Drug-excipient compatibility studies represent an important phase in drug development. Before a drug substance is formulated into the desired dosage form, there is need for the formulation scientist to fully consider the chemical structure of the drug substance, the type of delivery system required and the proposed manufacturing process. Drug substances are usually combined with excipients which serve different and specialized purpose. Although excipients are pharmacologically inert, they can undergo chemical reactions and physical interactions with drug substances under favourable environmental conditions. These interactions can lead to instability resulting in the formation of new entities with different physicochemical properties and pharmacological effects.
Drug-excipient compatibility studies have been used as an approach for accepting/rejecting excipients for use in pharmaceutical formulations, thus allowing the rapid optimization of a dosage form with respect to patentability, processing, drug release, elegance, and physicochemical stability. In order to obtain rapid stability assessment of drug and excipients, drug stability is investigated under the stress condition according to standard protocol and/or existing knowledge on potential degradation pathway or incompatibilities.
It maximizes the stability of a dosage form.
It bridges drug discovery and development.
It is essential investigational new drug submission (IND).
It helps to avoid surprise problems during formulation processes.
To find out how compatible an excipient is with Active Pharmaceutical Ingredient (API) or candidate drug molecules.
To find out the excipient that stabilizes an unstable API.
To assign a relative risk level to each excipient.
To design and develop selective and stability indicating analytical methods to determine their impurities.
These types of interactions are quite common but are very difficult to detect in dosage forms. Drug substances and excipients interact without undergoing changes involving breaking or formation of new bonds. The components of the drug product retain their chemical structure but undergo changes which alter their physical properties. Physical interactions may result in changes in dosage uniformity, colour, odour, flow properties, solubility, sedimentation rate, dissolution rate etc. Incompatibilities are assessed by physically observing the test samples. Physical interactions can be either beneficial or detrimental to the product performance depending on its application.
Improves bioavailability of sparingly water-soluble drugs: The bioavailability of sparingly water-soluble drugs can be enhanced using complexing agents e.g., complexation of cyclodextrin with ursodeoxycholic acid increases the rate and extent of drug dissolution which in turn increases the bioavailability of the drug substance.
Increases surface area of drugs available for dissolution: Adsorption of drugs on excipient surface can increase the surface area of the drug available for dissolution. Thus, an increase in bioavailability of drug substance. E.g., formulation of indomethacin using kaolin as adsorbent increases its bioavailability as a result of increased dissolution rate.
Improves dissolution rate and bioavailability of hydrophobic drugs: Physical interactions of drugs with excipient improve the dissolution rate and bioavailability of hydrophobic drugs. E.g., improved dissolution rates of drugs like piroxicam, norfloxacin, nifedipine and ibuprofen were achieved when these drugs were formulated into solid dispersions using polyethylene glycol of different molecular weights.
Decreases dissolution and absorption rates of drug substances due to the formation of insoluble complexes e.g., tetracycline forms an insoluble complex with calcium carbonate leading to slower dissolution and decreased absorption in the gastrointestinal tract. Formulation of chlorpromazine with polysorbate 80 and sodium lauryl sulphate decreased membrane permeability of the drug.
Reduces bioavailability of drugs available for dissolution: Adsorption of drugs on excipient surface can also lead to reduced bioavailability as the drug is not available for dissolution. E.g., the marked reduction in the antibacterial activity of cetyl pyridinium chloride cations in tablets containing cetyl pyridinium chloride is due to the adsorption of cetyl pyridinium chloride on the surface of magnesium stearate which acts as a lubricant.
Slow dissolution of drugs: Ion interactions can result in slow dissolution of drugs. E.g., solid dispersion product formed due to interactions between povidone and stearic acid in a capsule showed slow dissolution of the drugs.
Inhibition of diclofenac sodium release from matrix tablet by polymer chitosan at low pH. This occurs possibly via formation of ionic complex between diclofenac sodium and ionized cationic polymer.
Oxidation of diethylstilbestrol to the peroxide and conjugated quinone degradation products by Silicon dioxide which acts as a catalyst.
The interaction is between the medicine (drug substance and excipients) and the body fluids.
The interactions have the tendency to influence the rate of absorption of the drug.
Premature breakdown of enteric coat – Enteric coating polymers e.g., cellulose acetate phthalate and hydroxyl propyl cellulose acetate phthalate, dissolve prematurely in the stomach in the presence of antacids or drugs that cause increase in the pH of the stomach. This results in premature release of active pharmaceutical ingredient in stomach itself, which case results in degradation of drug in stomach e.g., pro-drugs or side effects like gastric bleeding as in the case of NSAIDs.
Interactions due to adjunct therapy– A classic biopharmaceutical incompatibility is the interaction between tetracycline antibiotics and antacids containing aluminium, calcium, magnesium, bismuth and zinc ions. The tetracycline antibiotics chelates with these metallic ions to form complexes which only are not poorly absorbed, but also have reduced antibacterial effects.
Increase in gastrointestinal motility – Certain excipients such as sorbitol and xylitol have the tendency to increase gastrointestinal motility, thus reducing the available time for absorption of drugs like metoprolol. The effect is very much dependent on the amount of the excipient administered at one time. Polyethylene glycol 400 has also been reported to influence the absorption of ranitidine.
The key to the early assessment of instability in formulations is the availability of analytical methods to detect low levels of degradation products, generally less than 2%. Below are some of the analytical methods which are used in drug-excipient compatibility studies.
Thermal methods of analysis comprise a group of techniques in which the physicochemical properties of drug substances are measured as a function of temperature. In this method, the test samples are subjected to a controlled temperature over a given period of time. This method of analyses plays a vital role in drug-excipient compatibility studies and has been frequently used for quick identification of physicochemical interaction between drugs and excipients.
DSC represents a leading thermal screening technique that has been increasingly used for excipient compatibility studies for over five decades. In this technique, the DSC curves of pure samples are compared to that obtained from 50% mixture of the drug and excipient (usually 5mg of the drug in a ratio of 1:1 with the excipient). It is assumed that the thermal properties (melting point, change in enthalpy, etc.) of blends are the sum of the individual components if the components are compatible with each other. An absence, a significant shift in the melting of the components or appearance of a new exo/endothermic peak and/or variation in the corresponding enthalpies of reaction in the physical mixture indicates incompatibility. However, slight changes in peak shape height and width are expected due to possible differences in the mixture geometry.
Conclusions based on DSC results alone may be misleading and have to be interpreted carefully.
DSC cannot be used if thermal changes are very small. Therefore, it should always be supported by some non-thermal methods like TLC or FT-IR or XRPD.
DSC cannot detect the incompatibilities which might occur after long-term storage.
This is an extremely sensitive and invaluable tool used to determine drug-excipient incompatibilities. It measures minute amounts of heat emitted or absorbed by a sample in a variety of processes. This method of analysis is used to characterize pharmaceutical solid to obtain heats of solution, heats of crystallization, heats of reaction, heats of dilution and heats of adsorption – since nearly all physicochemical processes are accompanied by a heat exchange within their surroundings. In a typical drug-excipient compatibility study, a solution, suspension, or solid mixture of drug substance and excipient is placed in the calorimeter and the thermal activity (heat gained or evolved) at a constant temperature is monitored. The thermal activity observed is assumed to be proportional to the rate of chemical and/or physical processes taking place in the sample. The thermal activity of the test sample is compared to the "non-interaction" curve constructed from the control (i.e., thermal activity of drug substance and excipient that were measured individually). If an experimentally significant difference is observed, the excipient is considered to be potentially incompatible with the drug substance.
Samples are not heated, and so the changes are observed as it might typically occur at ambient conditions.
It is sensitive to small changes in heat gained or evolved, thus small samples, or slow processes, may be investigated.
Does not require long storage times, thus saving valuable time and effort during the formulation process.
Isothermal microcalorimetry is not discriminatory. The exact nature of the transition must be known in order to interpret the data.
Differential Thermal Analysis (DTA) is an analytical technique in which the changes in temperature between a test sample and an inert reference under controlled and identical conditions is used to identify and quantitatively analyze the chemical composition of a substance. When the test sample and inert reference are heated to a sufficient temperature, the thermal changes in the test sample which lead to the absorption or emission of heat can be detected relative to the inert reference (control). The differences in temperature are then plotted against time, or against temperature. Drug-excipient interactions can be identified by comparing DTA curves obtained from the test sample with those of inert reference. Incompatibilities are indicated by the appearance of one or more new DTA peaks or the disappearance of one or more DTA peaks corresponding to those of the components of the test sample. In the absence of any interaction, the DTA peak of the test sample show patterns corresponding to those of the individual components.
DTA technique yield data that are considerably more fundamental in nature.
Enthalpy change (under a DTA peak) is not affected by the heat capacity of the sample.
Differential Thermal Analysis is usually performed on powders and for this reason, the resulting data may not be representative of bulk samples, where transformations may be controlled by the buildup of strain energy.
The rate of heat evolution may be high enough to saturate the response capability of the measuring system. This limitation may be overcome by diluting the test sample with inert material.
Problems are encountered in transferring heat uniformly away from the specimen at temperature range of 200 to 500◦C. This problem may be solved by using flat disc-like thermocouples to ensure optimum thermal contact with the now flat bottomed sample container.
Spectroscopic analytical methods include all techniques which probe certain features of a given sample by measuring the amount of radiation emitted or absorbed by molecular or atomic species of interest. This method of analysis uses electromagnetic radiation to interact with matter and thus investigate certain features of a sample as a function of wavelength (λ). Because these methods of analysis use a common set of optical devices for collimating and focusing the radiation, they often are identified as optical spectroscopies. Some of the most frequently used spectroscopic methods of analysis include vibrational spectroscopy, diffuse reflectance spectroscopy, fluorescence spectroscopy, FT-IR spectroscopy etc. and each operates over different, limited frequency ranges within this broad spectrum, depending on the processes and degree of the energy changes.
Using this method, information on the molecular structure and environment of organic compounds are generated by measuring the vibrations of chemical bonds that result from exposure to electromagnetic energy at various frequencies. These vibrations are commonly studied by infrared and Raman spectroscopies. While infrared spectroscopy uses the infrared region of the electromagnetic spectrum (from about 400 cm-1 to 4000 cm-1) to measures the change in dipole moment, Raman spectroscopy uses inelastic scattering process to measures the change in polarization of the sample. The spectra obtained are indicative of the nature of chemical bonds present in the test sample, and when pieced together can be used to identify the chemical structure or composition of a given sample. Vibrational spectroscopy are not only used to investigate solid state properties of drug substances and their formulations, but are also used as compatibility study tool as the vibrational changes serve as probe of potential intermolecular interactions among the components. Thus, drug-excipient interactions that occur during processing can easily be detected with the aid of these spectroscopic techniques.
Sensitive and can be used for process monitoring.
Provides complex fingerprint which is unique to the compound under investigation (IR spectroscopy).
Presence of overlapping peaks in the spectra may hinder the analysis.
Rarely used as a quantitative technique because of relative difficulty in sample preparation and complexity of spectra (IR spectroscopy).
Carrying out limit test where the impurities are fluorescent or can simply be rendered fluorescent.
Determination of fluorescent drugs in low dose formulations containing non-fluorescent excipients.
Studying the binding of drugs to components in complex formulations and measuring small amount of drugs and for studying drug-protein binding in bioanalysis.
It is highly sensitive, specific and easy to carry out.
Samples are analyzed at low cost as compared to other analytical techniques.
It is a selective detection method, thus, it can be used to quantify a strongly fluorescent compound in the presence of a larger amount of non-fluorescent materials.
Can be used to monitor changes in complex molecules e.g., proteins which are increasingly used as drugs.
The technique only applies to a limited number of molecules as there are relatively small numbers of compounds that have characteristic fluorescence.
The technique is subject to interferences by UV absorbing species and heavy ions in solution.
Fluorescence is affected by temperature.
Chromatography is an analytical technique frequently used in pharmaceutical research for separating sample mixture into its individual components. This technique is based on selective adsorption of the components on a stationary phase (usually a solid or liquid with high surface area). As the solute mixture passes over the stationary phase, the components are adsorbed and released at the surface at varying rates depending on differential affinities of individual components towards stationary and mobile phase. Compared to other available analytical techniques used in drug-excipient compatibility studies, chromatography is known for its characteristics of high resolution and detection power, making it suitable for detecting multiple components in a complex mixture with high accuracy, precision, specificity, and sensitivity. Various chromatographic methods of analysis have been used in drug-excipient compatibility studies, all following the same basic principles of operation.
TLC is a chromatographic method of analysis carried out on glass, plastic or metal plates coated on one side with a thin layer of adsorbent. The thin layer of adsorbent serves as the stationary phase and is usually made of silica, alumina, polyamide, cellulose or ion exchange resin. In TLC, solutions of the test samples (that is, a mixture of the drug and the excipient) and the controls (individual drug and excipients) are prepared and spotted on the same baseline at the end of the plate (the origin). The plate is then placed upright in a closed chamber containing mixtures of organic solvents which serve as the mobile phase. The analyte moves up the plate, under the influence of the mobile phase which moves through the stationary phase by capillary action. The distance moved by the analyte is dependent on its relative affinity for the stationary or the mobile phase. Incompatibilities are indicated by the formation of a spot with Rf value (retardation factor) different from that of the controls after the plate has been developed with solvent. An excipient on the other hand is considered to be potentially compatible with the drug substance if the spots produced have identical Rf value with those of the controls. Because some samples undergo negligible thermal changes which might be difficult to detect by thermal methods of analysis, TLC is widely used in drug-excipient compatibility study as a confirmative test of compatibility after performing DSC.
The compound formed as a result of incompatibilities between the drug and the excipient can be detected if a suitable detection reagent is used.
Unlike gas chromatography and high-performance liquid chromatography in which some components of a mixture may elute from the chromatographic system, there is no risk of losing any component of the mixture in TLC since all component of a mixture can be seen in the chromatographic system.
Batch chromatography can be used to analyze many samples at a time, thus increasing the speed of analysis.
This technique is not suitable for volatile substances.
HPLC is a chromatographic technique widely used in drug-excipient compatibility studies by quantitative estimation of test samples that have been subjected to isothermal stress testing (IST). This method of analysis is based on mechanisms of adsorption, partition and ion exchange, depending on the nature of the stationary phase used. In HPLC, a liquid mobile phase is pumped under high pressure through the stationary phase (a stainless-steel column packed with tiny particles with a diameter of 3 to 10 micron). A small volume of the test sample is loaded onto the head stainless-steel column via a loop valve. Separation of a sample mixture occurs according to the relative lengths of time spent by its components in the stationary phase. Column effluent can be monitored with a variety of flow-through device/detector that measures the amount of the separated components. HPLC results that show a percentage loss similar to the control (drug considered individually) indicate no interaction between drug and the excipients and vice versa.
Suitable for separating nonvolatile or thermally sensitive molecules such as amino acids, steroids etc.
Has broad applicability, that is, it can be used for both organic and inorganic samples.
Can be very sensitive and accurate.
Provides better precision relative to the changes being investigated.
Less risk of sample degradation since heating is not required in the process.
Solvents used cannot be recycled.
There is still need for reliable and inexpensive detectors which can monitor compounds that lack chromophores.
Drug-excipient compatibility study is a necessary prerequisite to the development of drug products that are safe and stable for use. Proper selection and assessment of possible incompatibilities between the drug and excipients during preformulation studies is of paramount importance to accomplish the target product profile and critical quality attributes. In order to avoid stability problems encountered during drug development and post-commercialization, there is need for proper assessment of possible incompatibilities between the drug and excipients using appropriate analytical techniques. These analytical techniques are needed not only to generate useful information with regards to which excipient is compatible with a drug substance, but also for troubleshooting unexpected problems which might arise during formulation processes. Drug-excipient interactions may take a long time to be manifested in conventional stability testing programs, and are not always predicted by stress and pre-formulation studies. It is hoped that this write-up provides valuable information concerning the drug–excipient interactions that aid in the selection of appropriate excipients for safe, stable and bioavailable dosage form.
Ajit, S. N. and, Sai, H. S. (2015). Excipient Applications in Formulation Design and Drug Delivery. Switzerland: Springer International Publishing.
Ashok, K. and Mahesh, C. (2006). Excipient Development for Pharmaceutical, Biotechnology, and Drug Delivery Systems. Taylor & Francis Group. LLC.
Brown, M. E. (1998). Handbook of Thermal Analysis and Calorimetry: Principles and Practice. Netherlands: Elsevier Science B.V.
Lee, D. C. and Webb, M. L. (2003). Pharmaceutical Analysis. UK: Blackwell Publishing Ltd.
Onyishi, I. V. (2015). Lecture on Preformulation. Personal Collection of Onyishi, University of Nigeria, Nsukka, Enugu State.
Qiu, Y., Chen, Y., Zhang, G. G., Liu, L. and Porter, W. (2009). Developing Solid Oral Dosage Forms: Pharmaceutical Theory and Practice. USA: Elservier Inc.
Smith, R. J. and Webb, M. L. (2007). Analysis of Drug Impurities. UK: Blackwell Publishing.
Watson D. G. (1999). Pharmaceutical Analysis: A Textbook for Pharmacy Students and Pharmaceutical Chemist. UK: Harcourt Publishers Limited.
This article is very well written in a very simple language that the message is easily apprehended. I look forward to be reading more because I would love to work in the big pharma setting one day.


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Three great reasons to use dedicated servers
When you're looking for solutions for your website, chances are you'll have a few options available when it comes to the servers you use as a platform. Although most people recognise the need for high-quality hosting services, they may find what is available confusing, with one of the main decisions being between shared hosting, Virtual Private Servers (VPSs) or Dedicated Servers.
While shared and virtual solutions may be adequate for smaller users and those with less demanding requirements, if you really want to take full control over your web server, a dedicated solution is the best way to go. In fact, technology news provider Sys-con.com highlighted three key reasons why you should choose a dedicated server over a VPS alternative.
Power of a Dedicated Server
If you opt for a solution from SnelServer.com, you'll be able to build your own dedicated server to your exact requirements. This means you can choose exactly how much memory and storage capacity you need, as well as the number and size of the processors.
This gives you the freedom to ensure you get a solution that meets your unique power requirements, without you having to pay extra for capacity you don't need. It also means you can scale up your system as and when you require without having to miss a beat.
Unlike shared hosting services, the entirety of your dedicated server's capacity and bandwidth is allocated to your own services, so you'll never have to worry about high traffic from other users affecting your website.
Similarly, not having to share services means you're able to get the peace of mind that your data is secure and private, something that could be crucial in the current environment. As Sys-con.com's article explained: "In a world full of frights and perils, Windows dedicated Servers and Linux dedicated servers provide the end user with security and lots of resources." These are just three of the great reasons for opting for a dedicated server in order to give the control and security desired by businesses today, so why not see what SnelServer.com can offer your organisation.
Oracle Java 'most vulnerable software'
If you're looking to set up dedicated servers or a Cloud VPS to be used as the base of your data center, you need to be thinking carefully about the software solutions you add to it in order to make your life as easy as possible. For many enterprises, one of the most commonly-used solutions is Oracle's Java platform, which can be used to create powerful applications for business computing and web servers. However, it seems the popularity of this is being increasingly recognised by criminals.
Most frequently exploited by cybercriminals
This is because research conducted by Kaspersky as part of its 2012 Security Bulletin has revealed Java has become the most frequently exploited software by cybercriminals in the past 12 months. This has seen it overtake the previous most vulnerable software, Adobe Reader, which slipped back to second.
In 2011, Adobe Reader was responsible for 35% of all exploit-related incidents, while for Java the figure was 25% and Microsoft Windows 11%. But in 2012, Java jumped to 50%, with Adobe Reader falling to 28%.
Used by criminals
What this might mean for you is that you could be leaving your business open to malware, as exploiting known vulnerabilities in software is one of the most common ways to access networks and place malicious programs on a network. Kaspersky explained: "Cybercriminals exploit applications or software that has unpatched security vulnerabilities, which exist because either the individual or business have failed to patch their vulnerable applications with the latest security updates from vendors."
Therefore, if you're using software such as Java, it's vital to ensure you always have the lastest version and update it with new patches as soon as they become available. If you don't do this, you're leaving yourself open to problems that could have a potentially disastrous impact on your business' network.
Now obviously this isn't the only thing you need to be taking care of to make sure your operations are safe. For example, it was recently observed by CIO.com that taking steps to keep websites free from vulnerabilities is hugely important to small firms, as they have limited resources available to them and might be especially targeted by criminals because of this.
Why should you consider Windows Server 2012 Essentials?
If you're a small business looking to run your data center on dedicated servers, your choice of operating system is clearly going to be an important decision.
Small businesses might not be able to justify investing in Windows Server 2012 Standard Edition, but happily, this isn't the only option if you want to use Microsoft technology as the basis for your data center.
If you've got fewer than 25 users of your network, you should look at Windows Server 2012 Essentials. While you don't get access to features such as Microsoft Hyper-V with this, information website ServerWatch said you should find it does offer all the vital tools to get your firm up and running.
New capabilities
For example, it does offer a number of new capabilities that weren't present in previous editions of Small Business Server, such as the ability to hook up to Microsoft's cloud services, like Azure and Office 365.
This could be important for many businesses in the coming years, as news publication Windows IT Pro stated Microsoft's vision for the future is a 'cloud OS' environment where much of a network's operations are hosted remotely.
Simple management
ServerWatch also noted one of the great things about Windows Server 2012 Essentials is that it comes with an easy to use Dashboard interface that lets an administrator take complete control of all crucial management functions.
This offers an intuitive graphical user interface with point and click controls that can help users find information, view warning messages and perform some of the most commonly-used actions.
It was noted: "The management tools are designed to make it easy for anyone to administer the system with a minimal amount of experience."
The publication concluded that although the product is more limited than the Standard edition, the access it provides to Microsoft's cloud offerings makes for a solid product that's capable of meeting the basic server needs of any small business.
Toughening the defences of your Linux server
These days, keeping your network activities safe from attacks is vital, as we're being warned all the time that cyber crime and malware is constantly on the rise. Obviously, having strong anti-malware software in place is a must, but if you're using Linux-based dedicated servers or Cloud VPS, there are several things you can do to keep your system safe. Some of these have been highlighted this week by IT World. The publication noted its tips are intended to apply specifically to servers running Red Hat Enterprise Linux (RHEL) 5, but most of its suggestions can be used on almost any Linux-based distribution, as well as many Unix options.
Keep your software lean
The internet news provider explained the more applications you have installed on a server, the more potential vulnerabilities you open yourself up to. Therefore, for the best protection, it was recommended you restrict the tools you add, maintain what is clearly required and actively keep an eye out for new vulnerabilities.
It added: "The more critical a server, the less tolerance you should have for anything beyond the essential services."
Encrypt your data
Ensuring any information passed over a network seems obvious, but you'd be surprised how many people are still using protocols that don't encrypt key details such as passwords.
It was noted it's not difficult for an individual to download and use tools to monitor this data and capture sensitive information, so it you aren't taking basic precautions, you've only got yourself to blame if you suffer a breach.
Maintain user accounts
IT World added you need to keep a close eye of who has access to your servers. It stressed the importance of deleting or at least disabling unused accounts as quickly as possible - ideally as soon as an individual leaves an organisation or moves to another project.
Related to this, you also need to create and enforce a good password policy. On RHEL, there are inbuilt password complexity controls that will ensure they users do not pick weak passwords for themselves - for example by mandating on minimum length and a mix of character types.
It was noted these are just some of the basic general principles you need to be following, as there as many things you can do to keep your servers secure.
Top HTML5 sites of 2012 highlighted
If you're looking to set up a website on a server, these days it's clear one of the best solutions is to take advantage of HTML5 technology. Over the last year, this has taken some huge leaps forward, driven by better support from the latest web browsers and a push by the World Wide Web Consortium to raise awareness and improve its capabilities.
There's so much you can do with HTML5 to make your site stand out, but with such a range of features available, where do you start? If this is something you're wondering, perhaps you might like to take a look at a few of the sites that have been highlighted by web developer publication .net magazine as some of the finest examples of the technology.
HTML5 as a development standard
The publication picked out several major sites from around the world that used HTML5 successfully from the ground up as the standard for their site. These included barackobama.com, the home page for the US president's re-election campaign. "Built by a team of industry vets, it uses semantic elements, data- attributes and schema.org and is built on HTML5 Boilerplate," .net stated. If you want to see how to make a clean, easy to navigate site, this was said to be a great example.
Eslewher, the UK government was praised for its Gov.uk site, which aimed to bring information and services from all its departments under one portal. Frontend developer of the project James Weiner observed: "HTML5 is where everything is going, so it was the logical choice."
Multimedia and interactivity
However, some of the key benefits of using HTMLs are its multimedia capabilities and the way it can seamlessly integrate interactive elements into a web page due to tools such as Web Audio API and WebGL. Websites highlighted by .net for the way they do this included music app JAM with Chrome and online game HexGL, a browser-based project based on the famous Wipeout title.
The publication added 2012 saw HTML5 become undeniably the new standard for web design and predicted this is only set to improve. It stated: "We're just getting started: expect 2013 to rock the browser even harder than this year. It's a great time to be developing for the web."
How can you make use of big data?
One of the key trends in IT over the last 12 months has been the rise of big data, which it has been said could lead to huge changes in the way firms do business. By adequately analysing and evaluating the information firms collect from their customers, it's said to be easier than ever to identify trends and patterns early and react accordingly. In the past though, it's been mainly thought of as a solution only for large enterprises. After all, it takes up a large amount of resources to not only store, but process this data. But this may no longer be the case. Dedicated servers are affordable enough for any firms, while the applications needed to analyse the information are also more freely available than ever.
'New democracy' for data
Business and financial management solution provider Intuit said technology advances are driving in a new era of "data democracy" that enables businesses of all sizes to make smarter, better informed decisions thanks to the wealth of extra information available to them. Partner at Emergent Research Steve King added: "We are at the onset of a data revolution that will provide new and meaningful ways for data-empowered consumers and small businesses to connect and engage with their communities, make decisions and simplify their lives."
What does it mean for you?
While this might seem complex, what it could mean in real terms for your business is an ability to spot changing or emerging trends quickly and alter your operations to take full advantage ahead of your rivals. It could also allow you to identify any weaknesses in your current activities - for example if you're an ecommerce firm, it could highlight where in the shopping process potential customers abandon their carts. This can let you zero in on a problem and fix it before it costs you any more sales. Intuit added consumers will also benefit from big data, using the insights gained to stay connected and easily "navigate the maze of modern life".

redpajama_set_name: RedPajamaCommonCrawl


In late December we asked the provocative question "Should Animals Be Considered People?" in exploring the philosophy of legal scholar Steven Wise. Since 1984, Wise has followed a 25-year plan to have animals declared "legal persons" and afforded basic common law rights.
An adjunct professor at Oregon's Lewis and Clark Law School, Wise is the founder and president both of the Center for the Expansion of Fundamental Rights and the Nonhuman Rights Project, the world's first nonprofit dedicated to achieving legal rights for nonhuman primates. The rights project currently comprises dozens of political scientists, sociologists, psychologists, lawyers, statisticians, cognitive scientists, primatologists, cetacean experts, public policy experts and others working quietly to ready the most powerful lawsuit they can. They are working to identify judges and jurisdictions that have previously shown themselves open to considering and embracing legal change. The lawsuit, Wise emphasized, had to be exactly right or it would be doomed to fail.
Last week Wise moved, not on his own lawsuit but as a so-called "friend of the court" in a previously filed case where the plaintiffs are "Tilikum, Katina, Corky, Kasatka and Ulises, five orcas." And while the center's amicus curiae motion and Wise's individual affidavit have been accepted by the court, neither the defendants nor the group representing the plaintiffs want him involved.
In October 2011, the animal rights activists' group, People for the Ethical Treatment of Animals, jumped the gun in Wise's eyes by filing a federal lawsuit against SeaWorld and its theme parks in San Diego and Orlando claiming the orcas were subject to "involuntary servitude." The orcas regularly entertain crowds at SeaWorld's theme parks. And the PETA humans behind the lawsuit, three marine-mammal experts and two former trainers — the orcas' "next friends," in legal parlance — want to see the five relocated from confined spaces to suitable sanctuaries.
"All five of these orcas were violently seized from the ocean and taken from their families as babies," PETA President Ingrid E. Newkirk was quoted in a statement. "They are denied freedom and everything else that is natural and important to them while kept in small concrete tanks and reduced to performing stupid tricks. The 13th Amendment prohibits slavery, and these orcas are, by definition, slaves." That the 13th Amendment applies only to people, does seem to present a problem.
Wise agrees with PETA that the orca plaintiffs are, in moral terms, enslaved, and he sympathizes with PETA, but he is against the group's constitutionally based case. He considers it ill conceived, impossible to win, and capable of damaging future animal rights law cases.
On January 26, over the objections of PETA and SeaWorld, District Court Judge Jeffrey T. Miller granted the Rights Project's request. SeaWorld has moved to dismiss PETA's case and on January 13, PETA filed a brief opposing its motion. Oral arguments will be heard Monday.
Was Shamu a Legal Person?
Re-visiting animal rights in the wake of SeaWorld's decision to end its orca shows.


Worldsoft AG takes the protection of your personal data very seriously. We want you to know what data we collect and how it is used. We will technically and organizationally ensure that the data protection regulations are observed both by us and by external service providers.
The following privacy notices are intended to inform you comprehensively about how your data is handled.


Ref: (i) Railway Board's leffer No.PC/V/2017/A/TA/1 dated 17/08/2017 (RBE No.96/2017).
(ii) NFIR's letter No.IV/NFIR/7 CPC/Allowance/2016/Part I dated 28/08/2017.
(iii) Railway Board's letter No.PC-V/2015/PNM/NFIR/4 dated 17/20-11-2017.
II. Federation reiterates that as a result of issuance of instructions dated 17/08/2017, a situation has arisen wherein the Railway employees in Pay Level 3, drawing pay Rs. 21,700/- and above upto Level 8 hitherto entitled for Transport Allowance @ Rs. 3600 + DA thereon (in A1/A class cities and in other cities @ Rs.1800 + DA thereon) have been deprived of the said rate due to the new norm for entitlement only when their pay reaches Rs. 24,200/-.
Above position reveals that all the employees working in pay scale below Rs. 6500-10500 i.e. upto Rs. 6000-9800 (S1 to S10A) were allowed Transport Allowance at the uniform rate of Rs. 100/- p.m. in A1/A class cities irrespective of their pay.
IV. From the comparison of two tables mentioned above, it could be seen that the Railway employees were allowed higher rate of Transport Allowance on drawing pay Rs. 7440/- irrespective of Grade Pay/Pay Band. The modified Board's instructions issued vide letter dated 03/08/2017 and 17/08/2017, have deprived the Transport Allowance @ Rs. 3600+DA thereon to those in Pay Level 1 and 2 (7th CPC) due to imposition of restriction i.e. reaching the pay Rs.24700/- ignoring the fact that the staff were already drawing pay @ Rs.7440 in 6th CPC Pay Band/Grade Pay.
Federation, therefore requests the Railway Ministry to kindly arrange to make out case in the light of NFIR's contentions for rendering justice to those staff of Pay Level 1 & 2 for granting Transport Allowance at rate i.e. 3600/- + DA thereon when they reach the corresponding pay @ Rs.21700/- and not 24200/- to meet the ends of justice and refer to MoF. A copy of the reference made to the MoF may be endorsed to the Federation for taking follow up action.


South Dakota State University is a public educational institution and is located in Brookings. The university was founded in 1881 and has an undergraduate student population of 9,208. It is the largest university in the state of South Dakota. The university began as an agricultural college but later expanded to include other disciplines. Today it is known for its excellent programs in pharmacy, engineering, nursing, liberal arts and agriculture. One notable graduate is Theodore Schultz, the winner of the 1979 Nobel Prize in Economics. The estimated total cost for residents per year is $11,126 and $12,438 for non-residents.
The University of South Dakota is a public educational institution and was founded in 1862. The university also happens to be the oldest in the state; it also has the honor of being the state's only liberal arts university. The university is located in Vermillion and has an undergraduate student population of 6,408. The University of South Dakota has seven colleges and schools: Law, Medicine, the School of Education, the Beacom School of Business, the School of Health Sciences, the College of Fine Arts and the College of Arts and Sciences. The university has the only law and medical schools in the state of South Dakota. The undergraduate tuition cost for residents is $2,643.20 and $4,108.80 for non-residents.
Black Hills State University, located in Spearfish, is a public educational institution. The university was founded in 1883 and has a student population of 4,004. This university is relatively small and began as a teacher's college. Now the university has grown to include 56 degree programs that entering freshmen or freshwomen can choose from. The university is made up of three separate colleges: the College of Business and Technology, the College of Arts and Sciences and the College of Education. The undergraduate tuition for residents is $5,803 and $7,123 for non-residents.
Northern State University, located in Aberdeen, is a public educational institution. The university was founded in 1901 and has a student population of 2,200. The university is primarily focused on undergraduate degrees; however, it does confer nine graduate degrees. Northern State University's academic programs are divided among four schools and colleges: Education, Business, Arts and Sciences and Fine Arts. The undergraduate estimated cost for residents is $5,066 and $7,942 for non-residents.
Dakota State University is a public educational institution and was founded in 1881. Located in Madison, Dakota State University has a student population of 2,507. Dakota State University places more emphasis on technology and skills-oriented programs of study. Many students that attend this university major in business, education, physical science or computer programming. Graduate programs are offered in educational technology, information assurance and information systems. The university also allows its students to use tablet PCs in classrooms. The undergraduate tuition cost for residents is $5,373 and $6,611 for non-residents.


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» Sales & Use Tax Database, Commercial Edition
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ZIPCode char(5) ZIP stands for Zoning Improvement Plan. It is used to signify a delivery route in the United States as designated by the USPS. In most cases a ZIP Code is a geographic region with a center point.
Combined Rate Decimal(5,3) Total Sales tax which is the combination of State Rate ,County Rate ,City Rate and Special Rate
State Rate Decimal(5,3) Tax rate implemented by the State
County Rate Decimal(5,3) Tax rate implemented by the County
City Rate Decimal(5,3) Tax rate implemented by the City
Special Rate Decimal(5,3) Some special rate implement by governing body
State Abbr char(2) A state code or abbreviation is a two character designation for that state - for example, California is CA and Texas is TX, etc.
State FIPS char(2) A state FIPS is a two-digit code used to uniquely define each state as designated by the National Institute of Standards and Technology (NIST).
State Name varchar(64) A state in our database is a state, territory, province, or region as designated by the USPS. The database includes all United States territories and possessions that have been assigned ZIP Codes.
County FIPS char(5) Each county in the United States is assigned a unique number for identification purposes - a Federal Information Processing Standards or FIPS code. The County FIPS code is a combination of a 2-digit state FIPS code as well as a 3-digit county code as designated by the National Institute of Standards and Technology (NIST).
County Name varchar(64) A county is the largest administrative division in most states. In our 5-digit USA Commercial Edition database, if a ZIP Code covers two counties, the primary county is used. In the Multi-county databases, all possible counties are listed with each county as a separate record.
City Name varchar(64) The name of the city (and in some cases, organization) designated by that ZIP Code or postal code.
City Type char(1) In many cases, a ZIP Code can have multiple names, meaning cities, towns, or subdivisions, in its boundaries. However, it will ALWAYS have exactly 1 default name.
MSA Code char(4) MSAs or Metropolitan Statistical Areas, are 4-digit codes assigned to the roughly 340 metropolitan areas as designated by the Office of Management and Budget (OMB). They are primarily used to group cities together for statistical purposes or types of analysis. Latitude and longitude are a much more efficient way of accomplishing the same task.
Area Code varchar(16) In our USA 5-digit Premium Edition database, the area code listed is the primary or foremost area code for each ZIP Code. In our Commercial Edition databases (both the USA and Canada), if multiple area codes belong to one postal code, all area codes are listed and delimited by a slash / character.
Time Zone varchar(16) The time zone to which that ZIP Code belongs. Only the primary time zone is listed for each ZIP Code.
ZIPType char(1) The USPS has assigned each ZIP Code a type. Why? It helps them sort mail more quickly.
UTC decimal(3,1) The UTC offset is the number of hours the particular ZIP Code is from Universal Time Co-ordinated (UTC), the international time standard, also known as Greenwich Meridian Time (GMT).
DST char(1) The daylight savings time flag indicates if a particular ZIP Code obeys, or, in other words adjusts their clocks forward and back with the seasons. This information is particularly useful to determine time in other time zones with areas that may or may not use daylight savings time - for example, Arizona, Hawaii, and, of all places - Indiana.
Latitude decimal(9,6) The latitude coordinate listed is an exact north/south point (to 6 decimal places) on the globe of the centroid or middle of the ZIP Code.
Longitude decimal(9,6) The longitude coordinate listed is an exact east/west point (to 6 decimal places) on the globe of the centroid or middle of the ZIP Code.
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Lisicki breaks Venus' record for fastest serve
Sabine Lisicki unloads a record 131-mph (210.8-kph) serve in her
loss to fifth-seeded Ana Ivanovic today in the Bank of the West
Classic at Stanford. Photo courtesy of Bank of the West Classic.
STANFORD, Calif. — Venus Williams lost her record for the world's fastest serve by a woman but won her match.
Sabine Lisicki unleashed a 131-mph (210.8-kph) rocket in a 7-6 (2), 6-1 loss to fifth-seeded Ana Ivanovic today in the first round of the Bank of the West Classic at the Taube Family Tennis Stadium.
Lisicki was aided by hot (84 degrees/28.9 Celsius), dry weather but not elevation (Stanford is 30 feet/9.1 meters above sea level).
"Well ... at least I broke the world record for fastest serve," tweeted Lisicki, the runner-up to Marion Bartoli at Wimbledon last year.
Williams, who held the previous mark of 129 mph (207.6 kph), overpowered qualifier Paula Kania of Poland 6-3, 6-2 in the featured night match.
Meanwhile, rising star Garbine Muguruza ousted defending champion Dominika Cibulkova, seeded sixth, 6-2, 4-6, 6-2. It was the Bank of the West debut for the 6-foot (1.82-meter) Muguruza, who's ranked 28th in the world at 20 years old.
Muguruza plays for Spain, where she lives, but might switch to Venezuela, her native country. Her father is Spanish and her mother Venezuelan.
Muguruza reached her first Grand Slam quarterfinal last month in the French Open, routing top-ranked Serena Williams 6-2, 6-2 in the second round. Cibulkova, 25, of Slovakia advanced to her first Grand Slam final in January in the Australian Open, falling to Li Na.
Also losing was seventh-seeded Carla Suarez Navarro. The 5-foot-4 (1.62-meter) Spaniard, ranked 16th, fell 6-3, 7-5 to Monica Puig of Puerto Rico despite holding three set points at 5-4 in the second set.
Qualifier Carol Zhao, a Stanford sophomore, won her first WTA main-draw match when Yanina Wickmayer, a U.S. Open semifinalist in 2009, retired because of a viral illness with Zhao leading 6-2, 1-0. A disoriented Serena Williams recently retired from her second-round doubles match at Wimbledon with older sister Venus for the same reason.
Lisicki, a 5-foot-10 (1.78-meter) German, crushed her record-breaking serve down in the middle in the ad court at 5-5, 40-30 in the first set. Ivanovic returned the ball solidly but sprayed it wide cross-court.
Williams set her serving mark in the 2007 U.S. Open.
Williams said she was glad Lisicki broke her record.
"I think it's time it's broken," Williams, 34, said with her characteristic graciousness after her serve topped out at a mere 120 mph (193.1 kph) against Kania. "That's a good thing, I think. I guess I have to start trying to serve harder. Clearly, she serves really hard. That's good encouragement.
"I'm not really trying to serve hard, though. I used to. When I really want the point, that's when I start to serve a little bit harder, but I (usually) hit a medium serve that goes somewhere above 110 (177.0 kph).
"I'm trying more for placement these days. It takes a lot of energy to serve, so if you can take off 10 miles an hour (16.1 kph) and place it, this is smarter. I need to serve harder now, I guess."
Samuel Groth of Australia holds the men's record for the world's fastest serve, 163.7 mph (263.4 kph) in the 2012 Busan (South Korea) Challenger. Ivo Karlovic, a 6-foot-11 (2.11-meter) Croat, owns the mark at the top level of men's tennis with a 156-mph (251.1-kph) blast in the first round of the 2011 Davis Cup against Germany.
Williams, playing in the Bank of the West Classic for the first time since losing to Bartoli in the 2009 final, will meet fourth-seeded Victoria Azarenka on Thursday in the second round. Azarenka, who will turn 25 on Thursday, received a first-round bye.
Williams and Azarenka are both former top-ranked players, multiple Grand Slam singles champions (seven titles for Williams; two for Azarenka) and past Bank of the West titlists (Williams in 2000 and 2010; Azarenka in 2010).
Both also have battled health issues. Williams was diagnosed with Sjogren's Syndrome, an energy-sapping autoimmune disease, in 2011. Azarenka has missed most of this year with a left foot injury.
Williams, a lean 6-foot-1 (1.85 meters), has fallen to 25th and hasn't won a major singles title in six years, but she remains a threat. Last month, the five-time Wimbledon singles champion came within two points of beating eventual winner Petra Kvitova in the third round at the All England Club.
Williams said she'll continue playing "as long as I'm good. I'm running pretty fast. If I get slow and terrible, then I'll stop.
"I'm not having kids right now, it seems, and I don't have a husband telling me what to do and we don't have to argue every day," Williams continued with a laugh, "so for me it's easy to keep playing tennis."
Williams made her pro debut 20 years ago at 14 in the Bank of the West Classic, beating American veteran Shaun Stafford in the first round before losing to top-seeded and second-ranked Arantxa Sanchez-Vicario of Spain. At the time, the tournament was held across San Francisco Bay in the Oakland Coliseum Arena in the fall.
"It's great to still be feeling well enough to play on this tour," said Williams, a two-time Bank of the West champion (2000 and 2002) and five-time runner-up (1998, 1999, 2004, 2005 and 2009). "It's much more competitive than 20 years ago, and it's great to be looking pretty solid, too.
"It's been a long journey. I don't know at that age if I would have envisioned that I'd still be playing, but I'm glad I am because you get one shot at it, and then you fade to gray somewhere and someone else is better. So while I'm here, I'm going to go for it."
BANK OF THE WEST CLASSIC
At Stanford
First-round singles
Carol Zhao, Canada, def. Yanina Wickmayer, Belgium, 6-2, 1-0, retired.
Monica Puig, Puerto Rico, def. Carlo Suarez Navarro (7), Spain, 6-3, 7-5.
Garbine Muguruza, Spain, def. Dominika Cibulkova (6), Slovakia, 6-2, 4-6, 6-2.
Ana Ivanovic (5), Serbia, def. Sabine Lisicki, Germany, 7-6 (2), 6-1.
Venus Williams, United States, def. Paula Kania, Poland, 6-3, 6-2.
Daniela Hantuchova, Slovakia, def. Paula Ormaechea, Argentina, 6-3, 6-4.
First-round doubles
Varvara Lepchenko, United States, and Ajla Tomljanovic, Croatia, def. Mari Osaka, Japan, and Marina Shamayko, Russia, 6-1, 6-0.
Carolina Garcia, France, and Shuai Zhang, China, def. Kristie Ahn, United States, and Carol Zhao, Canada, 3-6, 6-1 [12-10].
Doubles quarterfinals
Alla Kudryavtseva, Russia, and Anastasia Rodionova (2), Australia, def. Mirjana Lucic-Baroni, Croatia, and Karolina Pliskova, Czech Republic, 6-1, 6-0.
Wednesday's schedule
(Starting at 11 a.m.)
Monica Puig, Puerto Rico, vs. Sachia Vickery, United States.
(Not before 1:30 p.m.)
Agnieszka Radwanska (2), Poland, vs. Varvara Lepchenko, United States.
Andrea Petkovic (8), Germany, vs. Naomi Osaka, Japan.
(Not before 7 p.m.)
Serena Williams (1), United States, vs. Karolina Pliskova, Czech Republic.
Hao-Ching Chan, Taiwan, and Andrea Petkovic (4), Germany, vs. Paula Kania, Poland, and Katerina Siniakova, Czech Republic.
Court 6
(Starting at 1:30 p.m.)
Daniela Hantuchova, Slovakia, and Arantxa Parra Santonja, Spain, vs. Daria Gavrilova, Russia, and Yi-Fan Xu, China.
Caroline Garcia, France, and Shuai Zhang, China, vs. Garbine Muguruza and Carla Suarez Navarro (3), Spain.
Labels: Bank of the West, Cibulkova, Lisicki, Muguruza, Venus Williams, Zhao
Venus tops Azarenka in Bank of the West
Serena advances, No. 2 seed falls at Stanford
Japanese teen stuns Stosur in Bank of the West
Venus to play qualifier on Tuesday at Stanford
Lucic-Baroni, with troubled past, upset at Stanford
Serena to play at Stanford after weird Wimbledon exit
Fendick-McCain retires from college coaching
Rankings mover of the week: Nicole Gibbs (up)
TV schedule, calendar (Serena in Bank of the West)
Riffice earns national boys doubles title on clay
Mayo wins National Clay Courts in boys 14s
Mayo reaches boys 14 final in National Clay Courts
Little Lao has the write stuff
Rankings movers of the week: Gibbs (down), Harkins...
TV schedule, calendar
Former Capital Davenport enters Hall of Fame
Australia's Rogowska stars in the late show
Rogowska, Boserup reach Gold River Challenger final
Roommates to meet in Gold River Challenger semis
U.S. teens Loeb, Chirico outclass seeds in Challenger
U.S. teen Crawford upsets seed in Challenger
Stevenson to face Gibbs in Gold River Challenger
Brady surprises top seed in Challenger qualifying
Results of all 2014 Wimbledon finals
Wimbledon Day 13 highlights: Djokovic wins classic
15-year-olds advance in Challenger qualifying
Wimbledon Day 12 highlights: Kvitova crushes Bouchard
Gold River Challenger qualifying schedule
Wimbledon Day 11: Djokovic, Federer in final
Larcher de Brito pulls out of Gold River Challenger
Wimbledon Day 10 highlights: Bouchard, Kvitova in ...
Wimbledon Day 9 highlights: Dimitrov topples Murray
Wimbledon Day 8 highlights: Sharapova, Nadal fall


The band was founded in 1998 by six individuals with a passion for music rooted in Americana and Celtic folk rock. From the beginning The Elders seemed to be channeling something ancient and enduring – something unaffected by fads, trends and the giant maw of mind-numbing commercialism. Their ability to bring together the art of story telling with elements both musically progressive and rooted in tradition, has won them a broad international fan base, as well as critical acclaim in numerous publications such as PASTE Magazine, Folk & Acoustic Music Exchange, Music Row Magazine, Goldmine Magazine, TRAD Magazine (France), Chicago Sun-Times, Kansas City Star and more.
Their 8th studio album,True, builds upon The Elders' song-writing reputation. The songs feature story lines with vibrant narratives that explore history, legends, tall tales and true-life experiences. In addition to the band's trademark mesh of styles, textures, and soaring vocals, the album features a few barn-burning instrumentals.
Their critically acclaimed albums serve as reflections of the group dynamic, but fans who are wild about The Elders can tell you that the real magic happens on stage, where their powerful personal and musical chemistry forges a deep sense of community with their audience.
The Elders have headlined major Celtic Festivals in North America and Europe. For the past 15 years they have sponsored a tour of Ireland in which fans are invited to join in on an extraordinary 12 day excursion visiting historical and geographical sights during the day and gathering at a local pub or ballroom at night for pints and performances by the band.
"These boys don't just pick and grin, they damn near set their instruments on fire... The Elders really do play a style of music fused in a fashion no others have captured quite so well. They are marrow deep in their unique art, and it's not only pleasing as hell, but infectious."
"The key to the band's success is in its flawless blending of the Celtic storytelling tradition with contemporary instrumentation and, perhaps more importantly, their ability to write original songs that sound as timeless and authentic as the ancient jigs and reels that have inspired them."
"What I hear is absolutely amazing ... The Elders are without a doubt one of the greatest finds this century."
"Named the Elders for good reason. Decades of combined experience have taught the band smart stagecraft, superb showmanship and taut professionalism. Many superstar acts would envy the level of audience participation the Elders achieve."


Last month I attended a very interesting lecture with the title of "Healthy Longevity." Now it may be because I am part of the Baby Boomer generation, or it could have something to do with just officially retiring from one of my jobs, but I found the topic and the speaker gave me lots to think about later.
The speaker, an ISU professor of sociology who specializes in gerontology, believes that longevity is the Social Revolution of the 21st century. And here I thought that aging is just something that, if we're blessed, we all cope with.
There was a nearly audible gasp in the room when the lecturer said that this factor contributes only 20 percent to how long we live. It's very easy to blame our problems on heredity, but that doesn't seem to be the case. This could be good news or bad news, depending on your family.
This trait is valuable at any age, and probably even more as we age. It seems to me that if resilience is a lifelong habit, it would be especially valuable at this stage of life.
This is one of my favorites, because I'm a big fan of community in any setting, And I think most people are looking for that in their lives, whether they realize it or not. It is truly a blessing to have friends and family who are your people. It turns out that can influence how long one lives.
I guess we all understand this one, whether we like or not. We must take care of ourselves.
Healthy food choices and activity have an impact on how long we live, of course. It sounds like it's worth the investment of time and energy to implement healthy choices. We all know what we should do, of course, and we are bombarded on all sides with information on the topic. So why is it difficult to just do it?
Of course, we can choose to influence our healthy longevity by engaging in effective lifestyles (exercise, nutrition, support). Or we can just sit back and do nothing. What makes it a challenge is that engaging in a healthy lifestyle brings with it no guarantee that we will have a good, rewarding old age.


These days, I'll use any excuse to pretty up my surroundings – funny how I didn't feel the need to do this when I lived among the constant beauty and magnificent scenery of Tenerife – so yesterday, I stuck up a bit of Easter bunting, peppered a small wreath with artificial daffodils (the eggs I was hoping to decorate it with caused me so much grief, they ended up just being thrown in a basket) and, finally arranged a few silk Spring flowers.
Just that caused unbearable pain in my feet and ankles (from, yet again, the pooling of blood that my heart can't pump to my head) that was so severe, I couldn't get comfortable in bed and spent a whole night with poor sleep, even though I'd spent the afternoon with my feet elevated to help mitigate it.
Today, I can bearly stand up at all without my feet and legs giving way or my head going swimmy and the waves of malaise and nausea crashing over me.
To arrange the flowers, I needed to cut half a dozen relatively thin plastic covered wire stems with wire cutters. Clearly, I shouldn't have really: it was difficult – I hardly had the strength and grip – and painful at the time; so much so that my mother (87) had to help me finish doing this. By last night, my hands and wrists were so painful, I couldn't even bear to rest them on the bed. The pain in them is making me feel sick today, despite medication.
This seems an inordinately high price to pay just for some "cheap", transient decorations and the physical pain right now is threatening to overpower any psychological benefit that I might have derived from cheering myself up.
On a positive note, however, while we are on the subject of hand and wrist pain, I finally broke down and bought myself a Kindle.
For years now I've not been able to read books because I couldn't comfortably hold a book for long enough. It would hurt my arms and wrists, then neck and shoulders; leaning the book on my stomach would hurt; the light or angle would never be right for me to be able to see well enough: in short, it had stopped being the pleasure I'd once enjoyed.
There's still the problem that I can't often concentrate or take in more than a few pages at a time, but at least the Kindle is proving to be a great help towards alleviating the physical problems. I still can't hold it up, as suggested in the advertising images, but I can hold it for a lot longer than I could have held a small paperback book, provided I rest my arm and hand on something.
Turning the pages is a much easier task with a button either side of the Kindle, so I can alternate hands too and, the screen is much clearer and easier for me to see than print, especially as I can change the size of the text.
Whilst I probably won't use it often, even the robot voices that read out the text-to-speech function are bearable enough to listen to, if all else fails.
If you have any similar afflictions and are considering a Kindle, but are not sure if it's worth the investment, my hunch and experience says it is.
So far, I've downloaded all the free classics I never previously got around to reading (I do hope to one day, even though the experience may be a little tainted, having already seen the DVD), plus some reference materials that may come in handy.
Additionally, I'm already about a quarter of the way through reading John Mole's "It's All Greek To Me!", which is a fairly amazing feet given my usual ability, since I only opened the Kindle box on Saturday.
There will still be a handful of books printed on dead trees that I shall keep for the time being, while I already have them and they're not (yet?) available as a Kindle edition, but those which are, I intend to swap. Hopefully, selling my books will help fund their replacements.
It's funny, but despite all the advantages, the fact that I'm not resistant to change and consider myself tech-friendly, it still doesn't quite feel natural holding this small technological version of the old school slate instead of a "proper" book. I'm sure I'll make that adaptation rapidly though.
Above all, I want the freedom that not lugging books around, whether one-by-one to read, or in bulk when removing, which this gadget will bring and, better, no more trees need be cut down to provide my reading material.
So, Pam, how did your Kindle work out? I got mine in the first release and, over two years on - feels like longer - still get the urge, occasionally, to try to turn a page. Brilliant device, though, and I wouldn't be without it.
It has, however, done absolutely nothing to save trees, as I reckon I've bought more print books since buying the Kindle, not fewer, which was my intention as I'm out of space.
On a not unrelated note, I recently bought an iPad 3, a bit of a toy - sorry, Apple fanboys, but it is - compared to real computers, but it's great for reading colour publications, like magazines.
Of course, with the Kindle app I can read Kindle books, but they stay remorselessly monochrome, and I haven't yet had a rummage through the iBook store to see if their books are optimised for the iPad. They should be but, being Apple, that's no guarantee.
By the way, despite what Apple would love you to believe, the iPad makes a rubbish ereader - it's just too heavy, and the screen far too reflective, to make it viable.


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Zitouni is a Maghrebian surname. Notable people with the surname include:

Ahmed Zitouni (born 1949), Algerian writer
Ali Zitouni (born 1981), Tunisian football player
Djamel Zitouni (1964-1996), leader of the Algerian Armed Islamic Group (terrorist group)
Malika Zitouni (born 1973), French-Algerian bodybuilder
Mustapha Zitouni (1928–2014), French-Algerian football player

redpajama_set_name: RedPajamaWikipedia


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Medical marijuana and gun ownership an illegal combination, Florida representative says
As more medical marijuana dispensaries open in Florida, one state representative is warning users that they can face serious legal consequences if they also own a gun.
Thursday, November 30th 2017, 8:38 PM EST
(WFTV)-- As more medical marijuana dispensaries open in Florida, one state representative is warning users that they can face serious legal consequences if they also own a gun.
Rep. Cord Byrd is a lifetime outdoorsman and hunter and has dubbed himself the "Florida gun lawyer" in his private practice.
With his history and knowledge of gun laws, Byrd has taken it upon himself to make sure medical marijuana users in the state know that their medicine and guns don't mix.
"(People think) 'I have a constitutional right in Florida (to use) medical marijuana. I have my state-issued card,'" Byrd said. "And they're not thinking about the Second Amendment implications."
Speaking to Channel 9 via Facetime, Byrd explained that possessing medical marijuana while having or buying a gun can carry a penalty of up to 10 years in prison.
"I won't say it will happen, but I will advise someone who calls me that it certainly is a possibility," he said.
The prohibition is clearly explained on forms required when a person is purchasing a firearm, Byrd said.
Federal law prohibits any "unlawful user" of a controlled substance to purchase a firearm, and it doesn't matter if Florida has legalized medical marijuana, he said.
"People are going to look at that and say, 'Oh, I'm not unlawful. I'm licensed in my state,'" Byrd said.
The forms clarify that "the use or possession of marijuana remains unlawful under federal law, regardless of whether it has been legalized or decriminalized for medicinal or recreational purposes in the state where you reside."
The rule was challenged in U.S. Circuit Court last year, but was upheld by a federal court.
Byrd said he doesn't believe it is fair to force people to navigate the complex divide between state and federal laws.
"(It is) the choice of, 'Do I get the medicine that I need, or lose a constitutional right?' and we've got to figure this out," he said.


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THIS LEAGUE IS LAST YEAR'S OLD Est. 2017
One and Done - FFL: Preseason | NFL: Week 1
Thu Jul 18 6:06pm ET
In this Jan. 20, 2019, file photo, Los Angeles Rams' Nickell Robey-Coleman breaks up a pass intended for New Orleans Saints' Tommylee Lewis during the second half of the NFL football NFC championship game in New Orleans. The non-call on the play involving Rams Nickell Robey-Coleman in the NFC championship game cost the Saints a trip to the Super Bowl. (Or, at least that's how they see it in New Orleans) After taking tons of flak, then admitting the call was wrong, but doing nothing to alter the outcome of the game, the NFL rule-makers met a few months later and declared pass interference would now be reviewable.(AP Photo/Gerald Herbert, File)
NEW ORLEANS (AP) A Louisiana judge won't stop a lawsuit against the NFL over the playoff ''no-call'' that led to the Rams beating the Saints and advancing to the 2019 Super Bowl.
State Civil District Court Judge Nicole Sheppard ruled Thursday in the damage suit filed by attorney Antonio LeMon.
LeMon says that means Commissioner Roger Goodell and game officials can be questioned in depositions. The officials failed to call either pass interference or roughness penalties when a Rams player leveled a Saints receiver with a helmet-to-helmet hit at a crucial point in the NFC title game. A lawyer for the NFL did not immediately respond to a request for comment.
LeMon says he and three others filed the lawsuit to get at the truth of what happened in the game.
Lawsuit over no-call can proceed vs. NFL
Raiders add WR Pierson-El, cut Blacknall
Haynesworth on to outpatient treatment
Broncos LB Davis injures leg at camp
Broncos out to forge new identity
Falcons extend LB Jones 4 years, $57M
Broncos clear Sanders, Lindsay for camp
Cardinals cut OT Harrison after arrest
Vikings backup RB Thomas gets 3-game ban
Falcons give DT Jarrett 4-year extension
49ers sign K Gould to 4-year contract
Raiders sign free agent G Cooper
QB Smith out of brace from grisly injury
Giants S Moore punched, stepped on woman
Bengals G Boling retires after 8 seasons
Titans LB-DL Morgan says he's retiring
NFL opens football academy in London
Caldwell to take leave for health issue
Man charged in shooting of draft pick
Officials preparing for replay increases
The Paur Report
Early ADP Trends
Champions Draft Owner Comments
Drafting Todd Gurley
Running Back Strength of Schedule
Tight End Strength of Schedule
Receiver Strength of Schedule
The Fantasy Championship increases Grand Prize
Player Notes
LeSean McCoy Jul 18 7:30pm ET
Buffalo Bills general manager Brandon Beane had encouraging words to say about LeSean McCoy to beat reporters. "Were focused on this year," Beane said. "Thats what we have him under contract for, and I definitely think hes got enough left in the tank to help us in 2019. McCoy is 31 years old and entering a contract season. His 3.2 yards per carry last year was a career-worst mark, but the Bills have added some offensive line help as well as more reliable backups in Frank Gore and T.J. Yeldon. Don't reach for McCoy on draft day, but there's some sneaky value in McCoy if he falls in your draft. As of now, he stands to receive a good amount of carries in what should be an improved Buffalo offense.
From RotoBaller
Randy Gregory Jul 18 6:50pm ET
Dallas Cowboys defensive end Randy Gregory will reportedly apply for reinstatement this week. Gregory recorded six sacks last season, playing in 16 games including playoff games. He was suspended in February for violating the NFL's substance-abuse policy. It seems that Dallas feels Gregory at least has a good chance at being reinstated however, as the team signed him to a one-year extension in April. For now, the talented defensive lineman is suspended "indefinitely" but no one knows what that means in the NFL's discipline department.
Jalen Mills Jul 18 6:50pm ET
Philadelphia Eagles cornerback Jalen Mills (foot) is unlikely to be ready to go for the start of training camp. Mills was placed on injured reserve in October after suffering a foot injury and did not participate in any of the offseason program. Reports state that Mills was not even on the field working with the other injured Eagles players. It's unknown for now if Mills is expected to be ready for Week 1, but he'd need to get a lot of work in soon for that to be a realistic possibility. The Eagles may have some depth chart issues in their secondary if some of their guys don't heal quickly.
Philadelphia Eagles cornerback Avonte Maddox could have a bigger role in the defensive secondary this season. He played very well in his rookie season last year and reports stated he was "one of the best players on the field" throughout the Eagles offseason program. Ronald Darby and Jalen Mills seem to be atop the depth chart, but both have legitimate injury concerns which could open up a starting role for Maddox. Even if both guys are healthy, Maddox has looked good enough to earn some time in base packages besides playing his role as slot corner.
Deebo Samuel Jul 18 2:40pm ET
Approaching training camp, the San Francisco 49ers first two picks of 2019 remain unsigned. Defensive end Nick Bosa, the second overall pick, and wide receiver Deebo Samuel represent two of the eight total 2019 NFL draftees that have not reached a deal. Bosa, who many experts expect to make an immediate impact, could lift the Niners defense from its 28th-ranked fantasy DST. More worrisome is Samuel, who will miss valuable reps with quarterback Jimmy Garoppolo if hes unable to report to camp on time. With a crowded receiving corps, the rookie could conceivable sink on the depth chart, severely negating any redraft value he currently possesses.
Jalen Mills Jul 18 10:43am ET
Philadelphia Eagles CB Jalen Mills (foot) is unlikely to be ready when training camp opens.
From TheHuddle
Sidney Jones Jul 18 10:43am ET
Philadelphia Eagles CB Sidney Jones could wind up being trade bait for a team that is patient as Jones develops in the weight room.
Damon Harrison Jul 18 9:03am ET
Detroit Lions CB Darius Slay and DT Damon Harrison's agent, Drew Rosenhaus, will meet with the Lions this week to discuss contract extensions for both players.
Matt Judon Jul 18 8:40am ET
Baltimore Ravens linebacker Matt Judon said this week that his representatives have opened contract extension talks with the team. He is entering the final season of a four-year, $2.595 million rookie deal, and he can be an unrestricted free agent after the 2019 season. Judon has registered 131 total tackles with 19 sacks, three forced fumbles and seven passes defensed in three NFL seasons, and he has 15 sacks over the past two campaigns. He is a key member of a Ravens defense which will be a Top 5 fantasy DST again this season.
Miles Boykin Jul 18 8:20am ET
The Baltimore Ravens signed rookie wide receiver Miles Boykin to a four-year contract this week. Boykin signed his four-year rookie deal, the team announced on Wednesday, and the club now has all of its rookies signed just in time for them to report to training camp. Boykin, a third-round pick out of Notre Dame, missed time during offseason training activities (OTAs) due to a hamstring injury. He will be jockeying with Willie Snead, Seth Roberts and Chris Moore for a meaningful role in the Baltimore offense to start.
Luke Stocker Jul 18 8:10am ET
The Atlanta Falcons brought in free-agent tight ends Logan Paulsen and Luke Stocker during the offseason to provide depth behind Austin Hooper, who is in a contract year. Stocker, who signed a two-year, $5.5 million deal in the offseason, received a $1.5 million signing bonus. He might also see some time at fullback in addition to tight end, but neither is expected to move the needle in terms of fantasy appeal unless disaster strikes Hooper. TE Jaeden Graham has also seen some time at fullback during offseason practices.
Eric Saubert Jul 18 8:10am ET
Atlanta Falcons tight end Eric Saubert was one of the team's three players at the position in 2018, but team re-signed Logan Paulsen while adding Luke Stocker in free agency. And Austin Hooper is the unquestioned starter and one of the more productive tight ends in the NFC. Saubert might be the odd-man out heading into training camp and the preseason unless they elect to keep four tight ends on the 53-man roster. Either way, Saubert isn't someone to bother with in fantasy football.
Austin Hooper Jul 18 8:00am ET
Atlanta Falcons head coach Dan Quinn feels tight end Austin Hooper might be primed and ready to step up his play in 2019. Hooper, who is in a contract year, posted career highs across the board with 71 grabs, 660 yards and four touchdown in 2018 while being targeted 88 times. "Now, he's ready to go to another level, and I'm looking forward to seeing him make that growth," Quinn said. "The addition of having (tight ends coach Mike Mularkey) here, he's done everything that Mike has asked in terms of getting him ready." Hooper is worth targeting as a low-end TE1 in most fantasy leagues heading into 2019.
Grady Jarrett Jul 18 7:50am ET
The Atlanta Falcons and middle linebacker Deion Jones have agreed to a four-year contract extension worth $57 million, with $28.5 million guaranteed. The deal comes on the heels of a long-term pact with defensive tackle Grady Jarrett, who inked a four-year, $68 million deal earlier in the week. Jones bounced back to record 53 tackles in six games after suffering a broken foot in the regular-season opener. While the Falcons have some key components on their defense locked up for the long haul, they're still nothing more than a streamer DST in most fantasy formats heading into 2019.
Atlanta Falcons TE Eric Saubert could be released if the team elects to carry just three tight ends on its 53-man roster, in the opinion of The Atlanta Journal-Constitution's D. Orlando Ledbetter.
Zach Zenner Jul 18 2:43am ET
Detroit Lions RB Zach Zenner could challenge veteran RB C.J. Anderson for the No. 2 spot behind RB Kerryon Johnson, in the opinion of The Detroit News' Justin Rogers, who notes that Zenner's north-south running style is a good fit for the team's blocking scheme.
Fantasy Spin: At this point, Johnson is the only sure thing in the Lions backfield, so you'll need to keep an eye on the preseason to see how Anderson, Zenner and Theo Riddick slot in behind him to see if anyone other than Johnson warrants a selection in fantasy drafts.
Derrick Henry Jul 18 12:00am ET
Tennessee Titans running back Derrick Henry finished the 2018 season on a tear, rushing for 625 yards and eight touchdowns in the month of December alone. New Titans offensive coordinator Arthur Smith has stated that he plans to "ride" Henry going forward, but perhaps expectations should be tempered. While the Titans did improve their offensive line through free agency and the draft this offseason, Henry's involvement should remain game-script sensitive with receiving back Dion Lewis still in Tennessee. Henry is likely going to win you some matchups this season with his big play ability and touchdown upside, but he is also likely to lose you some weeks should the Titans fall behind early, making Henry a risky pick in the late second or early third rounds of fantasy drafts.
Cameron Brate Jul 17 10:13pm ET
Tampa Bay Buccaneers TE Cameron Brate could see 60 targets in 2019 while working as the backup to starter O.J. Howard, according to Taylor Jenkins of PewterReport.com.
Fantasy Spin: Jenkins projected just 45 targets for RB Peyton Barber, leaving extra work in the passing game for Brate. The 28-year-old has been a reliable red-zone threat over the past four years, but the chance for more catches and yards could make him a more reliable option in fantasy leagues. He's best left to the waiver wire, but he'll be worth starting as a bye-week replacement.
Peyton Barber Jul 17 10:03pm ET
Tampa Bay Buccaneers RB Peyton Barber will receive close to 45 targets in 2019, according to Taylor Jenkins of PewterReport.com.
Fantasy Spin: Jenkins projects Barber to be the every-down back for the Bucs this season. The 25-year-old caught 20 of 29 targets while starting all 16 games last year, but he went for just 92 yards and one touchdown through the air. He's an adequate RB3 play in standard leagues if he's able to hold off Ronald Jones II in training camp, but Jones has the higher upside.
Deion Jones Jul 17 5:43pm ET
Atlanta Falcons LB Deion Jones agreed to terms on four-year contract extension with the Falcons Wednesday, July 17, worth $57 million. The deal includes $34 million in guaranteed money.