text:
Country profile - Distinguishing factors ()
Montenegro is located in south-eastern Europe on the coast of the Adriatic Sea. Its geographical coordinates are 4° 30' N, 19°18' E. The total area of the country is 13,812 km2 of which 13,452 km2 is land and 360 km2 water. Land boundaries bordering five countries total 625 km and the coastline 300 km. Montenegro has a Mediterranean climate with hot dry summers and autumns and relatively cold winters with heavy snowfalls inland. The terrain is a highly indented coastline with a narrow coastal plain backed by rugged high limestone mountains and plateau. The elevation varies between 0 m on the coast to a highest point of 2 522 m above sea level at Bobotov Kuk. Agricultural land covers 5 165 km2 of the country, 37.4 %, arable land 13.7 % and permanent crops 1 %. Agricultural crops grown are cereals, potatoes, tobacco, grapes, citrus fruit, olives and figs. The main natural hazard in Montenegro is destructive earthquakes.
Browse by topic
For references, please go to www.eea.europa.eu/soer or scan the QR code.
This briefing is part of the EEA's report The European Environment - State and Outlook 2015. The EEA is an official agency of the EU, tasked with providing information on Europe's environment.
PDF generated on 06 Mar 2015, 02:19 PM


text:
dual boot with suse n rehhat
Hi all,
I goal is to install suse 10 and RHEL 5 on different LUNs, and in the bootloader i need to get option to switch.I have installed SUSE in LUN 0 successfully completed the installation it came up.For the second OS ie.RHEL i changed the boot sequnce in BIOS to LUN 1 and installed (with out boot loader) succesfully....I went to /boot/grub/menu.lst and added the the new OS to the grub like
title suse
kernal Path
initr path
But when i select SUSE in grub it is showing grub loaderror.
Can anyone tell me what are all the configuration changes i should make to achive my goal..
You Should be Close
This is a bit confusing, you installed SuSE and it boots, then you installed RedHat and it doesn't boot, yet the grub entries you're trying to "fix" refer to SuSE... I'll assume that that's a typo and it's actually RedHat that won't boot from the second drive.
The most likely problem is that you have the "root" entry incorrect, you're probably specifying the wrong drive.
Boot into SuSE and run:
$ grub --device-map=test.map grub> quit $ cat test.map (fd0) /dev/fd0 (hd0) /dev/sda (hd1) /dev/sdb
Use the map that grub creates to verify that the drive you've specified in your "root" entry corresponds to the drive that contains RedHat.
If that doesn't help post your menu.lst file here and also your /boot/grub/device.map file.
Also note that you probably made this more complicated than it needed to be, most modern Linux installers will allow you to install on a second drive and will correctly fix/install the boot loader so that everything works. At least in theory.
Mitch Frazier is an Associate Editor for Linux Journal.
dual boot with suse n rehhat
I have checked the test.map file it is fine.and the output of /boot/grub/device.map is
(hd0) /dev/sda
(hd1) /dev/sdb
can u please tell me what are all the configuration changes should be made for SAN boot with single boot loader right from the installation of suse and RHEL.I am new to linux.During installation i have made only the changes like RHEL with bootloader at /dev/sda and SUSE with boot from root partition.Is it correct? If not can u guide me to do this..........
I am able to install windows in LUN 2 and i am able to boot from it....Then y is it not possible for SUSE..?Please guide me....
thanks in advance........
More Info
Post a copy of your /boot/grub/menu.lst and also a listing of the partitions that you have on the two drives. You can get a list of the partitions via:
$ fdisk /dev/sda ... Command (m for help): p ... Command (m for help): q
Then do the same for /dev/sdb.
Also, explain to me how you're getting Windows to boot from the second drive? Is it booting via grub or ...?
Mitch Frazier is an Associate Editor for Linux Journal.
As Linux continues to play an ever increasing role in corporate data centers and institutions, ensuring the integrity and protection of these systems must be a priority. With 60% of the world's websites and an increasing share of organization's mission-critical workloads running on Linux, failing to stop malware and other advanced threats on Linux can increasingly impact an organization's reputation and bottom line.
Sponsored by Bit9
Most companies incorporate backup procedures for critical data, which can be restored quickly if a loss occurs. However, fewer companies are prepared for catastrophic system failures, in which they lose all data, the entire operating system, applications, settings, patches and more, reducing their system(s) to "bare metal." After all, before data can be restored to a system, there must be a system to restore it to.
In this one hour webinar, learn how to enhance your existing backup strategies for better disaster recovery preparedness using Storix System Backup Administrator (SBAdmin), a highly flexible bare-metal recovery solution for UNIX and Linux systems.
Sponsored by Storix
Trending Topics
Geek Guide: The DevOps Toolbox | Mar 06, 2015 |
Nmap—Not Just for Evil! | Mar 05, 2015 |
Resurrecting the Armadillo | Mar 04, 2015 |
March 2015 Issue of Linux Journal: System Administration | Mar 02, 2015 |
March 2015 Video Preview | Mar 02, 2015 |
High-Availability Storage with HA-LVM | Feb 26, 2015 |
- Geek Guide: The DevOps Toolbox
- Download "The DevOps Toolbox: Tools and Technologies for Scale and Reliability"
- Nmap—Not Just for Evil!
- High-Availability Storage with HA-LVM
- Resurrecting the Armadillo
- DNSMasq, the Pint-Sized Super Dæmon!
- Real-Time Rogue Wireless Access Point Detection with the Raspberry Pi
- Localhost DNS Cache
- March 2015 Issue of Linux Journal: System Administration
- Days Between Dates: the Counting

subset: commoncrawl


text:
Disclaimer: This information sheet is for education purposes only. Please consult with your doctor or other health professional to make sure this information is right for your child.
Generally during development, children learn to hold back certain responses and behaviours that are not appropriate for a situation. Following a brain injury, there may be damage to the parts of the brain that contribute to a child's ability to control their own behaviour and they may say things or behave in ways that are not acceptable. Although children, and particularly adolescents, may sometimes behave in ways that seem inappropriate to others, following a brain injury the degree of this problem may be increased, the nature of it may be different and the level of control that the child has over it, and the level of insight they have may be decreased.
Examples of inappropriate/disinhibited behaviour
It is important to be aware that the child may not have insight that the behaviour is inappropriate.
If the behaviours occur frequently and are impacting on the family, referral to a Clinical Psychologist may be recommended. The clinical psychologist can develop individual strategies to modify and cope with the child's disinhibition. A program would usually involve ways to develop alternative responses as well as consequences for problem behaviours.


text:
Of course you want to record your conference … but who's really going to view it all?
Why not offer choice:
- Edited highlights of key speakers
- Delegate feedback and voxpops endorsing the event
- An Intro Overview for those in a rush
1 day shoot | 2 day shoot | 3 day shoot |
from | from | from |
£3,845 |
£5,495 |
£7,145 |
Plus interactivity from £1,000
Perhaps you need a conference presentation video to start your conference with a wow?
Why have a Conference DVD?
Deliver a compelling interactive DVD of your next conference to use as:
- A valuable promotional tool for customers
- A custom-produced training tool for your management
- A shareholders' AGM offering
We deliver:
- A professional camera and sound crew with everything you'll need to shoot your conference
- A crisp final DVD with all the speakers' asides and unessential anecdotes edited out
- An interactive widescreen DVD, with animated menus so viewers can select the precise sections of the conference programme they wish to view
Look what else you get:
- Enhanced speaker performances, with the pictures postproduced to make your VIP speakers gleam.
- Voxpop interviews with delegates, endorsing your conference with video testimonials and valuable feedback.
- Internet-ready video clips which you can stream from anywhere on your website.
Interactive Conference DVD
Prices from £4,449
- Initial Project Briefing to establish what video is needed, and how it fits into The Conference Day
- Crew arrival the evening before or early am for setup, as required
- Director, Camera Op and Sound Recordist as minimum crew
- All cables & equipment safely taped down, with signage where appropriate in delegate areas
- Remote wireless microphones available for better sound recording quality
- Interview delegates for testimonial voxpops and feedback on their conference experience
- All footage pregraded prior to online editing
- Full editing
- Client invited to Studio to assist for ½ to 1 day with the editing decisions
- DVD authoring to develop an interactive DVD master
- On-body artwork supplied
- 5 DVD copies supplied
- For bulk duplication requirements we advise using a dedicated duplication house, who will offer best rates on a wide variety of possible delivery packages.
- Streaming-ready video files supplied, with graphic launch icons if required.
The above specification is flexible, but will be ample for many conferences, and will deliver you – your interactive conference DVD.
The Viewer DVD Experience
The Viewer's DVD Experience is everything.
Your Viewer expects the most streamlined, useful and inspiring conference DVD experience that technology can deliver.
The moment The Viewer receives their DVD copy it looks impressive, with corporate style artwork on the disk. This helps them realise that this is a high quality production, one relevant to them, and one worth looking at now!
On loading the disk into their DVD player, multimedia PC or laptop, The Viewer sees a brief animated title screen, designed to complement your corporate style (complete with copyright notices if required)
This unfolds into a graphic animated menu, with video images set to music playing in the background.
A interactive menu approach allows The Viewer to very easily tailor the presentation to their requirements either by clicking "Play All", or by selecting individual modules.
For example, one module in the DVD could be the CEO's strategy presentation, while another module could be the Marketing Director's Report on the last 12 months, with asides and unessential anecdotes edited out.
The Intro Module would be a brief synopsis of all the key points.
The Viewer selects only what they want to see, without having to skip through areas that are irrelevant to them. On completion, each module will return to the main menu screen.
When a module is selected, the speaker is seen in widescreen, which makes them look more important. Widescreen also shows more of the conference setting and their multimedia presentation running behind.
Widescreen offers better viewing when there are two or more speakers on stage together. Together with the video post-production employed to cosmeticise speakers, The Viewer will obtain the best possible view.
Above and behind the speaker is the multimedia presentation. This will cut in fullscreen where required, highlighting the key presentation points, as seen on The Conference Day.
Because we closely involve you with the editing decisions, The Viewer only gets to see a conference DVD with the very best of what was said on The Day, with all lesser material deleted, or stored in a simple video archive.
Web Visitors can interactively view selected modules of your conference online as streaming clips on your website. Graphic icons can be used to launch each video clip. We can offer you a choice of streaming files including Windows wmv, Quicktime .mov, or the infinitely superior H264 .mp4


text:
Designer Candice Olson's sophisticated touch is on display in this divine table lamp design. This lamp features a chrome finish base with geometric forms and a cream silk rectangular shade. With a 3-way socket that makes it easy to set the desired lighting level.
Candace Olson's sophisticated yet accessible style has made her one of North America's leading interior designers. Since opening her own practice in 1994, Olson has built a reputation for creativity, practicality, and timelessness. In 2002, Olson became the host of HGTV's "Divine Design" which immediately became the channel's #1 rated prime-time show. Her intelligent and stylish designs continue to define practical and contemporary lighting.
Shipping and Delivery Information - For item EUF9868 if ordered by 1 pm Pacific Time


text:
This chart gives you easy kitchen conversions to make baking and cooking not only easier, but even more fun!
Hand signed by the artist. This two color silkscreen poster is printed on Accent Opaque Smooth White 100# cover stock using non-toxic inks. Also known as silk screening, serigraphy is a process by which multiple layers of ink are manually pressed through fine screens, resulting in an art print that resembles a painting on paper. Price
Other ways to order:
Call Us: 1-800-952-5592 |
30-DAY RETURN POLICY If for any reason you are not completely satisfied with your purchase, you can receive a replacement or refund within 30 days Learn More
Ship time indicates the typical time it takes for your item(s) to leave our facilities. This includes any framing or customizing services ordered as well as careful packaging to prevent damage in transit.
Items that ship same day normally leave our facilities on the same business day if your order is placed before 5:00pm EST. Orders that contain multiple items with different ship times will be shipped out based on the item with the longest ship time. Shipping FAQ Shipping Rates |
Reviewed by 1 customer
Displaying review 1
Purchase Reason
Not impressed with the Serigraph material. It didn't have a shiny finish and felt like it was just printed off from a computer. However, when put in a frame it looks very nice.
Displaying review 1
© Art.com Inc. All Rights Reserved. | Privacy Policy | Terms of Use | Terms of Sale
Art.com, You+Art, and Photos [to] Art are trademarks or registered trademarks of Art.com Inc.
Various aspects of this website are covered by issued US patent No. 7,973,796 and other pending patent applications.


text:
Gyrodata External Resources
Links to Gyrodata's resources have been removed from this site and moved to our intranet site. They've been moved to the left hand side of the first page of the intranet portal.
Click here to access the Gyrodata intranet site.
Please use your Gyrodata network credentials to log into this system.
Page last modified: February 28, 2011 - 00:00:00


text:
EXCLUSIVE: Hard 'n Phirm & Friends Sing "Gersberms (Yer Gervin Mah)"
By Perry Michael Simon on November 13, 2012
Take one of the funnier Internet memes of recent times, put it to a smooth boy band-style-R&B groove, and you get "Gersberms (Yer Gervin Mah)," the new hit video exclusive to the Nerdist Channel from… oh, wait, I forgot a few ingredients:
The artists: Hard 'n Phirm.
Featured vocals from Hayley Williams of Paramore and the Swedish Chef.
The acting talents of The Big Bang Theory's Melissa Rauch.
And a special message at the end.
Plus, the guys wear hats. Several hats.
Serbscribe tehr teh Nerdist Churnel fehr mehr.
chef, chris, gersberms, goosebumps, hard, Hard 'n Phirm, hardwick, hats, hayley, melissa, mike, Muppets, paramore, phirm, Phirman, rauch, swedish, williams


text: Am Dienstag, 27. November 2001 15:16 schrieben Sie: > On Wednesday 28 November 2001 23:21, Naitik Shah wrote: > > Is apmd what i need to install to be able to use kde's > > powermanagement?... > > Yes. Not only. You'll need apmd too. I suggest you look at the kernel Documentation about Powermanagement: /usr/src/linux/Documentation/pm.txt. > > > I've compiled powermanagement stuff in the kernel. But i wanna be able to > > suspend and standby my system. But the apmd readme says something like > > the stuff is over a few years old! > > That's no guarantee that it doesn't work. > > > someone must be using a laptop! I am. But my IBM thinkpad i1200 doesn't like APM. So I'm using ACPI. > > Not me -- mine died. > > > oh yeah, is there any special software for P-III-Mobile for better power > > management and extending battery life? Not yet, because ACPI4Linux is still under heavy development. There's no APM mode to get into the CPU settings. > > That one, I don't know about. I'd just advise you to let things power down > after short idle times, even if (disk access most of all) things slow down > a lot because of it. > > > rgds, > Peter de Freitas LX -- Unsubscribe: send email to listar at linuxfromscratch.org and put 'unsubscribe alfs-discuss' in the subject header of the message


text:
Article ID: 287566 - View products that this article applies to. This article was previously published under Q287566 NoticeThis article applies to Windows 2000. Support for Windows 2000 ends on July 13, 2010. The Windows 2000 End-of-Support Solution Center
is a starting point for planning your migration strategy from Windows 2000. For more information see the Microsoft Support Lifecycle
.SYMPTOMS With roaming user profiles, if you do not disable the cache
option for Offline Files, synchronization problems may occur. The user profile
can be placed in an unstable state as both Offline Files and the roaming user
profiles attempt to synchronize the files in a user's profile. CAUSE This behavior can occur because the cache option in Offline
Files is based on the server message block (SMB) protocol, and is SMB
share-based. If the cache option is enabled on a share, any files that are created on the remote share from the local computer can be cached. This action, however, can result in synchronization problems if the cache option is enabled on a share where roaming user profiles are located, or are accessed by means of a path where the cache option is enabled. If a roaming user profile is located below a share where the cache option is enabled, Offline Files caches files in the users profile, as they are copied to and from the server. The reason this occurs is to handle situations where programs work with new copies of a file, and then rename the original file. (Offline Files caches all files created on the remote share from the local computer.) Because a roaming user profile can copy the files in the user's profile to temporary files on the server share, and then rename them, Offline Files adds the files in the user's profile to the cache. RESOLUTION To work around this behavior, create a separate share to
store the users' profiles, and then disable the cache option on that share.
(The cache option can only be disabled on shares that are hosted by computers
that run Windows 2000.) Microsoft recommends that you store the roaming user profiles and offline-enabled shares on a separate server, whenever possible. To disable the cache option by means of the command line:
To disable the cache option by means of the user interface:
STATUS This behavior is by design. MORE INFORMATION The cache option for Offline Files must be disabled on
shares where roaming user profiles are stored. If you want to store
offline-enabled redirected folders and roaming user profiles on the same
server, they must be on separate shares. For additional information regarding IntelliMirror and user data management, visit the following Microsoft Web sites: For user data and settings management: http://technet2.microsoft.com/windowsserver/en/library/95cdb400-afd5-4297-a728-78ca96cc6d311033.mspx
For IntelliMirror tips and tricks: http://technet.microsoft.com/en-us/library/cc750595.aspx
PropertiesArticle ID: 287566 - Last Review: January 31, 2007 - Revision: 4.7 APPLIES TO


text:
Join our network of non-profits, companies and individuals who believe social change can happen through design.
Become A MemberPopular Blogs
- winema gaven
1 Votes / 1 Posts - LogicGateOne Corp
0 Votes / 3 Posts - zwanen burgh
0 Votes / 2 Posts - jelly peers
0 Votes / 2 Posts
Most Active Members
- Kate Andrews
321 Recent Posts - v-neeta
305 Recent Posts - steven landau
157 Recent Posts - Douglas Best
126 Recent Posts
Recent Work Samples
- vasilis capellas
Designer - Vina Domingo-Roy
Designer (Product Design) - fert det
Designer (Journalism) - HeatherRose Studios
Designer (Illustration)
Gillian Puckett
United States
Member since November 20, 2012
Do you know how to make dollars on the web from house very easily? Ahead of receiving included in an on the web business, somebody advised me that this is quite uncomplicated. You you should not require to search for a job and work for 8 several hours. You can easily make cash from home devoid of any any financial commitment.
So, I desired to discover about from residence. I study on the net marketer biography. I participated in make funds message boards, content, answering make money fast websites and far more. My purpose was raising the know-how for creating income on-line.
Now, I had a nicely knowledge for generate money online. Also I discovered that there are no mystery driving make funds on the net. I study review about money producing software, but the doing work action was identical. Also, possessing very own web page is incredibly important for prolonged time revenue.
I purchased a domain and internet hosting. I didn't invest cash for how to make money layout and build of site. My good friend suggest for use wordpress that is very straightforward to set up and several cost-free concept readily available for free. I invested some time for discover how to set up a wordpress website.
I experienced no dollars for selecting a freelance articles writer. My English was weak, but I put in 6-seven several hours for crafting a site post before publishing. I posted 1 post daily. I examine about on page how to make fast money optimization and composing ideas. So, I knew how to create a Search engine optimization welcoming submit.
Following that, I required to encourage my site for receiving visitors. I read about search motor optimization. I commence subsequent Web optimization site like SEOMOZ, Google webmaster. I submitted my website in search engine. I started directory submission, cultural ebook-marking, guest posting and other function.
After three months, my common month-to-month traffic was typical 1500. Now, I imagined how to make money fast to make some dollars from my internet site. My pal suggests me for Google AdSense. I applied for an AdSense account. Inside of 7days, my account was approved. My day-to-day earning was regular one.50 every day.
Some time later on, I noticed about affiliate marketing and advertising, CPA gives, referring packages, promoting for make funds from a internet site. I experimented with all procedures. Following 1 12 months, my earning was about $300 USD from household.
make money online So, I believe make dollars on the net option for all people. This is a wonderful chance also for individuals persons who have no university degree, unemployed. Also, some persons are failing simply because of numerous elements this kind of as possessing no enthusiasm, no difficult function, no plan for achieving objective-I earned my very first revenue from my internet site following 6 months.
Kumar Krishna is an on the internet marketer and giving tips about . You can check out to know additional .
My Interests
- Industrial Design
- Environmental Design
- Communication Design
- Fashion Design
- Audio/Visual Design


text:
Accuracy is one of several data elements required for assay validation.
Bioanalytical Method Development And Validation:Guidelines
Sponsored Links
Selective and sensitive analytical methods for the quantitative evaluation of drugs and their metabolites (analytes) are critical for the successful conduct of preclinical and/or biopharmaceutics and clinical pharmacology studies. Bioanalytical method validation includes all of the procedures that demonstrate that a particular method used for quantitative measurement of analytes in a given biological matrix, such as blood, plasma, serum, or urine, is reliable and reproducible for the intended use.1,2. It is essential to employ well-characterized and fully validated bioanalytical methods to yield reliable results that can be satisfactorily interpreted. Applications of bioanalytical method in routine drug analysis also take into consideration in this article. These various essential development and validation characteristics for bioanalytical methodology have been discussed with view to improving the standard and acceptance in this area of research.
Keywords: Bioanalytical method, development, validation, bioanalytical applications.
Introduction: 1,2,3
Characterization of the stability of analytes in biological samples collected during clinical studies together with that of critical assay reagents, including analyte stock solutions, is recognized as an important component of bioanalytical assay validation. Selective and sensitive analytical methods for the quantitative evaluation of drugs and their metabolites (analytes) are critical for the successful conduct of preclinical and/or biopharmaceutics and clinical pharmacology studies. Bioanalytical method validation includes all of the procedures that demonstrate that a particular method used for quantitative measurement of analytes in a given biological matrix, such as blood, plasma, serum, or urine, is reliable and reproducible for the intended use.1,2 The fundamental parameters for this validation include :(1) accuracy, (2) precision, (3) selectivity, (4) sensitivity, (5) reproducibility, and (6) stability.
Validation involves documenting, through the use of specific laboratory investigations, that the performance characteristics of the method are suitable and reliable for the intended analytical applications. The acceptability of analytical data corresponds directly to the criteria used to validate the method. This guideline provides assistance to sponsors of investigational new drug applications (INDs), new drug applications (NDAs), abbreviated new drug applications (ANDAs), and supplements in developing bioanalytical method validation information used in human clinical pharmacology, bioavailability (BA), and bioequivalence (BE) studies requiring pharmacokinetic (PK) evaluation. This guideline also applies to bioanalytical methods used for non-human pharmacology/toxicology studies and preclinical studies. For studies related to the veterinary drug approval process, this guidance applies only to blood and urine BA, BE, and PK studies. The information in this guideline generally applies to bioanalytical procedures such as7,8,9,10,12,17
1.Gas Chromatography(GC)
2.High-pressure Liquid chromatography (LC)
3.combined GC and LC mass spectrometric (MS)
6.GC-MS and
These procedures are generally performed for the quantitative determination of drugs and/or metabolites in biological matrices such as blood, serum, plasma, or urine. This guideline also applies to other bioanalytical methods, such as immunological and microbiological procedures, and to other biological matrices, such as tissue and skin samples. This guideline provides general recommendations for bioanalytical method validation. The recommendations can be adjusted or modified depending on the specific type of analytical method used. The increased number of biological agents used as therapeutics (in the form of recombinant proteins, monoclonal antibodies, vaccines, etc) has prompted the pharmaceutical industry to review and refine aspects of the development and validation of bioanalytical methods for the quantification of these therapeutics in biological matrices in support of preclinical and clinical studies.
Most of these methodologies are used in quantitative assays supporting pharmacokinetic and toxicokinetic parameters6 of the therapeutic agents. The methods that are primarily used in these evaluations are ligand binding assays (LBAs or Immunoassays), where the specificity and selectivity of the assays depend on the interactions of other biological molecules, such as receptors, antibodies against the therapeutic candidates, and aptamers3. The response observed in these methods is indirectly related to the concentration of the therapeutic, that is, the basis of the detection is an enzymatic or radiochemical response tied to a variety of binding interactions. There is no direct physicochemical property of a macromolecule that can be used in this determination (unlike for a small-molecule drug candidate). Because of the nature of these binding interactions, the dynamic range of the standard curves is narrow as well as nonlinear/sigmoidal. Bioanalytical method validation (BMV) employed for the quantitative determination of drugs and their metabolites in biological fluids plays a significant role in the evaluation and interpretation of bioavailability, bioequivalence, pharmacokinetic, and toxicokinetic study data. These studies generally support regulatory filings. The quality of these studies is directly related to the quality of the underlying bioanalytical data. It is therefore important that guiding principles for the validation of these analytical methods be established and disseminated to the pharmaceutical community.
Need Of Bionalytical Method Validation1, 2:
It is essential to employ well-characterized and fully validated bioanalytical methods to yield reliable results that can be satisfactorily interpreted. It is recognized that bioanalytical methods and techniques are constantly undergoing changes and improvements; and in many instances, they are at the cutting edge of the technology. It is also important to emphasize that each bioanalytical technique has its own characteristics, which will vary from analyte to analyte—in these instances, specific validation criteria may need to be developed for each analyte. Moreover, the appropriateness of the technique may also be influenced by the ultimate objective of the study. When sample analysis for a given study is conducted at more than one site, it is necessary to validate the bioanalytical method(s) at each site and provide appropriate validation information for different sites to establish interlaboratory reliability.
Bionalytical Mehtod Development And Validation: 1,2,23,24,25
The process by which a specific bioanalytical method is developed, validated, and used in routine sample analysis can be divided into
1.Reference Standard preparation
2.Bioanalytical method develo`pment and establishment of assay procedure
3.Application of validated bioanalytical method to routine drug analysis and acceptance criteria for the analytical run and/or batch.
1. Reference Standard: 1,2,23,24,25
Analysis of drugs and their metabolites in a biological matrix is carried out using samples spiked with calibration (reference) standards and using quality control (QC) samples. The purity of the reference standard used to prepare spiked samples can affect study data. For this reason, an authenticated analytical reference standard of known identity and purity should be used to prepare solutions of known concentrations. If possible, the reference standard should be identical to the analyte. When this is not possible, an established chemical form (free base or acid, salt or ester) of known purity can be used. Three types of reference standards are usually used:
1.Certified reference standards (e.g., USP compendial standards)
2.Commercially supplied reference standards obtained from a reputable commercial source; and/or
3.Other materials of documented purity custom-synthesized by an analytical laboratory or other noncommercial establishment.
The source and lot number, expiration date, certificates of analyses when available, and/or internally or externally generated evidence of identity and purity should be furnished for each reference standard.
2. Bioanalytical Method Development: 1,2,4
The method development and establishment phase defines the chemical assay. Typical method development and establishment for a bioanalytical method include determination of (1) selectivity, (2) accuracy, precision, recovery, (3) calibration curve, and (4) stability of analyte in spiked samples.
It is the ability of an analytical method to differentiate and quantify the analyte in the presence of other components in the sample. For selectivity, analyses of blank samples of the appropriate biological matrix (plasma, urine, or other matrix) should be obtained from at least six sources. Each blank sample should be tested for interference, and selectivity should be ensured at the lower limit of quantification (LLOQ). Potential interfering substances in a biological matrix include endogenous matrix components, metabolites, decomposition products, and in the actual study, concomitant medication and other exogenous xenobiotics. If the method is intended to quantify more than one analyte, each analyte should be tested to ensure that there is no interference.
B. Accuracy, Precision, and Recovery 24, 10, 5
Accuracy –
The accuracy of an analytical method describes the closeness of mean test results obtained by the method to the true value (concentration) of the analyte. Accuracy is determined by replicate analysis of samples containing known amounts of the analyte. Accuracy should be measured using a minimum of five determinations per concentration. A minimum of three concentrations in the range of expected concentrations is recommended. The mean value should be within 15% of the actual value except at LLOQ, where it should not deviate by more than 20%. The deviation of the mean from the true value serves as the measure of accuracy.
Precision -
The precision of an analytical method describes the closeness of individual measures of an analyte when the procedure is applied repeatedly to multiple aliquots of a single homogeneous volume of biological matrix. Precision should be measured using a minimum of five determinations per concentration. A minimum of three concentrations in the range of expected concentrations is recommended. The precision determined at each concentration level should not exceed 15% of the coefficient of variation (CV) except for the LLOQ, where it should not exceed 20% of the CV. Precision is further subdivided into
1.Within-run, intra-batch precision or repeatability: This assesses precision during a single analytical run,
2.Between-run, inter-batch precision or repeatability: This measures precision with time, and may involve different analysts, equipment, reagents, and laboratories.
Recovery -
The recovery of an analyte in an assay is the detector response obtained from an amount of the analyte added to and extracted from the biological matrix, compared to the detector response obtained for the true concentration of the pure authentic standard. Recovery pertains to the extraction efficiency of an analytical method within the limits of variability. Recovery of the analyte need not be 100%, but the extent of recovery of an analyte and of the internal standard should be consistent, precise, and reproducible. Recovery experiments should be performed by comparing the analytical results for extracted samples at three concentrations (low, medium, and high) with unextracted standards that represent 100% recovery.
C.Calibration/Standard Curve 1,2,23,24,25,26
A calibration (standard) curve is the relationship between instrument response and known concentrations of the analyte. A calibration curve should be generated for each analyte in the sample. A sufficient number of standards should be used to adequately define the relationship between concentration and response. A calibration curve should be prepared in the same biological matrix as the samples in the intended study by spiking the matrix with known concentrations of the analyte. The number of standards used in constructing a calibration curve will be a function of the anticipated range of analytical values and the nature of the analyte/response relationship. Concentrations of standards should be chosen on the basis of the concentration range expected in a particular study. A calibration curve should consist of
i.A blank sample (matrix sample processed without internal standard)
ii.A zero sample (matrix sample processed with internal standard)
iii. Six to eight non-zero samples covering the expected range, including LLOQ.
1. Lower Limit of Quantification (LLOQ)
The lowest standard on the calibration curve should be accepted as the limit of quantification if the following conditions are met:
·The analyte response at the LLOQ should be at least 5 times the response compared to blank response.
·Analyte peak (response) should be identifiable, discrete, and reproducible with a precision of 20% and accuracy of 80-120%.
2. Calibration Curve/Standard Curve - Concentration-Response:
The simplest model that adequately describes the concentration-response relationship should be used. Selection of weighting and use of a complex regression equation should be justified. The following conditions should be met in developing a calibration curve:
·20% deviation of the LLOQ from nominal concentration
·15% deviation of standards other than LLOQ from nominal concentration
At least four out of six non-zero standards should meet the above criteria, including the LLOQ and the calibration standard at the highest concentration. The standards when excluded should not should not change the model used.
Bioanalytical Method Validation: 1,2,4,5,13,14,17,25,26
Validation Selectivity:3
Bioanalytical method validation selectivity depends upon stage of development of the drug as 1: Table 1:
Development stage |
Assay Objectives |
Validation requirement |
1.Discovery |
Comparison of some related compounds |
Similar selectivity towards all compound examined |
2. Pre Clinical |
Toxicology/metabolism support regulatory standard |
Reliable selective; for blood /plasma/other animal matrices |
3.Cinical Healthy volunteers |
Definitive clinical studies; high throughput; usable in other labs |
Excellent selectivity in human biofluids-plasma, urine, saliva, CSF,perhaps facial homogenates |
4.Clinical Patients |
Worldwide routine monitoring of patients varying in medication and dietary background |
Reliable selectivity in the presence of numerous substances |
Pre-Validation Study:
Before going for the actual validation process so called pre validation is done. In Pre- validation study large numbers of replicate spiked matrix samples are analyzed in single batch before a method validation is started. The utility of this pre-validation approach is illustrated using actual laboratory data. The process of interpreting the results and drawing conclusions about assay viability is demonstrated. The resulting conclusions provide sufficient background information to indicate if an assay is ready to enter the validation process. Following validation criteria is studied in Pre-validation and Validation steps
Validation criteria to be studied in Pre-validation and validation steps: 1 Table 2:
Criteria |
Pre – validation step |
Validation step |
Absolute recovery Selectivity Response function Linearity Accuracy Precision Limit of detection Limit of quantification Range |
+ (+) (+) + (+) (+) + |
+ + + + + + + |
(+): estimation of the criteria; +: validation of the criteria
A.Full Validation
§Full validation is important when developing and implementing a bioanalytical method for the first time.
§ Full validation is important for a new drug entity.
§A full validation of the revised assay is important if metabolites are added to an existing assay for quantification.
B.Partial Validation
Partial validations are modifications of already validated bioanalytical methods. Partial validation can range from as little as one intra-assay accuracy and precision determination to a nearly full validation. Typical bioanalytical method changes that fall into this category include, but are not limited to:
§Bioanalytical method transfers between laboratories or analysts
§Change in analytical methodology (e.g., change in detection systems)
§Change in anticoagulant in harvesting biological fluid
§ Change in matrix within species (e.g., human plasma to human urine)
§ Change in sample processing procedures
§ Change in species within matrix (e.g., rat plasma to mouse plasma)
§ Change in relevant concentration range
§Changes in instruments and/or software platforms
§ Limited sample volume (e.g., pediatric study)
§Rare matrices
§ Selectivity demonstration of an analyte in the presence of concomitant medications
§ Selectivity demonstration of an analyte in the presence of specific metabolites
C. Cross-Validation
Cross-validation is a comparison of validation parameters when two or more bioanalytical methods are used to generate data within the same study or across different studies. An example of cross-validation would be a situation where an original validated bioanalytical method serves as the reference and the revised bioanalytical method is the comparator. The comparisons should be done both ways. When sample analyses within a single study are conducted at more than one site or more than one laboratory, cross-validation with spiked matrix standards and subject samples should be conducted at each site or laboratory to establish inter laboratory reliability. Cross-validation should also be considered when data generated using different analytical techniques (e.g., LC-MS-MS vs. ELISA) in different studies are included in a regulatory submission.
Stability In A Biological Fluid: 1, 2,4,7,21,22,23,24
Drug stability in a biological fluid is a function of the storage conditions, the chemical properties of the drug, the matrix, and the container system. The stability of an analyte in a particular matrix and container system is relevant only to that matrix and container system and should not be extrapolated to other matrices and container systems. Stability procedures should evaluate the stability of the analytes during sample collection and handling, after long-term (frozen at the intended storage temperature) and short-term (bench top, room temperature) storage, and after going through freeze and thaw cycles and the analytical process. Conditions used in stability experiments should reflect situations likely to be encountered during actual sample handling and analysis. The procedure should also include an evaluation of analyte stability in stock solution.
All stability determinations should use a set of samples prepared from a freshly made stock solution of the analyte in the appropriate analyte-free, interference-free biological matrix. Stock solutions of the analyte for stability evaluation should be prepared in an appropriate solvent at known concentrations.
Freeze and Thaw Stability:
Analyte stability should be determined after three freeze and thaw cycles. At least three aliquots at each of the low and high concentrations should be stored at the intended storage temperature for 24 hours and thawed unassisted at room temperature. When completely thawed, the samples should be refrozen for 12 to 24 hours under the same conditions. The freeze-thaw cycle should be repeated two more times, then analyzed on the third cycle. If an analyte is unstable at the intended storage temperature, the stability sample should be frozen at -700C during the three freeze and thaw cycles.
Short-Term Temperature Stability:
Three aliquots of each of the low and high concentrations should be thawed at room temperature and kept at this temperature from 4 to 24 hours (based on the expected duration that samples will be maintained at room temperature in the intended study) and analyzed.
Long-Term Stability:
The storage time in a long-term stability evaluation should exceed the time between the date of first sample collection and the date of last sample analysis. Long-term stability should be determined by storing at least three aliquots of each of the low and high concentrations under the same conditions as the study samples. The volume of samples should be sufficient for analysis on three separate occasions. The concentrations of all the stability samples should be compared to the mean of back-calculated values for the standards at the appropriate concentrations from the first day of long-term stability testing.
Stock Solution Stability:
The stability of stock solutions of drug and the internal standard should be evaluated at room temperature for at least 6 hours. If the stock solutions are refrigerated or frozen for the relevant period, the stability should be documented. After completion of the desired storage time, the stability should be tested by comparing the instrument response with that of freshly prepared solutions.
Post-Preparative Stability:
The stability of processed samples, including the resident time in the autosampler, should be determined. The stability of the drug and the internal standard should be assessed over the anticipated run time for the batch size in validation samples by determining concentrations on the basis of original calibration standards. Although the traditional approach of comparing analytical results for stored samples with those for freshly prepared samples has been referred to in this guidance, other statistical approaches based on confidence limits for evaluation of an analyte stability in a biological matrix can be used. SOPs should clearly describe the statistical method and rules used. Additional validation may include investigation of samples from dosed subjects.
Microbiological And Ligand-Binding Assays: 18,19,20
In these evaluations, the specificity and selectivity of the assays depend on the interactions of other biological molecules, such as receptors, antibodies against the therapeutic candidates, and aptamers. The response observed in these methods is indirectly related to the concentration of the therapeutic, that is, the basis of the detection is an enzymatic or radiochemical response tied to a variety of binding interactions. There is no direct physicochemical property of a macromolecule that can be used in this determination (unlike for a small-molecule drug candidate). Because of the nature of these binding interactions, the dynamic range of the standard curves is narrow as well as nonlinear/sigmoidal. The purpose here is to highlight the key elements of validation of bioanalytical methods that support the pharmacokinetic and toxicokinetic assessments of macromolecules
Many of the bioanalytical validation parameters and principles discussed above are also applicable to microbiological and ligand-binding assays. However, these assays possess some unique characteristics that should be considered during method validation against that of small molecule (Drug) as below:
Comparison of the Characteristics of Small-Molecule (Drugs) and Macromolecule Compounds: 18
Characteristic |
Small Molecules |
Macromolecule |
Size |
Small (<1000 Da) |
Large (>5000 Da) |
Structure |
Organic molecules |
Amino acid biopolymers; could be multimeric |
Purity |
Homogeneous |
Heterogeneous |
Solubility |
Often hydrophobic |
Often hydrophilic |
Stability |
Chemical |
Chemical, physical, and biological |
Presence in matrix |
Xenobiotic (foreign) |
Endogenous |
Synthesis |
Organic synthesis |
Biological production |
Metabolism |
Defined |
Not well defined; could be biotransformed depending on the environment as well as in vivo conditions |
Serum binding |
Albumin |
Specific carrier proteins |
A. Selectivity Issues
As with chromatographic methods, microbiological and ligand-binding assays should be shown to be selective for the analyte. The following recommendations for dealing with two selectivity issues should be considered:
1. Interference from substances physicochemically similar to the analyte
·Cross-reactivity of metabolites, concomitant medications, or endogenous compounds should be evaluated individually and in combination with the analyte of interest.
·When possible, the immunoassay should be compared with a validated reference method (such as LC-MS) using incurred samples and predetermined criteria for agreement of accuracy of immunoassay and reference method.
·The dilutional linearity to the reference standard should be assessed using study (incurred) samples.
· Selectivity may be improved for some analytes by incorporation of separation steps prior to immunoassay.
2. Matrix effects unrelated to the analyte
·The standard curve in biological fluids should be compared with standard in buffer to detect matrix effects.
·Parallelism of diluted study samples should be evaluated with diluted standards to detect matrix effects.
· Nonspecific binding should be determined.
B. Quantification Issues
Microbiological and immunoassay standard curves are inherently nonlinear and, in general, more concentration points may be recommended to define the fit over the standard curve range than for chemical assays. In addition to their nonlinear characteristics, the response-error relationship for immunoassay standard curves is a nonconstant function of the mean response (heteroscadisticity). For these reasons, a minimum of six non-zero calibrator concentrations, run in duplicate, is recommended. The concentration-response relationship is most often fitted to a 4- or 5-parameter logistic model, although others may be used with suitable validation. The use of anchoring points in the asymptotic high- and low-concentration ends of the standard curve may improve the overall curve fit. Generally, these anchoring points will be at concentrations that are below the established LLOQ and above the established ULOQ. Whenever possible, calibrators should be prepared in the same matrix as the study samples or in an alternate matrix of equivalent performance. Both ULOQ and LLOQ should be defined by acceptable accuracy, precision, or confidence interval criteria based on the study requirements.
For all assays the key factor is the accuracy of the reported results. This accuracy can be improved by the use of replicate samples. In the case where replicate samples should be measured during the validation to improve accuracy, the same procedure should be followed as for unknown samples.
The following recommendations apply to quantification issues:
§If separation is used prior to assay for study samples but not for standards, it is important to establish recovery and use it in determining results. Possible approaches to assess efficiency and reproducibility of recovery are
1.The use of radiolabeled tracer analyte (quantity too small to affect the assay)
2.The advance establishment of reproducible recovery
3.The use of an internal standard that is not recognized by the antibody but can be measured by another technique.
§ Key reagents, such as antibody, tracer, reference standard, and matrix should be characterized appropriately and stored under defined conditions.
§Assessments of analyte stability should be conducted in true study matrix (e.g., should not use a matrix stripped to remove endogenous interferences).
§Acceptance criteria: At least 67% (4 out of 6) of QC samples should be within 15% of their respective nominal value, 33% of the QC samples (not all replicates at the same concentration) may be outside 15% of nominal value. In certain situations, wider acceptance criteria may be justified.
§ Assay reoptimization or validation may be important when there are changes in key reagents, as follows
Labeled analyte (tracer)
§Binding should be reoptimized.
§Performance should be verified with standard curve and QCs.
§Key cross-reactivities should be checked.
§Tracer experiments above should be repeated.
§Tracer experiments above should be repeated.
Method development experiments should include a minimum of six runs conducted over several days, with at least four concentrations (LLOQ, low, medium, and high) analyzed in duplicate in each run.
Specific Recommendation For Bioanalytical Method Validation: 1, 2, 9,10,13,14,25,26
§The matrix-based standard curve should consist of a minimum of six standard points, excluding blanks, using single or replicate samples. The standard curve should cover the entire range of expected concentrations.
§ Standard curve fitting is determined by applying the simplest model that adequately describes the concentration-response relationship using appropriate weighting and statistical tests for goodness of fit.
§LLOQ is the lowest concentration of the standard curve that can be measured with acceptable accuracy and precision. The LLOQ should be established using at least five samples independent of standards and determining the coefficient of variation and/or appropriate confidence interval. The LLOQ should serve as the lowest concentration on the standard curve and should not be confused with the limit of detection and/or the low QC sample. The highest standard will define the upper limit of quantification (ULOQ) of an analytical method.
§For validation of the bioanalytical method, accuracy and precision should be determined using a minimum of five determinations per concentration level (excluding blank samples). The mean value should be within 15% of the theoretical value, except at LLOQ, where it should not deviate by more than 20%. The precision around the mean value should not exceed 15% of the CV, except for LLOQ, where it should not exceed 20% of the CV. Other methods of assessing accuracy and precision that meet these limits may be equally acceptable.
§The accuracy and precision with which known concentrations of analyte in biological matrix can be determined should be demonstrated. This can be accomplished by analysis of replicate sets of analyte samples of known concentrations QC samples from an equivalent biological matrix. At a minimum, three concentrations representing the entire range of the standard curve should be studied: one within 3x the lower limit of quantification (LLOQ) (low QC sample), one near the center (middle QC), and one near the upper boundary of the standard curve (high QC).
§Reported method validation data and the determination of accuracy and precision should include all outliers; however, calculations of accuracy and precision excluding values that are statistically determined as outliers can also be reported.
§The stability of the analyte in biological matrix at intended storage temperatures should be established. The influence of freeze-thaw cycles (a minimum of three cycles at two concentrations in triplicate) should be studied.
§The stability of the analyte in matrix at ambient temperature should be evaluated over a time period equal to the typical sample preparation, sample handling, and analytical run times.
§ Reinjection reproducibility should be evaluated to determine if an analytical run could be reanalyzed in the case of instrument failure.
§The specificity of the assay methodology should be established using a minimum of six independent sources of the same matrix. For hyphenated mass spectrometry-based methods, however, testing six independent matrices for interference may not be important. In the case of LC-MS and LC-MS-MS-based procedures, matrix effects should be investigated to ensure that precision, selectivity, and sensitivity will not be compromised. Method selectivity should be evaluated during method development and throughout method validation and can continue throughout application of the method to actual study samples.
§Acceptance/rejection criteria for spiked, matrix-based calibration standards and validation QC samples should be based on the nominal (theoretical) concentration of analytes. Specific criteria can be set up in advance and achieved for accuracy and precision over the range of the standards, if so desired.
Documentation: 1,2,13,14,25,26
The validity of an analytical method should be established and verified by laboratory studies, and documentation of successful completion of such studies should be provided in the assay validation report. General and specific SOPs and good record keeping are an essential part of a validated analytical method. The data generated for bioanalytical method establishment and the QCs should be documented and available for data audit and inspection. Documentation for submission to the Agency should include
1)Summary information
2) Method development and establishment
3) Bioanalytical reports of the application of any methods to routine sample analysis
4)Other information applicable to method development and establishment and/or to routine sample analysis.
A.Summary Information
Summary information should include:
§Summary table of validation reports, including analytical method validation, partial revalidation, and cross-validation reports. The table should be in chronological sequence, and include assay method identification code, type of assay, and the reason for the new method or additional validation (e.g., to lower the limit of quantitation).
§ Summary table with a list, by protocol, of assay methods used. The protocol number, protocol title, assay type, assay method identification code, and bioanalytic report code should be provided.
§A summary table allowing cross-referencing of multiple identification codes should be provided (e.g., when an assay has different codes for the assay method, validation reports, and bioanalytical reports, especially when the sponsor and a contract laboratory assign different codes).
B. Documentation for Method Establishment
Documentation for method development and establishment should include:
§An operational description of the analytical method
§Evidence of purity and identity of drug standards, metabolite standards, and internal standards used in validation experiments
§A description of stability studies and supporting data
§ A description of experiments conducted to determine accuracy, precision, recovery, selectivity, limit of quantification, calibration curve (equations and weighting functions used, if any), and relevant data obtained from these studies
§ Documentation of intra- and inter-assay precision and accuracy
§In NDA submissions, information about cross-validation study data, if applicable
§Legible annotated chromatograms or mass spectrograms, if applicable
§Any deviations from SOPs, protocols, or GLPs (if applicable), and justifications for deviations
C.Application to Routine Drug Analysis 1, 6,24,25,26
Documentation of the application of validated bioanalytical methods to routine drug analysis should include:
§Evidence of purity and identity of drug standards, metabolite standards, and internal standards used during routine analyses
§ Summary tables containing information on sample processing and storage. Tables should include sample identification, collection dates, storage prior to shipment, information on shipment batch, and storage prior to analysis. Information should include dates, times, sample condition, and any deviation from protocols.
§ Summary tables of analytical runs of clinical or preclinical samples. Information should include assay run identification, date and time of analysis, assay method, analysts, start and stop times, duration, significant equipment and material changes, and any potential issues or deviation from the established method.
§ Equations used for back-calculation of results
§Tables of calibration curve data used in analyzing samples and calibration curve summary data
§ Summary information on intra- and inter-assay values of QC samples and data on intra- and inter-assay accuracy and precision from calibration curves and QC samples used for accepting the analytical run. QC graphs and trend analyses in addition to raw data and summary statistics are encouraged.
§Data tables from analytical runs of clinical or preclinical samples. Tables should include assay run identification, sample identification, raw data and back-calculated results, integration codes, and/or other reporting codes.
§Complete serial chromatograms from 5-20% of subjects, with standards and QC samples from those analytical runs. For pivotal bioequivalence studies for marketing, chromatograms from 20% of serially selected subjects should be included. In other studies, chromatograms from 5% of randomly selected subjects in each study should be included. Subjects whose chromatograms are to be submitted should be defined prior to the analysis of any clinical samples.
§Reasons for missing samples
§Documentation for repeat analyses. Documentation should include the initial and repeat analysis results, the reported result, assay run identification, the reason for the repeat analysis, the requestor of the repeat analysis, and the manager authorizing reanalysis. Repeat analysis of a clinical or preclinical sample should be performed only under a predefined SOP.
§Documentation for reintegrated data. Documentation should include the initial and repeat integration results, the method used for reintegration, the reported result, assay run identification, the reason for the reintegration, the requestor of the reintegration, and the manager authorizing reintegration. Reintegration of a clinical or preclinical sample should be performed only under a predefined SOP.
§ Deviations from the analysis protocol or SOP, with reasons and justifications for the deviations
D.Other Information
Other information applicable to both method development and establishment and/or to routine sample analysis could include:
§Lists of abbreviations and any additional codes used, including sample condition codes, integration codes, and reporting codes
§Reference lists and legible copies of any references
§SOPs or protocols covering the following areas:
-Calibration standard acceptance or rejection criteria
- Calibration curve acceptance or rejection criteria
- Quality control sample and assay run acceptance or rejection criteria
- Acceptance criteria for reported values when all unknown samples are assayed in duplicate
-Sample code designations, including clinical or preclinical sample codes and bioassay sample code
-Assignment of clinical or preclinical samples to assay batches
-Sample collection, processing, and storage
-Repeat analyses of samples Reintegration of samples
3. Application Of Validated Method To Routine Drug Analysis: 1,2,6,23,24,25,26
Assays of all samples of an analyte in a biological matrix should be completed within the time period for which stability data are available. In general, biological samples can be analyzed with a single determination without duplicate or replicate analysis if the assay method has acceptable variability as defined by validation data. This is true for procedures where precision and accuracy variabilities routinely fall within acceptable tolerance limits. For a difficult procedure with a labile analyte where high precision and accuracy specifications may be difficult to achieve, duplicate or even triplicate analyses can be performed for a better estimate of analyte.
The following recommendations should be noted in applying a bioanalytical method to routine drug analysis:
§A matrix-based standard curve should consist of a minimum of six standard points, excluding blanks (either single or replicate), covering the entire range.
§Response Function: Typically, the same curve fitting, weighting, and goodness of fit determined during prestudy validation should be used for the standard curve within the study. Response function is determined by appropriate statistical tests based on the actual standard points during each run in the validation. Changes in the response function relationship between prestudy validation and routine run validation indicate potential problems.
§The QC samples should be used to accept or reject the run. These QC samples are matrix spiked with analyte.
§System suitability: Based on the analyte and technique, a specific SOP (or sample) should be identified to ensure optimum operation of the system used.
§Any required sample dilutions should use like matrix (e.g., human to human) obviating the need to incorporate actual within-study dilution matrix QC samples.
§ Repeat Analysis: It is important to establish an SOP or guideline for repeat analysis and acceptance criteria. This SOP or guideline should explain the reasons for repeating sample analysis. Reasons for repeat analyses could include repeat analysis of clinical or preclinical samples for regulatory purposes, inconsistent replicate analysis, samples outside of the assay range, sample processing errors, equipment failure, poor chromatography, and inconsistent pharmacokinetic data. Reassays should be done in triplicate if sample volume allows. The rationale for the repeat analysis and the reporting of the repeat analysis should be clearly documented.
§ Sample Data Reintegration: An SOP or guideline for sample data reintegration should be established. This SOP or guideline should explain the reasons for reintegration and how the reintegration is to be performed. The rationale for the reintegration should be clearly described and documented. Original and reintegration data should be reported.
Acceptance Criteria For The Run: 1,2,9,10,11
The following acceptance criteria should be considered for accepting the analytical run:
§Standards and QC samples can be prepared from the same spiking stock solution, provided the solution stability and accuracy have been verified. A single source of matrix may also be used, provided selectivity has been verified.
§ Standard curve samples, blanks, QCs, and study samples can be arranged as considered appropriate within the run.
§Placement of standards and QC samples within a run should be designed to detect assay drift over the run.
§Matrix-based standard calibration samples: 75%, or a minimum of six standards, when back-calculated (including ULOQ) should fall within 15%, except for LLOQ, when it should be 20% of the nominal value. Values falling outside these limits can be discarded, provided they do not change the established model.
§Specific Recommendation for Method Validation, should be provided for both the intra-day and intra-run experiment.
§Quality Control Samples: Quality control samples replicated (at least once) at a minimum of three concentrations (one within 3x of the LLOQ (low QC), one in the midrange (middle QC), and one approaching the high end of the range (high QC)) should be incorporated into each run. The results of the QC samples provide the basis of accepting or rejecting the run. At least 67% (four out of six) of the QC samples should be within 15% of their respective nominal (theoretical) values; 33% of the QC samples (not all replicates at the same concentration) can be outside the 15% of the nominal value. A confidence interval approach yielding comparable accuracy and precision is an appropriate alternative.
The minimum number of samples (in multiples of three) should be at least 5% of the number of unknown samples or six total QCs, whichever is greater.
§Samples involving multiple analytes should not be rejected based on the data from one analyte failing the acceptance criteria.
§The data from rejected runs need not be documented, but the fact that a run was rejected and the reason for failure should be recorded
Bioanalysis and the production of pharmacokinetic, toxicokinetic and metabolic data play a fundamental role in pharmaceutical research and development; therefore the data must be produced to acceptable scientific standards. For this reason and the need to satisfy regulatory authority requirements, all bioanalytical methods should be properly validated and documented. The lack of a clear experimental and statistical approach for the validation of bioanalytical methods has led scientists in charge of the development of these methods to propose a practical strategy to demonstrate and assess the reliability of chromatographic methods employed in bioanalysis. The aim of this article is to provide simple to use approaches with a correct scientific background to improve the quality of the bioanalytical method development and validation process. Despite the widespread availability of different bioanalytical procedures for low molecular weight drug candidates, Ligand Binding Assay remain of critical importance for certain bioanalytical applications in support of drug development such as for antibody, receptor etc. This article gives an idea about which criteria bioanalysis based on immunoassay should follow to reach for proper acceptance. Applications of bioanalytical method in routine drug analysis also take into consideration in this article. These various essential development and validation characteristics for bioanalytical methodology have been discussed with view to improving the standard and acceptance in this area of research.
1.Eric Reid, Ian D. Wilson, Methodological Survey in Biochemistry and Analysis Volume 20: Analysis for Drug and Metabolites, Including Anti-infective Agents, 1990,1-57
2.U.S .Department of Health and Human Services, Food and Drug Administration., Guidance for Industry, Bioanalytical Method Validation, May2001
3.Nowatzke W, Woolf E, Best Practices during Bioanalytical Method Validation for the Characterization of Assay Reagents and the Evaluation of Analyte Stability in Assay Standards, Quality Controls, and Study Samples, AAPS Journal. 9(2), 2007,E117-E122.
4.Braggio S., Barnaby R. J., Grosi P , Cugola M., A strategy for validation of bioanalytical methods,Journal of Pharmaceutical and Biomedical Analysis 1996, 14, 375- 388
5.Breda C.A., Breda M., Frigerio E.,Bioanalytical method validation: a risk-based approach?, Journal of Pharmaceutical and Biomedical Analysis,35, 2004, 887–89
6.Nakashima Kenichiro, High-Performance Liquid Chromatography of drug of abuse in biological samples, Journal of Health Science, 51(3) 272-277 (2005)
7. Boulanger B. , Chiap P. Dewe W., Crommen J., Hubert Ph., An analysis of the SFSTP guide on validation of chromatographic bioanalytical methods: progresses and limitations Journal of Pharmaceutical and Biomedical Analysis,32, 2003,753-765
8.Causon Roger, Validation of chromatographic methods in biomedical analysis viewpoint and discussion, Journal of Chromatography B, 689 (1997) 175-180
9.Hartmann C., Smeyers-Verbeke J., Massart D. L., McDowall R.D., Validation of bioanalytical chromatographic methods, Journal of Pharmaceutical and Biomedical Analysis17, 1998,193–218
10.Hubert Ph., Chiap P., Crommena J., Boulanger B., Chapuzet E., N., Mercier S. Bervoas-Martin, Chevalier P., Grandjean D., Lagorce P., Lallier M., Laparra M.C., Laurentie M., Nivet J.C., The SFSTP guide on the validation of chromatographic methods for drug bioanalysis: from the Washington Conference to the laboratory, Analytica Chimica Acta 391,1999, 135-148
11.Causon Roger, Validation of chromatographic methods in biomedical analysis Viewpoint and discussion, Journal of Chromatography B, 689, 1997, 175-180
12.Hartmann C., Smeyers-Verbeke J., Massart D.L., R.D. McDowall , Validation of bioanalytical chromatographic methods, Journal of Pharmaceutical and Biomedical Analysis,17 ,1998, 193–218
13.International Conference on Harmonization (ICH). Validation of Analytical Methods: Definitions and Terminology. ICH Q2 A. 1994.
14.International Conference on Harmonization (ICH). Validation of Analytical Methods: Methodology. ICH Q2 B. 1996.
15.International Organization for Standardization. Accuracy (Trueness and Precision) of Measurement Methods and Results. ISO/DIS 5725-1 to 5725-3. 1994.
16.Catirla Maria Cruz, Vallee Framcois, Xu Allan , Assay Method Validation and Bioanalysis: Barcelona's Workshop, March 2004
17.Zhoua Shaolian, Songb Qi, Tangb Yong, Weng Naidonga, Critical Review of Development, Validation, and Transfer for High Throughput Bioanalytical LC-MS/MS Methods ,Current Pharmaceutical Analysis, 2005, 1, 3-14 3
18.Kelley M, DeSilva, B.,Key Elements of Bioanalytical Method Validation for Macromolecules., AAP Journal. 2007, 9(2), E156-E163.
19.Findlay J.W.A. , Smith W.C. , Lee J.W.,Nordblom G.D. , Das I. , DeSilva B.S. , Khan M.N. , Bowsher R.R. ,Validation of immunoassays for bioanalysis: a pharmaceutical industry perspective Journal of Pharmaceutical and Biomedical Analysis ,2000, 21,1249–1273
20.Shah Vinod P., Ph. D, History of Bioanalytical Validation and Regulation: Evolution of a Guidance Document on Bioanalytical Method Validation, AAPS 3rd Bioanalytical Workshop on Quantitative Bioanalytical Methods Validation and Implementation: Best Practices for Chromatographic and Ligand Binding Assays Crystal City, Arlington, VA, May 1-3, 2006
21.Mohammad A.,Tabrizi-Fard, Ho-Leung, Fung, ,Reversed-phase high-performance liquid chromatography method for the analysis of nitro-arginine in rat plasma and urine, Journal of Chromatography B, 679, 1996, 7-12
22.Bmscheck Torsten, Meyer Hartmut, Wellhrner Hans Herbert,a High-performance liquid chromatographic assay for the measurement of azathioprine in human serum samples, Journal of Chromatography B, 675, 1996,287-294
23.Kees Frieder, Jehnich Doris, Grobecker Horst, Simultaneous determination of acetylsalicylic acid and salicylic acid in human plasma by high-performance liquid chromatography, Journal of Chromatography B, 677, 1996, 172-177
24. Xu Raymond Naxing, Fan Leimin, Rieser Matthew J., Tawakol A. El-Shourbagy,Recent advances in high-throughput quantitative bioanalysis by LC–MS/MS, Journal of Pharmaceutical and Biomedical Analysis ,44,2007,342–355
25. Lau Yau Yi , Hanson Glenn D. , Carel Barbara J., Determination of rifampin in human plasma by high-performance liquid chromatography with ultraviolet detection ,Journal of Chromatography B, 676,1996 ,147- 152
26.Compagnon P., Thiberville L., Moore N., Thudlez C., Lacroix C., Simple high-performance liquid chromatographic method for the quantitation of 5-fluorouracil in human plasma ,Journal of Chromatography B, 677,1996,380-383
About Authors:
Shamkant .S. Patil, Pandurang .N. Dhabale, Bhanudas .S. Kuchekar
Mr.Shamkant S. Patil
Govt. College of pharmacy, Vidyanagar, Karad-415124, Maharashtra, India.
E-mail:- email@example.com, Ph.no. :- (M) +91-9766701167.
Govt. College of pharmacy, Vidyanagar, Karad-415124, Maharashtra, India
Bhanudas .S. Kuchekar
Principal, Maharashtra Institute of Pharmacy, Pune, India
Similar Entries
Changes were made to the USP method for the preparation of assay samples of ibuprofen (IBP) tablets (1).
This article describes a software solution for automating the chromatographic method validation process starting from experimental planning, data
Mr. Bhavadip B. Tanna
A simple high-performance liquid chromatographic method for the determination of etoricoxib in human plasma has been developed.
Hi friends in this blog I would like to putforth few aspects regarding the analytical method validation parameters and its procedure.
Mr.Sohan S.Chitlange


text:
For status updates, visit lucyburns.org.
Water, Land, and Housing Committee, Hawaii State Senate (decommissioned)
From Ballotpedia
(Redirected from Water, Land, and Housing Committee, Hawaii State Senate)
The Water, Land, and Housing Committee is a former standing committee of the Hawaii State Senate. It was formed for the 2011 session, but not reformed for the 2013-2014 session. Prior to 2011, it was a part of the Water, Land, Agriculture and Hawaiian Affairs Committee. In the 2013-2014 session, the committee's topical titles were distributed between the Economic Development, Government Operations and Housing Committee and the Water and Land Committee.
Committee members
The following table describes committee membership at the beginning of the 2011 legislative session.
Water, Land, and Housing Members, 2011 | ||||
Democratic members (6) | Republican members (1) | |||
• Donovan Dela Cruz, Chair | • Samuel Slom | |||
• Malama Solomon, Vice Chair | ||||
• Carol Fukunaga | ||||
• Pohai Ryan | ||||
• Maile Shimabukuro | ||||
• Jill Tokuda |
External links


text:
Bank Guarantees
Are you finding a customer hesitant to sign a contract because they have concerns regarding your company's credibility? Perhaps you are bidding on a huge project where there are serious financial implications if you fail to deliver? If so, you should consider a bank guarantee from Absa.
A bank guarantee from Absa will provide credibility and surety to any deal you have with your clients by ensuring that, in the event that you are unable to deliver on your promises of services, equipment or products, your customer will be reimbursed for the value of what was required.
A bank guarantee from Absa will also help you manage your cash flow since you won't have to set aside capital to pay for unexpected mishaps, such as losing products when shipped, and are likely to have to pay a smaller deposit to secure the contract.
A Bank Guarantee could be the right choice if you:
- Have a customer who is concerned about your capacity to ship equipment or products to them
- Would like the credibility a bank guarantee brings to your negotiations with customers
- Would like to offer additional surety to your customers
- Would like to minimise the amount of money you need to put aside to deal with defaulting on customers
- Would like to decrease the amount you need to deposit as part of a contract or tender
Did You Know?
- Contract Guarantee, should you become unable to meet your financial obligations, a contract guarantee will ensure that your customer is reimbursed so that they may seek a third party to complete any work you started.
- Performance Guarantee if you cannot, or fail to, comply with any contractual obligations, a performance guarantee ensures suitable payment to your customer.
- Shipping guarantee, if you are shipping to a client, but are unable to pay for the delivery of the equipment or products, the shipping company may hold on to the goods until these bills have been paid. A shipping guarantee ensures that your customer will be able to obtain their goods in such a dilemma.
- Customs and Excise Guarantee occasionally, you may need to obtain equipment from overseas to perform a temporary contract or task. You can avoid customs duty on the equipment by obtaining a customs and excise guarantee, which will prevent you from selling it locally once the contract or task has been completed.
- Retention Guarantee as it is not uncommon for payments on large contracts to be made in stages. In the event that your work proves to be sub-par or fails to meet the expectations of your customer, a retention guarantee will reimburse the client any of the stage payments they may have made prior to the deficiency being discovered.
Call us on
0860 040 302


text:
Science News
Science News Staff's Articles
- Letters to the Editor
Water's unclear origins, shaky solutions to climate change and more reader feedback
Readers discuss the pitfalls of carbon storage, whether a recent movie got Alan Turing's story right and more. - Letters to the Editor
Mineral hunting, mob math and more reader feedback
Readers ask about Earth's most abundant mineral and discuss the notoriously unpredictable behavior of pedestrians. - Letters to the Editor
Smell circuitry, stalled stem cells and more reader feedback
Readers discuss a journal's publishing practices, ask about the human sense of smell and weigh in on their favorite picks from our Top 25 stories of the year. - Letters to the Editor
Readers discuss volcanoes and brain studies involving chocolate, and recommend some science-based options for game night. - Letters to the Editor
Readers discuss oil spills, the dangers of fracking and what teams need to succeed on long space missions. - Science Ticker
Precursors of human sperm and eggs made from stem cells
Reprogrammed adult human cells can produce germ cells, precursors of sperm and eggs. - Letters to the Editor
Online favorites of 2014
Science News' website traffic reveals the most-read news stories and blog posts of 2014. - Science Ticker
Grazing crater rim may have saved comet lander
Bumping off the rim of a crater probably saved the robotic comet Philae from a cold, dark death, a new analysis of images suggests. - Science Ticker
Air pollution linked to autism
Air pollution may double a pregnant woman's risk of having a child with autism, a new study suggests. - Feature
Ebola, Rosetta, e-cigarettes and more top stories of 2014
West Africa's Ebola epidemic captured the attention of both the scientific world, and the world at large in 2014, placing it first among the Top 25 stories of the year.


text:
WILSONVILLE, Ore., November 15, 2012—Mentor Graphics Corporation (NASDAQ: MENT) today announced its Mentor® Embedded Nucleus® Innovate Program designed to help businesses with less than $1M in annual revenue kick start their embedded development projects. Qualified companies can accelerate their embedded system development with software provided at no cost, including the Nucleus Real Time Operating System (RTOS), the popular Sourcery™ CodeBench GNU toolchain, and an ARM-based board support package (BSP) supporting Texas Instruments Incorporated (TI) Stellaris ARM Cortex-M microcontrollers.
"The Nucleus Innovate Program is another great offering for our customers and a valuable reason why they are making the switch to TI's Stellaris Cortex-M4F microcontrollers," said Matt Muse, general manager of Stellaris Cortex-M MCUs, Texas Instruments. "The software package will benefit many small businesses reaching new markets and new customers, and we're happy Mentor and Stellaris can help them achieve those goals."
The Nucleus Innovate Program is ideal for applications where small footprint, high-performance, and low power matter. Customers using 32-bit single core or dual core processors, as well as MCUs can use the Nucleus RTOS and Mentor Embedded tool capabilities. Easy-to-use demonstrations and configurations help shorten development time for medical, industrial, automotive and consumer applications—from days to minutes. Details on qualification and the software provided through the Nucleus Innovate Program is available at http://go.mentor.com/innovate.
"The Nucleus Innovate Program demonstrates our shared commitment with leading semiconductor partners to promote embedded product innovation, particularly within start-ups and other small companies," stated Scot Morrison, general manager of runtime solutions, Mentor Graphics Embedded Software division. "The advantage to start-up companies is that they can feel confident that their products are being developed with proven tools used by major global companies."
About Mentor Embedded
The Mentor Graphics® Embedded Software Division comprises the Mentor Embedded family of products and services, including embedded software intellectual property (IP), tools, and professional consultant services to help embedded developers and silicon partners optimize their products for design and cost efficiency. The Mentor Embedded team continues to lead the industry with involvement in the open source community, with Inflexion 2D and 3D UI development, the Sourcery open source tools, and the Nucleus RTOS solutions. More information on Mentor Embedded products and services can be found at www.mentor.com/embedded.
(Mentor, Mentor Graphics, and Nucleus are registered trademarks of Mentor Graphics Corporation. Sourcery is used under license from CodeSourcery, Inc. All other company or product names are the registered trademarks or trademarks of their respective owner.


text: On Mon, March 27, 2006 12:41 pm, Alexander E. Patrakov wrote: > both LFS and BLFS packages are lagging behind the development books on > the CD. Please update the versions (including the LFS book date), with the > following exceptions: Thanks for the notes Alex. Tuesday and Wednesday is my "weekend" so I will have some time to do those things and take a look. I'm trying a few more test builds of the 6.1.1 branch for the off chance something works. By the way, was my addition to the "Starting init..." bug useful at all? I took screenshots of the debug info. Just was curious. Justin


text:
Biographical and Playing Info
Given Name: Leslie Charles Spikes
Born: Bogalusa, LA, USA, in 1951
School: Did not attend college.
Primary Position: Right Field
Batted: Right Threw: Right
Major League Games: 670
Primary Team: Cleveland Indians
Played For
New York Yankees (1972)
Cleveland Indians (1973-1977)
Detroit Tigers (1978)
Atlanta Braves (1979-1980)
First major league game: 9/1/1972
Final major league game: 10/5/1980
Hall of Fame Voting
No Hall of Fame elections.
See his complete statistical record at baseball-reference.com


text:
Village taxes won't increase next year due to changes in health-insurance premiums and employee turnover.
A display on early Altamont inventors is featured at Village Hall.
Hometown traditions persisted in Altamont in 2013 despite fire and arrests.
ALTAMONT — A devoted family man, Rocco "Rocky" Fallone knew how to fix just about anything.
"His strongest characteristic was a sense of persistence," said his son, John Fallone. "In the dictionary, there should be a picture of Rocky next to the word 'persistence.'"
Like the princes of Serindip, an Airedale walker makes some unexpected discoveries one wintry day.
"Santa's here, Santa's here!" screamed the children gathered by the train track in Altamont as Santa rolled into town, culminating the annual Victorian Holiday Celebration. Inside the boxcar, tots whispered their wishes to the jolly old elf.
Agawum Lane, on the shoulder of the Helderberg escarpment, could become the site for a cell tower in Altamont.
Altamont adopted its first law of 2013 to increase its sewer fees.
Nurturing people and plants takes time and love, not money. The essence of home can be found in the low-income housing complex often overlooked in the village.
A small country community named Knowersville was developing around the railroad station following the Civil War. With rail access, it was becoming a summer retreat for families from New York and Albany.
There were several hotels by the railway and a resort hotel on the hill beyond named Kushaqua.


text:
Vehicle Input
$37.76 - $578.42
Hotchkis Sport Leaf SpringsLower your truck or muscle car, reduce roll and increase handling with our Sport Leaf Springs. Hotchkis Sport leafs represent the latest technology in performance spring. For the truck kits, special polyurethane bump stops are included with each spring kit. For the muscle car kits, springs utilize a 3/4 length over load spring reducing axle wrap and feature urethane rear bushings and rubber front bushings offering both performance and comfort. Included are heavy duty shackles, u-bolts, spring pads, and nut clips. Hotchkis sport leaf springs are designed to work on both Mono and Multi Leaf equipped vehicles. |


text:
Lego Mindstorms NXT 2. 0 for Teens
Learn how to create amazing robotic creations with LEGO MINDSTORMS NXT 2.0 FOR TEENS. This step-by-step guide shows beginners how to use the Lego Mindstorms NXT 2.0 kit and their computer to build fantastic robots, animals, vehicles, and so much more. Everything you need is included in the Lego Mindstorms kit, including a microcomputer, electronic motors and sensors, as well as various Lego Bricks and Lego Technic pieces like beams, axles, and gears. The kit also includes a software programming language called NXT-G, which is used to write the programs that are downloaded into your robotic creations in order to bring them to life. NXT-G is an icon based, drag-and-drop language, which means that there is no complex programming language that must be mastered. Throughout the book, you'll follow hands-on instruction through the three-step process needed to build your creations. First you use Lego Bricks to create your robot. Then you use NXT-G to write the program code that makes your creations work. Then you download the program code into the NXT Brick, a small microcomputer that is the brain of your creations, and then step back and watch them come alive. With this book you'll learn how to build all sorts of robotic creations and how to program the code that will make them come to life. The only limit is your imagination.
Boston, Mass. : Course Technology, 2011
Branch Call Number:
Electronic Book
xvii, 318 p. :,ill
Additional Contributors:
Alternate Title:
Public Library Complete


text:
Dwell Design & Drive Presented by Lincoln
An Exclusive Design & Drive Event Presented by Lincoln and Dwell at NewSchool of Architecture + Design.
Ticket holders of the Dwell San Diego Home Tours and their guests are invited to help raise money for Architecture for Humanity by test-driving a NEW Lincoln vehicle.
Guests are invited to mingle with the design-loving crowd; meet architects and designers from homes on the Sunday tour; sample fine, chef-prepared cuisine; view current NewSchool of Architecture + Design student work (pictured above); and raise money for Architecture for Humanity by test-driving a NEW Lincoln.
When anyone 21 or older with a valid driver's license test drives a Lincoln vehicle on November 11, Lincoln will donate $25 to Dwell Home Tours non-profit partner Architecture for Humanity for providing sustainable design solutions to the global community. Each test drive will last about 7 to 10 minutes. You don't have to be a Dwell San Diego Home Tour ticket-holder to participate. The event is open to the public. However, RSVP is requested, as space is limited.
- Enjoy exclusive access to an exhibition of graduate student school work (further information TBD)
- Mingle with the architects, designers and contributors responsible for the private homes on that day's tour
- Test-drive a new Lincoln and help raise additional funds for Architecture for Humanity
- Experience and learn from Giuseppe Restaurants & Fine Catering experts about the flavors of their delicious cuisine
4pm to 7pm
Sunday, November 11, 2012
NewSchool of Architecture + Design
NewSchool of Architecture + Design | 710 13th Street, Gallery 304 | San Diego | See Map
Since 1999, Architecture for Humanity has been putting Architects in service of those communities who need them most. After disaster strikes, AfH uses its expansive network of contacts to get well-designed buildings built – and fast. Today, AfH has built over 2,000 structures that have positively impacted about 2 million people worldwide.
Co-founders Kate Stohr and Cameron Sinclair also run design competitions, manage the Open Design Network, WorldChanging, and have published the best-selling books "Design Like You Give a Damn" and "Design Like You Give A Damn [2]". Together, and with the Architects who work for them, they are redefining the role of Architecture and Design: to truly make an impact on our world.


text:
How To Create 14 Sparkly Craft Projects Using Krylon Glitter Blast
Bonus: Get our newsletter & special offers for free. We will not share or sell your email address. View our Privacy Policy
My Sweet Girl Birthday Party
By: Angi Barrs for Lifestyle Crafts
Wish your little lady a very Happy Birthday with this My Sweet Girl Birthday Party idea. With instructions on how to make cupcake toppers, favor boxes, and invitations, you can have a party put together in no time.
- Sweet Girl paper collection by Echo Park Paper
- Ring Cupcake Liner die
- Pop up Box die
- Toothpicks
- Die cutting machine
- Fancy Envelope Tabs
- Variety of embellishments
- Cardstock
MMmmm... a cupcake is a sure way to make your party guests smile. I used the Ring Cupcake Liner for this adorable treat and topped it with a butterfly from the Pop-Up Box fastened to a toothpick. Easy right!?
Next I pit together a quick party favor box using the Pop-Up Box. This can be filled with candy, jewelry, mini nail polishes, lip gloss, you name it!
Last but not least, I used the Fancy Envelope Tabs to create a unique card for each guest. Giving each guest a cupcake, card and favor box makes them feel special and cared for. Plus, with cute paper and easy to use template dies, it's easy!
Tags / Related Topics
Your Recently Viewed Projects
Love these projects? Get MORE delivered to your Inbox – FREE Click Here!
What's Hot
- Cute as a Button Party Decor
- 16 Graduation Party Decorations, Gifts, and Cards
- Butterfly Birthday Boxes Centerpiece
- Rosette Cupcake Topper
- Cardboard Tube Party Favor Pouches
- Mad Tea Party Centerpiece DIY Craft Project
- Bottle Koozies
- Buzzworthy Glass Party Lanterns
- No Fray Tassel Party Garland
- Butterfly Themed Baby Shower
Something worth saving?
- SAVE all your favorite crafts
- ADD personal notes
- QUICKLY reference your crafts
Free eBooks
- 12 Thrifty Trash to Treasure Crafts
- 17 Flower Craft Ideas: How To Make Paper Flowers, Easy Fabric Flowers and More
- 18 Crafts with Felt: Simple Craft Ideas, Felt Flowers & More
- 24 Tie-Dye Techniques: Free Tie-Dye Patterns
- 24 Valentine's Day Crafts for Kids: Lovely Kids Crafts Ideas and Projects
- 25 Cool Things to Do with Wine Bottles
- 26 Spring Crafts for Kids
- 41 Valentine's Day Crafts: Valentine's Day Cards, Gifts and More
- Cupid's Handmade Crafts
- Irish for a Day: St. Patrick's Day Craft and Recipe Guide
Our Newest Projects & Articles
- Learn to Embroider with the Best of Leisure Arts
- Colorful Ladybugs Toilet Paper Roll Craft
- Reworked Rainbow Table DIY Craft Project
- Leisure Arts Book Bundle
- Polyform Sculpey Clay Beginner Pack
- Red Heart Fancy Yarn Pack
- 13 Spring Crafts: Easter Craft Ideas, Spring DIY Home Decor, and More free eBook
- American Quilter's Society Gift Card
- Marvy Uchida Easy Crystal Applicator
- Sizzix eclips2 DIY Electric Cutter Starter Kit


text:
Episode Information
Connecticut Magazine has ranked the best and worst places to live in the state, grouped by size and ranked by statistics like crime, cost and culture. It's great when your town's on top - or even in the middle of the pack. But what does it mean when the place you live finishes last? Join the conversation today with Charles Monagan, editor of Connecticut Magazine.
Charles Monagan and ranking of towns
Numbers and statistics are quantative. Rankings are made by people who do so within the context of their own value judgments.The word "best" as used in town rankings by Mr Monagan is a qualitative statement. If he wants to put all the facts with numbers out there then he should leave it up to the beholder of that information to make a judgment about what it tells us.
I was glad to hear Mr. Kendzior of Meriden challenge Mr Monagan and if it were a debate Mr. Knedzior was clearly the winner as was evidenced by the noticable strident tone in Mr. Monagan's as voice in his summing up the discussion. Mr Monagan authoritatively expounded on how this should be a motivation to "do better". Did he add up and do a statistical ananysis on the number of people who are already putting countless hours into making the town a good placeto be?This type of advertising can certainly go a long way toward limiting the possiblities of bringing additional talent into town.
I can see that no good purpose is served by this type of ranking and wide publication of such. It is difficult to quantatively calculate the harm done by this glossy cover advertising of a very poorly designed pseudo study.Too many Conecticut towns are struggling now. We don't need a "wanna be" sophisticated and intellectual magazine touting themselves as knowing so much about where we live.
Listener Email from Laurie
I take issue with the way in which Connecticut Magazine measures the quality of towns in the state. I also challenge Connecticut Magazine's motives in producing this list.
First of all, this List should NOT be the "first" thing that people moving to CT should look at, as Charles Monagan says! To say this is such a self-aggrandizing statement!!! This list does more harm than good, causing people to form over-generalized opinions of towns. For example, Greenwich also has poor areas, so you don't HAVE to be rich to "get in there," as Monagan says.
But here's what I'm most incensed about:
A GOOD EDUCATION is NOT measured by how well students perform on standardized tests!!! Standardized tests only measure the ability of students to do well on the test. This has very little relevance to future success or fulfillment in life. There's so much more to life than test scores.
There are many excellent teachers working with poor, underachieving, minority students in big cities; there are also poor teachers working with affluent, privileged, high-scoring white students. To say that test scores mean good education is absolutely backwards.
Perhaps more importantly, given what we know about the Achievement Gap, to say that a town is good based on high test scores is to imply that a town is good when its population is richer and whiter.
This is obviously marketing to affluent people who have the ability to choose where to live from ALL CT towns and who prefer to live around rich white folks like themselves and ignore the fact that there are other people out there. CT Mag is just feeding into the gentrification problem, and the national education crisis.
Town of Winsted
I was interested to hear you mention that you live in Winsted. My brother just bought a condominium in Winsted, and I will be his roommate. We are both moving from Hebron, a town that, to my way of thinking, holds no charms whatsoever. Having driven through Winsted a few times over the years, and traveling to the Motor Vehicle office once, I found the downtown pleasant, in an old mill-town sense that it shares with much of the Naugatuck valley. I enjoy this look and feel, in contrast to what has become of the Fairfield County, "Gold Coast" where I lived for more than thirty years (in Fairfield.) In fact, driving north on route 8 is like driving back in time, at least in a commercial sense, through the "prosperity" of recent decades, and arriving at the late Seventies of the Winsted area.
I will be looking for work nearby, though I understand this may be problematic, given the depressed economy, both local and national. I wonder if you have had the impression that came to me regarding the Winsted area; it reminded me of Vermont, due, I suppose, to the severe topography, and the scale and age of the housing stock. In any event, I am looking forward to living in a city with an actual downtown, and to getting to know the people there.