Clinical trials in cystic fibrosis

In patients with cystic fibrosis (CF), clinical trials are of paramount importance. Here, the current status of drug development in CF is discussed and future directions highlighted. Methods for pre-clinical testing of drugs with potential activity in CF patients including relevant animal models are described. Study design options for phase II and phase III studies involving CF patients are provided, including required patient numbers, safety issues and surrogate end point parameters for drugs, tested for different disease manifestations. Finally, regulatory issues for licensing new therapies for CF patients are discussed, including new directives of the European Union and the structure of a European clinical trial network for clinical studies involving CF patients is proposed.

PLUMED 2: New feathers for an old bird

Enhancing sampling and analyzing simulations are central issues in molecular simulation. Recently, we introduced PLUMED, an open-source plug-in that provides some of the most popular molecular dynamics (MD) codes with implementations of a variety of different enhanced sampling algorithms and collective variables (CVs). The rapid changes in this field, in particular new directions in enhanced sampling and dimensionality reduction together with new hardware, require a code that is more flexible and more efficient. We therefore present PLUMED 2 here a,complete rewrite of the code in an object-oriented programming language (C++). This new version introduces greater flexibility and greater modularity, which both extends its core capabilities and makes it far easier to add new methods and CVs. It also has a simpler interface with the MD engines and provides a single software library containing both tools and core facilities. Ultimately, the new code better serves the ever-growing community of users and contributors in coping with the new challenges arising in the field.

Program summary

Program title: PLUMED 2

Catalogue identifier: AEEE_v2_0

Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AEEE_v2_0.html

Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland

Licensing provisions: Yes

No. of lines in distributed program, including test data, etc.: 700646

No. of bytes in distributed program, including test data, etc.: 6618136

Distribution format: tar.gz

Programming language: ANSI-C++.

Computer: Any computer capable of running an executable produced by a C++ compiler.

Operating system: Linux operating system, Unix OSs.

Has the code been vectorized or parallelized?: Yes, parallelized using MPI.

RAM: Depends on the number of atoms, the method chosen and the collective variables used.

Classification: 3, 7.7, 23. Catalogue identifier of previous version: AEEE_v1_0.

Journal reference of previous version: Comput. Phys. Comm. 180 (2009) 1961.

External routines: GNU libmatheval, Lapack, Bias, MPI. (C) 2013 Elsevier B.V. All rights reserved.

Improving Bandwidth Efficiency in E-band Communication Systems

The allocation of a large amount of bandwidth by regulating bodies in the 70/80 GHz band, i.e., the E-band, has opened up new potentials and challenges for providing affordable and reliable Gigabit per second wireless point-to-point links. This article first reviews the available bandwidth and licensing regulations in the E-band. Subsequently, different propagation models, e.g., the ITU-R and Cane models, are compared against measurement results and it is concluded that to meet specific availability requirements, E-band wireless systems may need to be designed with larger fade margins compared to microwave systems. A similar comparison is carried out between measurements and models for oscillator phase noise. It is confirmed that phase noise characteristics, that are neglected by the models used for narrowband systems, need to be taken into account for the wideband systems deployed in the E-band. Next, a new multi-input multi-output (MIMO) transceiver design, termed continuous aperture phased (CAP)-MIMO, is presented. Simulations show that CAP-MIMO enables E-band systems to achieve fiber-optic like throughputs. Finally, it is argued that full-duplex relaying can be used to greatly enhance the coverage of E-band systems without sacrificing throughput, thus, facilitating their application in establishing the backhaul of heterogeneous networks.

A self-learning teaching-learning based optimization for dynamic economic/environmental dispatch considering multiple plug-in electric vehicle loads

Economic and environmental load dispatch aims to determine the amount of electricity generated from power plants to meet load demand while minimizing fossil fuel costs and air pollution emissions subject to operational and licensing requirements. These two scheduling problems are commonly formulated with non-smooth cost functions respectively considering various effects and constraints, such as the valve point effect, power balance and ramp rate limits. The expected increase in plug-in electric vehicles is likely to see a significant impact on the power system due to high charging power consumption and significant uncertainty in charging times. In this paper, multiple electric vehicle charging profiles are comparatively integrated into a 24-hour load demand in an economic and environment dispatch model. Self-learning teaching-learning based optimization (TLBO) is employed to solve the non-convex non-linear dispatch problems. Numerical results on well-known benchmark functions, as well as test systems with different scales of generation units show the significance of the new scheduling method.

Oil and Dependency::The Case of Kazakhstan

Following the collapse of the Soviet Union in 1991, the newly independent oil-rich country of Kazakhstan has become a major recipient of foreign direct investment (FDI). Although international organisations such as the IMF and UNCTAD have claimed that FDI could be considered an engine in the transition from state socialism and as a powerful force for integration of this region into the global economy; this investment also poses significant risks to Kazakhstan. These risks fall into two broad categories: The first category can be broadly described as issues associated with the “resource curse” or the “Dutch Disease”. The term Dutch Disease describes a situation where booming demand in oil exporting countries, due to high oil revenues, leads to shift of an economy’s productive resources from the tradeable sector to the non-tradeable sector. The second category is associated with the over-dependency of oil exporting countries on a relatively small number of large multinational corporations (MNCs). This over-dependency can lead to a situation where licenses and concessions are granted at less favourable conditions than if they were auctioned in an efficient market. Examining the licensing policy of the Kazakhstani Energy and Mineral Resource Ministry, this paper notes that the latter issue of over-dependency has become less of a risk due to deliberate efforts to diversify investment relationships. Notwithstanding this situation there is some evidence that it remains difficult for oil exporting nations such as Kazakhstan to ensure that oil revenues are channelled into sustainable economic development.

Protocol-driven adjustment of ocular hypotensive medication in patients at low risk of conversion to glaucoma

AIM: To investigate the safety and potential savings of decreasing medication use in low-risk patients with ocular hypertension (OH).
METHODS: Patients with OH receiving pressure-lowering medication identified by medical record review at a university hospital underwent examination by a glaucoma specialist with assessment of visual field (VF), vertical cup-to-disc ratio (vCDR), central corneal thickness and intraocular pressure (IOP). Subjects with estimated 5-year risk of glaucoma conversion <15% were asked to discontinue ≥1 medication, IOP was remeasured 1 month later and risk was re-evaluated at 1 year.
RESULTS: Among 212 eyes of 126 patients, 44 (20.8%) had 5-year risk >15% and 14 (6.6%) had unreliable baseline VF. At 1 month, 15 patients (29 eyes, 13.7%) defaulted follow-up or refused to discontinue medication and 11 eyes (5.2%) had risk >15%. The remaining 69 patients (107 eyes, 50.7%) successfully discontinued 141 medications and completed 1-year follow-up. Mean IOP (20.5±2.65 mm Hg vs 20.3±3.40, p=0.397) did not change, though mean VF pattern SD (1.58±0.41 dB vs 1.75±0.56 dB, p=0.001) and glaucoma conversion risk (7.31±3.74% vs 8.76±6.28%, p=0.001) increased at 1 year. Mean defect decreased (-1.42±1.60 vs -1.07±1.52, p=0.022). One eye (0.47%) developed a repeatable VF defect and 13 eyes (6.1%) had 5-year risk >15% at 1 year. The total 1-year cost of medications saved was US$4596.
CONCLUSIONS: Nearly half (43.9%) of low-risk OH eyes in this setting could safely reduce medications over 1 year, realising substantial savings.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Charter vessel licenses

Each year the South Carolina Department of Natural Resources publishes a summary of the laws and regulations of commercial fishing in the state. This publication provides the license requirements, definitions, restrictions, and laws and regulations for the licensing of charter boats.

E news

The South Carolina Board of Landscape Architectural Examiners publishes a newsletter with program information and news.

ENews

The South Carolina Board of Landscape Architectural Examiners publishes a newsletter with program information and news.

FOURTH ANNUAL REPORT OF THE AUDUBON SOCIETY OF SOUTH CAROLINA

Annual report of the Audubon Society of South Carolina, 1 January 1911, discusses hunting licensing, fish and game laws, educational bird work performed by the Charleston Museum, and membership information.

E news

The South Carolina Board of Landscape Architectural Examiners publishes a newsletter with program information and news. This newsletter deals with the SC Soil Classifiers Advisory Council.

Labour and the politics of alcohol: the decline of a cause

This paper shows that, contrary to existing historiography, the politics of alcohol remained important within the Labour party. It explains how and why the party thereafter moved away from this issue and the consequences in terms of party policy up to the 2003 Licensing Act.

Estratégias e internacionalização na manutenção e produção

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica

Um olhar sobre a Descrição a partir das Séries " Licenciamento Industrial" e "Registo do Trabalho Nacional" da Direcção Regional de Economia do Centro

O presente trabalho resulta do estágio realizada na Secretaria Geral do Ministério da Economia e do Emprego. O estágio consistiu na descrição de duas Séries documentais. Com o presente trabalho pretende-se demonstrar a importância do uso das normas de descrição arquivística, mostrando a importância da descrição dos produtores, das funções e das entidades responsáveis pela sua custódia, conjugada com a descrição dos documentos.

Fitness to drive and cannabis: Validation of two blood THCCOOH thresholds to distinguish occasional users from heavy smokers.

Many studies based on either an experimental or an epidemiological approach, have shown that the ability to drive is impaired when the driver is under the influence of cannabis. Baseline performances of heavy users remain impaired even after several weeks of abstinence. Symptoms of cannabis abuse and dependence are generally considered incompatible with safe driving. Recently, it has been shown that traffic safety can be increased by reporting the long-term unfit drivers to the driver licensing authorities and referring the cases for further medical assessment. Evaluation of the frequency of cannabis use is a prerequisite for a reliable medical assessment of the fitness to drive. In a previous paper we advocated the use of two thresholds based on 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) concentration in whole blood to help to distinguish occasional cannabis users (≤3μg/L) from heavy regular smokers (≥40μg/L). These criteria were established on the basis of results obtained in a controlled cannabis smoking study with placebo, carried out with two groups of young male volunteers; the first group was characterized by a heavy use (≥10 joints/month) while the second group was made up of occasional users smoking at most 1 joint/week. However, to date, these cutoffs have not been adequately assessed under real conditions. Their validity can now be evaluated and confirmed with 146 traffic offenders' real cases in which the whole blood cannabinoid concentrations and the frequency of cannabis use are known. The two thresholds were not challenged by the presence of ethanol (40% of cases) and of other therapeutic and illegal drugs (24%). Thus, we propose the following procedure that can be very useful in the Swiss context but also in other countries with similar traffic policies: if the whole blood THCCOOH concentration is higher than 40μg/L, traffic offenders must be directed first and foremost toward medical assessment of their fitness to drive. This evaluation is not recommended if the THCCOOH concentration is lower than 3μg/L and if the self-rated frequency of cannabis use is less than 1 time/week. A THCCOOH level between these two thresholds cannot be reliably interpreted. In such a case, further medical assessment and follow-up of the fitness to drive are also suggested, but with lower priority.