries. In consideration of the above findings, we provide five options for the resolution of this issue from the viewpoint of victim relief. PMID:25624784

Conflicts between Public Car Insurance and Public Medical Insurance in Japan: International Comparison Survey.

PubMed

Sakaguchi, Kazuki; Mori, Koichiro

2014-04-01

This paper clarifies essential issues regarding conflicts between public car insurance and public medical insurance in Japan, presenting the findings of an international survey to detect similar problems in other countries and discussing possible options for the resolution of these problems. Three essential issues are important to note: (i) Different prices between the two systems of public insurance provide stakeholders with the irrelevant incentive to apply public medical insurance in the case of car accidents; (ii) Public medical insurance sometimes covers medical expenses due to car accidents, although it should not cover them in principle; and (iii) The costs are imposed on tax payers unconsciously when people use public medical insurance for car accidents. Five findings were obtained from the international survey: (1) Most countries have compulsory car insurance; (2) Private insurance companies manage the financial affairs of compulsory car insurance in most developed countries; (3) Fault for casualties is not considered in the compensation of medical expenses in most countries; (4) Japan is unique in that people can choose between the two systems of public insurance; and (5) Prices for the same medical services differ between the two systems of public insurance in only a few countries. In consideration of the above findings, we provide five options for the resolution of this issue from the viewpoint of victim relief.

Frequency assessment of spatially distributed generations of flood scenarios: an application on Italian territory

NASA Astrophysics Data System (ADS)

Lomazzi, M.; Roth, G.; Rudari, R.; Taramasso, A. C.; Ghizzoni, T.; Benedetti, R.; Espa, G.; Terpessi, C.

2009-12-01

The flooding risk impact on society cannot be understated: it influences land use and territorial planning and development at both physical and regulatory levels. To cope with it, a variety of actions can be put in place, involving multidisciplinary competences. Mitigation measures goes from the improvement of monitoring systems to the development of hydraulic structures, throughout land use restrictions, civil protection and insurance plans. All of those options present social and economic impacts, either positive or negative, whose proper estimate should rely on the assumption of appropriate - present and future - scenarios, i.e. quantitative event descriptions in terms of i) the flood hazard, with its probability of occurrence, extension, intensity, and duration, ii) the exposed values and iii) their vulnerability. At present, initial attention has been devoted to the design of flood scenarios, or ensembles of them, and to the evaluation of their frequency of occurrence. In the present work, a model for spatially distributed flood scenarios generation and frequency assessment is proposed and applied to the Italian territory. The study area has been divided into homogeneous regions according to their hydrologic, orographic and meteoclimatic characteristics. A statistical model for flood scenarios simulation has been implemented throughout a conditional approach based on MCMC simulations by using i) a historical flood events catalogue; ii) a homogeneous regions correlation matrix; and iii) an auxiliary variables data set. In this framework, the role of the information stored in the historical flood events catalogue "Aree Vulnerate Italiane" (AVI, http://avi.gndci.cnr.it/), produced by the Italian National Research Council, is of crucial importance.

Pharmaceuticals in the environment: scientific evidence of risks and its regulation

PubMed Central

Küster, Anette; Adler, Nicole

2014-01-01

During the past two decades scientists, regulatory agencies and the European Commission have acknowledged pharmaceuticals to be an emerging environmental problem. In parallel, a regulatory framework for environmental risk assessment (ERA) of pharmaceutical products has been developed. Since the regulatory guidelines came into force the German Federal Agency (UBA) has been evaluating ERAs for human and veterinary pharmaceutical products before they are marketed. The results show that approximately 10% of pharmaceutical products are of note regarding their potential environmental risk. For human medicinal products, hormones, antibiotics, analgesics, antidepressants and antineoplastics indicated an environmental risk. For veterinary products, hormones, antibiotics and parasiticides were most often discussed as being environmentally relevant. These results are in good correlation with the results within the open scientific literature of prioritization approaches for pharmaceuticals in the environment. UBA results revealed that prospective approaches, such as ERA of pharmaceuticals, play an important role in minimizing problems caused by pharmaceuticals in the environment. However, the regulatory ERA framework could be improved by (i) inclusion of the environment in the risk–benefit analysis for human pharmaceuticals, (ii) improvement of risk management options, (iii) generation of data on existing pharmaceuticals, and (iv) improving the availability of ERA data. In addition, more general and integrative steps of regulation, legislation and research have been developed and are presented in this article. In order to minimize the quantity of pharmaceuticals in the environment these should aim to (i) improve the existing legislation for pharmaceuticals, (ii) prioritize pharmaceuticals in the environment and (iii) improve the availability and collection of pharmaceutical data. PMID:25405974

Space station data system analysis/architecture study. Task 2: Options development, DR-5. Volume 3: Programmatic options

NASA Technical Reports Server (NTRS)

1985-01-01

Task 2 in the Space Station Data System (SSDS) Analysis/Architecture Study is the development of an information base that will support the conduct of trade studies and provide sufficient data to make design/programmatic decisions. This volume identifies the preferred options in the programmatic category and characterizes these options with respect to performance attributes, constraints, costs, and risks. The programmatic category includes methods used to administrate/manage the development, operation and maintenance of the SSDS. The specific areas discussed include standardization/commonality; systems management; and systems development, including hardware procurement, software development and system integration, test and verification.

Identification of miRNA Signatures Associated with Epithelial Ovarian Cancer Chemoresistance with Further Biological and Functional Validation of Identified Key miRNAs

DTIC Science & Technology

2015-02-01

OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE 2. REPORT TYPE Annual 3 . DATES COVERED (From - To) 1/30...specimens from women diagnosed with stage III, grade 3 , papillary serous adenocarcinoma all treated with platinum-based chemotherapy. Furthermore, we...and reveal that targeting this miRNA as a novel therapeutic option in ovarian cancer (Task 3 ). 15. SUBJECT TERMS microRNA, ovarian cancer, platinum

Aqueous electrolytes for redox flow battery systems

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

Liu, Tianbiao; Li, Bin; Wei, Xiaoliang

An aqueous redox flow battery system includes an aqueous catholyte and an aqueous anolyte. The aqueous catholyte may comprise (i) an optionally substituted thiourea or a nitroxyl radical compound and (ii) a catholyte aqueous supporting solution. The aqueous anolyte may comprise (i) metal cations or a viologen compound and (ii) an anolyte aqueous supporting solution. The catholyte aqueous supporting solution and the anolyte aqueous supporting solution independently may comprise (i) a proton source, (ii) a halide source, or (iii) a proton source and a halide source.

New advances in ovarian autotransplantation to restore fertility in cancer patients

PubMed Central

2016-01-01

Human ovary autotransplantation is a promising option for fertility preservation of young women and girls undergoing gonadotoxic treatments for cancer or some autoimmune diseases. Although experimental, it resulted in at least 42 healthy babies worldwide. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review was performed for all relevant full-text articles published in English from 1 January 2000 to 01 October 2015 in PubMed to explore the latest clinical and research advances of human ovary autotransplantation. Human ovary autotransplantation involves ovarian tissue extraction, freezing/thawing, and transplantation back into the same patient. Three major forms of human ovary autotransplantation exist including (a) transplantation of cortical ovarian tissue, (b) transplantation of whole ovary, and (c) transplantation of ovarian follicles (artificial ovary). According to the recent guidelines, human ovary autotransplantation is still considered experimental; however, it has unique advantages in comparison to other options of female fertility preservation. Human ovary autotransplantation (i) does not need prior ovarian stimulation, (ii) allows immediate initiation of cancer therapy, (iii) can restore both endocrine and reproductive ovarian functions, and (iv) may be the only fertility preservation option suitable for prepubertal girls or for young women with estrogen-sensitive malignancies. As any other fertility preservation option, human ovary autotransplantation has both advantages and disadvantages and may not be feasible for all cases. The major challenges facing this option are how to avoid the risk of reintroducing malignant cells and how to prolong the lifespan of ovarian transplant as well as how to improve artificial ovary results. PMID:26589603

New advances in ovarian autotransplantation to restore fertility in cancer patients.

PubMed

Salama, Mahmoud; Woodruff, Teresa K

2015-12-01

Human ovary autotransplantation is a promising option for fertility preservation of young women and girls undergoing gonadotoxic treatments for cancer or some autoimmune diseases. Although experimental, it resulted in at least 42 healthy babies worldwide. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review was performed for all relevant full-text articles published in English from 1 January 2000 to 01 October 2015 in PubMed to explore the latest clinical and research advances of human ovary autotransplantation. Human ovary autotransplantation involves ovarian tissue extraction, freezing/thawing, and transplantation back into the same patient. Three major forms of human ovary autotransplantation exist including (a) transplantation of cortical ovarian tissue, (b) transplantation of whole ovary, and (c) transplantation of ovarian follicles (artificial ovary). According to the recent guidelines, human ovary autotransplantation is still considered experimental; however, it has unique advantages in comparison to other options of female fertility preservation. Human ovary autotransplantation (i) does not need prior ovarian stimulation, (ii) allows immediate initiation of cancer therapy, (iii) can restore both endocrine and reproductive ovarian functions, and (iv) may be the only fertility preservation option suitable for prepubertal girls or for young women with estrogen-sensitive malignancies. As any other fertility preservation option, human ovary autotransplantation has both advantages and disadvantages and may not be feasible for all cases. The major challenges facing this option are how to avoid the risk of reintroducing malignant cells and how to prolong the lifespan of ovarian transplant as well as how to improve artificial ovary results.

5 CFR 410.203 - Options for developing employees.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Planning and Evaluating Training § 410.203 Options for developing employees. Agencies may use a full range...-development activities, coaching, mentoring, career development counseling, details, rotational assignments...

5 CFR 410.203 - Options for developing employees.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Planning and Evaluating Training § 410.203 Options for developing employees. Agencies may use a full range...-development activities, coaching, mentoring, career development counseling, details, rotational assignments...

5 CFR 410.203 - Options for developing employees.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Planning and Evaluating Training § 410.203 Options for developing employees. Agencies may use a full range...-development activities, coaching, mentoring, career development counseling, details, rotational assignments...

5 CFR 410.203 - Options for developing employees.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Planning and Evaluating Training § 410.203 Options for developing employees. Agencies may use a full range...-development activities, coaching, mentoring, career development counseling, details, rotational assignments...

High-heat-load monochromator options for the RIXS beamline at the APS with the MBA lattice

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

Liu, Zunping, E-mail: zpliu@anl.gov; Gog, Thomas, E-mail: gog@aps.anl.gov; Stoupin, Stanislav A.

2016-07-27

With the MBA lattice for APS-Upgrade, tuning curves of 2.6 cm period undulators meet the source requirements for the RIXS beamline. The high-heat-load monochromator (HHLM) is the first optical white beam component. There are four options for the HHLM such as diamond monochromators with refrigerant of either water or liquid nitrogen (LN{sub 2}), and silicon monochromators of either direct or indirect cooling system. Their performances are evaluated at energy 11.215 keV (Ir L-III edge). The cryo-cooled diamond monochromator has similar performance as the water-cooled diamond monochromator because GaIn of the Cu-GaIn-diamond interface becomes solid. The cryo-cooled silicon monochromators perform better,more » not only in terms of surface slope error due to thermal deformation, but also in terms of thermal capacity.« less

Modelling determinants of child mortality and poverty in the Comoros.

PubMed

Lachaud, Jean-Pierre

2004-03-01

Based on the Demographic and Health Survey of the Comoros of 1996, the analysis of the determinants of child mortality reaches three conclusions. Firstly, differentiated analytical options generate partially convergent results and provide different dimensions of child mortality. Secondly, the study shows that the low standard of living of households in terms of assets is associated with high child mortality. Thirdly, the determinants of infant and infanto-juvenile mortality are relatively comparable. On the one hand, some common factors to both analytical options affect negatively child health: (i) geographical location in rural zones and/or on the islands of Anjouan and Mohéli; (ii) the low standard of living of households in terms of assets; (iii) some community elements, in particular morbidity, the insufficiency of vaccination and the absence of childbirth assisted by qualified persons. On the other hand, characteristics of mothers and births have an impact on infant and infanto-juvenile survival.

Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises.

PubMed

Aragon-Ching, Jeanny B; Trump, Donald L

2016-09-01

Bladder urothelial cancers remain an important urologic cancer with limited treatment options in the locally advanced and metastatic setting. While neoadjuvant chemotherapy for locally advanced muscle-invasive cancers has shown overall survival benefit, clinical uptake in practice have lagged behind. Controversies surrounding adjuvant chemotherapy use are also ongoing. Systemic therapies for metastatic bladder cancer have largely used platinum-based therapies without effective standard second-line therapy options for those who fail, although vinflunine is approved in Europe as a second-line therapy based on a Phase III trial, and most recently, atezolizumab, a checkpoint inhibitor, was approved by the US FDA. Given increasing recognition of mutational signatures expressed in urothelial carcinomas, several promising agents with use of VEGF-targeted therapies, HER2-directed agents and immunotherapies with PD-1/PD-L1 antibodies in various settings are discussed herein.

Ceftaroline fosamil salvage therapy: an option for reduced-vancomycin-susceptible MRSA bacteraemia.

PubMed

Espedido, Björn A; Jensen, Slade O; van Hal, Sebastiaan J

2015-03-01

To examine the activity of ceftaroline against reduced-vancomycin-susceptible MRSA isolates. One-hundred and three MRSA blood culture isolates (predominantly ST239-MRSA-III), with varying vancomycin phenotypes, had their ceftaroline MICs determined by broth microdilution and MIC Evaluator strip (Oxoid-Thermo Fisher). Statistical analyses were performed that examined relationships with vancomycin and daptomycin MICs. Mutations in mecA were also examined. All 103 isolates (including 60 heteroresistant vancomycin-intermediate Staphylococcus aureus/vancomycin-intermediate S. aureus) were susceptible to ceftaroline, with one isolate displaying heteroresistance that may be related to a mecA mutation. Higher ceftaroline MICs were associated with vancomycin-susceptible S. aureus isolates. This study highlights that ceftaroline fosamil is an option for salvage therapy based on in vitro activity. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Current Standard and Investigational Approaches to the Management of Hormone-Refractory Prostate Cancer

PubMed Central

Mendiratta, Prateek; Armstrong, Andrew J; George, Daniel J

2007-01-01

Prostate cancer is a common cause of death in men and remains incurable in the metastatic setting. In 2004, 2 landmark trials using docetaxel-based chemotherapy, TAX 327 and SWOG 99-16, showed a survival benefit for the first time in metastatic, hormone-refractory prostate cancer. Current research suggests that several distinct mechanisms of androgen-refractory disease may converge in patients with disease progression on androgen deprivation therapy. These findings have identified several potential targets for therapeutic intervention. Current standard and investigational treatment options for this disease are discussed, including chemotherapy and rapidly evolving therapies in phase II/III trials involving antiangiogenic therapies, signal transduction inhibitors, immunomodulatory agents, and nuclear receptor targets. In light of a growing array of treatment options and an increasingly chronic natural history, this review supports a multidisciplinary care approach to these patients, including medical oncologists, urologists, and radiation oncologists, to optimize survival and quality of life. PMID:17387372

NCCN Guidelines Insights: Central Nervous System Cancers, Version 1.2017.

PubMed

Nabors, Louis Burt; Portnow, Jana; Ammirati, Mario; Baehring, Joachim; Brem, Henry; Butowski, Nicholas; Fenstermaker, Robert A; Forsyth, Peter; Hattangadi-Gluth, Jona; Holdhoff, Matthias; Howard, Steven; Junck, Larry; Kaley, Thomas; Kumthekar, Priya; Loeffler, Jay S; Moots, Paul L; Mrugala, Maciej M; Nagpal, Seema; Pandey, Manjari; Parney, Ian; Peters, Katherine; Puduvalli, Vinay K; Ragsdale, John; Rockhill, Jason; Rogers, Lisa; Rusthoven, Chad; Shonka, Nicole; Shrieve, Dennis C; Sills, Allen K; Swinnen, Lode J; Tsien, Christina; Weiss, Stephanie; Wen, Patrick Yung; Willmarth, Nicole; Bergman, Mary Anne; Engh, Anita

2017-11-01

For many years, the diagnosis and classification of gliomas have been based on histology. Although studies including large populations of patients demonstrated the prognostic value of histologic phenotype, variability in outcomes within histologic groups limited the utility of this system. Nonetheless, histology was the only proven and widely accessible tool available at the time, thus it was used for clinical trial entry criteria, and therefore determined the recommended treatment options. Research to identify molecular changes that underlie glioma progression has led to the discovery of molecular features that have greater diagnostic and prognostic value than histology. Analyses of these molecular markers across populations from randomized clinical trials have shown that some of these markers are also predictive of response to specific types of treatment, which has prompted significant changes to the recommended treatment options for grade III (anaplastic) gliomas. Copyright © 2017 by the National Comprehensive Cancer Network.

Arbitrary-Order Conservative and Consistent Remapping and a Theory of Linear Maps: Part II

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

Ullrich, Paul A.; Devendran, Dharshi; Johansen, Hans

2016-04-01

The focus on this series of articles is on the generation of accurate, conservative, consistent, and (optionally) monotone linear offline maps. This paper is the second in the series. It extends on the first part by describing four examples of 2D linear maps that can be constructed in accordance with the theory of the earlier work. The focus is again on spherical geometry, although these techniques can be readily extended to arbitrary manifolds. The four maps include conservative, consistent, and (optionally) monotone linear maps (i) between two finite-volume meshes, (ii) from finite-volume to finite-element meshes using a projection-type approach, (iii)more » from finite-volume to finite-element meshes using volumetric integration, and (iv) between two finite-element meshes. Arbitrary order of accuracy is supported for each of the described nonmonotone maps.« less

A study of method robustness for arsenic speciation in drinking water samples by anion exchange HPLC-ICP-MS.

PubMed

Day, Jason A; Montes-Bayón, María; Vonderheide, Anne P; Caruso, Joseph A

2002-08-01

Regulating arsenic species in drinking waters is a reasonable objective, since the various species have different toxicological impacts. However, developing robust and sensitive speciation methods is mandatory prior to any such regulations. Numerous arsenic speciation publications exist, but the question of robustness or ruggedness for a regulatory method has not been fully explored. The present work illustrates the use of anion exchange chromatography coupled to ICP-MS with a commercially available "speciation kit" option. The mobile phase containing 2 mM NaH(2)PO(4) and 0.2 mM EDTA at pH 6 allowed adequate separation of four As species (As(III), As(V), MMAA, DMAA) in less than 10 min. The analytical performance characteristics studied, including method detection limits (lower than 100 ng L(-1) for all the species evaluated), proved the suitability of the method to fulfill the current regulation. Other parameters evaluated such as laboratory fortified blanks, spiked recoveries, and reproducibility over a certain period of time produced adequate results. The samples analyzed were taken from water utilities in different areas of the United States and were provided by the U.S. EPA. The data suggests the speciation setup performs to U.S. EPA specifications but sample treatment and chemistry are also important factors for achieving good recoveries for samples spiked with As(III) as arsenite and As(V) as arsenate.

Is there still a role for the classical Cox-Maze III?

PubMed

Yap, Cheng-Hon; Prior, David; Kenny, James; Zimmet, Adam; Chao, Victor; Mooney, Donald; Yii, Michael

2006-05-01

The incidence of surgery for atrial fibrillation (AF) is rising, paralleled by an increase in the types of lesion sets and energy sources used. These alternate energy sources have simplified the surgery at the expense of increased cost of consumables. The classical Cox-Maze III is the gold standard therapy with a proven efficacy in curing AF. Our complete experience with this procedure is presented. All 28 patients undergoing the classical Cox-Maze III procedure at our institution underwent preoperative assessment and were followed prospectively. Twenty-eight patients underwent the Cox-Maze III procedure between January 2001 and May 2003. Their mean age was 65 years (range, 44-80 years). Twenty-five patients had concomitant cardiac procedures. Mean duration of AF was 8.3 years. Permanent AF was present in 82%. Mean follow-up time was 15 +/- 8 months (range, 4-30 months). There were no perioperative or late deaths, or thromboembolic events. Sixty-one per cent had early (<3 months) atrial arrhythmia. Freedom from AF at most recent clinical follow up was 93%. Freedom from late atrial arrhythmia was 82%. Freedom from late AF or atrial flutter by pacemaker interrogation or Holter assessment was 77%. Anti-arrhythmic medication use was reduced. New York Heart Association class improved from an average of 2.8 preoperatively to 1.3 postoperatively. The result of the present study shows the safety and efficacy of the classical Cox-Maze III procedure. With the advantage of proven long-term efficacy, demonstrable safety and avoidance of costly technology, the Cox-Maze III should not be discounted as a treatment option in patients because of its perceived complexity.

Flexible design in water and wastewater engineering--definitions, literature and decision guide.

PubMed

Spiller, Marc; Vreeburg, Jan H G; Leusbrock, Ingo; Zeeman, Grietje

2015-02-01

Urban water and wastewater systems face uncertain developments including technological progress, climate change and urban development. To ensure the sustainability of these systems under dynamic conditions it has been proposed that technologies and infrastructure should be flexible, adaptive and robust. However, in literature it is often unclear what these technologies and infrastructure are. Furthermore, the terms flexible, adaptive and robust are often used interchangeably, despite important differences. In this paper we will i) define the terminology, ii) provide an overview of the status of flexible infrastructure design alternatives for water and wastewater networks and treatment, and iii) develop guidelines for the selection of flexible design alternatives. Results indicate that, with the exception of Net Present Valuation methods, there is little research available on the design and evaluation of technologies that can enable flexibility. Flexible design alternatives reviewed include robust design, phased design, modular design, modular/component platform design and design for remanufacturing. As developments in the water sector are driven by slow variables (climate change, urban development), rather than market forces, it is suggested that phased design or component platform designs are suitable for responding to change, while robust design is an option when operations face highly dynamic variability. Copyright © 2014 Elsevier Ltd. All rights reserved.

Developing a spinal cord injury research strategy using a structured process of evidence review and stakeholder dialogue. Part III: outcomes.

PubMed

Middleton, J W; Piccenna, L; Lindsay Gruen, R; Williams, S; Creasey, G; Dunlop, S; Brown, D; Batchelor, P E; Berlowitz, D J; Coates, S; Dunn, J A; Furness, J B; Galea, M P; Geraghty, T; Kwon, B K; Urquhart, S; Yates, D; Bragge, P

2015-10-01

Focus Group. To develop a unified, regional spinal cord injury (SCI) research strategy for Australia and New Zealand. Australia. A 1-day structured stakeholder dialogue was convened in 2013 in Melbourne, Australia, by the National Trauma Research Institute in collaboration with the SCI Network of Australia and New Zealand. Twenty-three experts participated, representing local and international research, clinical, consumer, advocacy, government policy and funding perspectives. Preparatory work synthesised evidence and articulated draft principles and options as a starting point for discussion. A regional SCI research strategy was proposed, whose objectives can be summarised under four themes. (1) Collaborative networks and strategic partnerships to increase efficiency, reduce duplication, build capacity and optimise research funding. (2) Research priority setting and coordination to manage competing studies. (3) Mechanisms for greater consumer engagement in research. (4) Resources and infrastructure to further develop SCI data registries, evaluate research translation and assess alignment of research strategy with stakeholder interests. These are consistent with contemporary international SCI research strategy development activities. This first step in a regional SCI research strategy has articulated objectives for further development by the wider SCI research community. The initiative has also reinforced the importance of coordinated, collective action in optimising outcomes following SCI.

Lestaurtinib, a multitargeted tyrosine kinase inhibitor: from bench to bedside.

PubMed

Shabbir, Munira; Stuart, Robert

2010-03-01

Internal tandem duplication of the fms-like tyrosine kinase 3 (FLT3) gene (FLT3-ITD) is a common recurring mutation in acute myeloid leukemia (AML) with normal karyotype, and the presence of FLT3-ITD confers a poor prognosis on this large subgroup of AML patients. Since the discovery of lestaurtinib as a potent FLT3 inhibitor, in 1985, there has been considerable interest in the development of this agent (CEP-701, Cephalon, Frazer, PA, USA) for treatment of this population. An extensive literature search was conducted that included published articles and abstracts on the preclinical and clinical development of this agent spanning the last decade. The review describes the historical development of this agent and reviews the available preclinical and clinical data on lestaurtinib and expands on potential future directions in development of this agent. Lestaurtinib is a multi targeted tyrosine kinase inhibitor which has been shown to potently inhibit FLT3 at nanomolar concentrations in preclinical studies, leading to its rapid development as a potential targeted agent for treatment of AML. Phase I studies have shown lestaturtinib to be an active agent particularly when used in combination with cytotoxic drugs. Currently, Phase II and Phase III studies are underway aiming to establish the future of this agent as a treatment option for patients with FLT3-ITD AML.

[Gene Therapy for Inherited RETINAL AND OPTIC NERVE Disorders: Current Knowledge].

PubMed

Ďuďáková, Ľ; Kousal, B; Kolářová, H; Hlavatá, L; Lišková, P

The aim of this review is to provide a comprehensive summary of current gene therapy clinical trials for monogenic and optic nerve disorders.The number of genes for which gene-based therapies are being developed is growing. At the time of writing this review gene-based clinical trials have been registered for Leber congenital amaurosis 2 (LCA2), retinitis pigmentosa 38, Usher syndrome 1B, Stargardt disease, choroideremia, achromatopsia, Leber hereditary optic neuropathy (LHON) and X-linked retinoschisis. Apart from RPE65 gene therapy for LCA2 and MT-ND4 for LHON which has reached phase III, all other trials are in investigation phase I and II, i.e. testing the efficacy and safety.Because of the relatively easy accessibility of the retina and its ease of visualization which allows monitoring of efficacy, gene-based therapies for inherited retinal disorders represent a very promising treatment option. With the development of novel therapeutic approaches, the importance of establishing not only clinical but also molecular genetic diagnosis is obvious.Key words: gene therapy, monogenic retinal diseases, optic nerve atrophy, mitochondrial disease.

Gene therapy on the move

PubMed Central

Kaufmann, Kerstin B; Büning, Hildegard; Galy, Anne; Schambach, Axel; Grez, Manuel

2013-01-01

The first gene therapy clinical trials were initiated more than two decades ago. In the early days, gene therapy shared the fate of many experimental medicine approaches and was impeded by the occurrence of severe side effects in a few treated patients. The understanding of the molecular and cellular mechanisms leading to treatment- and/or vector-associated setbacks has resulted in the development of highly sophisticated gene transfer tools with improved safety and therapeutic efficacy. Employing these advanced tools, a series of Phase I/II trials were started in the past few years with excellent clinical results and no side effects reported so far. Moreover, highly efficient gene targeting strategies and site-directed gene editing technologies have been developed and applied clinically. With more than 1900 clinical trials to date, gene therapy has moved from a vision to clinical reality. This review focuses on the application of gene therapy for the correction of inherited diseases, the limitations and drawbacks encountered in some of the early clinical trials and the revival of gene therapy as a powerful treatment option for the correction of monogenic disorders. PMID:24106209

Plasma-Surface Interactions and RF Antennas

NASA Astrophysics Data System (ADS)

Jenkins, Thomas; Smithe, D. N.; Beckwith, K.; Davidson, B. D.; Kruger, S. E.; Pankin, A. Y.; Roark, C. M.

2015-11-01

Implementation of recently developed finite-difference time-domain (FDTD) modeling techniques on high-performance computing platforms allows RF power flow, and antenna near- and far-field behavior, to be studied in realistic experimental ion-cyclotron resonance heating scenarios at previously inaccessible levels of resolution. We present results and 3D animations of high-performance (10k-100k core) FDTD simulations of Alcator C-Mod's field-aligned ICRF antenna on the Titan supercomputer, considering (a) the physics of slow wave excitation in the immediate vicinity of the antenna hardware and in the scrape-off layer for various edge densities, and (b) sputtering and impurity production, as driven by self-consistent sheath potentials at antenna surfaces. Related research efforts in low-temperature plasma modeling, including the use of proper orthogonal decomposition methods for PIC/fluid modeling and the development of plasma chemistry tools (e.g. a robust and flexible reaction database, principal path reduction analysis capabilities, and improved visualization options), will also be summarized. Supported by U.S. DoE SBIR Phase I/II Award DE-SC0009501 and ALCC/OLCF.

Teachers' Guide to Music Appreciation III A and III B in the Senior High School.

ERIC Educational Resources Information Center

Scott, J. Mark; Dawkins, Barbara R.

This guide to music appreciation courses was developed for use in senior high schools in Duval County, Jacksonville, Florida. Music Appreciation III A examines the development of music, from the Gothic period through the Classical period. Music Appreciation III B examines the development of music from the Romantic period through the 1970s.…

30 CFR 90.3 - Part 90 option; notice of eligibility; exercise of option.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Part 90 option; notice of eligibility; exercise of option. 90.3 Section 90.3 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF... DEVELOPMENT OF PNEUMOCONIOSIS General § 90.3 Part 90 option; notice of eligibility; exercise of option. (a...

30 CFR 90.3 - Part 90 option; notice of eligibility; exercise of option.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Part 90 option; notice of eligibility; exercise... DEVELOPMENT OF PNEUMOCONIOSIS General § 90.3 Part 90 option; notice of eligibility; exercise of option. (a... meter of air. Each of these miners shall be notified in writing of eligibility to exercise the option...

30 CFR 90.3 - Part 90 option; notice of eligibility; exercise of option.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Part 90 option; notice of eligibility; exercise... DEVELOPMENT OF PNEUMOCONIOSIS General § 90.3 Part 90 option; notice of eligibility; exercise of option. (a... meter of air. Each of these miners shall be notified in writing of eligibility to exercise the option...

30 CFR 90.3 - Part 90 option; notice of eligibility; exercise of option.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Part 90 option; notice of eligibility; exercise... DEVELOPMENT OF PNEUMOCONIOSIS General § 90.3 Part 90 option; notice of eligibility; exercise of option. (a... meter of air. Each of these miners shall be notified in writing of eligibility to exercise the option...

Genetic diseases associated with an increased risk of skin cancer development in childhood.

PubMed

Fogel, Alexander L; Sarin, Kavita Y; Teng, Joyce M C

2017-08-01

Childhood skin cancers are relatively rare and may indicate an underlying genetic disorder. The increasing elucidation of genetic pathways is changing the diagnosis and management of genetic skin cancer susceptibility syndromes. In this review, we provide an overview of genetic conditions that predispose to skin cancer development in childhood and signs that providers should assess when evaluating affected individuals. In basal cell nevus syndrome (BCNS), the patched2 (PTCH2) and suppressor of fused (SUFU) genes have been implicated in disease pathogenesis. The sonic hedgehog (SHH) pathway inhibitor vismodegib was shown in a placebo-controlled phase III randomized trial to reduce the tumor burden in patients with BCNS. Epidermolysis bullosa (EB) has been classified into four major types and more than 30 subtypes based partly on specific mutations, and best clinical practice guidelines for the management of cutaneous squamous cell carcinoma in EB have been developed. Oculocutaneous albinism (OCA) has been associated with new mutations in genes named OCA5, OCA6, and OCA7, bringing to the total number of culprit genes to seven (OCA1-OCA7). Advances in our understanding of genetic conditions that predispose to childhood skin cancer include new disease classification systems, management guidelines, and treatment options.

24 CFR 982.636 - Homeownership option: Portability.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Homeownership option: Portability... Types Homeownership Option § 982.636 Homeownership option: Portability. (a) General. A family may... described in §§ 982.353 and 982.355 apply to the homeownership option and the administrative...

Current Status and Future Prospects for Esophageal Cancer Treatment

PubMed Central

Kuwano, Hiroyuki

2016-01-01

The local control effect of esophagectomy with three-field lymph node dissection (3FLD) is reaching its limit pending technical advancement. Minimally invasive esophagectomy (MIE) by thoracotomy is slowly gaining acceptance due to advantages in short-term outcomes. Although the evidence is slowly increasing, MIE is still controversial. Also, the results of treatment by surgery alone are limiting, and multimodality therapy, which includes surgical and non-surgical treatment options including chemotherapy, radiotherapy, and endoscopic treatment, has become the mainstream therapy. Esophagectomy after neoadjuvant chemotherapy (NAC) is the standard treatment for clinical stages II/III (except for T4) esophageal cancer, whereas chemoradiotherapy (CRT) is regarded as the standard treatment for patients who wish to preserve their esophagus, those who refuse surgery, and those with inoperable disease. CRT is also usually selected for clinical stage IV esophageal cancer. On the other hand, with the spread of CRT, salvage esophagectomy has traditionally been recognized as a feasible option; however, many clinicians oppose the use of surgery due to the associated unfavorable morbidity and mortality profile. In the future, the improvement of each treatment result and the establishment of individual strategies are important although esophageal cancer has many treatment options. PMID:28003586

Novel implications in the treatment of hepatocellular carcinoma

PubMed Central

Best, Jan; Schotten, Clemens; Theysohn, Jens M.; Wetter, Axel; Müller, Stefan; Radünz, Sonia; Schulze, Maren; Canbay, Ali; Dechêne, Alexander; Gerken, Guido

2017-01-01

Worldwide hepatocellular carcinoma remains one of the leading causes of cancer-related death, associated with a poor prognosis due to late diagnosis in the majority of cases. Physicians at care are frequently confronted with patients who are ineligible for curative treatment such as liver resection, transplantation or radiofrequency ablation. Besides established palliative locoregional therapies, such as ablation or chemoembolization, new treatment options, such as microwave ablation, drug-eluting bead transarterial chemoembolization or selective internal radiation therapy, are emerging; however, data from randomized controlled trials are still lacking. In order to achieve optimal tumor control, patients should receive tailored treatment concepts, considering their tumor burden, liver function and performance status, instead of strictly assigning patients to treatment modalities following algorithms that may be partly very restrictive. Palliative locoregional pretreatment might facilitate downstaging to ensure later curative resection or transplantation. In addition, the combined utilization of different locoregional treatment options or systemic co-treatment has been the subject of several trials. In cases where local tumor control cannot be achieved, or in the scenario of extrahepatic spread, sorafenib remains the only approved systemic therapy option. Alternative targeted therapies, such as immune checkpoint inhibitors have shown encouraging preliminary results, while data from phase III studies are pending. PMID:28042235

Rotigotine in Combination with the MAO-B Inhibitor Selegiline in Early Parkinson's Disease: A Post Hoc Analysis.

PubMed

Giladi, Nir; Asgharnejad, Mahnaz; Bauer, Lars; Grieger, Frank; Boroojerdi, Babak

2016-04-02

Monoamine oxidase B (MAO-B) inhibitors and dopamine receptor agonists are common first-line treatment options in early Parkinson's disease (PD). To evaluate the efficacy and safety of rotigotine transdermal patch as an add-on therapy to an MAO-B inhibitor in patients with early-PD. In two Phase III, randomized, double-blind, placebo-controlled studies in early-PD (SP512, SP513), patients were randomized to rotigotine (titrated to optimal dose ≤8 mg/24 h) or placebo, and maintained for 24 (SP512) or 33 (SP513) weeks. Post hoc analyses were performed on pooled data for patients receiving an MAO-B inhibitor (selegiline) at a stable dose at randomization and throughout the studies, with groups defined as "Selegiline+Rotigotine" and "Selegiline+Placebo". Outcome measures included change from baseline in Unified Parkinson's Disease Rating Scale (UPDRS) II (activities of daily living), III (motor), UPDRS II+III and responders (patients achieving ≥20%, ≥25% or ≥30% decrease in UPDRS II+III). As post hoc analyses, p-values are exploratory. 130 patients were evaluable for efficacy analyses ("Selegiline+Rotigotine": 84, "Selegiline+Placebo": 46). Combined treatment with rotigotine and selegiline improved UPDRS III and UPDRS II+III scores versus selegiline alone (LS-mean [95% CI] treatment difference for UPDRS III: -4.89 [-7.87 to -1.91], p = 0.0015; for UPDRS II+III: -5.76 [-9.71 to -1.82], p = 0.0045). Higher proportion of patients in the "Selegiline+Rotigotine" group were classified as ≥20%, ≥25% or ≥30% responders (all p < 0.001). Combined treatment appeared more effective in patients aged ≤65 years versus > 65 years (although patient numbers in the subgroups were low). Adverse event profile was consistent with the known safety profile of rotigotine. In these post hoc analyses, adjunctive treatment with rotigotine in patients already receiving an MAO-B inhibitor improved UPDRS II+III score; this appeared to be largely driven by improvements in the motor aspects of PD.

Rotigotine in Combination with the MAO-B Inhibitor Selegiline in Early Parkinson’s Disease: A Post Hoc Analysis

PubMed Central

Giladi, Nir; Asgharnejad, Mahnaz; Bauer, Lars; Grieger, Frank; Boroojerdi, Babak

2016-01-01

Background: Monoamine oxidase B (MAO-B) inhibitors and dopamine receptor agonists are common first-line treatment options in early Parkinson’s disease (PD). Objective: To evaluate the efficacy and safety of rotigotine transdermal patch as an add-on therapy to an MAO-B inhibitor in patients with early-PD. Methods: In two Phase III, randomized, double-blind, placebo-controlled studies in early-PD (SP512, SP513), patients were randomized to rotigotine (titrated to optimal dose ≤8 mg/24 h) or placebo, and maintained for 24 (SP512) or 33 (SP513) weeks. Post hoc analyses were performed on pooled data for patients receiving an MAO-B inhibitor (selegiline) at a stable dose at randomization and throughout the studies, with groups defined as “Selegiline+Rotigotine” and “Selegiline+Placebo”. Outcome measures included change from baseline in Unified Parkinson’s Disease Rating Scale (UPDRS) II (activities of daily living), III (motor), UPDRS II+III and responders (patients achieving ≥20%, ≥25% or ≥30% decrease in UPDRS II+III). As post hoc analyses, p-values are exploratory. Results: 130 patients were evaluable for efficacy analyses (“Selegiline+Rotigotine”: 84, “Selegiline+Placebo”: 46). Combined treatment with rotigotine and selegiline improved UPDRS III and UPDRS II+III scores versus selegiline alone (LS-mean [95% CI] treatment difference for UPDRS III: –4.89 [–7.87 to –1.91], p = 0.0015; for UPDRS II+III: –5.76 [–9.71 to –1.82], p = 0.0045). Higher proportion of patients in the “Selegiline+Rotigotine” group were classified as ≥20%, ≥25% or ≥30% responders (all p < 0.001). Combined treatment appeared more effective in patients aged ≤65 years versus > 65 years (although patient numbers in the subgroups were low). Adverse event profile was consistent with the known safety profile of rotigotine. Conclusions: In these post hoc analyses, adjunctive treatment with rotigotine in patients already receiving an MAO-B inhibitor improved UPDRS II+III score; this appeared to be largely driven by improvements in the motor aspects of PD. PMID:27061066

Secure voice for mobile satellite applications

NASA Technical Reports Server (NTRS)

Vaisnys, Arvydas; Berner, Jeff

1990-01-01

The initial system studies are described which were performed at JPL on secure voice for mobile satellite applications. Some options are examined for adapting existing Secure Telephone Unit III (STU-III) secure telephone equipment for use over a digital mobile satellite link, as well as for the evolution of a dedicated secure voice mobile earth terminal (MET). The work has included some lab and field testing of prototype equipment. The work is part of an ongoing study at JPL for the National Communications System (NCS) on the use of mobile satellites for emergency communications. The purpose of the overall task is to identify and enable the technologies which will allow the NCS to use mobile satellite services for its National Security Emergency Preparedness (NSEP) communications needs. Various other government agencies will also contribute to a mobile satellite user base, and for some of these, secure communications will be an essential feature.

Iron-based radiochromic systems for UV dosimetry applications

NASA Astrophysics Data System (ADS)

Lee, Hannah J.; Alqathami, Mamdooh; Blencowe, Anton; Ibbott, Geoffrey

2018-01-01

Phototherapy treatment using ultraviolet (UV) A and B light sources has long existed as a treatment option for various skin conditions. Quality control for phototherapy treatment recommended by the British Association of Dermatologists and British Photodermatology Group generally focused on instrumentation-based dosimetry measurements. The purpose of this study was to present an alternative, easily prepared dosimeter system for the measurement of UV dose and as a simple quality assurance technique for phototherapy treatments. Five different UVA-sensitive radiochromic dosimeter formulations were investigated and responded with a measurable and visible optical change both in solution and in gel form. Iron(III) reduction reaction formulations were found to be more sensitive to UVA compared to iron(II) oxidation formulations. One iron(III) reduction formulation was found to be especially promising due to its sensitivity to UVA dose, ease of production, and linear response up to a saturation point.

The clinical safety of ibrutinib in chronic lymphocytic leukemia.

PubMed

Molica, Stefano

2015-10-01

Ibrutinib , a targeted inhibitor of B-cell receptor signaling, achieved impressive clinical results for patients with chronic lymphocytic leukemia (CLL). These results allowed the approval of ibrutinib for the treatment of patients with CLL who have received at least one prior therapy and those with a 17p deletion regardless of line of therapy. Comprehensive data from either Phase I-II or randomized Phase III studies are analyzed in this article. In addition, we reviewed data on the prevalence and the clinical management of some peculiar toxicities ibrutinib related such as lymphocytosis, major bleeding and atrial fibrillation. Ibrutinib has radically changed the scenery of relapsed/refractory CLL treatment and established an important paradigm in the molecularly targeted approach of this disease. Discontinuation of ibrutinib is rarely due to adverse events related to the drug. Patients who discontinue treatment represent a challenge to the physicians because treatment options are very limited.

24 CFR 206.19 - Payment options.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Payment options. 206.19 Section 206... CONVERSION MORTGAGE INSURANCE Eligibility; Endorsement Eligible Mortgages § 206.19 Payment options. (a) Term payment option. Under the term payment option, equal monthly payments are made by the mortgagee to the...

Quadriceps Tendon Autograft in Anterior Cruciate Ligament Reconstruction: A Systematic Review.

PubMed

Hurley, Eoghan T; Calvo-Gurry, Manuel; Withers, Dan; Farrington, Shane K; Moran, Ray; Moran, Cathal J

2018-05-01

To systematically review the current evidence to ascertain whether quadriceps tendon autograft (QT) is a viable option in anterior cruciate ligament reconstruction. A literature review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Cohort studies comparing QT with bone-patellar tendon-bone autograft (BPTB) or hamstring tendon autograft (HT) were included. Clinical outcomes were compared, with all statistical analyses performed using IBM SPSS Statistics for Windows, version 22.0, with P < .05 being considered statistically significant. We identified 15 clinical trials with 1,910 patients. In all included studies, QT resulted in lower rates of anterior knee pain than BPTB. There was no difference in the rate of graft rupture between QT and BPTB or HT in any of the studies reporting this. One study found that QT resulted in greater knee stability than BPTB, and another study found increased stability compared with HT. One study found that QT resulted in improved functional outcomes compared with BPTB, and another found improved outcomes compared with HT, but one study found worse outcomes compared with BPTB. Current literature suggests QT is a viable option in anterior cruciate ligament reconstruction, with published literature showing comparable knee stability, functional outcomes, donor-site morbidity, and rerupture rates compared with BPTB and HT. Level III, systematic review of Level I, II, and III studies. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Update on human rabies in a dog- and fox-rabies-free country.

PubMed

Stahl, J-P; Gautret, P; Ribadeau-Dumas, F; Strady, C; Le Moal, G; Souala, F; Maslin, J; Fremont, B; Bourhy, H

2014-07-01

Rabies is responsible for 50,000 deaths per year worldwide. Mainland France has been officially freed from rabies in non-flying animals since 2001. We wanted to provide an update on the French situation, using published data, and describe possible options since official guidelines are lacking. Post-exposure prophylaxis (PEP) (early and careful cleaning and dressing of the wound, vaccination, and in case of high-risk exposure, injection of specific anti-rabies immunoglobulins) is known to be efficient except in rare cases. It is recommended after grade II contact (+specific immunoglobulins in immunodepressed patients), or grade III contact (vaccination+immunoglobulins). Mainland France being rabies-free, 3 options may be considered in case of bite by a dog or a cat that cannot be monitored in France: (a) consider the risk of rabies as null, so no PEP should be administrated, whatever the severity of bites; (b) consider there is a weak but lethal risk, so the international recommendations should be applied, using immunoglobulins in some cases; (c) consider that the risk is extremely low but cannot be excluded, and that the patient should be vaccinated to be protected, but without adding immunoglobulins (whether in case of grade II or III bites). There are no national guidelines for rabies in France, and so the physician managing the patient is the one who will decide to treat or not. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Single agent vinorelbine in pediatric patients with progressive optic pathway glioma.

PubMed

Cappellano, Andrea Maria; Petrilli, Antonio Sergio; da Silva, Nasjla Saba; Silva, Frederico Adolfo; Paiva, Priscila Mendes; Cavalheiro, Sergio; Bouffet, Eric

2015-01-01

The management of progressive unresectable low-grade glioma remains controversial. Treatment options have included radiotherapy, and more recently chemotherapy, usually following an initial period of observation. Within this context, we evaluated vinorelbine, a semi-synthetic vinca alkaloid that has shown evidence of activity against glioma. From July 2007 an institutional protocol with vinorelbine (30 mg/m(2) days 0, 8, 22) for a total of 18 cycles, has been conducted at IOP/GRAACC/UNIFESP for children with optic pathway glioma (OPG). The main objectives were clinical and radiological response, as well as toxicity profile. Twenty-three patients with progressive OPG with a mean age of 69 months (4-179) were enrolled. Three patients had a diagnosis of neurofibromatosis type 1. Twenty-two patients were assessable for response with an overall objective response rate of 63 %, with eight patients showing stable disease. The most important toxicity was hematologic (grade III/IV neutropenia) observed in four patients. Gastrointestinal toxicity (grade I/II vomiting) was observed in seven patients and only 1 patient showed grade I peripheral neuropathy. The median progression-free survival (PFS) was 33 months (6.9-69) with a 3 and 5 year PFS of 64 ± 19 and 37 ± 20 %, respectively, for an overall 3 and 5 year-survival of 95 ± 10 %. This study suggests that vinorelbine may be an interesting option for pediatric low-grade gliomas, showing low toxicity profile and providing a good quality of life for patients with such chronic disease.

Abacavir/dolutegravir/lamivudine single-tablet regimen: a review of its use in HIV-1 infection.

PubMed

Greig, Sarah L; Deeks, Emma D

2015-04-01

A fixed-dose, single-tablet regimen comprising the integrase strand transfer inhibitor (INSTI) dolutegravir and the nucleos(t)ide reverse transcriptase inhibitors (NRTIs) abacavir and lamivudine (abacavir/dolutegravir/lamivudine; Triumeq®) is now available for the treatment of HIV-1 infection. In a randomized, double-blind, phase III trial in antiretroviral therapy (ART)-naive adults (SINGLE), once-daily dolutegravir plus abacavir/lamivudine had noninferior efficacy to once-daily efavirenz/tenofovir disoproxil fumarate (tenofovir DF)/emtricitabine with regard to establishing and sustaining virological suppression over 144 weeks, and subsequent superiority testing significantly favoured dolutegravir plus abacavir/lamivudine. This outcome was predominantly driven by more favourable rates of discontinuation due to adverse events versus the efavirenz/tenofovir DF/emtricitabine group. These data were generally supported by findings from other phase III trials in ART-naive adults receiving dolutegravir plus either abacavir/lamivudine or tenofovir DF/emtricitabine (SPRING-2 and FLAMINGO). Dolutegravir plus abacavir/lamivudine is generally well tolerated, with a tolerability profile that appears to be more favourable than efavirenz/tenofovir DF/emtricitabine. In the SINGLE trial, there were no major treatment-emergent INSTI or NRTI resistance-associated mutations in dolutegravir plus abacavir/lamivudine recipients with protocol-defined virological failure, indicating a high genetic barrier to resistance. Thus, triple combination therapy with abacavir, dolutegravir and lamivudine is an effective, generally well tolerated option for the management of HIV-1 infection, with the convenient once-daily fixed-dose tablet providing the first single-tablet regimen option without tenofovir DF.

Software architecture of the III/FBI segment of the FBI's integrated automated identification system

NASA Astrophysics Data System (ADS)

Booker, Brian T.

1997-02-01

This paper will describe the software architecture of the Interstate Identification Index (III/FBI) Segment of the FBI's Integrated Automated Fingerprint Identification System (IAFIS). IAFIS is currently under development, with deployment to begin in 1998. III/FBI will provide the repository of criminal history and photographs for criminal subjects, as well as identification data for military and civilian federal employees. Services provided by III/FBI include maintenance of the criminal and civil data, subject search of the criminal and civil data, and response generation services for IAFIS. III/FBI software will be comprised of both COTS and an estimated 250,000 lines of developed C code. This paper will describe the following: (1) the high-level requirements of the III/FBI software; (2) the decomposition of the III/FBI software into Computer Software Configuration Items (CSCIs); (3) the top-level design of the III/FBI CSCIs; and (4) the relationships among the developed CSCIs and the COTS products that will comprise the III/FBI software.

Microenterprise Development: An Employment Option for Welfare Recipients.

ERIC Educational Resources Information Center

Friedman, Pamela

2001-01-01

This document examines microenterprise development as an employment option for Temporary Assistance for Needy Families (TANF) recipients. The document begins with a brief discussion of the feasibility of self-employment as an option for TANF recipients, particularly in a slow economy. The next section answers policy questions pertaining to the…

24 CFR 206.107 - Mortgagee election of assignment or shared premium option.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Obligations Mortgage Insurance Premiums § 206.107 Mortgagee election of assignment or shared premium option... shared premium option. 206.107 Section 206.107 Housing and Urban Development Regulations Relating to... COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL...

24 CFR 206.107 - Mortgagee election of assignment or shared premium option.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Obligations Mortgage Insurance Premiums § 206.107 Mortgagee election of assignment or shared premium option... shared premium option. 206.107 Section 206.107 Housing and Urban Development Regulations Relating to... COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL...

SURFACE CHEMKIN-III: A Fortran package for analyzing heterogeneous chemical kinetics at a solid-surface - gas-phase interface

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

Coltrin, M.E.; Kee, R.J.; Rupley, F.M.

1996-05-01

This document is the user`s manual for the SURFACE CHEMKIN-III package. Together with CHEMKIN-III, this software facilitates the formation, solution, and interpretation of problems involving elementary heterogeneous and gas-phase chemical kinetics in the presence of a solid surface. The package consists of two major software components: an Interpreter and a Surface Subroutine Library. The Interpreter is a program that reads a symbolic description of a user-specified chemical reaction mechanism. One output from the Interpreter is a data file that forms a link to the Surface Subroutine Library, which is a collection of about seventy modular Fortran subroutines that may bemore » called from a user`s application code to return information on chemical production rates and thermodynamic properties. This version of SURFACE CHEMKIN-III includes many modifications to allow treatment of multi-fluid plasma systems, for example modeling the reactions of highly energetic ionic species with a surface. Optional rate expressions allow reaction rates to depend upon ion energy rather than a single thermodynamic temperature. In addition, subroutines treat temperature as an array, allowing an application code to define a different temperature for each species. This version of SURFACE CHEMKIN-III allows use of real (non-integer) stoichiometric coefficients; the reaction order with respect to species concentrations can also be specified independent of the reaction`s stoichiometric coefficients. Several different reaction mechanisms can be specified in the Interpreter input file through the new construct of multiple materials.« less

A Decade of Experience in Developing Preclinical Models of Advanced- or Early-Stage Spontaneous Metastasis to Study Antiangiogenic Drugs, Metronomic Chemotherapy, and the Tumor Microenvironment.

PubMed

Kerbel, Robert S

2015-01-01

The clinical circumstance of treating spontaneous metastatic disease, after resection of primary tumors, whether advanced/overt or microscopic in nature, is seldom modeled in mice and may be a major factor in explaining the frequent discordance between preclinical and clinical therapeutic outcomes where the trend is "overprediction" of positive results in preclinical mouse model studies. To evaluate this hypothesis, a research program was initiated a decade ago to develop multiple models of metastasis in mice, using variants of human tumor cell lines selected in vivo for enhanced spontaneous metastatic aggressiveness after surgical resection of established orthotopic primary tumors. These models have included breast, renal, and colorectal carcinomas; ovarian cancer (but without prior surgery); and malignant melanoma. They have been used primarily for experimental therapeutic investigations involving various antiangiogenic drugs alone or with chemotherapy, especially "metronomic" low-dose chemotherapy. The various translational studies undertaken have revealed a number of clinically relevant findings. These include the following: (i) the potential of metronomic chemotherapy, especially when combined with a vascular endothelial growth factor pathway targeting drug to successfully treat advanced metastatic disease; (ii) the development of relapsed spontaneous brain metastases in mice with melanoma or breast cancer whose systemic metastatic disease is successfully controlled for a period with a given therapy; (iii) foreshadowing the failure of adjuvant antiangiogenic drug-based phase III trials; (iv) recapitulating the failure of oral antiangiogenic tyrosine kinase inhibitors plus standard chemotherapy in contrast to the modest successes of antiangiogenic antibodies plus chemotherapy in metastatic breast cancer; and (v) revealing "vessel co-option" and absence of angiogenesis as a determinant of intrinsic resistance or minimal responsiveness to antiangiogenic therapy in lung metastases. Developing similar models of metastatic disease but involving mouse tumors grown in syngeneic immunocompetent mice may also prove useful for future translational studies of immune therapy-based treatments.

DRUMS: Disk Repository with Update Management and Select option for high throughput sequencing data

PubMed Central

2014-01-01

Background New technologies for analyzing biological samples, like next generation sequencing, are producing a growing amount of data together with quality scores. Moreover, software tools (e.g., for mapping sequence reads), calculating transcription factor binding probabilities, estimating epigenetic modification enriched regions or determining single nucleotide polymorphism increase this amount of position-specific DNA-related data even further. Hence, requesting data becomes challenging and expensive and is often implemented using specialised hardware. In addition, picking specific data as fast as possible becomes increasingly important in many fields of science. The general problem of handling big data sets was addressed by developing specialized databases like HBase, HyperTable or Cassandra. However, these database solutions require also specialized or distributed hardware leading to expensive investments. To the best of our knowledge, there is no database capable of (i) storing billions of position-specific DNA-related records, (ii) performing fast and resource saving requests, and (iii) running on a single standard computer hardware. Results Here, we present DRUMS (Disk Repository with Update Management and Select option), satisfying demands (i)-(iii). It tackles the weaknesses of traditional databases while handling position-specific DNA-related data in an efficient manner. DRUMS is capable of storing up to billions of records. Moreover, it focuses on optimizing relating single lookups as range request, which are needed permanently for computations in bioinformatics. To validate the power of DRUMS, we compare it to the widely used MySQL database. The test setting considers two biological data sets. We use standard desktop hardware as test environment. Conclusions DRUMS outperforms MySQL in writing and reading records by a factor of two up to a factor of 10000. Furthermore, it can work with significantly larger data sets. Our work focuses on mid-sized data sets up to several billion records without requiring cluster technology. Storing position-specific data is a general problem and the concept we present here is a generalized approach. Hence, it can be easily applied to other fields of bioinformatics. PMID:24495746

Development of an intervention to support patients and clinicians with advanced lung cancer when considering systematic anticancer therapy: protocol for the PACT study.

PubMed

Anagnostou, Despina; Sivell, Stephanie; Noble, Simon; Lester, Jason; Byrne, Anthony; Sampson, Catherine; Longo, Mirella; Nelson, Annmarie

2017-07-12

Patient-centred care is essential to the delivery of healthcare; however, this necessitates direct patient involvement in clinical decision-making and can be challenging for patients diagnosed with advanced non-small cell lung cancer where there may be misunderstanding of the extent of disease, prognosis and aims of treatment. In this context, decisions are complex and there is a need to balance the risks and benefits, including treatment with palliative intent. The aim of the PACT study is to identify the information and decision support needs of patients, leading to the development of an intervention to support patients with advanced lung cancer when considering treatment options. PACT is a five-stage, multimethod and multicentre study. Participants : Patients and health professionals will be recruited from three health boards. Methods : Non-participant observation of multidisciplinary team meetings (n=12) will be used to determine patients' allocation to treatment pathways (stage I). Non-participant observation of patient-clinician consultations (n=20-30) will be used to explore communication of treatment options and decision-making. Extent of participation in decision-making will be assessed using the Observing Patient Involvement in Shared Decision-Making tool. Interviews with patients (stage III) and their clinicians (stage IV) will explore the perception of treatment options and involvement in decision-making. Based on stages I-IV, an expert consensus meeting will finalise the content and format of the intervention. Cognitive interviews with patients will then determine the face validity of the intervention (stage V). Analysis : analysis will be according to data type and research question and will include mediated discourse analysis, thematic analysis, framework analysis and interpretative phenomenological analysis. Ethical approval has been granted. The study findings will contribute to and promote shared and informed decision-making in the best interest of patients and prudent healthcare. We therefore aim to disseminate results via relevant respiratory, oncology and palliative care journals and conferences. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Tsunami evacuation analysis, modelling and planning: application to the coastal area of El Salvador

NASA Astrophysics Data System (ADS)

Gonzalez-Riancho, Pino; Aguirre-Ayerbe, Ignacio; Aniel-Quiroga, Iñigo; Abad Herrero, Sheila; González Rodriguez, Mauricio; Larreynaga, Jeniffer; Gavidia, Francisco; Quetzalcoalt Gutiérrez, Omar; Álvarez-Gómez, Jose Antonio; Medina Santamaría, Raúl

2014-05-01

Advances in the understanding and prediction of tsunami impacts allow the development of risk reduction strategies for tsunami-prone areas. Conducting adequate tsunami risk assessments is essential, as the hazard, vulnerability and risk assessment results allow the identification of adequate, site-specific and vulnerability-oriented risk management options, with the formulation of a tsunami evacuation plan being one of the main expected results. An evacuation plan requires the analysis of the territory and an evaluation of the relevant elements (hazard, population, evacuation routes, and shelters), the modelling of the evacuation, and the proposal of alternatives for those communities located in areas with limited opportunities for evacuation. Evacuation plans, which are developed by the responsible authorities and decision makers, would benefit from a clear and straightforward connection between the scientific and technical information from tsunami risk assessments and the subsequent risk reduction options. Scientifically-based evacuation plans would translate into benefits for the society in terms of mortality reduction. This work presents a comprehensive framework for the formulation of tsunami evacuation plans based on tsunami vulnerability assessment and evacuation modelling. This framework considers (i) the hazard aspects (tsunami flooding characteristics and arrival time), (ii) the characteristics of the exposed area (people, shelters and road network), (iii) the current tsunami warning procedures and timing, (iv) the time needed to evacuate the population, and (v) the identification of measures to improve the evacuation process, such as the potential location for vertical evacuation shelters and alternative routes. The proposed methodological framework aims to bridge the gap between risk assessment and risk management in terms of tsunami evacuation, as it allows for an estimation of the degree of evacuation success of specific management options, as well as for the classification and prioritization of the gathered information, in order to formulate an optimal evacuation plan. The framework has been applied to the El Salvador case study through the project "Tsunami Hazard and Risk Assessment in El Salvador", funded by AECID during the period 2009-12, demonstrating its applicability to site-specific response times and population characteristics.

24 CFR 206.26 - Change in payment option.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Change in payment option. 206.26... in payment option. (a) General. The payment option may be changed as provided in this section. (b... credit payment option. Until the repairs are completed, the mortgagee shall make no line of credit...

Designing flexible engineering systems utilizing embedded architecture options

NASA Astrophysics Data System (ADS)

Pierce, Jeff G.

This dissertation develops and applies an integrated framework for embedding flexibility in an engineered system architecture. Systems are constantly faced with unpredictability in the operational environment, threats from competing systems, obsolescence of technology, and general uncertainty in future system demands. Current systems engineering and risk management practices have focused almost exclusively on mitigating or preventing the negative consequences of uncertainty. This research recognizes that high uncertainty also presents an opportunity to design systems that can flexibly respond to changing requirements and capture additional value throughout the design life. There does not exist however a formalized approach to designing appropriately flexible systems. This research develops a three stage integrated flexibility framework based on the concept of architecture options embedded in the system design. Stage One defines an eight step systems engineering process to identify candidate architecture options. This process encapsulates the operational uncertainty though scenario development, traces new functional requirements to the affected design variables, and clusters the variables most sensitive to change. The resulting clusters can generate insight into the most promising regions in the architecture to embed flexibility in the form of architecture options. Stage Two develops a quantitative option valuation technique, grounded in real options theory, which is able to value embedded architecture options that exhibit variable expiration behavior. Stage Three proposes a portfolio optimization algorithm, for both discrete and continuous options, to select the optimal subset of architecture options, subject to budget and risk constraints. Finally, the feasibility, extensibility and limitations of the framework are assessed by its application to a reconnaissance satellite system development problem. Detailed technical data, performance models, and cost estimates were compiled for the Tactical Imaging Constellation Architecture Study and leveraged to complete a realistic proof-of-concept.

Management of varicella infection (chickenpox) in pregnancy.

PubMed

Shrim, Alon; Koren, Gideon; Yudin, Mark H; Farine, Dan

2012-03-01

To review the existing data regarding varicella zoster virus infection (chickenpox) in pregnancy, interventions to reduce maternal complications and fetal infection, and antepartum and peripartum management. The maternal and fetal outcomes in varicella zoster infection were reviewed, as well as the benefit of the different treatment modalities in altering maternal and fetal sequelae. Medline was searched for articles and clinical guidelines published in English between January 1970 and November 2010. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table). 1. Varicella immunization is recommended for all non-immune women as part of pre-pregnancy and postpartum care. (II-3B) 2. Varicella vaccination should not be administered in pregnancy. However, termination of pregnancy should not be advised because of inadvertent vaccination during pregnancy. (II-3D) 3. The antenatal varicella immunity status of all pregnant women should be documented by history of previous infection, varicella vaccination, or varicella zoster immunoglobulin G serology. (III-C) 4. All non-immune pregnant women should be informed of the risk of varicella infection to themselves and their fetuses. They should be instructed to seek medical help following any contact with a person who may have been contagious. (II-3B) 5. In the case of a possible exposure to varicella in a pregnant woman with unknown immune status, serum testing should be performed. If the serum results are negative or unavailable within 96 hours from exposure, varicella zoster immunoglobulin should be administered. (III-C) 6. Women who develop varicella infection in pregnancy need to be made aware of the potential adverse maternal and fetal sequelae, the risk of transmission to the fetus, and the options available for prenatal diagnosis. (II-3C) 7. Detailed ultrasound and appropriate follow-up is recommended for all women who develop varicella in pregnancy to screen for fetal consequences of infection. (III-B) 8. Women with significant (e.g., pneumonitis) varicella infection in pregnancy should be treated with oral antiviral agents (e.g., acyclovir 800 mg 5 times daily). In cases of progression to varicella pneumonitis, maternal admission to hospital should be seriously considered. Intravenous acyclovir can be considered for severe complications in pregnancy (oral forms have poor bioavailability). The dose is usually 10 to 15 mg/kg of BW or 500 mg/m² IV every 8 h for 5 to 10 days for varicella pneumonitis, and it should be started within 24 to 72 h of the onset of rash. (III-C) 9. Neonatal health care providers should be informed of peripartum varicella exposure in order to optimize early neonatal care with varicella zoster immunoglobulin and immunization. (III-C) Varicella zoster immunoglobulin should be administered to neonates whenever the onset of maternal disease is between 5 days before and 2 days after delivery. (III-C).

Automatic Extraction of JPF Options and Documentation

NASA Technical Reports Server (NTRS)

Luks, Wojciech; Tkachuk, Oksana; Buschnell, David

2011-01-01

Documenting existing Java PathFinder (JPF) projects or developing new extensions is a challenging task. JPF provides a platform for creating new extensions and relies on key-value properties for their configuration. Keeping track of all possible options and extension mechanisms in JPF can be difficult. This paper presents jpf-autodoc-options, a tool that automatically extracts JPF projects options and other documentation-related information, which can greatly help both JPF users and developers of JPF extensions.

Peyronie's disease intervention trials: methodological challenges and issues.

PubMed

Müller, Alexander; Mulhall, John P

2009-03-01

Peyronie's Disease (PD) has been studied for more than 260 years since Francois de la Peyronie's description in 1743. Based on the current literature, the prevalence of PD seems 3-9% with an average age of onset in the fifth life decade. Much effort has been spent on developing nonsurgical treatment options to cure or at least prevent disease progression. The recent examination of drug trials for erectile dysfunction has led us to assess PD trial methodology more closely. An Iinternet search on PubMed was performed using MeSH words PD, clinical trials, oral, transdermal, intralesional and shock wave therapy focusing on 26 representing studies published over the last 15 years. Mean Outcome Measures. A comprehensive review of the current literature on nonsurgical treatment options for PD was conducted to address methodological issues and challenges in PD trials highlighting trial design, patient population, and symptom and sign assessment. The majority of the reviewed studies are underpowered and the heterogeneity in the methodological approach and patient assessment between the studies is one of the remarkable findings from our review. Studies should use a uniform means of defining the degree and type of penile deformity and a large enough cohort of patients should be studied for adequate study power. An ideally designed PD intervention trial should comprise: (i) a randomized, placebo-controlled design; (ii) with a PD patient set representative of the general PD population; and (iii) a comprehensive symptom and sign assessment before and at the end of treatment which includes an assessment of at least deformity, pain, and sexual function. A number of challenges exist for the design of PD intervention trials and deciphering the data generated from them. The field would benefit greatly from a consensus statement or guidelines development on the design and conduct of such trials.

Can't get no satisfaction? Will pay for performance help?: toward an economic framework for understanding performance-based risk-sharing agreements for innovative medical products.

PubMed

Towse, Adrian; Garrison, Louis P

2010-01-01

This article examines performance-based risk-sharing agreements for pharmaceuticals from a theoretical economic perspective. We position these agreements as a form of coverage with evidence development. New performance-based risk sharing could produce a more efficient market equilibrium, achieved by adjustment of the price post-launch to reflect outcomes combined with a new approach to the post-launch costs of evidence collection. For this to happen, the party best able to manage or to bear specific risks must do so. Willingness to bear risk will depend not only on ability to manage it, but on the degree of risk aversion. We identify three related frameworks that provide relevant insights: value of information, real option theory and money-back guarantees. We identify four categories of risk sharing: budget impact, price discounting, outcomes uncertainty and subgroup uncertainty. We conclude that a value of information/real option framework is likely to be the most helpful approach for understanding the costs and benefits of risk sharing. There are a number of factors that are likely to be crucial in determining if performance-based or risk-sharing agreements are efficient and likely to become more important in the future: (i) the cost and practicality of post-launch evidence collection relative to pre-launch; (ii) the feasibility of coverage with evidence development without a pre-agreed contract as to how the evidence will be used to adjust price, revenues or use, in which uncertainty around the pay-off to additional research will reduce the incentive for the manufacturer to collect the information; (iii) the difficulty of writing and policing risk-sharing agreements; (iv) the degree of risk aversion (and therefore opportunity to trade) on the part of payers and manufacturers; and (v) the extent of transferability of data from one country setting to another to support coverage with evidence development in a risk-sharing framework. There is no doubt that--in principle--risk sharing can provide manufacturers and payers additional real options that increase overall efficiency. Given the lack of empirical evidence on the success of schemes already agreed and on the issues we set out above, it is too early to tell if the recent surge of interest in these arrangements is likely to be a trend or only a fad.

The standardized live patient and mechanical patient models--their roles in trauma teaching.

PubMed

Ali, Jameel; Al Ahmadi, Khalid; Williams, Jack Ivan; Cherry, Robert Allen

2009-01-01

We have previously demonstrated improved medical student performance using standardized live patient models in the Trauma Evaluation and Management (TEAM) program. The trauma manikin has also been offered as an option for teaching trauma skills in this program. In this study, we compare performance using both models. Final year medical students were randomly assigned to three groups: group I (n = 22) with neither model, group II (n = 24) with patient model, and group III (n = 24) with mechanical model using the same clinical scenario. All students completed pre-TEAM and post-TEAM multiple choice question (MCQ) exams and an evaluation questionnaire scoring five items on a scale of 1 to 5 with 5 being the highest. The items were objectives were met, knowledge improved, skills improved, overall satisfaction, and course should be mandatory. Students (groups II and III) then switched models, rating preferences in six categories: more challenging, more interesting, more dynamic, more enjoyable learning, more realistic, and overall better model. Scores were analyzed by ANOVA with p < 0.05 being considered statistically significant. All groups had similar scores (means % +/- SD)in the pretest (group I - 50.8 +/- 7.4, group II - 51.3 +/- 6.4, group III - 51.1 +/- 6.6). All groups improved their post-test scores but groups II and III scored higher than group I with no difference in scores between groups II and III (group I - 77.5 +/- 3.8, group II - 84.8 +/- 3.6, group III - 86.3 +/- 3.2). The percent of students scoring 5 in the questionnaire are as follows: objectives met - 100% for all groups; knowledge improved: group I - 91%, group II - 96%, group III - 92%; skills improved: group I - 9%, group II - 83%, group III - 96%; overall satisfaction: group I - 91%, group II - 92%, group III - 92%; should be mandatory: group I - 32%, group II - 96%, group III - 100%. Student preferences (48 students) are as follows: the mechanical model was more challenging (44 of 48); more interesting (40 of 48); more dynamic (46 of 48); more enjoyable (48 of 48); more realistic (32/48), and better overall model (42 of 48). Using the TEAM program, we have demonstrated that improvement in knowledge and skills are equally enhanced by using mechanical or patient models in trauma teaching. However, students overwhelmingly preferred the mechanical model.

Values and assumptions in the development of DSM-III and DSM-III-R: an insider's perspective and a belated response to Sadler, Hulgus, and Agich's "On values in recent American psychiatric classification".

PubMed

Spitzer, R L

2001-06-01

It is widely acknowledged that the approach taken in the development of a classification of mental disorders is guided by various values and assumptions. The author, who played a central role in the development of DSM-III (American Psychiatric Association [1980] Diagnostic and statistical manual of mental disorders, 3rd ed. Washington, DC:Author) and DSM-III-R (American Psychiatric Association [1987] Diagnostic and statistical manual of mental disorders, 3rd ed, rev. Washington, DC:Author) will explicate the basic values and assumptions that guided the development of these two diagnostic manuals. In so doing, the author will respond to the critique of DSM-III and DSM-III-R made by Sadler et al. in their 1994 paper (Sadler JZ, Hulgus YF, Agich GJ [1994] On values in recent American psychiatric classification. JMed Phil 19:261-277). The author will attempt to demonstrate that the stated goals of DSM-III and DSM-III-R are not inherently in conflict and are easily explicated by appealing to widely held values and assumptions, most of which appeared in the literature during the development of the manuals. Furthermore, we will demonstrate that it is not true that DSM-III places greater emphasis on reliability over validity and is covertly committed to a biological approach to explaining psychiatric disturbance.

78 FR 47041 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

... methodology developed by NationsShares, a firm that develops proprietary derivatives-based indexes and options... Organizations; International Securities Exchange, LLC; Notice of Filing of Proposed Rule Change To List Options... the Exchange of options on the Nations VolDex index, a new index that measures changes in implied...

Enzymatic versus nonenzymatic mechanisms for Fe(III) reduction in aquatic sediments

USGS Publications Warehouse

Lovley, D.R.; Phillips, E.J.P.; Lonergan, D.J.

1991-01-01

The potential for nonenzymatic reduction of Fe(III) either by organic compounds or by the development of a low redox potential during microbial metabolism was compared with direct, enzymatic Fe(III) reduction by Fe(III)-reducing microorganisms. At circumneutral pH, very few organic compounds nonenzymatically reduced Fe(III). In contrast, in the presence of the appropriate Fe(IH)-reducing microorganisms, most of the organic compounds examined could be completely oxidized to carbon dioxide with the reduction of Fe(III). Even for those organic compounds that could nonenzymatically reduce Fe(III), microbial Fe(III) reduction was much more extensive. The development of a low redox potential during microbial fermentation did not result in nonenzymatic Fe(III) reduction. Model organic compounds were readily oxidized in Fe(III)-reducing aquifer sediments, but not in sterilized sediments. These results suggest that microorganisms enzymatically catalyze most of the Fe(III) reduction in the Fe(III) reduction zone of aquatic sediments and aquifers.

What the Hell Do We Do Now? A Policy Options Analysis of State, Local, and Tribal Law Enforcement Participation in Immigration Enforcement

DTIC Science & Technology

2013-09-01

less like adversaries and more like partners with the affected communities in the effort. 94 THIS PAGE INTENTIONALLY LEFT BLANK 95 LIST OF... INTENTIONALLY LEFT BLANK i REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704–0188 Public reporting burden for this collection of information is...ABSTRACT UU NSN 7540–01–280–5500 Standard Form 298 (Rev. 2–89) Prescribed by ANSI Std. 239–18 ii THIS PAGE INTENTIONALLY LEFT BLANK iii Approved

Framework for Comparative Risk Analysis of Dredged Material Disposal Options.

DTIC Science & Technology

1986-10-01

TC3898-62 DACU67-85-D-8829 UNCLASSIFIED F/G 24/3 NL 125 ൖ ൘ ilil;1III -I uPSDDAR UTReports m ~ Puget Sound Dredged DipslAnalysis e~ od Washington State...I rB T T for Puget Sound Dredged Disposal Analysis c/o U.S. Army Corps of Engineers Seattle District 1 A" October, 1986 l-jq .__ .. _ Tetra Tech, Inc...priority pollutants C-2 E-1 Hypothetical example of total or bulk contaminant concentrations in four Puget Sound sediments E-1 E-2 ’Hypothetical example

Pharmaceuticals in the environment: scientific evidence of risks and its regulation.

PubMed

Küster, Anette; Adler, Nicole

2014-11-19

During the past two decades scientists, regulatory agencies and the European Commission have acknowledged pharmaceuticals to be an emerging environmental problem. In parallel, a regulatory framework for environmental risk assessment (ERA) of pharmaceutical products has been developed. Since the regulatory guidelines came into force the German Federal Agency (UBA) has been evaluating ERAs for human and veterinary pharmaceutical products before they are marketed. The results show that approximately 10% of pharmaceutical products are of note regarding their potential environmental risk. For human medicinal products, hormones, antibiotics, analgesics, antidepressants and antineoplastics indicated an environmental risk. For veterinary products, hormones, antibiotics and parasiticides were most often discussed as being environmentally relevant. These results are in good correlation with the results within the open scientific literature of prioritization approaches for pharmaceuticals in the environment. UBA results revealed that prospective approaches, such as ERA of pharmaceuticals, play an important role in minimizing problems caused by pharmaceuticals in the environment. However, the regulatory ERA framework could be improved by (i) inclusion of the environment in the risk-benefit analysis for human pharmaceuticals, (ii) improvement of risk management options, (iii) generation of data on existing pharmaceuticals, and (iv) improving the availability of ERA data. In addition, more general and integrative steps of regulation, legislation and research have been developed and are presented in this article. In order to minimize the quantity of pharmaceuticals in the environment these should aim to (i) improve the existing legislation for pharmaceuticals, (ii) prioritize pharmaceuticals in the environment and (iii) improve the availability and collection of pharmaceutical data. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

IPCC Climate Change 2013: Mitigation of Climate Change - Key Findings and Lessons Learned

NASA Astrophysics Data System (ADS)

Sokona, Youba

2014-05-01

The Working Group III contribution to the Fifth Assessment Report of the Intergovernmental Panel on Climate Change, Mitigation of Climate Change, examines the results of scientific research about mitigation, with special attention on how knowledge has evolved since the Fourth Assessment Report published in 2007. Throughout, the focus is on the implications of its findings for policy, without being prescriptive about the particular policies that governments and other important participants in the policy process should adopt. The report begins with a framing of important concepts and methods that help to contextualize the findings presented throughout the assessment. The valuation of risks and uncertainties, ethical concepts and the context of sustainable development and equity are among the guiding principles for the assessment of mitigation strategies. The report highlights past trends in stocks and flows of greenhouse gases and the factors that drive emissions at global, regional, and sectoral scales including economic growth, technology or population changes. It provides analyses of the technological, economic and institutional requirements of long-term mitigation scenarios and details on mitigation measures and policies that are applied in different economic sectors and human settlements. It then discusses interactions of mitigation policies and different policy instrument types at national, regional and global governance levels and between economic sectors, The Working Group III report comprises 16 chapters and in assembling this assessment authors were guided by the principles of the IPCC mandate: to be explicit about mitigation options, to be explicit about their costs and about their risks and opportunities vis-à-vis other development priorities, and to be explicit about the underlying criteria, concepts, and methods for evaluating alternative policies.

Recent updates of precision therapy for gastric cancer: Towards optimal tailored management.

PubMed

Joo, Moon Kyung; Park, Jong-Jae; Chun, Hoon Jai

2016-05-21

Signaling pathways of gastric carcinogenesis and gastric cancer progression are being avidly studied to seek optimal treatment of gastric cancer. Among them, hepatocyte growth factor (HGF)/c-MET, phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathways have been widely investigated. Their aberrant expression or mutation has been significantly associated with advanced stage or poor prognosis of gastric cancer. Recently, aberrations of immune checkpoints including programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) have been suggested as an important step in the formation of a microenvironment favorable for gastric cancer. Accomplishments in basic research have led to the development of novel agents targeting these signaling pathways. However, phase III studies of selective anti-HGF/c-MET antibodies and mTOR inhibitor failed to show significant benefits in terms of overall survival and progression-free survival. Few agents directly targeting STAT3 have been developed. However, this target is still critical issue in terms of chemoresistance, and SH2-containing protein tyrosine phosphatase 1 might be a significant link to effectively inhibit STAT3 activity. Inhibition of PD-1/PD-L1 showed durable efficacy in phase I studies, and phase III evaluation is warranted. Therapeutic strategy to concurrently inhibit multiple tyrosine kinases is a reasonable option, however, lapatinib needs to be further evaluated to identify good responders. Regorafenib has shown promising effectiveness in prolonging progression-free survival in a phase II study. In this topic highlight, we review the biologic roles and outcomes of clinical studies targeting these signaling pathways.

Parenting roles and knowledge in neonatal intensive care units: protocol of a mixed methods study

PubMed Central

Alves, Elisabete; Amorim, Mariana; Fraga, Sílvia; Barros, Henrique; Silva, Susana

2014-01-01

Introduction There is a strong focus on the translation of scientific knowledge into evidence-based practice when dealing with very preterm births. The aim is to standardise and rationalise healthcare. The incorporation of parents’ perspectives with respect to the organisation of care and technical interventions in neonatal intensive care units (NICUs) is needed. This study aims to analyse the repertoire of meanings, knowledge and emotions actualised by the parents of very preterm infants hospitalised in NICUs in the decision process regarding parental care, treatment options and uses of information sources. Methods and analysis This is a mixed-methods, observational study. The methodological strategy will rely on: (1) Ethnographic observation, carried out in a level III NICU located in the North of Portugal, during 6 months; (2) NICU-based surveys of mothers and fathers of very preterm infants born between July 2013 and June 2014 and admitted at the seven public level III NICUs of the Northern Health Region of Portugal; (3) Single and couple semistructured interviews to a subsample of mothers and fathers of very preterm infants, 4 months after birth. Inferential statistics will be used to analyse the quantitative data and content analysis, with an iterative and reflexive process and will be implemented to assess qualitative data. Ethics and dissemination The study protocol was approved by the National Data Protection Commission and the Ethics Committee of all the hospitals involved. The current project will contribute to develop resources for enriched good medical practices in the context of neonatal services through integrating insights from social sciences, public health, epidemiology and ethics. The expected dissemination actions are effective tools in designing strategies that aim to develop family-centred care and to improve medical practices in the context of neonatal services. PMID:25011994

24 CFR 3285.503 - Optional appliances.

Code of Federal Regulations, 2011 CFR

2011-04-01

... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Optional Features § 3285.503 Optional... Manufactured Home Construction and Safety Standards in this chapter. (3) When the vent exhausts through the...

24 CFR 3285.503 - Optional appliances.

Code of Federal Regulations, 2010 CFR

2010-04-01

... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Optional Features § 3285.503 Optional... Manufactured Home Construction and Safety Standards in this chapter. (3) When the vent exhausts through the...

24 CFR 3285.503 - Optional appliances.

Code of Federal Regulations, 2012 CFR

2012-04-01

... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Optional Features § 3285.503 Optional... Manufactured Home Construction and Safety Standards in this chapter. (3) When the vent exhausts through the...

Saroglitazar for the treatment of dyslipidemia in diabetic patients.

PubMed

Joshi, Shashank R

2015-03-01

Diabetes and dyslipidemia are commonly associated modifiable risk factors for cardiovascular diseases. Majority of patients with diabetes also suffer from dyslipidemia (diabetic dyslipidemia). Diabetic dyslipidemia is more atherogenic as it is commonly associated with high triglyceride (TG) levels, high proportion of small dense low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol (HDL-C) level (atherogenic dyslipidemia). Currently used pharmacotherapies for the management of diabetes and dyslipidemia like thiazolidinediones (PPAR-γ agonist; for insulin resistance) and fibrates (PPAR-α agonist; for hypertriglyceridemia) have many limitations and side effects. Saroglitazar , a dual PPAR-α/γ agonists, is an emerging therapeutic option with its dual benefit on glycemic and lipid parameters. This paper reviews the clinical development of saroglitazar for the management of diabetic dyslipidemia. The efficacy and safety profile of saroglitazar is reviewed in context to currently available therapy like pioglitazone for diabetes and fibrates for hypertriglyceridemia. In addition, this paper also reviews the association between diabetes and dyslipidemia and the role of TG in reducing cardiovascular events. Saroglitazar, a dual PPAR-α/γ agonist, is a potential therapeutic option for the management of diabetic dyslipidemia. It has dual benefit of significant improvement in glycemic parameters (glycated hemoglobin and fasting blood glucose) and significant improvement in dyslipidemia (TGs, apolipoprotein B, non-HDL-C). The results of Phase III clinical trials indicate that saroglitazar is devoid of conventional side effects of fibrates and pioglitazone. Future clinical trials of saroglitazar will further establish its place in the management of diabetes, dyslipidemia and associated cardiovascular risk.

Decision analysis and drug development portfolio management: uncovering the real options value of your projects.

PubMed

Rosati, Nicoletta

2002-04-01

Project selection and portfolio management are particularly challenging in the pharmaceutical industry due to the high risk - high stake nature of the drug development process. In the recent years, scholars and industry experts have agreed that traditional Net-Present-Value evaluation of the projects fails to capture the value of managerial flexibility, and encouraged adopting a real options approach to recover the missed value. In this paper, we take a closer look at the drug development process and at the indices currently used to rank projects. We discuss the economic value of information and of real options arising in drug development and present decision analysis as an ideal framework for the implementation of real options valuation.

Overview of the U.S. Environmental Protection Agency's Hazardous Air Pollutant Early Reduction Program.

PubMed

Laznow, J; Daniel, J

1992-01-01

Under provision of the Clean Air Act Amendments of 1990 Title III, the EPA has proposed a regulation (Early Reduction Program) to allow a six-year compliance extension from Maximum Achievable Control Technology (MACT) standards for sources that voluntarily reduce emissions of Hazardous Air Pollutants (HAPs) by 90 percent or more (95 percent or more for particulates) from a base year of 1987 or later. The emission reduction must be made before the applicable MACT standard is proposed for the source category or be subject to an enforceable commitment to achieve the reduction by January 1, 1994 for sources subject to MACT standards prior to 1994. The primary purpose of this program is to encourage reduction of HAPs emissions sooner than otherwise required. Industry would be allowed additional time in evaluating emission reduction options and developing more cost-effective compliance strategies, although, under strict guidelines to ensure actual, significant and verifiable emission reductions occur.

Target specific oral anticoagulants in the management of thromboembolic disease in the elderly.

PubMed

Maddula, Surekha; Ansell, Jack

2013-08-01

The elderly population represents a population at highest risk of thromboembolism, but also the most vulnerable to hemorrhage. In the community setting there is a general tendency to under- treat this patient group. Specific consideration must be taken with elderly patients because they have reduced renal function, co-morbidities and risk of falls, altered pharmacodynamics, and challenges with adherence. Vitamin K antagonists, most often warfarin, have been the first line choice of therapy for long-term anticoagulation and enjoyed an unopposed position in the market for the last 70 years. Recently several new oral anticoagulants have been developed and found to be equally effective as warfarin in phase III studies and may provide an optimal treatment option in the elderly population. In this review we explore the target-specific oral anticoagulants and the pharmacological differences between them with a focus on the elderly population in whom these new drugs would constitute a possible alternative to warfarin therapy.

Versatile and on-demand biologics co-production in yeast.

PubMed

Cao, Jicong; Perez-Pinera, Pablo; Lowenhaupt, Ky; Wu, Ming-Ru; Purcell, Oliver; de la Fuente-Nunez, Cesar; Lu, Timothy K

2018-01-08

Current limitations to on-demand drug manufacturing can be addressed by technologies that streamline manufacturing processes. Combining the production of two or more drugs into a single batch could not only be useful for research, clinical studies, and urgent therapies but also effective when combination therapies are needed or where resources are scarce. Here we propose strategies to concurrently produce multiple biologics from yeast in single batches by multiplexing strain development, cell culture, separation, and purification. We demonstrate proof-of-concept for three biologics co-production strategies: (i) inducible expression of multiple biologics and control over the ratio between biologic drugs produced together; (ii) consolidated bioprocessing; and (iii) co-expression and co-purification of a mixture of two monoclonal antibodies. We then use these basic strategies to produce drug mixtures as well as to separate drugs. These strategies offer a diverse array of options for on-demand, flexible, low-cost, and decentralized biomanufacturing applications without the need for specialized equipment.

Alectinib for ALK-positive non-small-cell lung cancer.

PubMed

Rossi, Antonio

2016-08-01

Anaplastic lymphoma kinase (ALK) rearrangements are present in about 5% of advanced non-small-cell lung cancer (NSCLC) patients. Despite the initial response, after a median of 1-2 years, ALK-positive patients developed an acquired resistance to the ALK-inhibitor crizotinib. Among the most promising second-generation ALK-inhibitors, alectinib is being investigated in crizotinib-naïve and -resistant ALK-positive NSCLC patients. The current state-of-the-art of ALK-inhibitors treatment, and in particular the role of alectinib in this setting, is reviewed and discussed. A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question was undertaken. Expert commentary: Alectinib reports promising results with a good safety profile, becoming a potentially very important option for ALK-translocated NSCLC patients. The preliminary results from the J-ALEX phase III randomized trial performed in ALK-rearranged NSCLC Japanese patients showed a better activity and tolerability of alectinib versus crizotinib.

Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence.

PubMed

Rothschild, Sacha I

2014-01-01

The therapeutic landscape in non-small-cell lung cancer (NSCLC) is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations) and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here.

Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence

PubMed Central

Rothschild, Sacha I

2014-01-01

The therapeutic landscape in non-small-cell lung cancer (NSCLC) is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations) and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here. PMID:28210142

Development and evaluation of the McKnight Risk Factor Survey for assessing potential risk and protective factors for disordered eating in preadolescent and adolescent girls.

PubMed

Shisslak, C M; Renger, R; Sharpe, T; Crago, M; McKnight, K M; Gray, N; Bryson, S; Estes, L S; Parnaby, O G; Killen, J; Taylor, C B

1999-03-01

To describe the development, test-retest reliability, internal consistency, and convergent validity of the McKnight Risk Factor Survey-III (MRFS-III). The MRFS-III was designed to assess a number of potential risk and protective factors for the development of disordered eating in preadolescent and adolescent girls. Several versions of the MRFS were pilot tested before the MRFS-III was administered to a sample of 651 4th through 12th- grade girls to establish its psychometric properties. Most of the test-retest reliability coefficients of individual items on the MRFS-III were r > .40. Alpha coefficients for each risk and protective factor domain on the MRFS-III were also computed. The majority of these coefficients were r > .60. High convergent validity coefficients were obtained for specific items on the MRFS-III and measures of self-esteem (Rosenberg Self-Esteem Scale) and weight concerns (Weight Concerns Scale). The test-retest reliability, internal consistency, and convergent validity of the MRFS-III suggest that it is a useful new instrument to assess potential risk and protective factors for the development of disordered eating in preadolescent and adolescent girls.

24 CFR 221.255 - Assignment option.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Assignment option. 221.255 Section... Assignment option. (a) A mortgagee holding a mortgage insured pursuant to a conditional or firm commitment issued on or before November 30, 1983 has the option to assign, transfer and deliver to the Commissioner...

24 CFR 35.120 - Options.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Options. 35.120 Section 35.120... and Definitions for All Programs. § 35.120 Options. (a) Standard treatments. Where interim controls are required by this part, the designated party has the option to presume that lead-based paint or...

24 CFR 221.770 - Assignment option.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Assignment option. 221.770 Section... § 221.770 Assignment option. A mortgagee holding a conditional or firm commitment issued on or before... mortgagee's approved underwriter on or before November 30, 1983) has the option to assign, transfer and...

Concurrent validity of the Alberta Infant Motor Scale to detect delayed gross motor development in preterm infants: A comparative study with the Bayley III.

PubMed

Albuquerque, Plínio Luna de; Guerra, Miriam Queiroz de Farias; Lima, Marília de Carvalho; Eickmann, Sophie Helena

2017-05-24

To investigate the concurrent validity of AIMS in relation to the gross motor subtest of the Bayley Scale III/GM in preterm infants. A total of 159 gross motor development assessments were performed with the AIMS and Bayley-III/GM. Linear regression was used to assess the correlation between AIMS and Bayley-III/GM scores. The intra-class correlation coefficient (ICC) and the Bland-Altman plot were used to analyze intra- and inter-rater reliability. There was a prevalence of delayed gross motor development of 20.8% according to the Bayley-III/GM, and 11.9% for the 5th percentile and 21.4% for the 10th percentile of AIMS. A good correlation of AIMS with Bayley-III/GM scores and intra- and inter-rater reliability was encountered in this study. AIMS proved very capable of detecting delayed gross motor development in preterm infants when compared with the Bayley-III/GM. The 10th percentile of AIMS provided the best combination of indicators, with greater specificity.

Extended-release intramuscular naltrexone (VIVITROL®): a review of its use in the prevention of relapse to opioid dependence in detoxified patients.

PubMed

Syed, Yahiya Y; Keating, Gillian M

2013-10-01

Naltrexone is a μ-opioid receptor antagonist that blocks the euphoric effects of heroin and prescription opioids. In order to improve treatment adherence, a once-monthly, intramuscular, extended-release formulation of naltrexone (XR-NTX) [VIVITROL(®)] has been developed, and approved in the USA and Russia for the prevention of relapse to opioid dependence, after opioid detoxification. The clinical efficacy of this formulation in patients with opioid dependence was demonstrated in a 24-week, randomized, double-blind, placebo-controlled, multicentre, phase III trial (ALK21-013; n = 250). In this trial, opioid-detoxified patients receiving XR-NTX 380 mg once every 4 weeks, in combination with psychosocial support, had a significantly higher median proportion of weeks of confirmed opioid abstinence during weeks 5-24, compared with those receiving placebo (primary endpoint). A significantly higher proportion of patients receiving XR-NTX achieved total confirmed abstinence during this period than those receiving placebo. XR-NTX was also associated with a significantly greater reduction in opioid craving and a significantly longer treatment retention period than placebo. XR-NTX was generally well tolerated in the phase III trial. The most common (incidence ≥5 %) treatment-emergent adverse events that also occurred more frequently with XR-NTX than with placebo were hepatic enzyme abnormalities, nasopharyngitis, insomnia, hypertension, influenza and injection-site pain. Thus, XR-NTX is a useful treatment option for the prevention of relapse to opioid dependence, following opioid detoxification.

Outcomes of operations for benign foregut disease in elderly patients: a National Surgical Quality Improvement Program database analysis.

PubMed

Molena, Daniela; Mungo, Benedetto; Stem, Miloslawa; Feinberg, Richard L; Lidor, Anne O

2014-08-01

The development of minimally invasive operative techniques and improvement in postoperative care has made surgery a viable option to a greater number of elderly patients. Our objective was to evaluate the outcomes of laparoscopic and open foregut operation in relation to the patient age. Patients who underwent gastric fundoplication, paraesophageal hernia repair, and Heller myotomy were identified via the National Surgical Quality Improvement Program (NSQIP) database (2005-2011). Patient characteristics and outcomes were compared between five age groups (group I: ≤65 years, II: 65-69 years; III: 70-74 years; IV: 75-79 years; and V: ≥80 years). Multivariable logistic regression analysis was used to predict the impact of age and operative approach on the studied outcomes. A total of 19,388 patients were identified. Advanced age was associated with increased rate of 30-day mortality, overall morbidity, serious morbidity, and extended length of stay, regardless of the operative approach. After we adjusted for other variables, advanced age was associated with increased odds of 30-day mortality compared with patients <65 years (III: odds ratio 2.70, 95% confidence interval 1.34-5.44, P = .01; IV: 2.80, 1.35-5.81, P = .01; V: 6.12, 3.41-10.99, P < .001). Surgery for benign foregut disease in elderly patients carries a burden of mortality and morbidity that needs to be acknowledged. Copyright © 2014 Mosby, Inc. All rights reserved.

The influence of recipe modification and nutritional information on restaurant food acceptance and macronutrient intakes.

PubMed

Stubenitsky, K; Aaron, J; Catt, S; Mela, D

2000-06-01

To examine the influences of nutritional information and consumer characteristics on meal quality expectations, food selection and subsequent macronutrient intakes of consumers offered a reduced-fat option in a restaurant. A target, full-fat (FF) main restaurant meal option was developed in a version substantially reduced in fat and energy (RF). Restaurant patrons were randomly placed into one of four treatment groups varying in provision of menu information about the target dish, and the actual version of that dish served (if ordered). A full-fat blind (FFB) control group was given no nutritional information in the menu and was served the FF version. The other three groups were all served the modified RF version: (i) reduced-fat blind (RFB), who were given no nutritional information; (ii) reduced-fat informed (RFI), who were given nutritional information; and (iii) reduced-fat informed with details (RFID), who were given the same nutritional information plus recipe modification details. Subjects rated their expected and actual liking, the pleasantness of taste, texture and appearance of the dish, how well the dish matched their expectations, and the likelihood of purchase again. Additional measures included the other dish selections, sociodemographic and attitudinal information. A silver service (training) restaurant. Members of the public (n = 279) consuming meals in the restaurant. The presence of nutritional information on the menu did not significantly increase subsequent intakes of energy and fat from the rest of the meal, and did not significantly influence sensory expectations or post-meal acceptance measures (which also did not differ between the FF and RF versions). Consumer characteristics relating to fat reduction attitudes and behaviours were significantly related to the selection of different dishes. Provision of RF alternatives in a restaurant can have significant positive dietary benefits. Menu nutritional information did not affect measures of meal acceptance. Further studies should identify which types of information formats might be most effective in enhancing the selection of 'healthy' options.

MERINOVA: Meteorological risks as drivers of environmental innovation in agro-ecosystem management

NASA Astrophysics Data System (ADS)

Gobin, Anne; Oger, Robert; Marlier, Catherine; Van De Vijver, Hans; Vandermeulen, Valerie; Van Huylenbroeck, Guido; Zamani, Sepideh; Curnel, Yannick; Mettepenningen, Evi

2013-04-01

The BELSPO funded project 'MERINOVA' deals with risks associated with extreme weather phenomena and with risks of biological origin such as pests and diseases. The major objectives of the proposed project are to characterise extreme meteorological events, assess the impact on Belgian agro-ecosystems, characterise their vulnerability and resilience to these events, and explore innovative adaptation options to agricultural risk management. The project comprises of five major parts that reflect the chain of risks: (i) Hazard: Assessing the likely frequency and magnitude of extreme meteorological events by means of probability density functions; (ii) Impact: Analysing the potential bio-physical and socio-economic impact of extreme weather events on agro-ecosystems in Belgium using process-based modelling techniques commensurate with the regional scale; (iii) Vulnerability: Identifying the most vulnerable agro-ecosystems using fuzzy multi-criteria and spatial analysis; (iv) Risk Management: Uncovering innovative risk management and adaptation options using actor-network theory and fuzzy cognitive mapping techniques; and, (v) Communication: Communicating to research, policy and practitioner communities using web-based techniques. The different tasks of the MERINOVA project require expertise in several scientific disciplines: meteorology, statistics, spatial database management, agronomy, bio-physical impact modelling, socio-economic modelling, actor-network theory, fuzzy cognitive mapping techniques. These expertises are shared by the four scientific partners who each lead one work package. The MERINOVA project will concentrate on promoting a robust and flexible framework by demonstrating its performance across Belgian agro-ecosystems, and by ensuring its relevance to policy makers and practitioners. Impacts developed from physically based models will not only provide information on the state of the damage at any given time, but also assist in understanding the links between different factors causing damage and determining bio-physical vulnerability. Socio-economic impacts will enlarge the basis for vulnerability mapping, risk management and adaptation options. A strong expert and end-user network will be established to help disseminating and exploiting project results to meet user needs.

The treatment of irritable bowel syndrome.

PubMed

Lacy, Brian E; Weiser, Kirsten; De Lee, Ryan

2009-07-01

Irritable bowel syndrome (IBS) is a highly prevalent functional bowel disorder routinely encountered by healthcare providers. Although not life-threatening, this chronic disorder reduces patients' quality of life and imposes a significant economic burden to the healthcare system. IBS is no longer considered a diagnosis of exclusion that can only be made after performing a battery of expensive diagnostic tests. Rather, IBS should be confidently diagnosed in the clinic at the time of the first visit using the Rome III criteria and a careful history and physical examination. Treatment options for IBS have increased in number in the past decade and clinicians should not be limited to using only fiber supplements and smooth muscle relaxants. Although all patients with IBS have symptoms of abdominal pain and disordered defecation, treatment needs to be individualized and should focus on the predominant symptom. This paper will review therapeutic options for the treatment of IBS using a tailored approach based on the predominant symptom. Abdominal pain, bloating, constipation and diarrhea are the four main symptoms that can be addressed using a combination of dietary interventions and medications. Treatment options include probiotics, antibiotics, tricyclic antidepressants, selective serotonin reuptake inhibitors and agents that modulate chloride channels and serotonin. Each class of agent will be reviewed using the latest data from the literature.

Implementing Policy Options to Strengthen the Nexus between Postsecondary Education and Workforce Development. Commission Report 08-07

ERIC Educational Resources Information Center

California Postsecondary Education Commission, 2008

2008-01-01

In December 2007, the California Postsecondary Education adopted the last in an initial series of reports on the nexus between postsecondary education and workforce development by requesting staff to return with plans and priorities to pursue implementation of ten general policy options, grouped into three categories. One option is already being…

Feasibility and efficacy of salvage lung resection after definitive chemoradiation therapy for Stage III non-small-cell lung cancer.

PubMed

Shimada, Yoshihisa; Suzuki, Kenji; Okada, Morihito; Nakayama, Haruhiko; Ito, Hiroyuki; Mitsudomi, Tetsuya; Saji, Hisashi; Takamochi, Kazuya; Kudo, Yujin; Hattori, Aritoshi; Mimae, Takahiro; Aokage, Keiju; Nishii, Teppei; Tsuboi, Masahiro; Ikeda, Norihiko

2016-12-01

For highly selected patients with Stage III non-small-cell lung cancer (NSCLC) who relapse or have residual disease after definitive chemoradiotherapy, salvage lung resection is likely to be one of the options for local control and possible better prognosis. However, the long-term benefit has not been verified. We conducted a retrospective study on salvage surgery on a multicentre basis. Patients included in this study met the following criteria: (i) prior treatment of lung cancer with curative-intent radiotherapy (≥60 Gy); (ii) no a priori plans for induction multimodality therapy; (iii) confirmation of loco-regional recurrence or persistent tumour in the irradiated area; (iv) pretherapeutic pathological results of NSCLC and (v) Stage III disease prior to chemoradiotherapy. A total of 18 patients were eligible for evaluation (Stage IIIA/IIIB, 14/4). The prior median radiation therapy dose was 60 Gy (60-74 Gy), and the median time between the last day of radiotherapy and resection was 38 weeks. The indications for surgery were primary tumour regrowth (10 patients) or tumour persistence (8 patients). Surgical procedures included lobectomy in 13 patients and pneumonectomy in 5 patients. Postoperative complications occurred in 5 patients (28%) without perioperative death. Complete resection was shown in 16 patients (89%) and a complete pathological response in 5 patients (28%). The median follow-up time was 1405 days, and the 3-year overall survival and recurrence-free survival rates were 78 and 72%, respectively. In the highly selected Stage III NSCLC after curative-intent chemoradiation therapy, salvage surgery was safely performed and contributed to satisfactory long-term survival. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Onyx Embolization Before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances.

PubMed

Luzzi, Sabino; Del Maestro, Mattia; Bongetta, Daniele; Zoia, Cesare; Giordano, Aldo V; Trovarelli, Donatella; Raysi Dehcordi, Sohelia; Galzio, Renato J

2018-05-09

Grade III Spetzler-Martin brain arteriovenous malformations (AVMs) are a specific set of AVMs with high variability in terms of site, size, angioarchitecture, flow dynamics, and involvement of eloquent areas. Surgery preceded by preoperative embolization has been reported as a useful treatment option for these lesions. The aim of this study is to report outcomes and personal experience of combined preoperative Onyx embolization and surgical resection on a consecutive series of grade III brain AVMs. Between 2005 and 2017, 27 grade III AVMs were treated by means of a staged Onyx embolization and subsequent surgical treatment. Site and size of the AVMs, embolization, and surgical specifics as well as complications and outcomes were retrospectively reviewed. All AVMs were supratentorial, 13 of which were hemorrhagic. Mean nidal volume was 19.5 mL. Average embolization sessions were 1.6. Mean embolization-related obliteration rate and morbidity were 28.8% and 3.7%, respectively. Surgery was performed within 3.7 days on average. In our experience, Onyx embolization made the nidus excision easier, facilitated the hemostasis, and contributed to the early identification of the lesion in cases of small or racemose nidus. The surgical obliteration rate was 92.6%. A good overall outcome (modified Rankin Scale score 0-2) was achieved in 70.4% of patients. In our experience, preoperative Onyx embolization helped the surgical management of grade III Spetzler-Martin brain AVMs. Careful evaluation of the angioarchitecture, a tailored strategy in the embolization process, and full cooperation within the neurosurgical-neuroendovascular team are mandatory. Copyright © 2018 Elsevier Inc. All rights reserved.

Secukinumab in the Treatment of Psoriasis and Psoriatic Arthritis: A Review of the Literature.

PubMed

Abrouk, M; Gandy, J; Nakamura, M; Lee, K; Brodsky, M; Singh, R; Zhu, H; Farahnik, B; Bhutani, T; Koo, J

2017-07-01

While there are several commercially available treatment options for psoriasis and psoriatic arthritis, there remains a large number of individuals who are refractory to current modalities. In the recent past, there has been increasing evidence that interleukin (IL)-17 plays a vital role in the pathophysiology of psoriasis. Preclinical, phase II, and phase III studies of secukinumab (Cosentyx®) targeting IL-17 and its receptor have thus far proved to be promising. We reviewed the results of phase II and phase III clinical trials for secukinumab in the treatment of psoriasis and psoriatic arthritis. Only published studies were considered in the present review. We also performed an English language literature search from January 2003 to September 2015 using PubMed with any of the following key words: (secukinumab OR AIN457) AND (psoriasis OR psoriatic arthritis). In our review of the literature, seven phase III and five phase II clinical trials, as well as open-label extension studies with unpublished findings were found. Results from phase III clinical trials indicated secukinumab to be efficacious and safe for the treatment of psoriasis and psoriatic arthritis according to Psoriasis Area and Severity Index (PASI) and American College of Rheumatology (ACR) scores. The safety profile of this agent was similar across all studies, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, headache, and injection site reaction. Secukinumab demonstrates rapid and robust clinical improvement accompanied by a favorable short- term safety profile. The results of the phase III trials continue to reinforce the theory that the IL-17 pathway is an essential target in psoriasis and psoriatic arthritis treatment. Additional extension studies of lower level evidence are needed to further understand the safety profile of the drug.

Percutaneous biliary approach as a successful rescue procedure after failed endoscopic therapy for drainage in advanced hilar tumors.

PubMed

Jang, Sung Ill; Hwang, Jin-Hyeok; Lee, Kwang-Hun; Yu, Jeong-Sik; Kim, Hee Wook; Yoon, Chang Jin; Lee, Yoon Suk; Paik, Kyu Hyun; Lee, Sang Hyub; Lee, Dong Ki

2017-04-01

Palliative endoscopic or percutaneous biliary drainage is used for unresectable advanced hilar cancer (HC). The best option for drainage in Bismuth type III or IV HC has not been established. The aims of this study are to identify factors predictive of endoscopic stenting failure and evaluate the effectiveness of rescue percutaneous stenting in patients with advanced HC. Data from 110 patients with inoperable advanced HC were retrospectively reviewed. All received bilateral self-expandable metallic stents. Patients were divided into three groups: I, successful initial endoscopic stenting; II, unsuccessful initial endoscopic stenting, followed by percutaneous stenting; and III, initial percutaneous stenting. We analyzed clinical results and radiologic tumor characteristics. Baseline characteristics and clinical outcomes of all groups were similar, except the hospital stay was longer in group III than group I. Technical success rate was higher in groups II and III (100%) than in group I (72.4%). The functional success rate, stent patency time, patient survival time, and complication rate were similar between groups. Endoscopic stenting failed because of guide-wire passage failure (n = 12) or stent passage failure (n = 7). The only factor significantly associated with endoscopic failure was a smaller left intrahepatic duct-common bile duct angle. As clinical outcomes were generally similar between approaches, percutaneous stenting is recommended for patients with Bismuth type III or IV advanced HC. Acute left intrahepatic duct-common bile duct angulation predicts endoscopic stenting failure. If endoscopic stenting fails, immediate conversion to the percutaneous approach is a necessary and effective rescue method. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Implementing international sexual counselling guidelines in hospital cardiac rehabilitation: development of the CHARMS intervention using the Behaviour Change Wheel.

PubMed

Mc Sharry, J; Murphy, P J; Byrne, M

2016-10-10

Decreased sexual activity and sexual problems are common among people with cardiovascular disease, negatively impacting relationship satisfaction and quality of life. International guidelines recommend routine delivery of sexual counselling to cardiac patients. The Cardiac Health and Relationship Management and Sexuality (CHARMS) baseline study in Ireland found, similar to international findings, limited implementation of sexual counselling guidelines in practice. The aim of the current study was to develop the CHARMS multi-level intervention to increase delivery of sexual counselling by healthcare professionals. We describe the methods used to develop the CHARMS intervention following the three phases of the Behaviour Change Wheel approach: understand the behaviour, identify intervention options, and identify content and implementation options. Survey (n = 60) and focus group (n = 14) data from two previous studies exploring why sexual counselling is not currently being delivered were coded by two members of the research team to understand staff's capability, opportunity, and motivation to engage in the behaviour. All potentially relevant intervention functions to change behaviour were identified and the APEASE (affordability, practicability, effectiveness, acceptability, side effects and equity) criteria were used to select the most appropriate. The APEASE criteria were then used to choose between all behaviour change techniques (BCTs) potentially relevant to the identified functions, and these BCTs were translated into intervention content. The Template for Intervention Description and Replication (TIDieR) checklist was used to specify details of the intervention including the who, what, how and where of proposed intervention delivery. Providing sexual counselling group sessions by cardiac rehabilitation staff to patients during phase III cardiac rehabilitation was identified as the target behaviour. Education, enablement, modelling, persuasion and training were selected as appropriate intervention functions. Twelve BCTs, linked to intervention functions, were identified for inclusion and translated into CHARMS intervention content. This paper details the use of Behaviour Change Wheel approach to develop an implementation intervention in an under-researched area of healthcare provision. The systematic and transparent development of the CHARMS intervention will facilitate the evaluation of intervention effectiveness and future replication and contribute to the advancement of a cumulative science of implementation intervention design.

Improving the use of crop models for risk assessment and climate change adaptation.

PubMed

Challinor, Andrew J; Müller, Christoph; Asseng, Senthold; Deva, Chetan; Nicklin, Kathryn Jane; Wallach, Daniel; Vanuytrecht, Eline; Whitfield, Stephen; Ramirez-Villegas, Julian; Koehler, Ann-Kristin

2018-01-01

Crop models are used for an increasingly broad range of applications, with a commensurate proliferation of methods. Careful framing of research questions and development of targeted and appropriate methods are therefore increasingly important. In conjunction with the other authors in this special issue, we have developed a set of criteria for use of crop models in assessments of impacts, adaptation and risk. Our analysis drew on the other papers in this special issue, and on our experience in the UK Climate Change Risk Assessment 2017 and the MACSUR, AgMIP and ISIMIP projects. The criteria were used to assess how improvements could be made to the framing of climate change risks, and to outline the good practice and new developments that are needed to improve risk assessment. Key areas of good practice include: i. the development, running and documentation of crop models, with attention given to issues of spatial scale and complexity; ii. the methods used to form crop-climate ensembles, which can be based on model skill and/or spread; iii. the methods used to assess adaptation, which need broadening to account for technological development and to reflect the full range options available. The analysis highlights the limitations of focussing only on projections of future impacts and adaptation options using pre-determined time slices. Whilst this long-standing approach may remain an essential component of risk assessments, we identify three further key components: 1.Working with stakeholders to identify the timing of risks. What are the key vulnerabilities of food systems and what does crop-climate modelling tell us about when those systems are at risk?2.Use of multiple methods that critically assess the use of climate model output and avoid any presumption that analyses should begin and end with gridded output.3.Increasing transparency and inter-comparability in risk assessments. Whilst studies frequently produce ranges that quantify uncertainty, the assumptions underlying these ranges are not always clear. We suggest that the contingency of results upon assumptions is made explicit via a common uncertainty reporting format; and/or that studies are assessed against a set of criteria, such as those presented in this paper.

7 CFR 1781.14 - Planning, options, and appraisals.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Planning, options, and appraisals. 1781.14 Section...) LOANS AND ADVANCES § 1781.14 Planning, options, and appraisals. (a) WS and RCD area plans are developed... designated agent when a WS loan, WS advance or RCD loan is made. (d) Options and appraisals related to the...

Dialogue for Change. Options for Re-Structuring K-12 Education. 3rd Edition, 1988.

ERIC Educational Resources Information Center

Metropolitan Affairs Corp., Detroit, MI.

This Third Edition of the 1985 report, "Dialogue for Change," discusses options and examples of educational choice and teacher empowerment and summarizes developments between 1985 and 1987. The following key options are discussed in Chapter 1, "Proposed Options for Change": (1) magnet schools; (2) open enrollment; (3) purchase…

A comparative analysis of the outcomes of aortic cuffs and converters for endovascular graft migration.

PubMed

Thomas, Bradley G; Sanchez, Luis A; Geraghty, Patrick J; Rubin, Brian G; Money, Samuel R; Sicard, Gregorio A

2010-06-01

Proximal attachment failure, often leading to graft migration, is a severe complication of endovascular aneurysm repair (EVAR). Aortic cuffs have been used to treat proximal attachment failure with mixed results. The Zenith Renu AAA Ancillary Graft (Cook Inc, Bloomington, Ind) is available in two configurations: converter and main body extension. Both provide proximal extension with active fixation for the treatment of pre-existing endovascular grafts with failed or failing proximal fixation or seal in patients who are not surgical candidates. We prospectively compared the outcomes of patient treatment with these two device configurations. From September 2005 to May 2008, a prospective, nonrandomized, postmarket registry was conducted to collect data from 151 patients treated at 95 institutions for proximal aortic endovascular graft failure using the Renu graft. Treatment indications included inadequate proximal fixation or seal, for example, migration, and type I and III endoleak. A total of 136 patients (90%) had migration, 111 (74%) had endoleak, and 94 (62%) had endoleaks and graft migration. AneuRx grafts were present in 126 patients (83%), of which 89 (59%) were treated with a converter and 62 (41%) with a main body extension. Outcomes using converters vs main body extensions for endoleak rates, changes in aneurysm size, and ruptures were compared. Preprocedural demographics between the two groups did not differ significantly. Procedural success rates were 98% for the converter group and 100% for the main body extension group. At a mean follow-up of 12.8 +/- 7.5 months, no type III endoleaks (0%)were identified in the converter group, and five (8%) were identified in the main body extension group. There were no aneurysm ruptures in patients treated with converters (0%) and three ruptures (5%) in patients treated with main body extensions. Each patient with aneurysm rupture had been treated with a Renu main body extension, developed a type III endoleak, and underwent surgical conversion. Two of the three patients died postoperatively. Proximal attachment failure and graft migration are potentially lethal complications of EVAR. Proximal graft extension using an aortic cuff is the easiest technique for salvaging an endovascular graft. Unfortunately, it has a predictable failure mode (development of a type III endoleak due to component separation) and is associated with a significantly higher failure rate than with the use of a converter. EVAR salvage with a converter and a femorofemoral bypass is a more complex but superior option for endovascular graft salvage. Copyright (c) 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Tolerance of cranial nerves of the cavernous sinus to radiosurgery

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

Tishler, R.B.; Loeffler, J.S.; Alexander, E. III

1993-09-20

Stereotactic radiosurgery is becoming a more accepted treatment option for benign, deep seated intracranial lesions. However, little is known about the effects of large single fractions of radiation on cranial nerves. This study was undertaken to assess the effect of radiosurgery on the cranial nerves of the cavernous sinus. The authors examined the tolerance of cranial nerves (II-VI) following radiosurgery for 62 patients (42/62 with meningiomas) treated for lesions within or near the cavernous sinus. Twenty-nine patients were treated with a modified 6 MV linear accelerator (Joint Center for Radiation Therapy) and 33 were treated with the Gamma Knife (Universitymore » of Pittsburgh). Three-dimensional treatment plans were retrospectively reviewed and maximum doses were calculated for the cavernous sinus and the optic nerve and chiasm. Median follow-up was 19 months (range 3-49). New cranial neuropathies developed in 12 patients from 3-41 months following radiosurgery. Four of these complications involved injury to the optic system and 8 (3/8 transient) were the result of injury to the sensory or motor nerves of the cavernous sinus. There was no clear relationship between the maximum dose to the cavernous sinus and the development of complications for cranial nerves III-VI over the dose range used (1000-4000 cGy). For the optic apparatus, there was a significantly increased incidence of complications with dose. Four of 17 patients (24%) receiving greater than 800 cGy to any part of the optic apparatus developed visual complications compared with 0/35 who received less than 800 cGy (p = 0.009). Radiosurgery using tumor-controlling doses of up to 4000 cGy appears to be a relatively safe technique in treating lesions within or near the sensory and motor nerves (III-VI) of the cavernous sinus. The dose to the optic apparatus should be limited to under 800 cGy. 21 refs., 4 tabs.« less

Antiproliferative effects of ruthenium-based nucleolipidic nanoaggregates in human models of breast cancer in vitro: insights into their mode of action

PubMed Central

Irace, Carlo; Misso, Gabriella; Capuozzo, Antonella; Piccolo, Marialuisa; Riccardi, Claudia; Luchini, Alessandra; Caraglia, Michele; Paduano, Luigi; Montesarchio, Daniela; Santamaria, Rita

2017-01-01

Looking for new metal-based anticancer treatments, in recent years many ruthenium complexes have been proposed as effective and safe potential drugs. In this context we have recently developed a novel approach for the in vivo delivery of Ru(III) complexes, preparing stable ruthenium-based nucleolipidic nanoaggregates endowed with significant antiproliferative activity. Herein we describe the cellular response to our ruthenium-containing formulations in selected models of human breast cancer. By in vitro bioscreens in the context of preclinical studies, we have focused on their ability to inhibit breast cancer cell proliferation by the activation of the intrinsic apoptotic pathway, possibly via mitochondrial perturbations involving Bcl-2 family members and predisposing to programmed cell death. In addition, the most efficient ruthenium-containing cationic nanoaggregates we have hitherto developed are able to elicit both extrinsic and intrinsic apoptosis, as well as autophagy. To limit chemoresistance and counteract uncontrolled proliferation, multiple cell death pathways activation by metal-based chemotherapeutics is a challenging, yet very promising strategy for targeted therapy development in aggressive cancer diseases, such as triple-negative breast cancer with limited treatment options. These outcomes provide valuable, original knowledge on ruthenium-based candidate drugs and new insights for future optimized cancer treatment protocols. PMID:28349991

Job Aids: Descriptive Authoring Flowcharts for Phase III--DEVELOP of the Instructional Systems Development Model.

ERIC Educational Resources Information Center

Schulz, Russel E.; Farrell, Jean R.

This resource guide for the use of job aids ("how-to-do-it" guidance) for activities identified in the third phase of the Instructional Systems Development Model (ISD) contains an introduction to the use of job aids, as well as descriptive authoring flowcharts for Blocks III.1 through III.5. The introduction includes definitions;…

Production of a monoclonal antibody and development of an immunoassay for detection of Cr(III) in water samples.

PubMed

Zhou, Y; Li, Y S; Meng, X Y; Zhang, Y Y; Yang, L; Li, Z H; Zhang, J H; Wang, X R; Liu, J Q; Lu, S Y; Ren, H L; Hu, P; Liu, Z S

2013-11-01

In this study we report the production of a monoclonal antibody (Mab) specific for Cr(III)-chelate and the development of a competitive immunoassay for detection of Cr(III) in water samples. In the assay, the complete antigen (Cr(III)-ITCBE-BSA) was used as coating antigen, and Cr(III)-ITCBE as competitor competes with coating antigen to bind with Mab. Using this approach, the spiked water samples with Cr(III) were detected. The linear range of the detection was 0.7-12.4 ng mL(-1). The limit of the detection (LOD) was 0.51 ng mL(-1). The spiked results were also confirmed by ICP-MS, which showed a good correlation (R(2)=0.997) between the two methods. The results indicated that the developed assay was reliable and suitable for the detection of Cr(III) in water samples. Copyright © 2013 Elsevier Ltd. All rights reserved.

Membrane-Based Characterization of a Gas Component — A Transient Sensor Theory

PubMed Central

Lazik, Detlef

2014-01-01

Based on a multi-gas solution-diffusion problem for a dense symmetrical membrane this paper presents a transient theory of a planar, membrane-based sensor cell for measuring gas from both initial conditions: dynamic and thermodynamic equilibrium. Using this theory, the ranges for which previously developed, simpler approaches are valid will be discussed; these approaches are of vital interest for membrane-based gas sensor applications. Finally, a new theoretical approach is introduced to identify varying gas components by arranging sensor cell pairs resulting in a concentration independent gas-specific critical time. Literature data for the N2, O2, Ar, CH4, CO2, H2 and C4H10 diffusion coefficients and solubilities for a polydimethylsiloxane membrane were used to simulate gas specific sensor responses. The results demonstrate the influence of (i) the operational mode; (ii) sensor geometry and (iii) gas matrices (air, Ar) on that critical time. Based on the developed theory the case-specific suitable membrane materials can be determined and both operation and design options for these sensors can be optimized for individual applications. The results of mixing experiments for different gases (O2, CO2) in a gas matrix of air confirmed the theoretical predictions. PMID:24608004

Erectile dysfunction in patients with chronic viral hepatitis: a systematic review of the literature.

PubMed

Fusco, Ferdinando; D'Anzeo, Gianluca; Rossi, Andrea; Sciorio, Carmine; Buonomo, Antonio Riccardo; d'Emmanuele di Villa Bianca, Roberta; Borgia, Guglielmo; Mirone, Vincenzo; Gentile, Ivan

2013-12-01

This article reviews the literature on epidemiology and pathogenetic factors of erectile dysfunction in patients with chronic viral hepatic (CVH) diseases in men and the potential implications for diagnosis and treatment. A search to identify original articles, reviews and any other article suitable for the purposes of this review was conducted by combining the following terms: erectile dysfunction and/or sexual dysfunction, chronic viral hepatitis, hepatitis B virus infection and hepatitis C virus infection. The results of this review have led to the following main observations: i) there is scarce documentation on the association between CVH and sexual dysfunction; ii) hormonal impairment seems to be a major component in the development of erectile dysfunction in CVH; however, published evidence concerning the contribution of other pathogenetic factors is rare and inconclusive and iii) available treatment options for CVH potentially contribute to the development of sexual dysfunction in these patients. Due to the scarce body of evidence, more research is needed to better clarify the mechanisms underlying the association between CVH and sexual dysfunction, the impact of therapy and associated comorbidities on sexual dysfunction and the role of pharmacological treatments in the management of these patients.

Methods from Information Extraction from LIDAR Intensity Data and Multispectral LIDAR Technology

NASA Astrophysics Data System (ADS)

Scaioni, M.; Höfle, B.; Baungarten Kersting, A. P.; Barazzetti, L.; Previtali, M.; Wujanz, D.

2018-04-01

LiDAR is a consolidated technology for topographic mapping and 3D reconstruction, which is implemented in several platforms On the other hand, the exploitation of the geometric information has been coupled by the use of laser intensity, which may provide additional data for multiple purposes. This option has been emphasized by the availability of sensors working on different wavelength, thus able to provide additional information for classification of surfaces and objects. Several applications ofmonochromatic and multi-spectral LiDAR data have been already developed in different fields: geosciences, agriculture, forestry, building and cultural heritage. The use of intensity data to extract measures of point cloud quality has been also developed. The paper would like to give an overview on the state-of-the-art of these techniques, and to present the modern technologies for the acquisition of multispectral LiDAR data. In addition, the ISPRS WG III/5 on `Information Extraction from LiDAR Intensity Data' has collected and made available a few open data sets to support scholars to do research on this field. This service is presented and data sets delivered so far as are described.

Systemic therapy after first-line docetaxel in metastatic castration-resistant prostate cancer.

PubMed

Beardsley, Emma K; Chi, Kim N

2008-09-01

There is an urgent need for systemic treatment options for patients with castration-resistant prostate cancer who have progressed after receiving first-line docetaxel chemotherapy. The purpose of this article is to review recent developments in this area. Retreatment with docetaxel has been employed with evidence of activity in selected populations. Mitoxantrone, the previous first-line standard based on its palliative effect, has also been used with clinical responses observed; however, the symptom benefit in this setting has not been established. Several classes of cytotoxic agents have been tested including platinum agents (satraplatin), epothilones (ixabepilone and patupilone) and taxanes (XRP-6258). A number of targeted therapies have also been clinically evaluated including inhibitors of cytoprotective chaperones (OGX-011) and the vascular endothelial growth factor receptor (sorafenib, sunitinib, and cediranib). An area generating great interest has been the development of agents that target the androgen receptor axis more effectively (MDV3100 and abiraterone) with encouraging early phase trial results. There is no accepted standard systemic treatment for patients with castration resistant prostate cancer and progressive disease after docetaxel. Novel agents are in phase II and III clinical testing in this setting.

MisTec - A software application for supporting space exploration scenario options and technology development analysis and planning

NASA Technical Reports Server (NTRS)

Horsham, Gary A. P.

1992-01-01

This structure and composition of a new, emerging software application, which models and analyzes space exploration scenario options for feasibility based on technology development projections is presented. The software application consists of four main components: a scenario generator for designing and inputting scenario options and constraints; a processor which performs algorithmic coupling and options analyses of mission activity requirements and technology capabilities; a results display which graphically and textually shows coupling and options analysis results; and a data/knowledge base which contains information on a variety of mission activities and (power and propulsion) technology system capabilities. The general long-range study process used by NASA to support recent studies is briefly introduced to provide the primary basis for comparison for discussing the potential advantages to be gained from developing and applying this kind of application. A hypothetical example of a scenario option to facilitate the best conceptual understanding of what the application is, how it works, or the operating methodology, and when it might be applied is presented.

MisTec: A software application for supporting space exploration scenario options and technology development analysis and planning

NASA Technical Reports Server (NTRS)

Horsham, Gary A. P.

1991-01-01

The structure and composition of a new, emerging software application, which models and analyzes space exploration scenario options for feasibility based on technology development projections is presented. The software application consists of four main components: a scenario generator for designing and inputting scenario options and constraints; a processor which performs algorithmic coupling and options analyses of mission activity requirements and technology capabilities; a results display which graphically and textually shows coupling and options analysis results; and a data/knowledge base which contains information on a variety of mission activities and (power and propulsion) technology system capabilities. The general long-range study process used by NASA to support recent studies is briefly introduced to provide the primary basis for comparison for discussing the potential advantages to be gained from developing and applying this king of application. A hypothetical example of a scenario option to facilitate the best conceptual understanding of what the application is, how it works, or the operating methodology, and when it might be applied is presented.

Valuation of buyout options in comprehensive development agreements : final report, December 2009.

DOT National Transportation Integrated Search

2009-12-01

This project investigates the feasibility of and develops an economic valuation model for buyout options in : Comprehensive Development Agreements (CDAs). A CDA is a form of public-private partnership in which : the right to price and collect revenue...

Complications of misdiagnosis of maxillary canine ectopic eruption.

PubMed

Garib, Daniela Gamba; Janson, Guilherme; Baldo, Taiana de Oliveira; dos Santos, Patrícia Bittencourt Dutra

2012-08-01

Ectopic eruption of maxillary canines can be associated with root resorption of adjacent teeth. This case report describes and discusses an interesting case of a 15-year-old girl with a Class III malocclusion and an impacted maxillary canine. Because of the unfavorable position of the ectopic canine and the severe root resorption of the maxillary left central and lateral incisors, the treatment options included extraction of the maxillary permanent canines. The mandibular first premolars were extracted to compensate for the Class III malocclusion. A panoramic radiograph taken earlier in the mixed dentition already indicated a possible eruption disturbance of the maxillary left permanent canine. The importance of early diagnosis of maxillary canine ectopic eruption is highlighted in this case report. The early identification of radiographic signs of an ectopic pathway of eruption should be followed by deciduous canine extraction to prevent canine retention and maxillary incisor root resorption. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Crystallization of probucol from solution and the glassy state.

PubMed

Kawakami, Kohsaku; Ohba, Chie

2017-01-30

Crystallization of probucol (PBL) from both solution and glassy solid state was investigated. In the crystallization study from solution, six solvents and three methods, i.e., evaporation, addition of a poor solvent, and cooling on ice, were used to obtain various crystal forms. In addition to common two crystal forms (forms I and II), two further forms (forms III and cyclohexane-solvate) were found in this study, and their thermodynamic relationships were determined. Forms I and II are likely to be enantiotropically related with thermodynamic transition temperature below 5°C. Isothermal crystallization studies revealed that PBL glass initially crystallized into form III between 25 and 50°C, and then transformed to form I. The isothermal crystallization appears to be a powerful option to find uncommon crystal forms. The crystallization of PBL was identified to be pressure controlled, thus the physical stability of PBL glass is higher than that of typical compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

Emergence and mechanism in the fractional quantum Hall effect

NASA Astrophysics Data System (ADS)

Bain, Jonathan

2016-11-01

For some authors, an adequate notion of emergence must include an account of a mechanism by means of which emergent behavior is realized. This appeal to mechanism is problematic in the case of the fractional quantum Hall effect (FQHE). There is a consensus among physicists that the FQHE exhibits emergent phenomena, but there are at least four alternative explanations of the latter that, arguably, appeal to ontologically distinct mechanisms, both at the microphysics level and at the level of general organizing principles. In light of this underdetermination of mechanism, one is faced with the following options: (I) deny that emergence is present in the FQHE; (II) argue for the priority of one mechanistic explanation over the others; or (III) temper the desire for a mechanism-centric account of emergence. I will argue that there are good reasons to reject (I) and (II) and accept (III). In particular, I will suggest that a law-centric account of emergence does just fine in explaining the emergent phenomena associated with the FQHE.

Repair-oriented classification of aortic insufficiency: impact on surgical techniques and clinical outcomes.

PubMed

Boodhwani, Munir; de Kerchove, Laurent; Glineur, David; Poncelet, Alain; Rubay, Jean; Astarci, Parla; Verhelst, Robert; Noirhomme, Philippe; El Khoury, Gébrine

2009-02-01

Valve repair for aortic insufficiency requires a tailored surgical approach determined by the leaflet and aortic disease. Over the past decade, we have developed a functional classification of AI, which guides repair strategy and can predict outcome. In this study, we analyze our experience with a systematic approach to aortic valve repair. From 1996 to 2007, 264 patients underwent elective aortic valve repair for aortic insufficiency (mean age - 54 +/- 16 years; 79% male). AV was tricuspid in 171 patients bicuspid in 90 and quadricuspid in 3. One hundred fifty three patients had type I dysfunction (aortic dilatation), 134 had type II (cusp prolapse), and 40 had type III (restrictive). Thirty six percent (96/264) of the patients had more than one identified mechanism. In-hospital mortality was 1.1% (3/264). Six patients experienced early repair failure; 3 underwent re-repair. Functional classification predicted the necessary repair techniques in 82-100% of patients, with adjunctive techniques being employed in up to 35% of patients. Mid-term follow up (median [interquartile range]: 47 [29-73] months) revealed a late mortality rate of 4.2% (11/261, 10 cardiac). Five year overall survival was 95 +/- 3%. Ten patients underwent aortic valve reoperation (1 re-repair). Freedoms from recurrent Al (>2+) and from AV reoperation at 5 years was 88 +/- 3% and 92 +/- 4% respectively and patients with type I (82 +/- 9%; 93 +/- 5%) or II (95 +/- 5%; 94 +/- 6%) had better outcomes compared to type III (76 +/- 17%; 84 +/- 13%). Aortic valve repair is an acceptable therapeutic option for patients with aortic insufficiency. This functional classification allows a systematic approach to the repair of Al and can help to predict the surgical techniques required as well as the durability of repair. Restrictive cusp motion (type III), due to fibrosis or calcification, is an important predictor for recurrent Al following AV repair.

Options and limitations for bromate control during ozonation of wastewater.

PubMed

Soltermann, Fabian; Abegglen, Christian; Tschui, Manfred; Stahel, Sandro; von Gunten, Urs

2017-06-01

Wastewater treatment plants (WWTPs) are important point sources for micropollutants, which are harmful to freshwater organisms. Ozonation of wastewater is a powerful option to abate micropollutants, but may result in the formation of the potentially toxic oxidation by-product bromate in bromide-containing wastewaters. This study investigates options to reduce bromate formation during wastewater ozonation by (i) reducing the bromide concentration of the wastewater, (ii) lowering the ozone dose during wastewater treatment and (iii) adding hydrogen peroxide to limit the lifetime of ozone and quench the intermediates of the bromate formation pathway. Two examples demonstrate that a high share of bromide in wastewater can originate from single point sources (e.g., municipal waste incinerators or landfills). The identification of major point sources requires laborious sampling campaigns, but may facilitate the reduction of the bromide load significantly. To reduce the bromate formation by lowering the ozone dose interferes with the aim to abate micropollutants. Therefore, an additional treatment is necessary to ensure the elimination of micropollutants. Experiments at a pilot-plant illustrate that a combined treatment (ozone/powdered activated carbon) allows to eliminate micropollutants with low bromate yields. Furthermore, the addition of hydrogen peroxide was investigated at bench-scale. The bromate yields could be reduced by ∼50% and 65% for a hydrogen peroxide dose of 5 and 10 mg L -1 , respectively. In conclusion, there are options to reduce the bromate formation during wastewater ozonation, however, they are not simple with sometimes limited efficiency. Copyright © 2017 Elsevier Ltd. All rights reserved.

Optimization of the strength of the efavirenz/lamivudine/abacavir fixed-dose combination for paediatric patients.

PubMed

Bouazza, Naïm; Cressey, Tim R; Foissac, Frantz; Bienczak, Andrzej; Denti, Paolo; McIlleron, Helen; Burger, David; Penazzato, Martina; Lallemant, Marc; Capparelli, Edmund V; Treluyer, Jean-Marc; Urien, Saïk

2017-02-01

Child-friendly, low-cost, solid, oral fixed-dose combinations (FDCs) of efavirenz with lamivudine and abacavir are urgently needed to improve clinical management and drug adherence for children. Data were pooled from several clinical trials and therapeutic drug monitoring datasets from different countries. The number of children/observations was 505/3667 for efavirenz. Population pharmacokinetic analyses were performed using a non-linear mixed-effects approach. For abacavir and lamivudine, data from 187 and 920 subjects were available (population pharmacokinetic models previously published). Efavirenz/lamivudine/abacavir FDC strength options assessed were (I) 150/75/150, (II) 120/60/120 and (III) 200/100/200 mg. Monte Carlo simulations of the different FDC strengths were performed to determine the optimal dose within each of the WHO weight bands based on drug efficacy/safety targets. The probability of being within the target efavirenz concentration range 12 h post-dose (1-4 mg/L) varied between 56% and 60%, regardless of FDC option. Option I provided a best possible balance between efavirenz treatment failure and toxicity risks. For abacavir and lamivudine, simulations showed that for option I >75% of subjects were above the efficacy target. According to simulations, a paediatric efavirenz/lamivudine/abacavir fixed-dose formulation of 150 mg efavirenz, 75 mg lamivudine and 150 mg abacavir provided the most effective and safe concentrations across WHO weight bands, with the flexibility of dosage required across the paediatric population. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Nuclear Fuel Cycle Options Catalog: FY16 Improvements and Additions

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

Price, Laura L.; Barela, Amanda Crystal; Schetnan, Richard Reed

2016-08-31

The United States Department of Energy, Office of Nuclear Energy, Fuel Cycle Technology Program sponsors nuclear fuel cycle research and development. As part of its Fuel Cycle Options campaign, the DOE has established the Nuclear Fuel Cycle Options Catalog. The catalog is intended for use by the Fuel Cycle Technologies Program in planning its research and development activities and disseminating information regarding nuclear energy to interested parties. The purpose of this report is to document the improvements and additions that have been made to the Nuclear Fuel Cycle Options Catalog in the 2016 fiscal year.

Optimizing spacecraft design - optimization engine development : progress and plans

NASA Technical Reports Server (NTRS)

Cornford, Steven L.; Feather, Martin S.; Dunphy, Julia R; Salcedo, Jose; Menzies, Tim

2003-01-01

At JPL and NASA, a process has been developed to perform life cycle risk management. This process requires users to identify: goals and objectives to be achieved (and their relative priorities), the various risks to achieving those goals and objectives, and options for risk mitigation (prevention, detection ahead of time, and alleviation). Risks are broadly defined to include the risk of failing to design a system with adequate performance, compatibility and robustness in addition to more traditional implementation and operational risks. The options for mitigating these different kinds of risks can include architectural and design choices, technology plans and technology back-up options, test-bed and simulation options, engineering models and hardware/software development techniques and other more traditional risk reduction techniques.

Activities of natural methyl farnesoids on pupariation and metamorphosis of Drosophila melanogaster

USDA-ARS?s Scientific Manuscript database

Methyl farnesoate (MF) and juvenile hormone (JH III), which respectively bind to the receptors USP and MET, and bisepoxy JH III (bisJHIII) were assessed for several activities during Drosophila larval development, and during prepupal development to eclosed adults. Dietary MF and JH III were similar...

Connection between nitrogen and manganese cycles revealed by transcriptomic analysis in Shewanella algae C6G3

NASA Astrophysics Data System (ADS)

Michotey, V.; Aigle, A.; Armougom, F.; Mejean, V.; Guasco, S.; Bonin, P.

2016-02-01

In sedimentary systems, the repartition of terminal electron-accepting molecules is often stratified on a permanent or seasonal basis. Just below to oxic zone, the suboxic one is characterized by high concentrations of oxidized inorganic compounds such as nitrate, manganese oxides (MnIII/IV) and iron oxides that are in close vicinity. Several studies have reported unexpected anaerobic nitrite/nitrate production at the expense of ammonium mediated by MnIII/IV, however this transient processes is difficult to discern and poorly understood. In the frame of this study, genes organization of nitrate and MnIII/IV respiration was investigated in S.algae. Additional genes were identified in S. algae compare to S. oneidensis: genes coding for nitrate and nitrite reductase (napA-a and nrfA-2) and an OMC protein (mtrH). In contrast to S. oneidensis, an anaerobic transitory nitrite accumulation at the expense of ammonium was observed in S. algae during growth with MnIII/IV, concomitantly with expression of nitrate/nitrite reductase genes (napA, nrfA, nrfA-2). Among the hypothesis explaining this data, the potential putative expression of unidentified gene able to perform ammonium oxidation was not observed on the global transcriptional level, however several signs of oxidative stress were detected and the existence of a secondary reaction generated by a putative oxidative s could not be excluded. Another option could be the action of reverse reaction by an enzyme such as NrfA or NrfA-2 due to the electron flow equilibrium. Whatever the electron acceptor (Nitrate/ MnIII/IV), the unexpected expression level of of omcA, mtrF, mtrH, mtrC was observed and peaked at the end of the exponential phase. Different expression patterns of the omc genes were observed depending on electron acceptor and growth phase. Only mtrF-2 gene was specifically expressed in Mn(III/IV) condition. Nitrate and Mn(III/IV) respirations seem connected at physiological as well as at transcriptional level

The HubBLe trial: haemorrhoidal artery ligation (HAL) versus rubber band ligation (RBL) for haemorrhoids.

PubMed

Tiernan, Jim; Hind, Daniel; Watson, Angus; Wailoo, Allan J; Bradburn, Michael; Shephard, Neil; Biggs, Katie; Brown, Steven

2012-10-25

Haemorrhoids (piles) are a very common condition seen in surgical clinics. After exclusion of more sinister causes of haemorrhoidal symptoms (rectal bleeding, perianal irritation and prolapse), the best option for treatment depends upon persistence and severity of the symptoms. Minor symptoms often respond to conservative treatment such as dietary fibre and reassurance. For more severe symptoms treatment such as rubber band ligation may be therapeutic and is a very commonly performed procedure in the surgical outpatient setting. Surgery is usually reserved for those who have more severe symptoms, as well as those who do not respond to non-operative therapy; surgical techniques include haemorrhoidectomy and haemorrhoidopexy. More recently, haemorrhoidal artery ligation has been introduced as a minimally invasive, non destructive surgical option.There are substantial data in the literature concerning efficacy and safety of 'rubber band ligation including multiple comparisons with other interventions, though there are no studies comparing it to haemorrhoidal artery ligation. A recent overview has been carried out by the National Institute for Health and Clinical Excellence which concludes that current evidence shows haemorrhoidal artery ligation to be a safe alternative to haemorrhoidectomy and haemorrhoidopexy though it also highlights the lack of good quality data as evidence for the advantages of the technique. The aim of this study is to establish the clinical effectiveness and cost effectiveness of haemorrhoidal artery ligation compared with conventional rubber band ligation in the treatment of people with symptomatic second or third degree (Grade II or Grade III) haemorrhoids. A multi-centre, parallel group randomised controlled trial. The primary outcome is patient-reported symptom recurrence twelve months following the intervention. Secondary outcome measures relate to symptoms, complications, health resource use, health related quality of life and cost effectiveness following the intervention. 350 patients with grade II or grade III haemorrhoids will be recruited in surgical departments in up to 14 NHS hospitals. A multi-centre, parallel group randomised controlled trial. Block randomisation by centre will be used, with 175 participants randomised to each group. The results of the research will help inform future practice for the treatment of grade II and III haemorrhoids. ISRCTN41394716.

A single-arm phase III study exploring the efficacy and safety of LNG-IUS 8, a low-dose levonorgestrel intrauterine contraceptive system (total content 13.5 mg), in an Asia-Pacific population.

PubMed

Fan, Guangsheng; Kang, Sukho; Ren, Mulan; Weisberg, Edith; Lukkari-Lax, Eeva; Roth, Katrin; Shin, SoYoung

2017-04-01

The objective was to evaluate the efficacy and safety of a low-dose levonorgestrel intrauterine system with total content 13.5 mg (average approximately 8 μg/24 h over the first year; LNG-IUS 8; Jaydess®) in an Asia-Pacific population. An open-label, single-arm phase III study conducted at 25 centers in China, Australia and Korea assessed LNG-IUS 8 use over 3 years in nulliparous and parous women (N=1114) aged 18-40 years with regular menstrual cycles (21-35 days). Primary outcome was pregnancy rate, expressed as the Pearl Index. Secondary outcomes included 3-year cumulative failure rate, treatment-emergent adverse events (TEAEs), discontinuation rate, bleeding profile and placement pain. The full analysis set comprised 925 women (mean age 31.6 years, 6.4% nulliparous). Overall unadjusted Pearl Index was 0.35 (95% confidence interval 0.15-0.70); the 3-year cumulative failure rate was 0.9% (95% confidence interval 0.4-1.9). TEAEs and study drug-related TEAEs were reported in 70.1% and 31.2% of women, respectively. Overall, 27.9% of women discontinued the study, 16.9% due to adverse events. Frequent or prolonged bleeding (World Health Organization criteria) decreased from the first to the twelfth 90-day reference intervals (from 5.0% to 0.7% and from 44.1% to 3.0%, respectively), and the percentage of women with amenorrhea increased over time (from 0.4% to 10.8%). Pain on placement was reported as "none" or "mild" in 91.9% of women. LNG-IUS 8 was an effective and well-tolerated contraceptive method, providing another option for women in the Asia-Pacific region. In this phase III study, LNG-IUS 8 was shown to be highly effective and well tolerated in an Asia-Pacific population and was not associated with any new or unexpected safety events. LNG-IUS 8 provides another contraceptive option for women in the Asia-Pacific region. Copyright © 2016. Published by Elsevier Inc.

Efficacy and safety of collagenase clostridium histolyticum in the treatment of proximal interphalangeal joints in dupuytren contracture: combined analysis of 4 phase 3 clinical trials.

PubMed

Badalamente, Marie A; Hurst, Lawrence C; Benhaim, Prosper; Cohen, Brian M

2015-05-01

To examine the results of proximal interphalangeal (PIP) joint contractures from 4 phase 3 clinical trials of collagenase clostridium histolyticum (CCH) injection for Dupuytren contracture. Patients enrolled in Collagenase Option for Reduction of Dupuytren I/II and JOINT I/II with one or more PIP joint contractures (20° to 80°) received CCH 0.58 mg/0.20 mL or placebo (Collagenase Option for Reduction of Dupuytren I/II only) injected directly into a palpable cord. The percentage of PIP joints achieving clinical success (0° to 5° of full extension), clinical improvement (50% or more reduction in baseline contracture), and range of motion improvement at 30 days after the first and last CCH injections was assessed. The PIP joint contractures were classified into low (40° or less) and high (more than 40°) baseline severity. Adverse events were recorded. A total of 506 adults (mean age, 63 ± 10 y; 80% male) received 1,165 CCH injections in 644 PIP joint cords (mean, 1.6 injections/cord). Most patients (60%) received 1 injection, with 24%, 16%, and 1% receiving 2, 3, and 4 injections, respectively. Clinical success and clinical improvement occurred in 27% and 49% of PIP joints after one injection and in 34% and 58% after the last injection. Patients with lower baseline severity showed greater improvement and response was comparable between fingers, as were improvements in range of motion. Adverse events occurring in more than 10% of patients were peripheral edema (58%), contusion (38%), injection site hemorrhage (23%), injection site pain (21%), injection site swelling (16%), and tenderness (13%). This incidence was consistent with data reported in phase 3 trials. Two tendon ruptures occurred. No further ruptures occurred after a modified injection technique was adopted. Collagenase clostridium histolyticum was effective and well tolerated in the short term in patients with Dupuytren PIP joint contractures. Therapeutic II. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Management of severe blunt hepatic injury in the era of computed tomography and transarterial embolization: A systematic review and critical appraisal of the literature.

PubMed

Melloul, Emmanuel; Denys, Alban; Demartines, Nicolas

2015-09-01

During the last decade, the management of blunt hepatic injury has considerably changed. Three options are available as follows: nonoperative management (NOM), transarterial embolization (TAE), and surgery. We aimed to evaluate in a systematic review the current practice and outcomes in the management of Grade III to V blunt hepatic injury. The MEDLINE database was searched using PubMed to identify English-language citations published after 2000 using the key words blunt, hepatic injury, severe, and grade III to V in different combinations. Liver injury was graded according to the American Association for the Surgery of Trauma classification on computed tomography (CT). Primary outcome analyzed was success rate in intention to treat. Critical appraisal of the literature was performed using the validated National Institute for Health and Care Excellence "Quality Assessment for Case Series" system. Twelve articles were selected for critical appraisal (n = 4,946 patients). The median quality score of articles was 4 of 8 (range, 2-6). Overall, the median Injury Severity Score (ISS) at admission was 26 (range, 0.6-75). A median of 66% (range, 0-100%) of patients was managed with NOM, with a success rate of 94% (range, 86-100%). TAE was used in only 3% of cases (range, 0-72%) owing to contrast extravasation on CT with a success rate of 93% (range, 81-100%); however, 9% to 30% of patients required a laparotomy. Thirty-one percent (range, 17-100%) of patients were managed with surgery owing to hemodynamic instability in most cases, with 12% to 28% requiring secondary TAE to control recurrent hepatic bleeding. Mortality was 5% (range, 0-8%) after NOM and 51% (range, 30-68%) after surgery. NOM of Grade III to V blunt hepatic injury is the first treatment option to manage hemodynamically stable patients. TAE and surgery are considered in a highly selective group of patients with contrast extravasation on CT or shock at admission, respectively. Additional standardization of the reports is necessary to allow accurate comparisons of the various management strategies. Systematic review, level IV.

Development of III-V p-MOSFETs with high-kappa gate stack for future CMOS applications

NASA Astrophysics Data System (ADS)

Nagaiah, Padmaja

As the semiconductor industry approaches the limits of traditional silicon CMOS scaling, non-silicon materials and new device architectures are gradually being introduced to improve Si integrated circuit performance and continue transistor scaling. Recently, the replacement of SiO2 with a high-k material (HfO2) as gate dielectric has essentially removed one of the biggest advantages of Si as channel material. As a result, alternate high mobility materials are being considered to replace Si in the channel to achieve higher drive currents and switching speeds. III-V materials in particular have become of great interest as channel materials, owing to their superior electron transport properties. However, there are several critical challenges that need to be addressed before III-V based CMOS can replace Si CMOS technology. Some of these challenges include development of a high quality, thermally stable gate dielectric/III-V interface, and improvement in III-V p-channel hole mobility to complement the n-channel mobility, low source/drain resistance and integration onto Si substrate. In this thesis, we would be addressing the first two issues i.e. the development high performance III-V p-channels and obtaining high quality III-V/high-k interface. We start with using the device architecture of the already established InGaAs n-channels as a baseline to understand the effect of remote scattering from the high-k oxide and oxide/semiconductor interface on channel transport properties such as electron mobility and channel electron concentration. Temperature dependent Hall electron mobility measurements were performed to separate various scattering induced mobility limiting factors. Dependence of channel mobility on proximity of the channel to the oxide interface, oxide thickness, annealing conditions are discussed. The results from this work will be used in the design of the p-channel MOSFETs. Following this, InxGa1-xAs (x>0.53) is chosen as channel material for developing p-channel MOSFETs. Band engineering, strain induced valence band splitting and quantum confinement is used to improve channel hole mobility. Experimental results on the Hall hole mobility is presented for InxGa1-xAs channels with varying In content, thickness of the quantum well and temperature. Then, high mobility InxGa 1-xAs heterostructure thus obtained are integrated with in-situ deposited high-k gate oxide required for high performance p-MOSFET and discuss the challenges associated with the gated structure and draw conclusions on this material system. Antimonide based channel materials such as GaSb and InxGa 1-xSb are explored for III-V based p-MOSFETs in last two chapters. Options for Sb based strained QW channels to obtain maximum hole mobility by varying the strain, channel and barrier material, thickness of the layers etc. is discussed followed by the growth of these Sb channels on GaAs and InP substrates using molecular beam epitaxy. The physical properties of the structures such as the heterostructure quality, alloy content and surface roughness are examined via TEM, XRD and AFM. Following this, electrical measurement results on Hall hole mobility is presented. The effect of strain, alloy content, temperature and thickness on channel mobility and concentration is reported. Development of GaSb n- and p-MOS capacitor structures with in-situ deposited HfO2 gate oxide dielectric using in-situ deposited amorphous Si (a-Si) interface passivation layer (IPL) to improve the interface quality of high-k oxide and (In)GaSb surface is presented. In-situ deposited gate oxides such as Al2O3 and combination oxide of Al 2O3 and HfO2 with and without the a-Si IPL are also explored as alternate gate dielectrics. Subsequently, MOS capacitor structures using buried InGaSb QWs are demonstrated. Development of an inversion type bulk GaSb with implanted source-drain contacts and in-situ deposited gate oxide HfO2 gate oxide is discussed. The merits of biaxial compressive strain is demonstrated on strained surface and buried channel In0.36 Ga0.64Sb QW MOSFETs with thin top barrier and in-situ deposited a-Si IPL and high-k HfO2 as well as combination Al 2O3+HfO2 gate stacks and ex-situ atomic layer deposited (ALD) combination gate oxide and with thin 2 nm InAs surface passivation layer is presented. Finally, summary of the salient results from the different chapters is provided with recommendations for future research.

[Classification of enuresis/encopresis according to DSM-5].

PubMed

von Gontard, Alexander

2014-03-01

Elimination disorders are common in childhood and adolescence. Enuresis is traditionally defined as wetting from the age of 5 years and encopresis as soiling from 4 years onwards - after all organic causes have been excluded. In the past decades, many subtypes of elimination disorders have been identified with different symptoms, etiologies, and specific treatment options. Unfortunately, the DSM-5 criteria did not integrate these new approaches. In contrast, classification systems of the International Children's Incontinence Society (ICCS) for enuresis and urinary incontinence as well as the ROME-III criteria for fecal incontinence offer new and relevant suggestions for both clinical and research purposes.

Squalene synthase inhibition: a novel target for the management of dyslipidemia.

PubMed

Davidson, Michael H

2007-01-01

A new class of compounds, known as squalene synthase inhibitors, has recently reached phase III clinical trials and may provide another therapeutic option for clinicians to improve risk management of low-density lipoprotein cholesterol (LDL-C). The clinical need for another LDL-C-lowering therapy is evident by the inability to achieve an LDL-C target of less than 70 mg/dL in the majority of very high-risk patients on statin monotherapy. Human clinical trial data with TAK-475, a novel and potent inhibitor of squalene synthase, have not yet been published.

Pharmacotherapy for Irritable Bowel Syndrome

PubMed Central

Camilleri, Michael

2017-01-01

Irritable bowel syndrome (IBS) is a disorder of the brain-gut axis; the pathophysiological mechanisms include altered colonic motility, bile acid metabolism, neurohormonal regulation, immune dysfunction, alterations in the epithelial barrier and secretory properties of the gut. This article reviews the mechanisms, efficacy, and safety of current pharmacotherapy, and medications that are in phase III trials for the treatment of IBS. There remains a significant unmet need for effective treatments—particularly for the pain component of IBS—although the introduction of drugs directed at secretion, motility and a non-absorbable antibiotic provide options for the bowel dysfunction in IBS. PMID:29077050

Update on the Management of Diarrhea-Predominant Irritable Bowel Syndrome: Focus on Rifaximin and Eluxadoline.

PubMed

Rivkin, Anastasia; Rybalov, Sergey

2016-03-01

Diarrhea-predominant irritable bowel syndrome (IBS-D) is one of the most common diagnoses made by gastroenterologists. Current pharmacologic treatments for IBS-D include fiber supplements, antidiarrheal over-the-counter medications, probiotics, antispasmodics, antidepressants, and a 5-hydroxytryptophan 3 receptor antagonist. All of these options have limited efficacy in managing IBS-D. Rifaximin, a nonabsorbable antibiotic, has been evaluated in patients with IBS-D. In two randomized, double-blind, placebo-controlled phase III trials evaluating rifaximin 550 mg by mouth 3 times/day for 14 days, the primary efficacy end point was achieved by 9% more patients randomized to the rifaximin group compared with placebo (40.7% vs 31.7%, p<0.001, number needed to treat ~11). The primary efficacy end point was defined as the proportion of patients having adequate relief of global IBS symptoms for at least 2 of the 4 weeks during the primary follow-up period (weeks 3-6). In the phase III trial examining the efficacy and safety of repeated courses of rifaximin in patients who responded to the initial 2-week course, rifaximin given for up to two additional courses provided a statistically significant incremental benefit (33% vs 25%, p=0.02). Eluxadoline is a gut-targeting μ and κ opioid receptor agonist and a δ opioid receptor antagonist. The dual mechanism of eluxadoline may explain the antidiarrheal and abdominal pain-modulating properties and lack of profound constipation. In two identically designed randomized, double-blind, placebo-controlled phase III studies, 10.3% more patients in an eluxadoline 100 mg by mouth twice/day group met the primary efficacy end point during the follow-up 1-12 week period compared with placebo (p<0.001). The primary efficacy end point was a composite response, defined as improvement in worst abdominal pain and stool consistency at the same time on most (50% or more) days during the follow-up period. This review evaluates evidence for the use of rifaximin and eluxadoline in patients with IBS-D. Rifaximin provides an additional modality for the management of IBS-D patients; it has mild to moderate efficacy similar to other currently available treatment options. Rifaximin is relatively safe, lacks significant drug-drug interactions, and can be used for up to two additional retreatment courses. This may make rifaximin a possible initial or second-line treatment option. Eluxadoline can also offer relief to patients with IBS-D. While effective, because of several limitations, including drug-drug interactions and drug disease contraindications, as well as current lack of clinical experience, it may be tried as a second- or third-line agent. © 2016 Pharmacotherapy Publications, Inc.

Indirect Treatment Comparisons of Ibrutinib Versus Physician's Choice and Idelalisib Plus Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia.

PubMed

Sorensen, Sonja; Wildgust, Mark; Sengupta, Nishan; Trambitas, Cristina; Diels, Joris; van Sanden, Suzy; Xu, Yingxin; Dorman, Emily

2017-01-01

Treatment options for patients with relapsed or refractory chronic lymphocytic leukemia (R/R CLL) are limited. Until recently, few effective treatment options existed, and even with the advent of new agents, studies evaluating comparative efficacy are scarce. In the Ibrutinib Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (RESONATE) Phase III study, ibrutinib, an oral, once-a-day, first-in-class covalent Bruton tyrosine kinase inhibitor, improved progression-free survival (PFS) and overall survival (OS) compared with ofatumumab (PFS hazard ratio [HR] = 0.106 and OS HR = 0.369 [adjusted for crossover] at a median of 16 months' follow-up). We sought to establish the relative efficacy of ibrutinib versus other treatment options for patients with R/R CLL using indirect comparison methods. A systematic literature review was conducted to identify clinical trials sharing a common treatment arm with the RESONATE Phase III trial such that a network meta-analysis or indirect treatment comparisons (ITCs) could be conducted. Two trials were identified, each using the same comparator (ofatumumab) as the RESONATE study. Two pairwise ITCs were conducted using the Bucher method to establish the relative treatment efficacy of ibrutinib versus (1) idelalisib plus ofatumumab in the first study and (2) physician's choice, defined as a mix of therapies commonly used in R/R CLL, in the second study. Odds ratios for these ITCs were calculated for overall response rate (ORR) and HRs for PFS and OS. A strong and consistent trend of superiority for ibrutinib was observed via these ITC models with idelalisib plus ofatumumab and physician's choice for ORR, PFS, and OS. Ibrutinib revealed prolonged PFS and OS versus comparators (PFS HR = 0.06; 95% CI, 0.04-0.11; and OS HR = 0.25; 95% CI, 0.12-0.54), physician's choice (PFS HR = 0.41; 95% CI, 0.25-0.66; and OS HR = 0.50; 95% CI, 0.23-1.08), and idelalisib plus ofatumumab. These findings were robust and continued to favor ibrutinib when adjusting (where appropriate) for underlying differences in patient population between the trials. Some trial differences were not accounted for in the models and thus some limitations remain; however, consistency of results supports the overall findings. In a randomized Phase III study, ibrutinib significantly improved ORR, PFS, and OS in patients with R/R CLL versus ofatumumab. In ITC models that used ofatumumab as the common comparator, ibrutinib appears to have higher ORR and longer PFS and OS versus both idelalisib plus ofatumumab and physician's choice. In the absence of head-to-head studies and taking into consideration inherent limitations of ITCs, these models provide useful estimates of comparative efficacy. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Osimertinib for EGFR T790M mutation-positive non-small cell lung cancer.

PubMed

Soejima, Kenzo; Yasuda, Hiroyuki; Hirano, Toshiyuki

2017-01-01

Significant advances have been made since the development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) targeting EGFR mutations in non-small-cell lung cancer (NSCLC), however, lung cancer cells eventually acquire resistance to those agents. Osimertinib (AZD9291) has been developed as 3 rd generation EGFR-TKI with activities against sensitizing mutations and T790 M resistance mutation, which account for about 50% of the mechanisms of acquired resistance to 1 st or 2 nd generation EGFR-TKIs. A recent phase I/II clinical trial with osimertinib for advanced NSCLC patients with known sensitizing EGFR mutations and documented disease progression on prior EGFR-TKIs revealed promising effect with acceptable toxicities. Areas covered: This article summarizes current understanding and available preclinical and clinical data on osimertinib and also discusses future directions. The literature search included PubMed and the latest articles from international conferences. Expert commentary: The development of osimertinib has provided new therapeutic options for NSCLC patients harboring T790 M. Compared with other EGFR-TKIs including rociletinib, osimertinib seems to possess an advantage with respect to the effect and safety profile among existing EGFR-TKIs. However, tumor progression still occurs even when treating with osimertinib. A further understanding of the mechanisms of resistance is eagerly anticipated in order to develop next generation EGFR-TKIs.

Development Of Regional Climate Mitigation Baseline For A DominantAgro-Ecological Zone Of Karnataka, India

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

Sudha, P.; Shubhashree, D.; Khan, H.

2007-06-01

Setting a baseline for carbon stock changes in forest andland use sector mitigation projects is an essential step for assessingadditionality of the project. There are two approaches for settingbaselines namely, project-specific and regional baseline. This paperpresents the methodology adopted for estimating the land available formitigation, for developing a regional baseline, transaction cost involvedand a comparison of project-specific and regional baseline. The studyshowed that it is possible to estimate the potential land and itssuitability for afforestation and reforestation mitigation projects,using existing maps and data, in the dry zone of Karnataka, southernIndia. The study adopted a three-step approach for developing a regionalbaseline,more » namely: i) identification of likely baseline options for landuse, ii) estimation of baseline rates of land-use change, and iii)quantification of baseline carbon profile over time. The analysis showedthat carbon stock estimates made for wastelands and fallow lands forproject-specific as well as the regional baseline are comparable. Theratio of wasteland Carbon stocks of a project to regional baseline is1.02, and that of fallow lands in the project to regional baseline is0.97. The cost of conducting field studies for determination of regionalbaseline is about a quarter of the cost of developing a project-specificbaseline on a per hectare basis. The study has shown the reliability,feasibility and cost-effectiveness of adopting regional baseline forforestry sectormitigation projects.« less

Development of other microtubule-stabilizer families: the epothilones and their derivatives.

PubMed

Brogdon, Cynthia F; Lee, Francis Y; Canetta, Renzo M

2014-05-01

Chemotherapy is the mainstay of treatment for numerous cancer types, but resistance to chemotherapy remains a major clinical issue and is one of the driving influences underlying the development of new anticancer medications. One of the most important classes of chemotherapy agents is the taxanes, which target the cytoskeleton and spindle apparatus of tumor cells by binding to the microtubules, thereby disrupting key cellular mechanisms, including mitosis. Taxane resistance, however, limits treatment options and creates a major challenge for clinicians. Ongoing research has identified several newer classes of microtubule-targeting chemotherapies that may retain activity despite clinical resistance to taxanes. Among these classes, the epothilones have been studied most extensively in the clinical setting. Like taxanes, epothilones stabilize microtubulin turnover, and they have properties favoring their development as anticancer agents. The most clinically advanced epothilone analog is ixabepilone, which is currently the only approved epothilone derivative. Ixabepilone is indicated for the treatment of metastatic or locally advanced breast cancer in combination with capecitabine after failure of an anthracycline and a taxane, or as monotherapy after failure of an anthracycline, a taxane, and capecitabine. In phase II and III trials, ixabepilone showed efficacy in several patient subgroups and in various stages of breast cancer. Common adverse reactions include peripheral sensory neuropathy and asthenia. This paper will discuss the preclinical and clinical development of epothilones and their derivatives across a variety of cancer types.

The future of anticoagulation management in atrial fibrillation in Europe: An assessment of today's challenges with recommendations for the future.

PubMed

Lichten, Catherine A; Castle-Clarke, Sophie; Manville, Catriona; Horvath, Veronika; Robin, Enora; Krapels, Joachim; Parks, Sarah; Sim, Megan; van Zijverden, Olga; Chataway, Joanna

2015-11-30

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia, affecting approximately 1-2 per cent of the population worldwide. Those who suffer from AF have a five times higher risk of stroke. AF prevalence increases with age and it affects roughly 18 per cent of the population over 85. Consequently, as populations age, AF is becoming an increasingly significant public health issue. Over recent years there have been developments in treatment and management options, both for treating the arrhythmia directly, and assessing and reducing the risk of AF-related stroke, but there is a need to ensure that available knowledge is applied optimally to benefit patients so that opportunities to prevent AF-related stroke are not missed. The aims of this project were to assess the current landscape and explore the direction of future developments in AF management in Europe, with a focus on the use of anticoagulants in the prevention of AF-related stroke. Through rapid evidence assessment, key informant interviews, PESTLE analysis and the development and exploration of future scenarios, we have developed sets of shorter- and longer-term recommendations for improving AF-related patient outcomes. The short-term recommendations are: i) improve AF awareness among the public and policymakers; ii) support education about AF management for healthcare professionals and patients; and iii) maintain engagement in AF-related research across the health services.

Does implied volatility of currency futures option imply volatility of exchange rates?

NASA Astrophysics Data System (ADS)

Wang, Alan T.

2007-02-01

By investigating currency futures options, this paper provides an alternative economic implication for the result reported by Stein [Overreactions in the options market, Journal of Finance 44 (1989) 1011-1023] that long-maturity options tend to overreact to changes in the implied volatility of short-maturity options. When a GARCH process is assumed for exchange rates, a continuous-time relationship is developed. We provide evidence that implied volatilities may not be the simple average of future expected volatilities. By comparing the term-structure relationship of implied volatilities with the process of the underlying exchange rates, we find that long-maturity options are more consistent with the exchange rates process. In sum, short-maturity options overreact to the dynamics of underlying assets rather than long-maturity options overreacting to short-maturity options.

Rural Energy Options Analysis Training Development and Implementation at NREL

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

Gilman, P.

2005-01-01

NREL has developed a rural energy options analysis training program for rural energy decision makers that provides knowledge, skills and tools for the evaluation of technologies, including renewables, for rural energy applications. Through the Department of Energy (DOE) Solar Energy Technologies Program (SETP), NREL has refined materials for the program and developed a module that offers hands-on training in the preparation of data for options analysis using HOMER, NREL's micropower optimization model. NREL has used the materials for training in Brazil, the Maldives, Mexico, and Sri Lanka.

Intentionally Short-Range Communications (ISRC) exploratory development plan

NASA Astrophysics Data System (ADS)

Yen, J.

1992-06-01

This document is an exploratory development plan for the Intentionally Short-Range Communications (ISRC) project. The USMC requirements and project objectives are quantified, then possible solutions identified and developed. Some of these ideas will be attempted to determine the best option(s) satisfying the USMC requirements.

Surgical options for lumbosacral fusion: biomechanical stability, advantage, disadvantage and affecting factors in selecting options.

PubMed

Yoshihara, Hiroyuki

2014-07-01

Numerous surgical procedures and instrumentation techniques for lumbosacral fusion (LSF) have been developed. This is probably because of its high mechanical demand and unique anatomy. Surgical options include anterior column support (ACS) and posterior stabilization procedures. Biomechanical studies have been performed to verify the stability of those options. The options have their own advantage but also disadvantage aspects. This review article reports the surgical options for lumbosacral fusion, their biomechanical stability, advantages/disadvantages, and affecting factors in option selection. Review of literature. LSF has lots of options both for ACS and posterior stabilization procedures. Combination of posterior stabilization procedures is an option. Furthermore, combinations of ACS and posterior stabilization procedures are other options. It is difficult to make a recommendation or treatment algorithm of LSF from the current literature. However, it is important to know all aspects of the options and decision-making of surgical options for LSF needs to be tailored for each patient, considering factors such as biomechanical stress and osteoporosis.