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It is always difficult for parents to separate the marketing speak with reality. At DSB we are a different kind of company in how we manufacture, market and service.
It seems now a days that most manufacturers have turned into marketing companies focusing their attention to branding. Somewhere along the way they forget about the reason of what brought them to the dance. They seem to be more interested in putting their name on a variety of objects and maybe not as focused on producing the most competitive product on the field. A lot of this has to do with who owns the company or more importantly how many people own the company. Some of these companies are publicly traded companies that have to perform on a quarterly basis. In doing so they have to manage their business with a short-term mentality which may not be best for the company in the long run (imagine if car companies discounted their product 50% every June!). Some are owned by private equity firms who require an exorbitant return on investment so they focus more on the marketing of the product and less on the performance.
At DSB we are passionate about making cylindrical shaped objects that are used to strike a ball the longest distance within the confine of the rules. Our second objective is figuring out how to make it durable enough so that customers feel that their investment is worthwhile and their wallet (vs the ball) is not taken for a ride. There has always be an inverse relationship between pop and durability. Get more of one and you would have less of the other. At DSB we have figured out how to get both. It is not easy and it is not cheap. It is what separates us from our competitors. Bean-counters do not run our company nor do they get to tell us that if you make a bat that hot it will lead to more warranties (this is why we do not have a CFO at the company).
Well what makes you so different and why should we believe this is not just more of the marketing speak?
Good question. Do your research and read the independent reviews of individual customers. You will find a common theme as follows: 1) The sound of the bat is completely unique and unlike anything we have heard; 2) The taper from the barrel to the handle decreases dramatically; 3) It sounds like a gun shot when you really connect with the ball; 4) I saw a kid hitting it and he was hitting bombs but I figured he was just a good hitter… Demo our bat and prove us and these reviews wrong. When you order from us we have a box that asks who referred you? Over 50% of our sales choose "Saw it action, Wow". Every time we get an order with that reason we beam with pride. Independent customer reviews are the best source. Going to websites that claim to be independent review sites are not such and are conflicted. We tried a few of them and they knew nothing about bats. Some do video and show an 8yr old kid swinging a 12yr old bat. Others would request a certain amount of sizes and then we would see them selling on Ebay 2 weeks later. Word of mouth, individual reviews and eye-witness accounts is all you should be paying attention to.
How many bats do you make a year?
DSB: We make around 5,000 bats a year. In theory one county in California could absorb our complete production.
Where do you make your bats?
DSB: We make them in Winder, Georgia which is an hour north of Atlanta.
Who designs your bats?
DSB: We design and R+D all of our bats in-house. We do not use any contractors or outside parties. All of our equipment was made by our employees and we continue to perfect our processes striving for improvement and efficiencies.
Do you make all of the parts of the bat?
Do you sell your bats anywhere else other than your website?
DSB: Not really. We do have a handful of end retailers who do carry our product, but we do not focus on this part of the sales process. We understand that we will not grow as fast a company, but that is ok, as it is a marathon for us and not a sprint. Plus we do not have to manage our business on a quarterly basis. By eliminating a middle man, we are able to keep the price of the bat lower. We realize that our bats are not inexpensive and if we had to rely on traditional means for resale, our bat would be priced closer to $500 (and worth every penny!). So we pass this savings on to our customers.
Don't you think it is risky for a customer to purchase a bat they have never seen or touched?
DSB: Yes we do think it is risky in theory. First, you are purchasing on the internet and we all worry about that don't we? This is why we use 3rd-party vendors who will process your transactions in a safe and secure environment. We do not get access to your credit card #, which is great, as that information remains private to you (but if you forget something on your order you will have to do a separate order as we cannot adjust the amount due). We are also listed with the BBB (Better Business Bureau). As far as not touching our bat, we do offer two ways to make you comfortable. 1) You can demo our bat for the cost of shipping both ways. 2) We have a 30 day return policy provided that the bat has not been used nor has the wrapper been removed.
What if my kid doesn't like your bat after using it?
DSB: Unfortunately due to liability reasons we cannot take back a used bat, a bat where the wrapper has been removed or refund the purchase. This is why we go to great lengths in providing our demo program. We are not aware of any manufacturer doing this direct.
Can I demo your bat anywhere else:
DSB: No we do not have other locations for you to demo, but have done team demos in the past if reasonably close to Georgia or we can accomplish it by shipping demo bats of all sizes to a facility. We do ask the person who is spearheading the demo to be responsible for the safe return of the bats. Such person organizing the demo would receive a discount on a purchase for their efforts.
What if I crack the bat when I am demoing the bat?
DSB: Our bat doesn't crack. Ok just kidding, but our bat is very durable. Provided that is normal wear and tear you would not be responsible.
Can other kids on my team demo the bat when I receive the demo?
DSB: Yes.
Do you ever go to tournaments?
DSB: Yes and we love going. We have a 32×8.5 merchandise trailer which has a stage when you flip down the side. We prefer going to larger events where we can set-up for 3-5 day tournament where most of the kids will be passing through the vendor setup area. We always bring demos with us where kids can use our bat during the games at no charge. If the event is large enough we also like to sponsor a HR derby with our bats and provide a free bat to the winner.
Do you ever discount your bats?
DSB: No. We realize a lot of retailers will discount last year's model by 50% in June when the existing bat is no longer subject to the MAP (minimum advertised price) policies from the manufacturer. They are playing a game of volume. We do not play that game.
Do you have team pricing?
DSB: Yes. Team purchases of bats can received a discount for 5+ purchases that get purchased at the same time and shipped to one address. The discount can range between 10-15% depending on the quantity and models chosen. You can mix and match.
Do you sponsor teams or can you make a donation?
DSB: This is always the most asked question and most difficult to answer. It is probably easier to say no to all of the above. But we do sponsor one or two teams out there, but they have to be playing at the major level, travel to different states and be ranked within the top 10 on a national level. Unfortunately due to the size of our company we are not able to help with donating product to individuals or teams to help them offset their costs. We realize baseball is expensive, but we are unable to help in that respect and do apologize upfront for it.
Why do you have a homerun club?
DSB:Because we are proud of the fact that a lot of kids hit their very first homerun over the fence with a DSB bat. The performance of our bat could add the distance necessary to clear the fence (of course every kid is different so we cannot guarantee that), but to a parent, that feeling of your son's first HR is absolutely priceless. We feel that DSB inspires confidence in kids to want to do better. We all know there are different levels of ability on the playing field and most of our kids will never see the pros. As parent's it is our responsibility to inspire our kids and make them confident in the abilities that they have. Hitting the ball a little further never hurt any batter's feelings. When you think of all the time and money we spend on this sport, the price of our bat pales to that overall investment.
Is there a Dirty South Mom Club?
DSB: No comment.
What is continuous compression barrel?
You may recall from your math days about a bell curve. This is what most manufacturer's compression (or pop) curve looks like. It is hottest in the middle and drops down at the taper and at the end-cap.
DSB has a Sweet Barrel as opposed to a Sweet Spot. There is no bell curve. It actually is a line that continues to increase as it gets to the end-cap i.e. the barrel maintains compression and is continuous. When you see big hits with a DSB it is because of two reasons 1) Our bat has excellent trampoline effect where the barrel will give (not the taper) which then in turn puts the trampoline (pop) at the impact of the ball to send it further. 2) Kids can mishit and still get the same effect as hitting on the sweet spot of other manufacturers. So our sweet barrel allows for a lot more room to hit the ball anywhere along the barrel. A good analogy is golf. The normal diameter of a putting cup is 4.25". Having a DSB barrel is like putting towards an 8" cup. It is much wider so you do not have to be as precise when you putt the ball to the cup. What would 8" cup due to your golf handicap?


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We did what any family fun loving family would do.
We grabbed our adventure bag, our coats and ipods (well the children did) and jumped into the car ready for an adventure. Big Boy soon fell asleep and Top Ender was engrossed in her playlists so Daddy and I had a great chat and listened to the radio. We found the library and the library book and the picture of Daddy's Grandma and after taking a minute to join the library we borrowed the book (and a couple of others) and then we were on our way back home.
|The girl in question is the middle head behind Mrs Bridge's arm.

subset: commoncrawl


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Bingley Music Festival
Bingley Music Festival Minibus and Coach Hire, welcome you to the opportunity to pre-book your travel arrangements for the entirety of this event. We are please to be able to offer you a convenient, comfortable and cost-effective service for you and your party, no job is too big or too small, regardless of: group size, time-frames, multiple-stopovers and we will also do our utmost to honour any specials requests that you may have. Bingley Music Festival Minibus and Coach Hire, offers disability access on all of our services.
The event runs from, Friday 1st September – Sunday 3rd September at Myrtle Park, Bradford.
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Snag postpones woman's sentencing
An unusual courtroom mistake delayed the sentencing on Friday for a mother who was arrested two years ago after her 23-month-old son was allegedly tortured and murdered by her live-in boyfriend.
Vanessa Elenes, 22, had entered a no-contest plea earlier this year to felony child-endangerment charges with the understanding that she would be sentenced to no more than 16 months in prison, said her attorney, Mark Broughton.
On Friday, however, she learned that she could face two years -- eight months longer than she had been told.
The inaccurate information stemmed from a meeting earlier this year during which Broughton, a prosecutor and Fresno County Superior Court Judge Wayne Ellison discussed her case, Broughton said.
After that meeting, he said, he told Elenes that she would face no more than 16 months in prison if she pleaded no contest, but her sentence could be longer if she went to trial and were found guilty.
Judge W. Kent Hamlin was to sentence Elenes on Friday, but Broughton asked him to postpone the sentencing and send the case back to Ellison on the grounds that she had been misinformed.
Elenes has one month to decide whether she will enter the same plea and face a prison sentence of two years or withdraw the plea and face trial.
If Elenes decides to go to trial and is convicted, she could face up to six years, Broughton said.
Elenes is scheduled to appear in Judge Ellison's courtroom on Oct. 12.
Elenes' boyfriend at the time of her son's death, Herman Herrera, is scheduled to appear in court Nov. 1 on charges of torture, murder and willful cruelty to a child.
Herrera has not yet entered a plea, Broughton said.
A police investigation determined Elenes' son, Angel Julian Rubio, had been tortured with burns and with blunt trauma over an extended period of time in her apartment on the 1200 block of South Winery Avenue in southeast Fresno.
Herrera, reportedly a self-described Bulldog gang member, was on probation for burglary at the time of the alleged offenses.


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The Sequenom scientific foundation
Finding sophisticated genetic insight in a common blood draw.
Sequenom Laboratories has a rich history of innovation. We were the first to offer noninvasive prenatal testing (NIPT) to analyze cell-free fetal DNA circulating in maternal blood. With the trust and confidence placed in our laboratory-developed tests, NIPT has become a standard for prenatal noninvasive genetic testing without the risk of miscarriage associated with invasive prenatal testing procedures.
At the heart of Sequenom Laboratories innovation is a deep understanding of the science surrounding cell-free DNA (cfDNA).
Cell-free fetal DNA in maternal blood comes from placental cells1, 2, 3. When genome-wide sequencing is applied to cfDNA, highly accurate identification of fetal chromosomal abnormalities is possible.
Scientific Publications
Peer-reviewed published studies
Noninvasive prenatal detection of aneuploidy.+ –
Robinson C1, van den Boom D, Bombard AT. Clin Obstet Gynecol. 2014 Mar;57(1):210-25. doi: 10.1097/GRF.0000000000000016.
Noninvasive prenatal testing (NIPT) uses cell-free fetal DNA from the plasma of pregnant women to provide valuable information about the potential risks for fetal aneuploidy. This article provides a historical overview of both invasive diagnostic testing and serum screening approaches, both biochemical and the newer molecular noninvasive prenatal testing assays, used to identify patients who would be best served by invasive testing.
Maternal plasma DNA testing for aneuploidy in pregnancies achieved by assisted reproductive technologies.+ –
Lambert-Messerlian G1, Kloza EM1, Williams J 3rd2, Loucky J3, O'Brien B4, Wilkins-Haug L5, Mahoney MJ6, De Biasio P7, Borrell A8, Ehrich M9, van den Boom D9, Bombard AT10, Deciu C11, Palomaki GE1. Genet Med. 2014 May;16(5):419-22. doi: 10.1038/gim.2013.149. Epub 2013 Oct 3.
We sought to compare measurements of circulating cell-free DNA as well as Down syndrome test results in women with naturally conceived pregnancies with those conceived using assisted reproductive technologies.
Data regarding assisted reproductive technologies were readily available from seven enrollment sites participating in an external clinical validation trial of nested case/control design. Measurements of circulating cell-free fetal and total DNA, fetal fraction (ratio of fetal to total DNA), chromosome-specific z-scores, and karyotype results were available for analysis.
Analyses were restricted to 632 euploid (5.2% assisted reproductive technologies) and 73 Down syndrome (13.7% assisted reproductive technologies), including 16 twin pregnancies. No differences were found for fetal or total circulating cell-free DNA, or for the fetal fraction in euploid (P = 0.70) or Down syndrome (P = 0.58) pregnancies by method of conception. There appeared to be systematic z-score reductions for chromosomes 21, 18, and 13 in assisted reproductive technologies versus natural euploid pregnancies (P = 0.048, 0.0032, and 0.36, respectively).
Assisted reproductive technologies and naturally conceived pregnancies contribute similar levels of circulating cell-free DNA into maternal circulation. Small differences in the z-scores of pregnancies achieved by assisted reproductive technologies were observed and do not appear to be test-related artifacts. However, the findings need confirmation before any consideration of changes to testing and reporting protocols.
Optimizing blood collection, transport and storage conditions for cell free DNA increases access to prenatal testing.+ –
Wong D1, Moturi S, Angkachatchai V, Mueller R, DeSantis G, van den Boom D, Ehrich M. Clin Biochem. 2013 Aug;46(12):1099-104. doi: 10.1016/j.clinbiochem.2013.04.023. Epub 2013 Apr 30.
Fetal mutations and fetal chromosomal abnormalities can be detected by molecular analysis of circulating cell free fetal DNA (ccffDNA) from maternal plasma. This comprehensive study was aimed to investigate and verify blood collection and blood shipping conditions that enable Noninvasive Prenatal Testing. Specifically, the impact of shipping and storage on the stability and concentration of circulating cell-free DNA (ccfDNA) in Streck® Cell-Free DNA™ Blood Collection Tubes (Streck BCTs, Streck, Omaha NE). These BCTs were designed to minimize cellular degradation, and thus effectively prevent dilution of fetal ccf DNA by maternal genomic DNA, was evaluated.
Peripheral venous maternal blood was collected into Streck BCTs to investigate four aspects of handling and processing conditions: (1) time from blood draw to plasma processing; (2) storage temperature; (3) mechanical stress; and (4) lot-to-lot tube variations.
Maternal blood stored in Streck BCTs for up to 7 days at ambient temperature provides stable concentrations of ccffDNA. The amount of fetal DNA did not change over a broad range of storage temperatures (4°C, 23°C, 37°C, 40°C), but the amount of total (largely maternal) DNA increased in samples stored at 23°C and above, indicating maternal cell degradation and genomic DNA release at elevated temperatures. Shipping maternal blood in Streck BCTs, did not affect sample quality.
Maternal plasma DNA stabilized for 0 to 7 days in Streck BCTs can be used for non-invasive prenatal molecular applications, when temperatures are maintained within the broad parameters assessed in this study.
High-throughput massively parallel sequencing for fetal aneuploidy detection from maternal plasma.+ –
Jensen TJ1, Zwiefelhofer T, Tim RC, Džakula Ž, Kim SK, Mazloom AR, Zhu Z, Tynan J, Lu T, McLennan G, Palomaki GE, Canick JA, Oeth P, Deciu C, van den Boom D, Ehrich M. PLoS One. 2013;8(3):e57381. doi: 10.1371/journal.pone.0057381. Epub 2013 Mar 6.
Circulating cell-free (ccf) fetal DNA comprises 3-20% of all the cell-free DNA present in maternal plasma. Numerous research and clinical studies have described the analysis of ccf DNA using next generation sequencing for the detection of fetal aneuploidies with high sensitivity and specificity. We sought to extend the utility of this approach by assessing semi-automated library preparation, higher sample multiplexing during sequencing, and improved bioinformatic tools to enable a higher throughput, more efficient assay while maintaining or improving clinical performance.
Whole blood (10mL) was collected from pregnant female donors and plasma separated using centrifugation. Ccf DNA was extracted using column-based methods. Libraries were prepared using an optimized semi-automated library preparation method and sequenced on an Illumina HiSeq2000 sequencer in a 12-plex format. Z-scores were calculated for affected chromosomes using a robust method after normalization and genomic segment filtering. Classification was based upon a standard normal transformed cutoff value of z = 3 for chromosome 21 and z = 3.95 for chromosomes 18 and 13.
Two parallel assay development studies using a total of more than 1900 ccf DNA samples were performed to evaluate the technical feasibility of automating library preparation and increasing the sample multiplexing level. These processes were subsequently combined and a study of 1587 samples was completed to verify the stability of the process-optimized assay. Finally, an unblinded clinical evaluation of 1269 euploid and aneuploid samples utilizing this high-throughput assay coupled to improved bioinformatic procedures was performed. We were able to correctly detect all aneuploid cases with extremely low false positive rates of 0.09%, <0.01%, and 0.08% for trisomies 21, 18, and 13, respectively.
These data suggest that the developed laboratory methods in concert with improved bioinformatic approaches enable higher sample throughput while maintaining high classification accuracy.
A new era in prenatal diagnosis: the use of cell-free fetal DNA in maternal circulation for detection of chromosomal aneuploidies.+ –
Shea JL1, Diamandis EP, Hoffman B, Lo YM, Canick J, van den Boom D. Clin Chem. 2013 Aug;59(8):1151-9. doi: 10.1373/clinchem.2012.201996. Epub 2013 Feb 20.
Noninvasive prenatal detection of sex chromosomal aneuploidies by sequencing circulating cell-free DNA from maternal plasma.+ –
Mazloom AR1, Džakula Ž, Oeth P, Wang H, Jensen T, Tynan J, McCullough R, Saldivar JS, Ehrich M, van den Boom D, Bombard AT, Maeder M, McLennan G, Meschino W, Palomaki GE, Canick JA, Deciu C. Prenat Diagn. 2013 Jun;33(6):591-7. doi: 10.1002/pd.4127.
Whole-genome sequencing of circulating cell free (ccf) DNA from maternal plasma has enabled noninvasive prenatal testing for common autosomal aneuploidies. The purpose of this study was to extend the detection to include common sex chromosome aneuploidies (SCAs): [47,XXX], [45,X], [47,XXY], and [47,XYY] syndromes.
Massively parallel sequencing was performed on ccf DNA isolated from the plasma of 1564 pregnant women with known fetal karyotype. A classification algorithm for SCA detection was constructed and trained on this cohort. Another study of 411 maternal samples from women with blinded-to-laboratory fetal karyotypes was then performed to determine the accuracy of the classification algorithm.
In the training cohort, the new algorithm had a detection rate (DR) of 100% (95%CI: 82.3%, 100%), a false positive rate (FPR) of 0.1% (95%CI: 0%, 0.3%), and nonreportable rate of 6% (95%CI: 4.9%, 7.4%) for SCA determination. The blinded validation yielded similar results: DR of 96.2% (95%CI: 78.4%, 99.8%), FPR of 0.3% (95%CI: 0%, 1.8%), and nonreportable rate of 5% (95%CI: 3.2%, 7.7%) for SCA determination
Noninvasive prenatal identification of the most common sex chromosome aneuploidies is possible using ccf DNA and massively parallel sequencing with a high DR and a low FPR.
Comment on "Clinical application of massively parallel sequencing-based prenatal non-invasive fetal trisomy test for trisomies 21 and 18 in 11,105 pregnancies with mixed risk factors".+ –
Kim S1, Zhao C, Bombard AT, Cantor C, van den Boom D, Deciu C. Prenat Diagn. 2013 Dec;33(13):1310-3. doi: 10.1002/pd.4231.
Letter of Response to "A New Era in Noninvasive Prenatal Testing".+ –
Ronald Lindsay; Daniel Farkas; Allan Bombard. New England Journal of Medicine:Nov-13
Noninvasive prenatal screening for fetal trisomies 21, 18, 13 and the common sex chromosome aneuploidies from maternal blood using massively parallel genomic sequencing of DNA.+ –
Porreco RP1, Garite TJ2, Maurel K3, Marusiak B3; Obstetrix Collaborative Research Network, Ehrich M4, van den Boom D4, Deciu C4, Bombard A4. Am J Obstet Gynecol. 2014 Oct;211(4):365.e1-12. doi: 10.1016/j.ajog.2014.03.042. Epub 2014 Mar 19.
The objective of this study was to validate the clinical performance of massively parallel genomic sequencing of cell-free deoxyribonucleic acid contained in specimens from pregnant women at high risk for fetal aneuploidy to test fetuses for trisomies 21, 18, and 13; fetal sex; and the common sex chromosome aneuploidies (45, X; 47, XXX; 47, XXY; 47, XYY).
This was a prospective multicenter observational study of pregnant women at high risk for fetal aneuploidy who had made the decision to pursue invasive testing for prenatal diagnosis. Massively parallel single-read multiplexed sequencing of cell-free deoxyribonucleic acid was performed in maternal blood for aneuploidy detection. Data analysis was completed using sequence reads unique to the chromosomes of interest.
A total of 3430 patients were analyzed for demographic characteristics and medical history. There were 137 fetuses with trisomy 21, 39 with trisomy 18, and 16 with trisomy 13 for a prevalence rate of the common autosomal trisomies of 5.8%. There were no false-negative results for trisomy 21, 3 for trisomy 18, and 2 for trisomy 13; all 3 false-positive results were for trisomy 21. The positive predictive values for trisomies 18 and 13 were 100% and 97.9% for trisomy 21. A total of 8.6% of the pregnancies were 21 weeks or beyond; there were no aneuploid fetuses in this group. All 15 of the common sex chromosome aneuploidies in this population were identified, although there were 11 false-positive results for 45,X. Taken together, the positive predictive value for the sex chromosome aneuploidies was 48.4% and the negative predictive value was 100%.
Our prospective study demonstrates that noninvasive prenatal analysis of cell-free deoxyribonucleic acid from maternal plasma is an accurate advanced screening test with extremely high sensitivity and specificity for trisomy 21 (>99%) but with less sensitivity for trisomies 18 and 13. Despite high sensitivity, there was modest positive predictive value for the small number of common sex chromosome aneuploidies because of their very low prevalence rate.
Whole Genome Bisulfite Sequencing of Cell Free DNA and its Cellular Contributors Uncovers Placenta Hypomethylated Domains.+ –
Taylor Jensen, Sung K Kim, Zhanyang Zhu, Christine Chin, Claudia Gebhard, Tim Lu, Cosmin Deciu, Dirk van den Boom, Mathias Ehrich. Genome Biology 2015, 16:78
Circulating cell free fetal DNA has enabled non-invasive prenatal fetal aneuploidy testing without direct discrimination of the genetically distinct maternal and fetal DNA. Current testing may be improved by specifically enriching the sample material for fetal DNA. DNA methylation may allow for such a separation of DNA and thus support additional clinical opportunities; however, this depends on knowledge of the methylomes of ccf DNA and its cellular contributors.
Whole genome bisulfite sequencing was performed on a set of unmatched samples including ccf DNA from 8 non-pregnant (NP) and 7 pregnant female donors and genomic DNA from 7 maternal buffy coat and 5 placenta samples. We found CpG cytosines within longer fragments were more likely to be methylated, linking DNA methylation and fragment size in ccf DNA. Comparison of the methylomes of placenta and NP ccf DNA revealed many of the 51,259 identified differentially methylated regions (DMRs) were located in domains exhibiting consistent placenta hypomethylation across millions of consecutive bases, regions we termed placenta hypomethylated domains (PHDs). We found PHDs were consistently located within regions exhibiting low CpG and gene density. DMRs identified when comparing placenta to NP ccf DNA were recapitulated in pregnant ccf DNA, confirming the ability to detect differential methylation in ccf DNA mixtures.
We generated methylome maps for four sample types at single base resolution, identified a link between DNA methylation and fragment length in ccf DNA, identified DMRs between sample groups, and uncovered the presence of megabase-size placenta hypomethylated domains. Furthermore, we anticipate these results to provide a foundation to which future studies using discriminatory DNA methylation may be compared.
Fetal Aneuploidy Detection by Cell-Free DNA Sequencing for Multiple Pregnancies and Quality Issues with Vanishing Twins.+ –
Grömminger S1, Yagmur E2, Erkan S3, Nagy S4, Schöck U5, Bonnet J6, Smerdka P7, Ehrich M8, Wegner RD9, Hofmann W10, Stumm M11. J Clin Med. 2014 Jun 25;3(3):679-92. doi: 10.3390/jcm3030679.
Non-invasive prenatal testing (NIPT) by random massively parallel sequencing of maternal plasma DNA for multiple pregnancies is a promising new option for prenatal care since conventional non-invasive screening for fetal trisomies 21, 18 and 13 has limitations and invasive diagnostic methods bear a higher risk for procedure related fetal losses in the case of multiple gestations compared to singletons. In this study, in a retrospective blinded analysis of stored twin samples, all 16 samples have been determined correctly, with four trisomy 21 positive and 12 trisomy negative samples. In the prospective part of the study, 40 blood samples from women with multiple pregnancies have been analyzed (two triplets and 38 twins), with two correctly identified trisomy 21 cases, confirmed by karyotyping. The remaining 38 samples, including the two triplet pregnancies, had trisomy negative results. However, NIPT is also prone to quality issues in case of multiple gestations: the minimum total amount of cell-free fetal DNA must be higher to reach a comparable sensitivity and vanishing twins may cause results that do not represent the genetics of the living sibling, as described in two case reports.
Comment on: Noninvasive prenatal testing for microdeletion syndromes and expanded trisomies: proceed with caution.+ –
Bombard AT1, Farkas DH, Monroe TJ, Saldivar JS. Obstet Gynecol. 2014 Aug;124(2 Pt 1):379. doi: 10.1097/AOG.0000000000000400.
The identification of circulating cell-free fetal DNA in maternal plasma has led to the introduction of noninvasive prenatal tests with high sensitivity and high specificity for common aneuploidies (trisomy 13, trisomy 18, trisomy 21). A new expanded noninvasive prenatal testing panel that includes five microdeletion syndromes (22q11 deletion syndrome, cri-du-chat [5p minus], Prader Willi or Angelman syndrome, 1p36 deletion syndrome) and two aneuploidies usually associated with nonviable pregnancies (trisomy 16 and trisomy 22) is now available. This expanded panel will be performed unless an opt-out box is checked. Because these disorders are so rare, the positive predictive value is expected to be low. As with all new screening tests and technologies, the expanded panel should be appropriately studied before it is widely adopted.
Designing a high-throughput somatic mutation profiling panel specifically for gynaecological cancers.+ –
Spaans VM1, Trietsch MD2, Crobach S2, Stelloo E2, Kremer D3, Osse EM2, Haar NT2, van Eijk R2, Muller S4, van Wezel T2, Trimbos JB5, Bosse T2, Smit VT2, Fleuren GJ2. PLoS One. 2014 Mar 26;9(3):e93451. doi: 10.1371/journal.pone.0093451. eCollection 2014.
Somatic mutations play a major role in tumour initiation and progression. The mutation status of a tumour may predict prognosis and guide targeted therapies. The majority of techniques to study oncogenic mutations requires high quality and quantity DNA or are analytically challenging. Mass-spectrometry based mutation analysis however is a relatively simple and high-throughput method suitable for formalin-fixed, paraffin-embedded (FFPE) tumour material. Targeted gene panels using this technique have been developed for several types of cancer. These current cancer hotspot panels are not focussed on the genes that are most relevant in gynaecological cancers. In this study, we report the design and validation of a novel, mass-spectrometry based panel specifically for gynaecological malignancies and present the frequencies of detected mutations. Using frequency data from the online Catalogue of Somatic Mutations in Cancer, we selected 171 somatic hotspot mutations in the 13 most important genes for gynaecological cancers, being BRAF, CDKN2A, CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A and PTEN. A total of 546 tumours (205 cervical, 227 endometrial, 89 ovarian, and 25 vulvar carcinomas) were used to test and validate our panel, and to study the prevalence and spectrum of somatic mutations in these types of cancer. The results were validated by testing duplicate samples and by allele-specific qPCR. The panel presented here using mass-spectrometry shows to be reproducible and high-throughput, and is usefull in FFPE material of low quality and quantity. It provides new possibilities for studying large numbers of gynaecological tumour samples in daily practice, and could be useful in guided therapy selection.
Noninvasive detection of a balanced fetal translocation from maternal plasma.+ –
Jensen TJ1, Kim SK1, van den Boom D2, Deciu C1, Ehrich M3. Clin Chem. 2014 Oct;60(10):1298-305. doi: 10.1373/clinchem.2014.223198. Epub 2014 Jul 16.
Massively parallel sequencing of circulating cell free (ccf) DNA from maternal plasma has been demonstrated to be a powerful method for the detection of fetal copy number variations (CNVs). Although the detection of CNVs has been described by multiple independent groups, genomic aberrations resulting in copy number-neutral events including balanced translocations have proven to be more challenging to detect noninvasively from ccf DNA.
Data modeling was initially performed to evaluate multiple methods, ultimately leveraging the short length of ccf DNA and paired-end sequencing to construct read-specific mapping characteristics. After testing in a model system, we evaluated the methods on ccf DNA isolated from the plasma of a donor known to be carrying a fetus with a balanced translocation [t(8;11)]. Sequencing was performed with Illumina sequencing technology.
Our methodology identified the known translocation (P = 1.21 × 10(-8)) and discounted the likelihood of others, enabling the base specific identification of the rearrangement positions. In total, 402 unique sequencing reads spanned the putative breakpoints, of which 76 contained the structural rearrangement. In addition, 38 of the chimeric reads were mapped to each of the resulting derivative chromosomes, supporting the presence of a reciprocal translocation. Finally, we identified a 6-bp deletion present within der(8) that was absent from the der(11) reciprocal rearrangement.
We have developed an algorithm to detect balanced rearrangements and applied our methodology to demonstrate the first proof-of-principle study on the noninvasive detection of a fetal-specific balanced translocation by sequencing ccf DNA from maternal plasma.
Noninvasive prenatal chromosomal aneuploidy testing--clinical experience: 100,000 clinical samples.+ –
McCullough RM1, Almasri EA1, Guan X1, Geis JA1, Hicks SC1, Mazloom AR1, Deciu C1, Oeth P1, Bombard AT1, Paxton B1, Dharajiya N1, Saldivar JS1. PLoS One. 2014 Oct 7;9(10):e109173. doi: 10.1371/journal.pone.0109173. eCollection 2014.
As the first laboratory to offer massively parallel sequencing-based noninvasive prenatal testing (NIPT) for fetal aneuploidies, Sequenom Laboratories has been able to collect the largest clinical population experience data to date, including >100,000 clinical samples from all 50 U.S. states and 13 other countries. The objective of this study is to give a robust clinical picture of the current laboratory performance of the MaterniT21 PLUS LDT.
The study includes plasma samples collected from patients with high-risk pregnancies in our CLIA-licensed, CAP-accredited laboratory between August 2012 to June 2013. Samples were assessed for trisomies 13, 18, 21 and for the presence of chromosome Y-specific DNA. Sample data and ad hoc outcome information provided by the clinician was compiled and reviewed to determine the characteristics of this patient population, as well as estimate the assay performance in a clinical setting.
NIPT patients most commonly undergo testing at an average of 15 weeks, 3 days gestation; and average 35.1 years of age. The average turnaround time is 4.54 business days and an overall 1.3% not reportable rate. The positivity rate for Trisomy 21 was 1.51%, followed by 0.45% and 0.21% rate for Trisomies 18 and 13, respectively. NIPT positivity rates are similar to previous large clinical studies of aneuploidy in women of maternal age ≥ 35 undergoing amniocentesis. In this population 3519 patients had multifetal gestations (3.5%) with 2.61% yielding a positive NIPT result.
NIPT has been commercially offered for just over 2 years and the clinical use by patients and clinicians has increased significantly. The risks associated with invasive testing have been substantially reduced by providing another assessment of aneuploidy status in high-risk patients. The accuracy and NIPT assay positivity rate are as predicted by clinical validations and the test demonstrates improvement in the current standard of care.
Maternal plasma cell-free DNA in the prediction of pre-eclampsia.+ –
Rolnik DL1, O'Gorman N, Fiolna M, van den Boom D, Nicolaides KH, Poon LC. Ultrasound Obstet Gynecol. 2015 Jan;45(1):106-11. doi: 10.1002/uog.14671. Epub 2014 Dec 4.
To examine whether maternal plasma concentrations of total cell-free (cf)DNA and fetal fraction at 11-13 and 20-24 weeks' gestation in pregnancies that subsequently develop pre-eclampsia (PE) are different from those without this complication.
Total cfDNA and fetal fraction were measured in 20 cases of early PE requiring delivery at < 34 weeks, in 20 cases of late PE with delivery at ≥ 34 weeks and in 200 normotensive controls, at 11-13 and 20-24 weeks' gestation. Total cfDNA and fetal fraction measured at 11-13 weeks were converted to multiples of the median (MoM), corrected for maternal characteristics and gestational age. The distributions of total cfDNA and fetal fraction at 20-24 weeks were expressed as MoM of values at 11-13 weeks. The Mann-Whitney U-test was used to determine the significance of differences in the median values in each outcome group relative to that in the controls.
In the early-PE group at 11-13 weeks, compared with controls, there was a significant increase in median total cfDNA (2104 genome equivalents (GE)/mL vs 1590 GE/mL) and a decrease in median fetal fraction (6.8% vs 8.7%). In the late-PE group at 20-24 weeks, compared with controls, there was a significant decrease in median fetal fraction (8.2% vs 9.6%). These significant differences between groups were not observed when the values were converted to MoM.
Measurements of total cfDNA and fetal fraction in maternal plasma at 11-13 and 20-24 weeks are not predictive of PE.
Strategies for validation and testing of DNA methylation biomarkers.+ –
Noehammer C1, Pulverer W, Hassler MR, Hofner M, Wielscher M, Vierlinger K, Liloglou T, McCarthy D, Jensen TJ, Nygren A, Gohlke H, Trooskens G, Braspenning M, Van Criekinge W, Egger G, Weinhaeusel A. Epigenomics. 2014;6(6):603-22. doi: 10.2217/epi.14.43.
DNA methylation is a stable covalent epigenetic modification of primarily CpG dinucleotides that has recently gained considerable attention for its use as a biomarker in different clinical settings, including disease diagnosis, prognosis and therapeutic response prediction. Although the advent of genome-wide DNA methylation profiling in primary disease tissue has provided a manifold resource for biomarker development, only a tiny fraction of DNA methylation-based assays have reached clinical testing. Here, we provide a critical overview of different analytical methods that are suitable for biomarker validation, including general study design considerations, which might help to streamline epigenetic marker development. Furthermore, we highlight some of the recent marker validation studies and established markers that are currently commercially available for assisting in clinical management of different cancers.
A flawed challenge but valid recommendation: a response to Takoudes and Hamar.+ –
Palomaki GE1, Ashwood ER, Weck KE. Ultrasound Obstet Gynecol. 2015 Jan;45(1):117. doi: 10.1002/uog.14739.
Circulating cell free DNA testing: are some test failures informative?+ –
Palomaki GE1, Kloza EM, Lambert-Messerlian GM, van den Boom D, Ehrich M, Deciu C, Bombard AT, Haddow JE. Prenat Diagn. 2015 Mar;35(3):289-93. doi: 10.1002/pd.4541. Epub 2015 Jan 8.
The proportion of circulating cell free DNA derived from the feto-placental unit (fetal fraction or FF) correlates with test success and interpretation reliability. Some fetal disorders are associated with systematically lower FF, sometimes resulting in noninformative results.
We analyzed results from pregnancies tested in a nested case/control study derived from a cohort of 4664 high-risk pregnancies. Low FF was defined before and after adjusting for maternal weight and gestational age.
Compared with euploid pregnancies, the median FF was significantly higher in Down syndrome pregnancies (ratio 1.17) and significantly lower in trisomy 18 and triploid pregnancies (ratios 0.71 and 0.19, respectively). Among 2157 pregnancies tested, 13 (0.6%) had FF <3.0% (all noninformative), including three trisomy 18 and three triploidy fetuses. After adjustment, 16 pregnancies (0.7%) had FF <0.3 multiples of the median (six informative), including one trisomy 18 and three triploidy fetuses. Modeled positive predictive values for low and high-risk populations were 7% and 30%, respectively.
Among women with noninformative results attributable to low FF, trisomy 18 and/or triploidy risk are sufficiently high to warrant offering additional assessments (e.g. ultrasound). If the testing indication is ultrasound abnormality, amniocentesis and karyotype/microarray should be considered.
Noninvasive prenatal testing using cell-free fetal DNA in maternal plasma.+ –
Dharajiya N1, Zwiefelhofer T, Guan X, Angkachatchai V, Saldivar JS. Curr Protoc Hum Genet. 2015 Jan 20;84:8.15.1-8.15.20. doi: 10.1002/0471142905.hg0815s84.
Noninvasive prenatal testing (NIPT) represents an outstanding example of how novel scientific discoveries can be quickly and successfully developed into hugely impactful clinical diagnostic tests. Since the introduction of NIPT to detect trisomy 21 in late 2011, the technology has rapidly advanced to analyze other autosomal and sex chromosome aneuploidies, and now includes the detection of subchromosomal deletion and duplication events. Here we provide a brief overview of how noninvasive prenatal testing using next-generation sequencing is performed.
Detection of fetal subchromosomal abnormalities by sequencing circulating cell-free DNA from maternal plasma.+ –
Zhao C1, Tynan J1, Ehrich M2, Hannum G1, McCullough R1, Saldivar JS1, Oeth P1, van den Boom D3, Deciu C4. Clin Chem. 2015 Apr;61(4):608-16. doi: 10.1373/clinchem.2014.233312. Epub 2015 Feb 20.
The development of sequencing-based noninvasive prenatal testing (NIPT) has been largely focused on whole-chromosome aneuploidies (chromosomes 13, 18, 21, X, and Y). Collectively, they account for only 30% of all live births with a chromosome abnormality. Various structural chromosome changes, such as microdeletion/microduplication (MD) syndromes are more common but more challenging to detect. Recently, several publications have shown results on noninvasive detection of MDs by deep sequencing. These approaches demonstrated the proof of concept but are not economically feasible for large-scale clinical applications.
We present a novel approach that uses low-coverage whole genome sequencing (approximately 0.2×) to detect MDs genome wide without requiring prior knowledge of the event's location. We developed a normalization method to reduce sequencing noise. We then applied a statistical method to search for consistently increased or decreased regions. A decision tree was used to differentiate whole-chromosome events from MDs.
We demonstrated via a simulation study that the sensitivity difference between our method and the theoretical limit was <5% for MDs ≥9 Mb. We tested the performance in a blinded study in which the MDs ranged from 3 to 40 Mb. In this study, our algorithm correctly identified 17 of 18 cases with MDs and 156 of 157 unaffected cases.
The limit of detection for any given MD syndrome is constrained by 4 factors: fetal fraction, MD size, coverage, and biological and technical variability of the event region. Our algorithm takes these factors into account and achieved 94.4% sensitivity and 99.4% specificity.
Case Studies in NIPT: NIPT for detection of subchromosomal deletions and duplications.+ –
Julie Jesiolowski, Thomas Monroe, Courtney Fitch, Jenna Wardrop, Theresa Boomer, Juan-Sebastian Saldivar. Contemporary OBGYN: March 5, 2015
Noninvasive prenatal testing (NIPT) has rapidly changed the prenatal landscape for pregnant women at increased risk of fetal aneuploidy. This technology provides high sensitivity and specificity for Trisomy 21, 18, and 13. Overrepresentation of a chromosome can be detected by an increased Z-score in comparison with a normal euploid genome. Here we report a case involving a partial chromosome 13 duplication that assisted in identifying a maternal balanced translocation and revealed the limitations of suboptimal karyotype resolution.
Maternal plasma samples were subjected to DNA extraction and library preparation followed by massively parallel sequencing as described by Palomaki et al. Sequencing data were analyzed using a novel algorithm to detect trisomies and other subchromosomal events as described by Chen et al.
: A 38-year-old G8P3043 presented for NIPT due to advanced maternal age and a previous pregnancy history of Trisomy 13, confirmed by low-resolution karyotype on peripheral blood. Ultrasound at 12 weeks, 6 days was suspicious for micrognathia. NIPT studies were ordered and results were positive for Trisomy 13. Sequencing data were reviewed based on the clinical history and revealed a 24.3Mb duplication of 13q31.2 and an apparent 27.85Mb deletion of 4q32.2. A fetal demise was noted on a 15 week, 0 day ultrasound. Products of conception (POC) studies were performed at 450–500 band resolution resulting in a normal female karyotype 46,XX, discordant from the NIPT results. Follow-up maternal studies at high-resolution karyotype analysis detected a balanced translocation: 46,XX,t(4;13)(q32;q31). After informing the tissue analysis laboratory of the translocation events, discordance between NIPT and POC studies was attributed to low karyotype resolution.
This case demonstrates the power of NIPT sequencing technology and optimized bioinformatics. Clinicians should be conscious that standard karyotyping does not have sufficient resolution to detect subchromosomal events detected by NIPT. Accurate clinical information provided to the laboratory may aid in additional interpretation. In these cases, microarray studies or high-resolution karyotype should be used to confirm a suspected abnormality.
Whole genome bisulfite sequencing of cell-free DNA and its cellular contributors uncovers placenta hypomethylated domains.+ –
Jensen TJ1, Kim SK2, Zhu Z3, Chin C4, Gebhard C5, Lu T6, Deciu C7, van den Boom D8, Ehrich M9. Genome Biol. 2015 Apr 15;16:78. doi: 10.1186/s13059-015-0645-x.
Circulating cell-free fetal DNA has enabled non-invasive prenatal fetal aneuploidy testing without direct discrimination of the maternal and fetal DNA. Testing may be improved by specifically enriching the sample material for fetal DNA. DNA methylation may allow for such a separation of DNA; however, this depends on knowledge of the methylomes of circulating cell-free DNA and its cellular contributors.
We perform whole genome bisulfite sequencing on a set of unmatched samples including circulating cell-free DNA from non-pregnant and pregnant female donors and genomic DNA from maternal buffy coat and placenta samples. We find CpG cytosines within longer fragments are more likely to be methylated. Comparison of the methylomes of placenta and non-pregnant circulating cell-free DNA reveal many of the 51,259 identified differentially methylated regions are located in domains exhibiting consistent placenta hypomethylation across millions of consecutive bases. We find these placenta hypomethylated domains are consistently located within regions exhibiting low CpG and gene density. Differentially methylated regions identified when comparing placenta to non-pregnant circulating cell-free DNA are recapitulated in pregnant circulating cell-free DNA, confirming the ability to detect differential methylation in circulating cell-free DNA mixtures.
We generate methylome maps for four sample types at single-base resolution, identify a link between DNA methylation and fragment length in circulating cell-free DNA, identify differentially methylated regions between sample groups, and uncover the presence of megabase-size placenta hypomethylated domains.
Use of cell-free DNA in the investigation of intrauterine fetal demise and miscarriage.+ –
Clark-Ganheart CA1, Fries MH, Leifheit KM, Jensen TJ, Moreno-Ruiz NL, Ye PP, Jennings JM, Driggers RW. Obstet Gynecol. 2015 Jun;125(6):1321-9. doi: 10.1097/AOG.0000000000000863
To estimate whether cell-free DNA is present in nonviable pregnancies and thus can be used in diagnostic evaluation in this setting.
We conducted a prospective cohort study of 50 participants at MedStar Washington Hospital Center, Washington, DC, between June 2013 and January 2014. Included were women with pregnancies complicated by missed abortion or fetal demise. All gestational ages were considered for study participation. Participants with fetal demise were offered the standard workup for fetal death per the American College of Obstetricians and Gynecologists. Maternal blood samples were processed to determine the presence of cell-free DNA, the corresponding fetal fractions, and genetic abnormalities.
Fifty samples from nonviable pregnancies were analyzed. The average clinical gestational age was 16.9 weeks (standard deviation 9.2). The mean maternal body mass index was 30.3 (standard deviation 9.1). Seventy-six percent (38/50) of samples yielded cell-free DNA results, that is, had fetal fractions within the detectable range of 3.7-65%. Among the 38, 76% (29) were classified as euploid, 21% (8) as trisomies, and 3% (1) as microdeletion. A cell-free DNA result was obtained more frequently at ultrasonographic gestational ages of 8 weeks or greater compared with less than 8 weeks (87.9% [n=29/33, 95% confidence interval (CI) 72.7-95.2; and 52.9%, n=9/17, 95% CI 31.0-73.8] of the time, respectively, P=.012). Time from demise was not associated with obtaining a result.
Among nonviable pregnancies, cell-free DNA is present in the maternal plasma with fetal fractions greater than 3.7% in more than three fourths of cases after an ultrasonographic gestational age of 8 weeks.
ClinicalTrials.gov, www.clinicaltrials.gov, NCT01916928.
Determination of fetal DNA fraction from the plasma of pregnant women using sequence read counts.+ –
Kim SK1, Hannum G1, Geis J1, Tynan J1, Hogg G1, Zhao C1, Jensen TJ1, Mazloom AR1, Oeth P1, Ehrich M1, van den Boom D1, Deciu C1. Prenat Diagn. 2015 Aug;35(8):810-5. doi: 10.1002/pd.4615. Epub 2015 Jun 3.
This study introduces a novel method, referred to as SeqFF, for estimating the fetal DNA fraction in the plasma of pregnant women and to infer the underlying mechanism that allows for such statistical modeling.
Autosomal regional read counts from whole-genome massively parallel single-end sequencing of circulating cell-free DNA (ccfDNA) from the plasma of 25,312 pregnant women were used to train a multivariate model. The pretrained model was then applied to 505 pregnant samples to assess the performance of SeqFF against known methodologies for fetal DNA fraction calculations.
Pearson's correlation between chromosome Y and SeqFF for pregnancies with male fetuses from two independent cohorts ranged from 0.932 to 0.938. Comparison between a single-nucleotide polymorphism-based approach and SeqFF yielded a Pearson's correlation of 0.921. Paired-end sequencing suggests that shorter ccfDNA, that is, less than 150 bp in length, is nonuniformly distributed across the genome. Regions exhibiting an increased proportion of short ccfDNA, which are more likely of fetal origin, tend to provide more information in the SeqFF calculations.
SeqFF is a robust and direct method to determine fetal DNA fraction. Furthermore, the method is applicable to both male and female pregnancies and can greatly improve the accuracy of noninvasive prenatal testing for fetal copy number variation.
Clinical outcome of subchromosomal events detected by whole-genome noninvasive prenatal testing.+ –
Helgeson J1, Wardrop J1, Boomer T1, Almasri E1, Paxton WB1, Saldivar JS1, Dharajiya N1, Monroe TJ2, Farkas DH3,4, Grosu DS1, McCullough RM1. Prenat Diagn. 2015 Jul 27. doi: 10.1002/pd.4640. [Epub ahead of print]
A novel algorithm to identify fetal microdeletion events in maternal plasma has been developed and used in clinical laboratory-based noninvasive prenatal testing. We used this approach to identify the subchromosomal events 5pdel, 22q11del, 15qdel, 1p36del, 4pdel, 11qdel, and 8qdel in routine testing. We describe the clinical outcomes of those samples identified with these subchromosomal events.
Blood samples from high-risk pregnant women submitted for noninvasive prenatal testing were analyzed using low coverage whole genome massively parallel sequencing. Sequencing data were analyzed using a novel algorithm to detect trisomies and microdeletions.
In testing 175,393 samples, 55 subchromosomal deletions were reported. The overall positive predictive value for each subchromosomal aberration ranged from 60% to 100% for cases with diagnostic and clinical follow-up information. The total false positive rate was 0.0017% for confirmed false positives results; false negative rate and sensitivity were not conclusively determined.
Noninvasive testing can be expanded into the detection of subchromosomal copy number variations, while maintaining overall high test specificity. In the current setting, our results demonstrate high positive predictive values for testing of rare subchromosomal deletions.
Scientific Posters
Sequenom Laboratories' posters
Optimized Detection of 22q11.2 Deletions Using Whole Genome Sequencing+ –
John A. Tynan, Yijin Wu, Tong Liu, Yang Zhong, Mark Whidden, Roy Lefkowitz, Amin Mazloom, Mathias Ehrich
Expanding noninvasive prenatal testing to average risk: MaterniT® 21 PLUS experience in the average vs. high risk population+ –
John A. Tynan, Yijin Wu, Tong Liu, Yang Zhong, Mark Whidden, Roy Lefkowitz, Amin Mazioom, Mathias Ehrich
Five years of precision – cfDNA as a case example+ –
Mathias Ehrich, Dirk van den Boom, Daniel Grosu
Success of NIPT based on Maternal Weight and Gestational Age+ –
Jenna Wardrop1, Theresa Boomer1, Eyad Almasri1, Samantha Caldwell1, Sidra Boshes1, Ron McCullough1 1Sequenom Laboratories, San Diego, CA
Expanding noninvasive prenatal testing (NIPT) for screening of unbalanced translocations.+ –
Samantha Caldwell, Sidra Boshes, Jenna Wardrop, Theresa Boomer, Phillip Cacheris, Hany Magharyous, Ron McCullough.
Sequenom Laboratories.
Genome wide detection of chromosomal gains and losses greater than 7Mb by cfDNA analysis.+ –
Roy B. Lefkowitz, John A. Tynan, Tong Liu, Yijin Wu, Amin R. Mazloom, Eyad Almasri, Grant Hogg, Theresa Boomer, Jenna Wardrop, Ron McCollough, Marcos Gonzales, Mathias Ehrich.
Sequenom Laboratories.
Abnormal ultrasound and increased yield of abnormal results with genome-wide cfDNA analysis.+ –
Jenna Wardrop, Marcos Gonzales, Theresa Boomer, Phillip Cacheris, Eyad Almasri, Ron McCullough.
Sequenom Laboratories.
Karyotype-level noninvasive prenatal testing by sequencing of circulating cell-free DNA from maternal plasma.+ –
Amin R. Mazloom, Tong Liu, Roy Lefkowitz, Yijin Wu, Grant Hogg, John Tynan, Timothy Burcham, Dirk van den Boom, Mathias Ehrich. Sequenom Laboratories.
- We previously demonstrated genome-wide detection of 3-40 Mb microdeletions and micro -duplications in maternal plasma at approximately ~16M reads per sample.+++
- Using a purely theoretic model, we find that ~16M reads per sample can theoretically provide a >95% sensitivity for events ≥7 Mb.
- Using whole genome sequencing results from plasma DNA, we were able to model in-silico genome-wide events. These simulations show >90% sensitivity for ≥7 Mb and >95% for events ≥10 Mb.
+++Zhao C, et al. Detection of fetal subchromosomal abnormalities by sequencing circulating cell-free DNA from maternal plasma. Clin Chem, 2015. 61(4), 608-616
Rings and things: Noninvasive prenatal testing's unique view of the biology and embryology behind chromosomal ring formation and segregation.+ –
Theresa Boomer, Judy Fisher Newell, Patricia Santiago-Munoz, Christina Settler, Michelle N Strecker, Jenna Wardrop, Julie Jesiolowski, Ron McCullough, Juan-Sebastian Saldivar, William B Paxton, Thomas Monroe4, Nilesh Dharajiya. Sequenom Laboratories, University of Texas Southwestern Medical Center, Department of Obstetrics and Gynecology, Dallas, TX and Combimatrix, Irvine, CA.
The emerging contribution of NIPT genomic data offers a unique view into the earliest forming layer of placenta (trophoblast). Providing a snapshot in an embryology timeline, NIPT can assist with deciphering the timing and origin of complex de novo events such as ring chromosomes. This invaluable insight can help explain chromosomal inconsistencies that result among tissue types, screening tests, and diagnostic technologies.
Clinicians need to be mindful of the biological strengths and limitations of NIPT, especially in regard to chromosomal mosaicism and complex structural rearrangements. Such awareness is invaluable when presented with seemingly discrepant prenatal results and promotes accurate clinical assessment, counseling, and overall case interpretation.
Furthermore, clinicians should also be aware of NIPT's ability to identify maternal subchromosomal abnormalities. Accurate clinical information provided to the laboratory may aid in additional interpretation.
Circulating cell-free DNA screening for fetal aneuploidy: The Newton-Wellesley Hospital Maternal Fetal Medicine experience.+ –
Jennifer Helgeson, Sharon Namaroff, Mary-Frances Garber, Lisa Dunn-Albanese, Daniel Katz, Yael Hoffman-Sage, Marney Brillinger. Sequenom Laboratories & Newton-Wellesley Hospital, Newton, MA.
The performance of the MaterniT21® Plus LDT in this high risk population, representative of patients typically treated in a Maternal Fetal Medicine setting, continues to show a very low overall false positive rate (0.13%) compared with traditional maternal serum screening modalities. Recently, it has been suggested that samples with a non-reportable ccfDNA result may be enriched for fetal aneuploidy++. This has not been the experience with this cohort.
++Pergament E, et al. Single-nucleotide polymorphism-based noninvasive prenatal screening in a high-risk and low-risk cohort; Obstet Gynecol. 2014;0:1-9.
Updated clinical experience of trisomy 16 and 22, and microdeletion detection by noninvasive prenatal testing (NIPT).+ –
Jenna Wardrop, Julie Jesiolowski, Nilesh Dharajiya, Thomas J Monroe, Theresa Boomer, Eyad Almasri, Ron McCullough. Sequenom Laboratories.
Initially used for detecting trisomy 21 only, MaterniT21® PLUS has advanced into a LDT for also detecting trisomy 18, trisomy 13, and sex chromosome aneuploidies. Here, we demonstrate continued expansion of the technological capabilities to effectively detect microdeletions and two additional rare trisomies.
Automated genomic interpretation of sub-chromosomal fetal copy number variation by sequencing circulating cell-free DNA from maternal plasma.+ –
Penn Whitley, John Tynan, Adam Simpson, Tim Burcham, Ali Torkamani, Ashley Van Zeeland, Mathias Ehrich, Ron M McCullough, Juan-Sebastian Saldivar, Tom Monroe, Paul Oeth, and Dirk van den Boom. Sequenom Laboratories and Cypher Genomics, Inc.
- The manual curation of Copy Number Variation in a NIPT setting is time consuming (~0.5-4hr/CNV/curator), subjective and potentially subject to error.
- Data provenance and standards are also difficult to maintain in an environment with manual curation and interpretation.
- The Cypher Genomics Mantis™ System provided highly concordant results with those from the working group when the initial call was pathogenic or likely pathogenic.
- Manual VOUS calls were less concordant with the automated results. This finding is likely reflective of the different data sources and scoring systems used by the methods.
- Discrepancy analysis resulted in several scoring reversals when the working groups re-evaluated the CNV calls. The reasons for these reversals may have been a result of updated data sources or more consistent scoring methodology used during the re-evaluation.
- These results suggest that an automated interpretation and curation system can provide an excellent 'first line of defense' in a clinical setting.
- The combination of the standardized output and interpretation generated by the Mantis™ system, along with the experience and judgment of a lab director, should provide excellent results to clinicians
Two cases of Wolf-Hirshhorn syndrome detected by noninvasive prenatal testing (NIPT).+ –
Thomas Monroe, Nilesh Dharajiya, Julie Jesiolowski, Theresa Boomer, Ron McCullough, Chen Zhao, Paul Oeth, Juan-Sebastian Saldivar. Sequenom Laboratories.
NIPT has rapidly become a part of the standard of care for aneuploidy testing in high-risk pregnancies. We demonstrated initial expansion of this technology by effectively detecting certain microdeletions. We also continue to augment the number of conditions we are screening, which now includes Wolf-Hirshhorn and other microdeletions of significant clinical relevance. This abstract provides evidence and further supports broadening the capabilities of noninvasive testing to detect subchromosomal deletion events, as well as the potential to derive fetal karyotypes in the future.
Noninvasive prenatal testing aids in detecting parental balanced translocation and highlights limitations of karyotyping.+ –
Julie Jesiolowski, Thomas Monroe, Courtney Fitch, Jenna Wardrop, Theresa Boomer, Juan-Sebastian Saldivar. Sequenom Laboratories and Lehigh Valley Maternal Fetal Medicine, Allentown, PA.This case demonstrates the unique insight NIPT data can provide, especially in relation to compromised POC samples. Clinicians should be aware that standard karyotyping may not have sufficient resolution to detect subchromosomal events detectable by NIPT. Accurate clinical information provided to the laboratory may aid in additional interpretation. In these cases, microarray studies or high resolution karyotyping are the preferred methods for confirming a suspected abnormality.
Identification of 22q11 microdeletions by noninvasive prenatal testing (NIPT) – the clinical experience.+ –
Ron M McCullough, Juan-Sebastian Saldivar, Thomas Monroe, Theresa Boomer, Jenna Wardrop, Julie Jesiolowski, Jennifer Hume, Nilesh Dharajiya. Sequenom Laboratories.
It is imperative when testing for rare conditions, such as 22q11 deletions, that NIPT tests perform with the utmost specificity to result in high positive predictive values. By using a whole genome sequencing approach, we have demonstrated that this objective is achievable. This abstract provides further evidence and support to broaden the scope of noninvasive testing to detect sub-chromosomal deletion/ duplication events and the potential to derive fetal karyotypes in the future.
Science by the people and for the people
Patient consent is the foundation on which Sequenom is built.
Since 2009, we have collected samples and verified clinical data from over 40,000 patients who willingly participated in one of 29 Sequenom-sponsored clinical studies at over 280 clinics in the US, Canada, Europe, and Australia.
You have the power to advance reproductive health.
We have clinical studies ongoing in noninvasive pregnancy testing. Currently listed on clinicaltrials.gov are studies enrolling the following patients:
- Patients who have an affected pregnancy as confirmed by amniocentesis or CVS.
- Patients who are at increased risk of fetal aneuploidy with outcome confirmed by amniocentesis or CVS.
- Patients who were pregnant with twins or triplets and were previously tested with the MaterniT® 21 PLUS test.
Help us build your diagnostic future
Sequenom science is built on the strength of clinical studies.
If you have a patient who may wish to participate in a research study or if you would like to be considered as a participating site in one of our clinical studies, contact email@example.com.
- Lo YM, Corbetta N, Chamberlain PF, Rai V, et al. Presence of fetal DNA in maternal plasma and serum. Lancet. 1997 Aug 16;350(9076):485-487.
- Finning KM, Martin PG, Soothill PW, Avent ND. Prediction of fetal D status from maternal plasma: introduction of a new noninvasive fetal RHD genotyping service. Transfusion. 2002 Aug;42(8):1079-1085.
- Bianchi DW. Circulating fetal DNA: its origin and diagnostic potential-a review. Placenta. 2004 Apr;25 Suppl A:S93-S101.


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Walkman is a free app which has an integrated GPS and foot tracking mechanism. Walkman motivates. . . read more »
November 25, 2018: Berger Paints has launched an interactive smartphone application 'Berger Paints Nepal'. The application. . . read more »
If you sing, play instruments or produce music and can't seem to connect with the right Musicians… Bandzilla is for you!. . . read more »
Nepali Dictionary - Offline is advanced levels dictionary by makers of popular Nepali calendar app Hamro. . . read more »
Nepal Lipi app converts the text typed in Nepali Devanagari into Nepal Lipi - Newa script. With this app, we can type Newa texts in Nepal. . . read more »
September 20, 2017: Most used and very popular Nepali mobile application, Hamro Patro brings widely played card games. . . read more »
September 20, 2017: Nepal Telecom (NT) users can now watch live TV, movies and various other videos using a single mobile. . . read more »
Nepal Immigration Android Mobile App is a fast access to information for all tourists who visits. . . read more »
Tiger trap is a based on popular traditional puzzle game of Nepal : Bhag Chal. It is developed by Ishani. . . read more »
The Ministry of Finance launched Budget Mobile Application in a bid to facilitate people to get. . . read more »
Hamrodoctor is the first health news portal in Nepal that commenced its services with both a website and a mobile application.. . . read more »
NiDARR is a smartphone application tool designed to provide individuals a secure and private platform to stay. . . read more »
Tootle is a ride sharing application, that connects the bikers and the commuters,. . . read more »
Thingsle is Nepal's first app for finding holiday destination, weekend getways, vacation ideas. This app lets you plan your holiday by. . . read more »
Visiting Nepal has never been this easy. Put on your headset and experience the nature and heritages of Nepal!. . . read more »
Page 1 of 3, showing 15 records out of 33 total, starting on record 1, ending on 15
November 11, 2019: Samsung has announced the launch of its new smartphone - Galaxy A20s in the market.. . . more »
Nobember 8, 2019: Nokia's mid-range offering, the Nokia 7.2 is on sale online exclusively via Sasto Deal.. . . more »
The ambitious are criticized by those that have given up.Grant Cardone


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This is ( mixed with water or sparkling wine ) a perfect vegan summer drink. It is also ideal for ice cream
This is ( mixed with water or sparkling wine ) a perfect vegan summer drink. It is also ideal for ice cream
This vegan jam is a special blend of fruit and flower
This vegan sensation captivates with the combination of fruits and chocolate
The combination of blueberries and a touch of cardamom makes this jam very special.
A great vegan gift. Quick and easy made. Smells good and makes a lot of pleasure.
best to cook ahead
excellent suitable for curing sore throat, but also as sweetening (tea ) or to garnish your pudding.
Of course you can also eat the ginger pieces because they are soft boiled.
INGREDIENTS 100 g salt 15 g hibiscus flower 5 cardamom pods 1 teaspoon coriander seeds PREPARATION grind all ingredients finely fill it in a glass and close tightly tastes excellent to Asian...
INGREDIENTS ( for about 150 g ) 100 g roasted onions 2 tablespoons curry powder 2 tablespoons sea salt 3 teaspoons curcuma powder 2 teaspoons coriander powder 2 teaspoons garlic salt 2 teaspoons chilli...
INGREDIENTS 50 g dried tomatoes 50 g sea salt 25 g peeled almonds PREPARATION step 1 chop the tomatoes up step 2 grind the tomatoes with the salt and the almonds step 3...


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The summer holidays here in Melbourne is marked by extremely hot days and really bored children who want to play outside but also do not want to burn to a crisp. So on slightly cool days, my boys (the big, bearded one included) relish some outdoor time in our backyard or the park nearby.
We've put a small blow-up pool in our backyard, which has upped the fun ratings in our household by at least ten-fold! The littlest one occasionally joins in the fun, but more often than not, he's happy just to watch. When he's in there, though, he's just one of the guys!
Of course, the park is where the real action happens. Between throwing planes and (pretty crappily-made) robot bats, and also using the skating half-pipe as a big slide, we can while away entire hours there. We're pretty lucky to be walking distance from a few parks. It's definitely helped quell some of the cabin fever these past few weeks. That, and the random wildlife that we see as we walk around the neighborhood, haha. Say hello to one of the many cockatoos that live in our neighborhood!
As much as I've enjoyed having all this time with the older boys (and being able to sleep in, hurrah!), I am definitely looking forward to school starting again soon. The boys feel the same way, I think!


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Make-a-Wish is giving a 5-year-old little boy, Miles, the surprise of a lifetime by turning San Francisco into Gotham for a day and calling on him to save the city. On November 15th, Miles will be...BatKid!
That morning, there will be a breaking news announcement in San Francisco from the police chief saying there is trouble in the city, and he desperately needs BatBoy's help. Miles will then spend the day living the life of a super hero fighting bad guys and solving crime.


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BREAST FACTS-backup
Breast Facts
The Facts: Women (2017) - About 1 in 8 U.S. women (about 12%) will develop invasive breast cancer over the course of her lifetime. Every 2 minutes a woman is diagnosed with breast cancer; every 13 minutes a woman in the U.S. will die of this disease.
The Facts: Men (2017) - About 2,470 new cases of invasive breast cancer are expected to be diagnosed in men in 2017. Breast cancer risk is much lower in men than in women. A man's lifetime risk of breast cancer is about 1 in 1,000 (about 1%).
The Facts: In the United States (2017):
In 2017, an estimated 255,180 new cases of invasive breast cancer are expected to be diagnosed in women in the U.S. along with 63,410 new cases of non-invasive (in situ) breast cancer.
More U.S. Women are Choosing Mastectomy Over Lumpectomy for Early Stage Breast Cancer. 35% vs 65% choose mastectomy over lumpectomy and that number has been increasing according to the U.S. National Institute of Health released a statement in 1990 saying that lumpectomy plus radiation was preferred over mastectomy to treat early-stage breast cancer. Still, some women who've been diagnosed with early-stage breast cancer in one breast choose to have that breast and the other healthy breast removed. Removing the other healthy breast is called contralateral prophylactic mastectomy.
The study published on Nov. 19, 2014 by JAMA Surgery "Nationwide Trends in Mastectomy for Early-Stage Breast Cancer." Researchers looked at medical records of more than 1.2 million women diagnosed with early-stage breast cancer in one breast and treated at centers across the U.S. from 1998 to 2011. The records are part of the National Cancer Data Base, a nationwide database created by the American Cancer Society and the American College of Surgeons Commission on Cancer.
- Breast cancer incidence rates in the U.S. began decreasing in the year 2000, after increasing for the previous two decades. They dropped by 7% from 2002 to 2003 alone. One theory is that this decrease was partially due to the reduced use of hormone replacement therapy (HRT) by women after the results of a large study called the Women's Health Initiative were published in 2002. These results suggested a connection between HRT and increased breast cancer risk.
- About 40,610 women in the U.S. are expected to die in 2017 from breast cancer, though death rates have been decreasing since 1989. Women under 50 have experienced larger decreases. These decreases are thought to be the result of treatment advances, earlier detection through screening, and increased awareness.
For Women in the U.S.: breast cancer death rates are higher than those for any other cancer, besides lung cancer. Besides skin cancer, breast cancer is the most commonly diagnosed cancer among American women. In 2016, it's estimated that just under 30% of newly diagnosed cancers in women will be breast cancers.
- In women under 45, breast cancer is more common in African-American women than white women. Overall, African-American women are more likely to die of breast cancer. For Asian, Hispanic, and Native-American women, the risk of developing and dying from breast cancer is lower.
- In 2016, there were more than 2.8 million women with a history of breast cancer in the U.S. This included women being treated and women who finished treatment.
- A woman's risk of breast cancer nearly doubles if she has a first-degree relative (mother, sister, daughter) who has been diagnosed with breast cancer. Less than 15% of women who get breast cancer have a family member diagnosed with it.
- About 5-10% of breast cancers can be linked to gene mutations (abnormal changes) inherited from one's mother or father. Mutations of the BRCA1 and BRCA2 genes are the most common. On average, women with a BRCA1 mutation have a 55-65% lifetime risk of developing breast cancer. For women with a BRCA2 mutation, the risk is 45%. Breast cancer that is positive for the BRCA1 or BRCA2 mutations tends to develop more often in younger women. An increased ovarian cancer risk is also associated with these genetic mutations. In men, BRCA2 mutations are associated with a lifetime breast cancer risk of about 6.8%; BRCA1 mutations are a less frequent cause of breast cancer in men.
- About 85% of breast cancers occur in women who have no family history of breast cancer. These occur due to genetic mutations that happen as a result of the aging process and life in general, rather than inherited mutations.
- The most significant risk factors for breast cancer are gender (being a woman) and age (growing older).
For Men in the U.S.: Rates of breast cancer incidence (new cases) and mortality (death) are much lower among men than among women. The fact is men do have breast tissue. Although rare, they can get breast cancer. In the U.S., more than 2,000 cases of breast cancer are diagnosed in men and more than 400 men will die from breast cancer each year. Men at any age may develop breast cancer, but it is usually detected (found) in men between 60 and 70 years of age. Male breast cancer makes up less than 1% of all cases of breast cancer. The following types of breast cancer are found in men:
Infiltrating ductal carcinoma: Cancer that has spread beyond the cells lining ducts in the breast. Most men with breast cancer have this type of cancer.
Ductal carcinoma in situ: Abnormal cells that are found in the lining of a duct; also called intra-ductal carcinoma.
Inflammatory breast cancer: A type of cancer in which the breast looks red and swollen and feels warm.
Paget disease of the nipple: A tumor that has grown from ducts beneath the nipple onto the surface of the nipple.
Lobular carcinoma in situ (abnormal cells found in one of the lobes or sections of the breast), which sometimes occurs in women, has not been seen in men].
If you are a man, who has recently been diagnosed with Breast Cancer or are in need of surgical treatment or may be in need of breast reduction surgery (Gynecomastia), there are new undergarments available -- the Joe & Arrow Men's Vests will provide post-op compression and hide under your dress shirt or casual t-shirts. One style has is strapless and the other is over the shoulder – both providing the same form of compression and will hold a removable drains on both sides if needed. Pouches are available for purchase. Feel Confident, Look Handsome!
The Facts: Around The World (2016):
Breast cancer is the most frequently diagnosed cancer in the world and the leading cause of cancer death in women, with an estimated 1.7 million new cases recorded in 2012.
Every 60 seconds, somewhere in the world, someone dies from breast cancer.
At the current rate, 13 million breast cancer deaths around the world will occur in the next 25 years.
Incidence (new cases) rates Overall, new cases of breast cancer is about the same for black and white women. However, African-American women under age 45 have a higher incidence of breast cancer than white women. Hispanic/Latina women are more likely than white women to be diagnosed with late stage breast cancers. They also tend to have larger tumors than white women. Breast cancer incidence is lower among Asian/Pacific Islander women than for white and black women. New Asian-American immigrants also have lower rates of breast cancer than those who have lived in the U.S. for many years. Yet, for those born in the U.S., the risk is about the same as that of white women.
January 10, 2017 at 11:00 AM Source: U.S. Breast Cancer Statistics.org
The CRISSCROSS Facts: Each garment was designed thinking about the length of time these undergarments must be worn during your recovery process. Once the fluids deplete, and your drains come out, the CRISSCROSS line will offer additional solutions to carry you through your entire recovery and days ahead from Day 1 - 180+. Today, we are introducing the initial Phase of the line (Days 1 - 90) and many other garments will follow. An assortment of trending colors and styles are available to ensure you feel good about yourself at home or in the workplace. That's what I had in mind when designing the brand. I hope you will enjoy your new CRISSCROSS product.
For more information about warning signs and prevention for both women and men, I invite you to follow Breast Cancer National Research Statistics and Susan G. Komen. As a former Board of Trustee of SGK/North Jersey, I continue to support local affiliates and their national organization. They are a great resource, trusted friend and neighbor to me as a Survivor and to all Survivors in our communities - don't be afraid to call upon your local breast friends.
Lookbook →


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So grateful!
Thanksgiving is a wonderful time of year to be with friends, family, or even off on your own adventure. I also think Thanksgiving offers a wonderful reminder of God's, divine Love's, goodness, bounty, and Her healing power that is always at hand to help and uplift our situation. God's grace is ever ready to save and heal — how wonderful is that? Love's abundant mercies are ever-present and always at hand. Wherever this finds you on Thanksgiving, I hope you take time to give thanks, primarily to God, and to honor all the good that comes with knowing that God, divine Love, is the one God and is the only power governing your life.
Sing to the Lord with thanksgiving; make melody to our God on the lyre.
—Psalms 147:7 (NRSV)
Are we really grateful for the good already received? Then we shall avail ourselves of the blessings we have, and thus be fitted to receive more. Gratitude is much more than a verbal expression of thanks. Action expresses more gratitude than speech.
—Mary Baker Eddy, Science and Health with Key to the Scriptures, p.3


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Current Page:product >Belkasoft Integrates Forensic IM Analyzer with Guidance Software
Belkasoft Integrates Forensic IM Analyzer with Guidance Software
Belkasoft announces the integration of Forensic IM Analyzer, a forensic tool helping investigators discover and analyze instant messenger conversations, with Guidance Software Encase, the industry-standard all-in-one computer investigation solution. With the integration in place, Encase users can easily access and analyze data produced by Forensic IM Analyzer in their familiar environment.
With the integration of Forensic IM Analyzer into the Encase family of forensic products, Encase users will gain the ability to automate their investigations of Internet chats performed by the suspects and stored locally on PCs under examination. Forensic IM Analyzer can now be seamlessly launched from Encase, collect all possible information on user's chats and instant messenger communications, and transmit all collected data back into Encase.
The integration became possible with the use of EnScript, the Encase built-in scripting language. Encase users can now access and analyze data extracted by Belkasoft Forensic IM Analyzer in highly advanced Encase environment. The integration script is available for free to customers with valid Encase and Belkasoft Forensic IM Analyzer or Forensic Studio licenses.
"Many of Belkasoft customers are also Encase users," said Yuri Gubanov, Belkasoft CEO. "These customers will greatly benefit from our integration with Encase, allowing them to combine the power of the two excellent tools."
"With the powerful EnScript programming language, Belkasoft can easily integrate with EnCase, extending the value of their Forensic IM Analyzer product," said Steve Salinas, product marketing manager with Guidance Software. "Now users of the Belkasoft products can take their findings and integrate them into EnCase. As our focus of EnCase Forensic v7 is improved efficiency, we see this integration as yet another great example of how EnScript can help investigators get their job done faster."
About Belkasoft Forensic IM Analyzer
Belkasoft forensic tool helps investigators, IT security and forensic specialists collecting digital evidence from PCs. Supporting more than 30 different instant messengers and chat products such as Skype, AIM, Yahoo!, MSN and Live! messengers, and the many various implementations of IRC, ICQ and Jabber protocols, Forensic IM Analyzer can perform in-depth analysis of user's Internet conversations. Forensic IM Analyzer can extract conversation history from the logs, recover deleted data ("carving"), and perform Live RAM analysis to extract non-logged conversations from the computer's operating memory dumps.
The combination of comprehensive feature set and unprecedented level of automation along with the number of messenger protocols supported make Belkasoft Forensic IM Analyzer one of the most advanced IM forensic investigation tools on the market. About Guidance Software Encase
With more than 40,000 installations of various EnCase forensic editions worldwide, the EnCase platform is used by over half of Fortune 100 companies, multiple government and commercial entities. The proven, powerful EnCase Forensic is the industry-standard computer investigation solution helping forensic practitioners to conduct efficient, forensically sound data collection and investigations using an accurate and repeatable process. Guidance Software and Encase are registered trademarks of Guidance Software, Inc.
About Belkasoft
Founded in 2002, Belkasoft is a software vendor specializing in computer forensics and IT security solutions. Used by IT security experts and forensic investigators all over the world, Belkasoft solutions live up to the company's slogan, "Forensics made easier". The company aims at producing forensic tools that work straight out-of-the-box, without imposing the requirements of deep and specific knowledge of IT systems or computer hardware. Belkasoft solutions are used by government and commercial customers worldwide. The company's clients include the FBI, U.S. Army, U.S. Secret Service, multiple police departments in Germany, Norway, Australia, New Zealand and many other countries, PricewaterhouseCoopers, Ernst & Young and other Fortune 100 corporations.
Copyright © 2009-2010 Convert Pdf to Word,Inc.Home | Product | Download | Buy now | Contanct us | Blog | How to


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Why Choose Emma?
Emmanuel College (known as 'Emma') is widely considered the friendliest college in the university. MCR members are a varied bunch; some join straight after their undergrad study, others have come back after a break from university. Members represent a wide range of subjects, too, with every kind of study: from MBAs to medics and from historians to mathmos.
A Place to Call Home
Most grads live in college housing for at least a year of their degree. The main site for grad rooms is Barnwell Hostel, located about 10 minutes' walk from Emma. There are also other grad rooms on Tenison Road, in houses near to Addenbrooke's Hospital for the medics and vets and in Park Lodge, on the college site itself.
While grad housing provides all you would expect from student accommodation, with cooking facilities enough to make an undergrad jealous and their own laundry machines, most grads find it just as easy to use college services. Meals in hall are always a good place to meet up with other students.
The MCR is not just a short-hand term for the student body; it's a room to call our own in college, too. The MCR room in the Queen's Building has a TV with skybox, a DVD player and HDMI connections for your own computers. There's a pool table (very popular after formals!), a foosball table and plenty of board games. During term time, the JCR-run bar is a good place to relax.
Being Sociable
Social activities are a key feature of College life and Emma is no exception. The MCR Committee has no less than three Social Secretaries who, along with their Committee colleagues, organise events throughout the terms and during the summer holiday. We have Formal Dinners three or four times a term. These are grand, three-course events in the Hall, where students and guests dress up and get waiter service. At each dinner we invite guests from other colleges to join us – and we get to attend Formal Dinners with them in return. This is a great way to see other colleges and as everyone wants to swap with Emma, we're never short of colleges to dine at.
It's not all eating and drinking! The MCR arranges an
Top of the Class
Emma MCR is not just a social hub. It's a great place for academic networking and development. Emma consistently ranks among the top three Colleges in the annual Tomkins Table and although that's undergraduate-focused, the grads do not shy from making their own contribution. Each term we host three Grad Talks, which provide opportunities for Grads and Fellows to come together and hear about the work of our MPhil and PhD students. Our Formal Dinners often provide a chance for students to mingle with the Fellows, too.
The range of research undertaken by our grad students, pushing boundaries in topics as varied as selection in South American butterflies, medieval child kings and literary translations, means that there's always someone around to give you a fresh perspective on your own research!
Finally… The Ducks
The college's well-tended grounds are a popular place for students and picnickers alike to relax, especially in the summer months. The Paddock, one of the few college spaces on which people can walk freely, is home to many ducks and moorhens, as well as people. Watching the ducks going crazy over their daily feed (or hanging round for scraps outside the Hall window) are sights to be seen!


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July 4 was our Declaration of Independence from Britain… the true birth of our country, which is now the largest and most powerful economy in the world… but it is so much more than that.
You see, in the mid-to-late 1700s, scientific thinking and discovery culminated in the Enlightenment. The world saw breakthroughs in countless areas of thought and philosophy, kind of like the breakthroughs Greeks had in the days of Aristotle and the first democratic movement.
The most important economic developments to arise out of the Enlightenment from my research were the invention of the steam engine by James Watt between 1763 and 1775 and Adam Smith's classic book and treatise, The Wealth of Nations, first published in 1776.
I don't have to comment much on the massive impacts that powered machinery and the Industrial Revolution has had on our standard of living ever since then. The longer-term stock market chart below makes the case very clearly.
(Note that this is a logarithmic chart that turns exponential trends into linear ones. The brain can better handle the information in this format. On a normal linear graph this acceleration of trends would be much more dramatic.)
But I do have to comment on the essential role Adam Smith played in how we live today.
He was the first economist that truly understood the power of free market capitalism and its "invisible hand." And his insights still stand today, as governments try to take over this powerful system with little regard for how it made us so rich in the first place.
Think of it this way: On the one hand, the Industrial Revolution and free-market capitalism is half the story… the more male side if you will, which I call Harry (named after me of course).
On the other hand is Sally… the more female side, and other half of the story that is equally as important as Harry. In fact, it was "Sally" that birthed the first real and deeply conceived democracy in history, in America.
Free market capitalism favors the strong, with its "survival of the fittest" and "creative destruction" principles. But with increasing trends toward urbanization and more and more diverse people having to live together in larger cities, a counterbalance was needed.
You can't have a society that continues to favor the strong while the less fortunate struggle and fall further behind… otherwise they'd revolt, as did the Americans and the French in the late 1700s.
The Declaration of Independence and Constitution that followed was not largely about America breaking from the monarchy of Great Britain. Like the French Revolution, it was about people revolting against total top-down control by such monarchies and favored classes.
Ultimately, the free-market system in all of its creative destruction and innovation does favor the upper rungs of society. It also favors mafias and strong groups who succeed and amass increasing power.
Seems all very testosterone driven… and headed for disaster and failure without some kind of balance.
That's where democracy came in. It brought the principle of certain inalienable human rights, namely "life, liberty and the pursuit of happiness." In other words, it ensured that the everyday person got an equal vote, allowing them to feel like they have a say and stake in the system.
As I've said in many articles and in my books, it's the dynamic play of opposites — in this case Harry and Sally — that drives innovation and the unprecedented progress the world has enjoyed since the late 1700s.
The greatest revolution in our standard of living, and the move toward more free and humane lifestyles, didn't just come with the Industrial Revolution. The Democratic Revolution played a vital role. In short, it came when Harry met Sally.
It was no coincidence that The Wealth of Nations and the Declaration of Independence came to life in the same year… 1776.
And that's something to celebrate.
It's also important to note that major political and economic revolutions occur every 250 years… and hence the next one is due just ahead!
There is ever the tendency for the more powerful and more fortunate to reassert their power and rig the free markets… to suppress the democratic urge. Take the Cold War as just one example. But the U.S. and western world won that war and dodged that bullet.
Now China has tried to have a top-down, state-driven capitalistic system without democracy and you know my opinion on the success of that experiment by now! (For those new to Economy & Markets, I believe China's efforts to operate a state-driven capitalistic system is not only a resounding failure, but a threat to the entire global economy.)
Even today, in the western democracies, governments are corrupting free market capitalism by taking over the markets and preventing failure. You've heard much from me on this in the last few years, but soon you can hear it from an even greater source, David Stockman, when he appears as our keynote speaker at our Irrational Economics Summit on June 16 to 18 in Miami. Don't miss this most informed and passionate of speakers on this topic from his recent book, The Great Deformation.
Something's going to give… soon.
For today though, celebrate not only our freedom and independence, but the day when Harry met Sally. An unprecedented surge of wealth has occurred throughout the western world, and now in East Asia. But its spark came in America in 1776.
Happy Fourth of July.
|Follow me on Twitter @HarryDentjr


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FREE: Cracked Yakima Space Booster ski box. Its lid was cracked so we replaced it with a new version. This box is about 18yo, and is a nice long length, perfect for XC skis. It is black and made from ABS so it is glue-able and can be repaired. If you need some black ABS material to repair it, we'll get you some for a very reasonable price. We will give this to any current or renewing KNSC member.
Contact Arlyn and Sandy at 370-2911 or email@example.com
[caption id="attachment_2738" align="alignnone" width="245"] The security dog watches while we leave to eat.[/caption]