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Ancient primate a missing link?

An artist's rendering shows what Archicebus achilles, which lived 55 million years ago, may have looked like in its natural habitat.

An artist’s rendering shows what Archicebus achilles, which lived 55 million years ago, may have looked like in its natural habitat.

(CNN) — Achilles’ heel was his weak spot in the Greek myth, but the heel of a newly discovered primate provides a strong connection between humans and their possible ancestors.

Scientists have discovered the oldest primate skeleton to date, from a creature that resembles humans’ evolutionary line — the anthropoids — and a different primate lineage called the tarsiers. They have named this specimen Archicebus achilles, making reference to its heel bone, which resembles those of modern monkeys.

Anthropoids include humans, apes and monkeys. Tarsiers are nocturnal primates that live only in Southeast Asia today. The study is published in the journal Nature.

“For the first time, it really shines a light on an important phase of primate and human evolution that we just had very little information about before,” said K. Christopher Beard, paleontologist at the Carnegie Museum of Natural History and senior author of the study.

The specimen’s completeness, age and position in the primate family tree make it special, said Erik Seiffert, associate professor at Stony Brook University, who was not involved in the study.

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“In my opinion, it is one of the most important discoveries in the history of paleoprimatology,” Seiffert said in an e-mail.

While fragments of other ancient primates have been found in the past, this skeleton — about 55 million years old — is by far the most complete example of a primate from this period, Beard said.

Archicebus achilles represents a never-before-seen link between the anthropoids and the tarsiers, Beard said, but he expects the creature’s exact position on the evolutionary tree to be quite controversial.

Some of its features suggest to his group that it is slightly more closely related to tarsiers than to anthropoids, but other scientists may reach different conclusions. Still, he said, it seems to be clearly related to both groups.

“Archicebus (achilles) gives us our first really detailed look at a species that branched off right near the base of the primate family tree — when anthropoids, tarsiers, and lemurs had just started out on their separate evolutionary pathways,” Seiffert said.

This creature was tiny — only 2.8 inches long — and weighed no more than 1 ounce, making it between the size of a shrew and a mouse.

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Scientists find the small size fascinating because until about a decade ago, researchers believed that anthropoids needed to be a lot bigger, Beard said. But there are counterexamples, even today: The pygmy mouse lemur, found in Madagascar, weighs only about an ounce as well.

A creature so tiny must have been “active and frenetic,” Beard said. Shrews, for instance, act anxious because they are always looking for their next meal, since they need a lot of food for their high metabolic rate.

Archicebus achilles, being small, probably also had a high metabolism, and likely ate high-calorie foods such as insects and very ripe fruits with lots of sugar content.

“When you’re that small, you can’t afford to eat salad,” Beard said. “You can’t ingest enough calories rapidly enough to keep your body going.”

Unlike modern tarsiers, Archicebus achilles was active during the day. Tarsiers also tend to have eyeballs that are the same volume as their brains, whereas this ancient creature had relatively small eye sockets compared to its face — an attribute of monkeys.

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The creature’s foot made a big impression on Beard because of how much it resembles the feet of modern-day marmosets. Its features are much more like those of a monkey than a tarsier.

On the other hand, other features — the hip, knee, elbow and pelvis — more closely resemble a tarsier.

Paleontologists can’t say that this specific creature is the ancestor of humans and tarsiers, but this is the best approximation so far of something resembling a hypothetical common ancestor, he said.

Archicebus achilles was discovered in an ancient lake in Hubei province, China, at a site called the lower Eocene Yangxi Formation, in the Jingzhou area.

The scientists plan on going back and looking for more, but it’s hard work. They were lucky to have found this creature, Beard said. It must have died near the lake and then its carcass was swept into the lake, perhaps by a stream. The body settled at the bottom, covered up by mud which then hardened.

For researchers digging at this site, ancient fish fossils are far more likely to turn up than primates, “which is cool — fossil fish are cool. I like fossil fish, but I’m not an expert on fossil fish,” Beard added.

But if you’re looking for ancient mammals at this site, “you have to have an incredible amount of patience because it’s probably going to be years before you find something that’s really, really exciting. But when you do, you hit the jackpot.”

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Ancient primate a missing link?

INCIVO® (telaprevir) Receives European Commission Approval for Twice Daily Dosing for Treatment of Genotype-1 Chronic Hepatitis C Virus (HCV)

Beerse, Belgium (ots/PRNewswire) – -INCIVO(R) triple therapy now offers a twice daily HCV treatment regimen

which should improve patient adherence[1] –

Janssen Infectious Diseases-Diagnostics BVBA (Janssen) announced today that the European Commission (EC) has approved a new twice daily (BID) dosing of INCIVO(R) (telaprevir), a direct acting antiviral (DAA) protease inhibitor, in combination with pegylated-interferon and ribavirin (PR) for naive and previous treatment experienced patients. The newly approved dosing regimen for INCIVO(R) is now 1,125 mg twice daily in combination with PR, which aligns a morning and evening dose to the already twice daily dosing schedule for ribavirin versus 750 mg every 8 hours in combination with PR.

The EC approval is based on results from OPTIMIZE, a randomized, open-label, multicenter Phase III study in treatment naive patients with genotype-1 chronic HCV infection, which demonstrated that twice daily dosing of INCIVO(R) 1,125mg in combination with PR was non-inferior to the previously approved dosing every 8 hours in the proportion of patients who achieved sustained virologic response (74% versus 73%).[2] Twice daily dosing also showed similar cure rates with twice daily or every 8 hours INCIVO dosing in patients with cirrhosis.[3]

“The approval of INCIVO(R) twice daily is good news for patients with genotype-1 chronic HCV infection. Making treatments more simple and easier to manage, without compromising efficacy, will help to increase adherence and give patients an even greater chance of achieving a cure,” said Dr Maria Buti, Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain.

The availability of new DAAs like telaprevir has transformed treatment options for HCV.[4] Telaprevir has already played a significant role in improving treatment outcomes with more than 80,000 patients treated with telaprevir combination therapy worldwide since it was first approved in 2011.[5] It also offers the shortest total treatment duration of any available HCV therapy, for a high proportion of treatment-naive or relapse patients.[6],[7]

“Before the availability of direct acting antivirals like telaprevir, the best clinicians could hope for was to cure only 40-50% of our genotype-1 HCV patients. DAAs now offer us the chance to cure approaching 80% of these patients, for many in a shorter amount of time. Successful treatment is effectively a cure and causes a massive reduction in the complications of HCV, such as liver cancer and cirrhosis. As with many diseases early therapy is most effective and has the greatest impact on complications. The twice daily dosing of telaprevir makes the treatment easier to administer and will make it easier for patients to take advantage of the opportunity for a cure. We now need to ensure that patients with HCV are identified and offered therapy, before their disease progresses,” said Graham Foster, Consultant Hepatologist, Barts Health London.

“We are pleased by the European Commission approval of twice daily dosing for telaprevir, which marks an improvement on an already important treatment option for HCV. This medicine is the cornerstone of our efforts to improve the lives of more people living with HCV and supporting healthcare professionals around the world,” said Gaston Picchio, Hepatitis Disease Area Leader at Janssen.

Telaprevir was first approved by the U.S. Food and Drug Administration (FDA) in May 2011, marketed by Vertex Pharmaceuticals under the brand name INCIVEK[TM], and by the European Commission in September 2011, marketed by Janssen Pharmaceutical Companies under the brand name INCIVO(R).

About OPTIMIZE

740 naive patients chronically infected with genotype-1 HCV were treated with either a twice daily dosing of INCIVO 1,125 mg or dosing every 8 hours of INCIVO 750 mg, each in combination with PR. At Week 12, telaprevir treatment ended and patients continued on PR alone for an additional 12 or 36 weeks depending on their viral response at Week 4. Patients were evaluated 12 weeks after treatment ended (SVR12) to monitor sustained virological response (SVR) rates.[2]

The SVR12 rate for the twice daily group was 74% (274/369) compared to 73% (270/371) in the every 8 hour group with 95% confidence interval of the difference: -4.9%, 12.0%. The lower limit of the 95% CI (-4.9%) was greater than the pre-determined non-inferiority margin of -11% and therefore the non-inferiority of twice daily group over every 8 hour group was demonstrated.[7]

About INCIVO(R) (telaprevir)

INCIVO(R) (telaprevir), in combination with peginterferon alfa and ribavirin (PR), is indicated for the treatment of genotype-1 chronic HCV in adult patients with compensated liver disease (including cirrhosis) who are treatment naive, and who have previously been treated with interferon alfa (pegylated or non pegylated) alone or in combination with ribavirin, including relapsers, partial responders and null responders.[7] INCIVO(R) is a small molecule, selective inhibitor of the HCV serine protease, and a member of the new class of medicine for the treatment of genotype-1 chronic HCV, direct acting antivirals (DAAs). Unlike previous treatments, DAAs act directly on viral enzymes and prevent the virus from replicating. INCIVO(R) was approved by the European Commission on the 19th September 2011.

INCIVO, 1,125 mg (three 375 mg film-coated tablets) should be taken orally twice daily (BID) with food. Alternatively, 750 mg (two 375 mg tablets) can be taken orally every 8 hours (q8h) with food. The total daily dose is 6 tablets (2,250 mg).[7]

Telaprevir was developed by Janssen Infectious Diseases-Diagnostics BVBA, one of the Janssen Pharmaceutical Companies, in collaboration with Vertex Pharmaceuticals Incorporated (Vertex) and Mitsubishi Tanabe Pharma Corporation (Mitsubishi Tanabe Pharma). Janssen has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK[TM]. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries where it is being marketed as TELAVIC(R).

Important Safety Information

Please see full Summary of Product Characteristics or visit http://www.emea.europa.eu for more details.

The overall safety profile of telaprevir is based on the Phase II/III clinical development programme containing 3,441 patients who received a telaprevir based regimen. In clinical trials, the incidence of adverse events of at least moderate intensity was higher in the telaprevir group than in the placebo group (both groups receiving peginterferon alfa and ribavirin). The most frequently reported adverse reactions (incidence greater than or equal to 5.0%) of at least grade 2 in severity were anemia, rash, pruritus, nausea, and diarrhoea during the telaprevir treatment phase, and the most frequently reported adverse reactions (incidence greater than or equal to 1.0%) of at least Grade 3 were anemia, rash, thrombocytopenia, lymphopenia, pruritus, and nausea.[7] INCIVO(R) prescribing information includes special warnings and pre-cautions for use with regards to rash including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and Stevens – Johnson syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), where INCIVO, peginterferon alfa and ribavirin should be immediately and permanently discontinued and a specialist in dermatology consulted.[7] In cases of mild and moderate rash discontinuation of INCIVO(R) is not always required and patients are advised to consult with a healthcare professional. In cases of severe rash immediate discontinuation of INCIVO(R) is required and consultation with a specialist in dermatology is recommended.[7]

Rash events were reported in 55% of patients with a telaprevir based regimen compared to 33% of patients treated with peginterferon alfa and ribavirin only and more than 90% of rashes were of mild or moderate severity. Severe rashes were reported with telaprevir combination treatment in 4.8% of patients. Rash led to discontinuation of telaprevir alone in 5.8% of patientsand 2.6% of patients discontinued telaprevir combination treatment for rash events compared to none of those receiving peginterferon alfa and ribavirin.[7]

Hemoglobin values of

About HCV

Hepatitis C (HCV) is a contagious liver disease which is spread through blood-to-blood contact and is usually symptomless at the outset.[8] With an estimated 150 million people infected worldwide,[9] and three to four million people newly infected each year, HCV puts a significant burden on patients and society.[10] Estimations indicate that HCV kills more than 350,000 people worldwide per year, accounting for approximately 1% of deaths worldwide.[9] It is the world’s primary cause of cirrhosis and liver cancer[11] with an estimated 20-30% of patients developing liver cirrhosis[12] and a further 7% developing liver cancer.[13] The estimated annual cost of HCV (medical and work loss) is more than $1 billion in the U.S. alone.[14]

About Janssen

At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in infectious diseases and vaccines, oncology, immunology, neuroscience, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Please visit http://www.janssenrnd.com for more information.

###

References:

1) Sievert W et al. Adherence with Telaprevir BID vs. Q8h Dosing in
  Treatment Naive HCV-infected Patients: Results from the Phase III OPTIMIZE Study. J
  Hepatol 2013; 58(Suppl 1): S373.
2) Buti M, Agarwal K, Horsmans Y, et al. OPTIMIZE Trial: Non-inferiority of
  twice-daily telaprevir versus administration of every 8 hours in treatment-naive,
  genotype 1 HCV infected patients. 2012. American Association for the Study of Liver
  Diseases (AASLD) Abstract. (Final ID: LB-8).
3) Horsmans Y, Brown Jr. RS, Buti M, et al. Safety and efficacy of twice daily
  versus every 8 hour telaprevir with peginterferon/ribavirin (PR) in patients with
  cirrhosis. 2013. European Association for the Study of the Liver (EASL) Abstract 862.
4) Casey L C, Lee W M. Hepatitis C Virus Therapy Update 2013. Curr Opin
  Gastroenterol. 2013;29(3):243-249.
5) Janssen data on file.
6) Sherman K, et al. Duration of Initial Telaprevir Treatment for HCV Infection:
  A phase 3 study of treatment duration. N Engl J Med. 2011;365:1014-24.
7) INCIVO(R) Summary of Product Characteristics updated 2013.
8) Centers for Disease Control and Prevention. Hepatitis C FAQs. Available at:
  http://www.cdc.gov/hepatitis/C/cFAQ.htm#transmission (last accessed May 2013).
9) World Health Organization. Hepatitis C Fact Sheet. Available at:
  http://www.who.int/mediacentre/factsheets/fs164/en/index.html (last accessed May
  2013).
  10) WHO. State of the art of vaccine research and development. Viral Cancers.
  Available at: http://www.who.int/vaccine_research/documents/Viral_Cancers.pdf
  (last accessed May 2013).
  11) Rosen HR. Clinical practice. Chronic hepatitis C infection. N Engl J Med.
  2011 Jun 23;364(25):2429-38.
  12) Hep C Trust: Overview of Stages. Available at:
  http://www.hepctrust.org.uk/Hepatitis_C_Info/Stages+of+Hepatitis+C/Overview+of+the+stages
  (last accessed May 2013). 
  13) Blachier M, Leleu H, Peck-Radosavljevic M, et al. The Burden of liver
  disease in Europe: A review of available epidemiological data. European Association
  for the Study of the Liver 2013.
  14) El Khoury A, Klimack W, Wallace C, et al. Economic burden of hepatitis
  C-associated diseases in the United States. J Viral Hep. 2012 March;19:153-160
 

Contact:

MEDIA  Ronan Collins, +44(0)7876-257-746, Ines Hammer,
+33(6)8809-33-35 

Link to article: 

INCIVO® (telaprevir) Receives European Commission Approval for Twice Daily Dosing for Treatment of Genotype-1 Chronic Hepatitis C Virus (HCV)

Perosphere and Daiichi Sankyo Enter into a Clinical Trial Agreement to Evaluate the Efficacy and Safety of PER977 to Reverse the Anticoagulant…

Mount Kisco, New York And Tokyo (ots/PRNewswire) – Daiichi Sankyo to support and co-sponsor phase 1 Clinical Study

Perosphere Inc. and Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) announced today that they have entered into a clinical trial agreement under which Daiichi Sankyo will support and co-sponsor a phase 1 clinical study testing the safety, tolerability and effectiveness of PER977 to reverse the anticoagulant activity of edoxaban, Daiichi Sankyo’s investigational oral, once-daily, direct factor Xa-inhibitor.[1 ],[2],[3]

PER977 is a synthetic, small new molecular entity being developed by Perosphere that has been shown in pre-clinical studies to directly bind to heparins as well as circulating direct factor Xa- and IIa-inhibitors and therefore has the potential to reverse their anticoagulant effect.[4],[5],[6],[7] PER977 does not bind to blood coagulation factors or other blood proteins.[5] In pre-clinical studies, PER977 has demonstrated the ability to reverse the anticoagulant effects of direct factor Xa- and IIa-inhibitors in vitro and ex vivo in animal and human models.[4],[6],[7] PER977 reverses anticoagulant activity within 30 minutes after intravenous administration and has a clearance half-life of approximately 1.5 hours.[5]

“Novel oral anticoagulants were developed to help address the limitations of older anticoagulant agents, such as the need for frequent dose adjustments and monitoring,” said Jack Ansell, M.D., Professor of Medicine, NYU School of Medicine, and an advisor to Perosphere. “However, during severe bleeding or the need for emergency intervention, there is no established therapy to reverse the anticoagulant activity of these agents.”

Edoxaban is an investigational, oral, once-daily anticoagulant that specifically and reversibly inhibits factor Xa, which is an important factor in the coagulation system that leads to blood clotting.[1],[8] Edoxaban is currently approved only in Japan, since April 2011, for the prevention of venous thromboembolism (VTE) after major orthopaedic surgery, under the brand name Lixiana(R).

Elsewhere, including Europe and the U.S., edoxaban is currently in phase 3 of clinical development and has not been approved. The global edoxaban clinical trial program includes two phase 3 clinical studies, Hokusai-VTE and ENGAGE AF-TIMI 48 (Effective aNticoaGulation with Factor XA Next GEneration in Atrial Fibrillation), which are evaluating edoxaban, administered once-daily, for treatment and prevention of recurrence of VTE in patients with deep vein thrombosis (DVT) and/or pulmonary embolism (PE), and for the prevention of stroke and systemic embolic events (SEE) in patients with non-valvular atrial fibrillation, respectively.[2],[3]

“Some potential reversal agents under evaluation for direct factor Xa- and IIa-inhibitors are recombinant proteins or fully humanized monoclonal antibody fragments,” stated Dr. Solomon S. Steiner, CEO of Perosphere. “PER977 is a synthetic agent that has the potential to be an antidote for both direct factor Xa- and IIa-inhibitors as well as heparins. In pre-clinical studies, PER977 has been shown to remain stable for more than one year.”

“The initiation of this study, in collaboration with Perosphere, is an important next step in the development of edoxaban,” said Mahmoud Ghazzi, M.D., Ph.D., Executive Vice President of Drug Development for the Americas and Chief Medical Advisor for Global Drug Development, Daiichi Sankyo. “Given our focus on optimizing patient care, the development of a reversal agent is a priority for Daiichi Sankyo in the event one may be needed by physicians.”

About Perosphere

Perosphere is a specialty pharmaceutical company with internationally recognized drug delivery expertise. The company identifies market opportunities where application of drug delivery technology to a drug already on the market can create a new medical use for that drug or enhance its safety, efficacy or ease of use. Perosphere also selectively identifies and develops new chemical entities and other therapeutics that can be used as “rescue” drugs. PER977, a clinical-stage anticoagulant reversal agent for direct factor Xa- and IIa-inhibitors, is Perosphere’s lead drug candidate. For more information, please visit http://www.perosphere.com.

About Daiichi Sankyo

The Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical products to address the diversified, unmet medical needs of patients in both mature and emerging markets. While maintaining its portfolio of marketed pharmaceuticals for hypertension, hyperlipidemia, and bacterial infections, the Group is engaged in the development of treatments for thrombotic disorders and focused on the discovery of novel oncology and cardiovascular-metabolic therapies. Furthermore, the Daiichi Sankyo Group has created a “Hybrid Business Model,” which will respond to market and customer diversity and optimize growth opportunities across the value chain. For more information, please visit http://www.daiichisankyo.com.

Forward-looking statements

This press release contains forward-looking statements and information about future developments in the sector, and the legal and business conditions of DAIICHI SANKYO, Co. Ltd and DAIICHI SANKYO, Inc. Such forward-looking statements are uncertain and are subject at all times to the risks of change, particularly to the usual risks faced by a global pharmaceutical company, including the impact of the prices for products and raw materials, medication safety, changes in exchange rates, government regulations, employee relations, taxes, political instability and terrorism as well as the results of independent demands and governmental inquiries that affect the affairs of the company. All forward-looking statements contained in this release hold true as of the date of publication. They do not represent any guarantee of future performance. Actual events and developments could differ materially from the forward-looking statements that are explicitly expressed or implied in these statements. DAIICHI SANKYO, Co. Ltd and DAIICHI SANKYO, Inc. assume no responsibility for the updating of such forward-looking statements about future developments of the sector, legal and business conditions and the company.

References

1) Ogata, K et al. Clinical Safety, Tolerability, Pharmacokinetics, and
  Pharmacodynamics of the Novel Factor Xa Inhibitor Edoxaban in Healthy Volunteers. J
  Clin Pharmacol. 2010;50:743-753.
2) Clinicaltrials.gov: NCT00986154. Comparative Investigation of Low Molecular
  Weight (LMW) Heparin/Edoxaban Tosylate (DU176b) Versus (LMW) Heparin/Warfarin in the
  Treatment of Symptomatic Deep-Vein Blood Clots and/or Lung Blood Clots (The Edoxaban
  Hokusai-VTE Study). Available at: http://clinicaltrials.gov/show/NCT00986154.
  [Last accessed: April 2013].
3) Clinicaltrials.gov: NCT00781391. Global Study to Assess the Safety and
  Effectiveness of Edoxaban (DU-176b) vs Standard Practice of Dosing With Warfarin in
  Patients With Atrial Fibrillation (ENGAGEAFTIMI48). Available at:
  http://clinicaltrials.gov/show/NCT00781391. [Last accessed: April 2013].
4) Laulicht, B et al. Small Molecule Antidote for Anticoagulants. Circulation.
  2012:126;A11395.
5) Perosphere Inc. Data on File.
6) Bakhru, S et al. Small Molecule Antidote for Anticoagulants. Presentation at
  the Thrombosis and Hemostasis Summit of North America, Chicago, Illinois, May 4, 2012.
  Available at http://www.perosphere.com/pdf/PER977-THSNA-Presentation_Slides.pdf.
  [Last accessed: April 2013].
7) Laulicht, B et al. Small Molecule Antidote for Anticoagulants. Presentation
  at the American Heart Association Meeting, Los Angeles, California, November 5, 2012.
  Available at: http://www.perosphere.com/pdf/PER977_AHA-presentation.pdf. [Last
  accessed: April 2013].
8) Comp, P. Selective Factor Xa Inhibition Improves Efficacy of Venous
  Thromboembolism Prophylaxis in Orthopedic Surgery. Pharmacotherapy. 2003;23(6
  ):772-787.
 

Contact:

Contact: Solomon S. Steiner, Ph.D., CEO, Perosphere Inc.,
+1-914-241-0191, s.steiner@perosphere.com. Philip N. Sussman, CFO,
Perosphere Inc., +1-212-769-0916, p.sussman@perosphere.com. Michaela
Paudler-Debus, PhD, Daiichi Sankyo Europe GmbH, +49-89-780-8685 
(office).
Daria Munsel, Daiichi Sankyo Europe, GmbH, +49-89-780-8728 (office). 

Link - 

Perosphere and Daiichi Sankyo Enter into a Clinical Trial Agreement to Evaluate the Efficacy and Safety of PER977 to Reverse the Anticoagulant…

Hämatopoetische Stammzellen: Vorstellung neuer Erkenntnisse beim 18. Kongress des Europäischen Hämatologenverbandes

Den Haag, Niederlande (ots/PRNewswire) – Hmatopoetische Stammzellen (HSZ) besitzen die Fhigkeit, ein Leben lang Blutzellen zu erneuern. Der HSZ-Pool muss in der Lage sein, den mit seiner lebenslangen Aktivitt einhergehenden zellulren Stressfaktoren standzuhalten. Die HSZ werden von besonderen Zonen im Knochenmark geschtzt, die “Nischen” genannt werden. Neue Technologien erlauben die Analyse verschiedener Kompartimente im Knochenmark und deren funktionale Auswirkungen auf HSZ. HSZ bestehen ein Leben lang; ihr Proliferations- und ihr Quieszenz- (oder Ruhe-) zustand befinden sich im Gleichgewicht. Daher wird der Zellzyklus der HSZ von Faktoren innerhalb und ausserhalb der Zelle kontrolliert.

Im Verlauf der Alterung kann sich dieses fein abgestimmte regulatorische Netzwerk verndern und zu einer abnormalen HSZ-Regulierung fhren. Die funktionale Qualitt der HSZ nimmt, zum Teil aufgrund einer Anhufung beschdigter DNA, mit dem Alter ab und fhrt zu einem vermehrten Auftreten von hmatologischen Malignomen. Die Faktoren, die die DNA der HSZ und den Schutzmechanismus innerhalb dieser Zellen beschdigen, werden allmhlich besser verstanden.

Die Erkenntnisse deuten darauf hin, dass Leukmie sich aus einer malignen Stammzelle entwickelt, die leukmische Stammzelle (LSZ) oder Krebsstammzelle (KSZ) genannt wird. Aktuelle Forschungsergebnisse legen nahe, dass humane Leukmien sich in einem schrittweisen Prozess entwickeln, dem multiple erworbene Mutationen in Zellklonen zugrunde liegen, die zur klinischen Erkrankung fhren. Neue Erkenntnisse ber die Biologie der LSZ werden uns helfen, Behandlungen mit hherer Wirksamkeit zu entwickeln.

Menschliche iPS-Zellen, induzierte pluripotente Stammzellen, die aus somatischen Zellen gewonnen werden, bieten vielversprechende Mglichkeiten fr die Zelltherapie in der regenerativen Medizin, die Stammzellenmodellierung humaner Erkrankungen und neue Methoden des Wirkstoff-Screenings. Es gibt jedoch ernsthafte Sicherheitsbedenken in Bezug auf den Einsatz von iPS-Zellen in der Zelltherapie. Aktuelle Erfolge in der Zelltherapie mit iPS-Zellen werden vorgestellt und diskutiert.

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Hämatopoetische Stammzellen: Vorstellung neuer Erkenntnisse beim 18. Kongress des Europäischen Hämatologenverbandes

How to cope with criticism at work

Management experts say criticism should never be delivered in front of others

Management experts say criticism should never be delivered in front of others

(CNN) — Criticism from bosses can be hard to swallow. But research shows there are more constructive ways for managers to deliver negative feedback, and that bosses should use positive comments a lot more — about six times more — than criticism.

The study, done by the University of Michigan Business School several years ago, compared team performance to the frequency of praise and criticism given within the teams.

The best-performing teams used about six times as many positive comments for every negative one. It found that the worst performing teams, on average, used three negative comments for every positive one.

American psychologist, John Gottman, has found a similar ratio for positive and negative comments from spouses leading to happier marriages.

“Negative interactions tend to dampen the enthusiasm and commitment of the individual,” says Jack Zenger, a leadership consultant, who was not part of the studies. “A manager should be very thoughtful and weigh the risks and benefits before giving any negative feedback.”

While positive feedback seems to be more helpful in the work setting, leadership experts say the effectiveness of both praise and criticism as motivators has a lot to do with how the message is delivered.

Read more: Are you cautious or courageous at work?

When a manager must give negative feedback to a worker, it helps not to do it abruptly, Zenger says. Managers can preface the conversation by letting the employee know that his or her contributions are appreciated, and that a specific suggestion is a way to improve effectiveness and nothing more than that.

When emotions become the dominant force and the quality of the ideas are taking a backseat, then feedback is given the wrong way
Jack Zenger, leadership consultant

“When we watch a movie, there is often background music that signals to us whether something terrible is about to happen or whether this is a happy scene in the movie. Ideally, managers need to provide a similar signal that provides an accurate context for any message,” he says.

Zenger adds that any criticism should be delivered in the utmost privacy, never in front of others.

Read more: Bullying bosses dominate their way to the top

Denmark-based Alexander Kjerulf, who studies happiness at work, said his organization conducted a survey that found lack of praise and recognition to be the No. 2 factor making people unhappy at their jobs. (The top reason was having coworkers who constantly complain.)

And even though the research shows it is unproductive to criticize more than praise, experts say it is still important to give negative feedback once in a while.

“Criticism is vitally important. We need to tell people what they do well and what they can do better,” Kjerulf says. “But many workplaces either give no feedback or only give criticism. This is a shame because we learn so much from being told what we get right.”

On the other end of the feedback spectrum, there are ways for praise to work better as a motivator.

Kjerulf says that praise, if delivered poorly, like when it seems obligatory or trivial, can have negative effects. “It makes us mistrust all future praise,” he said.

For praise to be constructive, it needs to be specific and heartfelt, Zenger says.

“A passing ‘good job’ or ‘well done’ means very little. But when a manager takes the time to tell the individual specifically what he or she had done and the consequences that it has had, then praise begins to have an extremely positive effect,” he says.

Read more: Work like a spy to be the best boss

But while praise should be delivered with conviction or an emotional connection, emotions should be taken out of the equation when giving negative feedback, Zenger says. Delivering criticism while either party is angry, for example, is usually not constructive.

“When emotions become the dominant force and the quality of the ideas are taking a backseat, then feedback is given the wrong way,” he says.

But managers should realize that feedback should go both ways: managers should seek feedback from their employees about their own behavior.

“The manager who asks, ‘what can I do to be a more effective supervisor for you’ is sending the signal that no one is expected to be perfect in that we can learn from each other,” Zenger says. “How the manager responds to the employees’ observations will serve as the example for how they respond to criticism.”

But in the case where an employee is upset about negative comments from managers, “there’s no way around it,” Kjerulf says, “you’ll have to talk to your boss. Be very specific and say what it is about the boss’ behavior you don’t like.”

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How to cope with criticism at work

Report: More women shacking up

Sarah Groom and Adam Sommer, pictured with daughter, have lived together for nearly eight years without getting married.

Sarah Groom and Adam Sommer, pictured with daughter, have lived together for nearly eight years without getting married.

(CNN) — Taylor Spearnak met her boyfriend in 2002, during her third year of college, when they were both congressional interns in Washington.

A friend set them up, and they laughed for hours over cheap burgers and a terrible action movie. They kept the relationship going when they returned to their schools in Boston, and when they studied law at schools in different states.

In 2007, when they reunited in New York City, they decided it made sense for them to move in together, Spearnak said. They lived in one of the most expensive cities in the country, and had law school loans to pay off. They’d be busy as new law firm associates, and knew they’d be spending nights at each other’s apartments, anyway. Spearnak’s parents trusted them, and thought it was a smart decision.

“We knew we were serious, but not ready for marriage. This was the next step for us,” the 30-year-old lawyer said. “We wanted to be able to spend as much time together as possible.”

As the stigma of “living in sin” fades and more people delay marriage, researchers are finding that living together before marriage can be a stabilizing force in relationships. It is often leading to marriage and children, demographer Casey Copen said.

Between 2006 and 2010, 48% of women between the ages of 15 and 44 moved in for the first time with a man to whom they weren’t married, according to a report released Thursday by the Centers for Disease Control and Prevention’s National Center for Health Statistics. In 2002, it was 43%. In 1995, it was 34%.

That’s 1 in 4 women living with a man by age 20 and almost 3 in 4 by 30, according to the report, “First Premarital Cohabitation in the United States,” which studied male-female relationships.

“Generations that were cohabitating less are now being replaced by a group of women and men that find cohabitation to be quite normal,” said Copen, the study’s lead author. “Overall, these unions are lasting longer, they’re more stable and the highest proportion of them transition to marriage.”

The increase doesn’t surprise psychotherapist Lisa Kift, who counsels married and unmarried couples in her San Francisco, California, practice. Just as social mores are changing what families look like, long-term partnering is changing, too, she said.

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The study, which is based on 12,279 interviews from 2006 to 2010, found a shrinking percentage of women moving in with a man for the first time because of marriage — 23% in 2012, down from 30% in 2002 and 39% in 1995.

“Long-term commitments are more broadly defined and for many, can mean cohabitation without a legal document or public declaration,” she said. “Many couples believe they are doing their due diligence by having the experience of living together before making a commitment to marry.”

But do these unions last? And do they lead to marriage?

The study found that 40% of women living with significant others for the first time between 2006 and 2010 transitioned to marriage within three years, while 32% of those relationships remained the same and 27% dissolved.

The numbers are growing across racial and ethnic groups, except for Asian women, the study said. Demographers use the information to explore how cultural and economic differences can change the experience, Copen said. Forty-four percent of white women married within three years of living together the first time, while 31% of black women and U.S.-born Hispanic women did so.

Fifty-three percent of women with a bachelor’s degree or higher had transitioned to marriage by the three-year mark, while 30% of women with less than a high school diploma had married by then.

Spearnak and her boyfriend intend to marry one day. But, they’ve been together so long that it sometimes feels like they’re already married, she said. Her parents want them to marry, she said, but by being committed and comfortable, they’ve pushed back against pressure. What’s the rush?

“Neither of us feels a need to put a ring on it,” she said. “We know we are solid. We survived the bar (exam), assembling IKEA furniture and moving.”

Cohabitation leads to childbearing with greater frequency, the study found. Nearly 20% of women became pregnant within a year of moving in with someone for the first time, up from 18% in 2002 and 15% in 1995. The chances of becoming pregnant were higher among women younger than 20, foreign-born Hispanic women and women with less than a high school diploma.

Montclair, New Jersey, resident Sarah Groom lives with her boyfriend of nearly nine years, and recently gave birth to a baby girl. They met at a fraternity house in Boulder, Colorado, in 2003 and developed an relationship a year later. It was a passionate, impulsive decision when they moved in together in 2005, but stressful, too, she said. They broke up, moved out, argued over who got the dog and reunited more than once.

They live together now, and she wants to get married, but it hasn’t happened. Along the way, there was “stress, chaos, self-doubt and even resentment,” but it seems to have worked out, she said.

But, her experiences have taught her the importance of foresight, she said.

“I have a beautiful baby girl now, so it is hard to say I regret my choice,” Groom said.

“I would advise people choosing to cohabitate prior to marriage, to not make the decision lightly and to discuss potential issues that may arise and how they would be handled well in advance.”

There are still benefits to getting married, she said.

“One works harder to preserve a relationship,” she said. “Its whole nature is less disposable.”

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Report: More women shacking up

9 tips for founders who want to hone their design chops

design 520x245 9 tips for founders who want to hone their design chops

In an increasingly crowded startup world, stunning visual design is often just as important as a killer user experience. In many cases, especially for Web startups, the two go hand in hand. But a startup founder is not necessarily a graphic designer, and entrepreneurs don’t always speak the same language as their design teams (or vice versa).

How do you go about bridging that gap, especially when you’re under pressure to bring an appealing new product to market quickly? I asked a panel of nine successful young entrepreneurs the following question:

What’s your best tip for honing what seems to be an increasingly important startup “skill” — your design chops?

Here are some of their best recommendations for the design-impaired among us:

1. Figure out your approach
Amanda Aitken 9 tips for founders who want to hone their design chops

If you’re a design person, you probably already know it. To hone your skills, start reading design blogs and visiting sites that showcase good design, such as D-lists. If you’re not a design person, however, you may need to approach this more like a science project. Try learning the basic principles of design (balance, scale, etc.), and apply them to your projects in a rigorous way.
- Amanda Aitken, The Girl’s Guide to Web Design

2. Sketch

Wade Foster 9 tips for founders who want to hone their design chopsSketching has been a great addition to my daily routine. I love to mock out an interface, show it to a few customers and see if they “get” it. It’s an easy way to make sure you’re stretching your design muscles.
- Wade Foster, Zapier

3. Read “Design for Hackers”

Nathalie Lussier 9 tips for founders who want to hone their design chops“Design for Hackers” by David Kadavy is a great primer on design, and it’s written for more left-brain thinkers, like programmers. Kadavy goes over the basics of design, and he also helps you develop your own eye for what works and what doesn’t. It’s not a book you’ll finish in one sitting, but it will make you a better designer.
- Nathalie Lussier, The Website Checkup Tool

4. Don’t hone it — delegate it

Liam Martin 9 tips for founders who want to hone their design chopsI’m not a designer. I can ramble on to designers for hours about what I want but there is no way I can reproduce it from a technical standpoint or from a theoretical standpoint. That’s why you need to either hire an experienced designer or you need to pay through the nose for a great one that can not only design your project, but take care of the user experience as well.
- Liam Martin, Staff.com

5. Use Adobe Illustrator and Lynda.com

Brian Moran 9 tips for founders who want to hone their design chopsGet Adobe Illustrator and a one-month subscription to Lynda.com, which provides great training. The best way to get better is to get your hands dirty. From basic trial and error, I’ve been able to design our sales material, website, Facebook page and more.
- Brian Moran, Get 10,000 Fans

6. Learn the lingo

doreen bloch 9 tips for founders who want to hone their design chopsIt’s hard to improve design skills without having an appreciation for, and grasp of, the language of design. Get to know your way around a wireframe and sitemap. Learn the difference between “global” and “tertiary” navigation bars. Know when it’s best to use vector-based graphics. Having knowledge of the jargon of design will help you improve your skills and communicate better with designers.
- Doreen Bloch, Poshly Inc.

7. Read design blogs

John Hall 9 tips for founders who want to hone their design chopsIt’s amazing how much you can learn by simply looking at the designs of, and reading content from, thought leaders within the industry. It’s one thing to know that you don’t like a design. It’s another skill to be able to communicate why this font doesn’t work or why the blue should be darker. If you want to work with good designers, you must learn to communicate your design goals and objections.
- John Hall, Digital Talent Agents

8. Study, then step back and direct

 9 tips for founders who want to hone their design chopsEvery startup needs a good designer and startup founders shouldn’t expect themselves to fulfill this role. However, you should learn to be a good art director. Study design like you would study any subject — research, be a slave to detail in your examination of other successful sites, and learn to express your ideas and communicate them well to your own designer.
- Brendan Mangus, Habidy

9. Value design and creativity

Adam DeGraide 9 tips for founders who want to hone their design chopsAt the end of the day, you have to value design and creativity. If you don’t value those two things, you won’t see a need to develop the skills. And just because you don’t see a value doesn’t mean you don’t need to do it!
- Adam DeGraide, Astonish

Image credit: Thinkstock

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9 tips for founders who want to hone their design chops

Adults Text While Driving More Than Teens, Says Survey

It’s often been assumed that teens are one of the main culprits in the texting-while-driving epidemic in the U.S. It makes sense — teens are new drivers, and thus more reckless, and they also happen to be expert texters. However, a new study funded by AT&T finds that adults actually text while driving more than kids. The study was taken from a pool of 1,011 consumers. According to the survey, nearly half of all adults text while driving, whereas slightly fewer (43 percent) of teens admit to texting while driving.

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Adults Text While Driving More Than Teens, Says Survey

Child suicide bombers find safe haven

Mia Bloom and John Horgan at Sabaoon which helps children taken in by the Pakistan Taliban to become suicide bombers.

Mia Bloom and John Horgan at Sabaoon which helps children taken in by the Pakistan Taliban to become suicide bombers.

Editor’s note: Dr. John Horgan is a psychologist at Penn State where he is director of the International Center for the Study of Terrorism. His latest book is ‘Divided We Stand: The Strategy and Psychology of Ireland’s Dissident Terrorists’ by Oxford University Press.

Swat, Pakistan (CNN) — Just over one week ago, Pakistani authorities paraded 11 children accused of terrorism in front of the local media. The boys, aged 10 to 16, were apprehended while attempting to plant home-made explosives on behalf of local militant groups operating in and around the city of Quetta, in Balochistan.

The boys’ arrest highlights Pakistan’s worsening civil strife and underscores how Pakistani terrorist groups continue to exploit children.

This is not a recent phenomenon. In fact, terrorist groups in Afghanistan and Pakistan are increasingly turning to children as operatives.

A few weeks ago, my colleague Mia Bloom and I traveled to Pakistan’s Swat Valley to see firsthand how the Pakistani government is working to solve this problem.

Swat District includes the city of Mingora, part of Khyber-Pakhtunkhwa province which borders Afghanistan.

This is the region where 14-year old Malala Yousafzai — an activist for girls’ education — narrowly survived a Taliban assassination attempt last year.

Renowned for its picturesque vistas, the Swat region fell victim to a brutal reign of terror by the Pakistani Taliban, or TTP in 2008. Faced with an emboldened TTP, Pakistan’s national army launched an 18-month counterinsurgency campaign. Law and order were restored and the Taliban forced to retreat.

An emerging success story — and the reason for our visit to Swat — is the establishment of “Sabaoon.” From the Urdu meaning “the first ray of light from the dawn”, Sabaoon is Pakistan’s rehabilitation facility for child militants who were formerly recruited by the TTP.

Some of these children were even prepared to become suicide bombers.

Sabaoon’s team of psychologists, social workers and military advisers share a principal objective — to prevent recidivism and ensure that its ‘graduates’ don’t return to the fight.

Sabaoon joins a growing list of similar initiatives that have cropped up around the globe since the mid-2000s. Perhaps the best-known terrorist rehabilitation program is in Saudi Arabia.

Read how a cagefighter in England de-radicalizes convicted terrorists

Collectively characterized as “de-radicalization” programs, it is more accurate to call them “risk reduction” initiatives. They represent a change in the way counterterrorism campaigns are waged, and share the goal of reducing the risk of re-engagement in terrorism once the program’s graduates are allowed to return to their communities.

So far, Sabaoon has had 188 ‘students’ fully participate in its program of risk assessment and rehabilitation.

All of the boys were captured by the army or police in raids on Pakistani Taliban training camps. The boys spend anywhere from six months to two years at Sabaoon. A few have spent as long as three years in rehabilitation.

In Pakistan, the TTP showed no hesitation in their use of children for terrorism. In fact, “recruitment” is hardly the right word. It became clear from our conversations at Sabaoon that these children had little if any say in their induction.

The younger children lacked the capability to refuse the terrorists, fearing their own safety or reprisals to their families. One mother explained to me that she had turned to the Taliban when she could no longer cope with her son’s alcohol and drug abuse — marijuana grows wild throughout Swat.

Targeting children at risk like this provided the Taliban with a perfect opportunity to reach out to parents with an offer to help “save” their children. The militants promised a future involving discipline, belonging, purpose, and meaningful work.

In some cases, families faced a horrible choice — pay an enormous financial tax (double the annual wage) or surrender a child to the movement.

Deception and manipulation have come to define the TTP’s child induction practices such that the prevention of children’s involvement in violent extremism in Pakistan can hardly be characterized as counterinsurgency.

It is instead a challenge of basic child protection.

Most of the children recalled overwhelmingly negative experiences at the training camps. After performing menial tasks, they were locked in a 4×5 meter room for the rest of the day. Some reported being repeatedly beaten, and in a few cases, sexually assaulted by senior figures.

One child with whom we spent some time graduated from such deplorable conditions only to be ‘allowed’ to become a martyr, changing his mind literally at the last second. That boy is now one of Sabaoon’s brightest hopes for successful rehabilitation and reintegration, and a potential role model for younger children at Sabaoon. But he remains profoundly traumatized by his experiences.

Other children actually reported having had positive experiences with the TTP. Some became involved through family members already in the movement. For them, adventure, camaraderie, and a sense of purpose proved all too real. Terrorism was the family business, and even if the children didn’t want to get involved, how could they refuse?

Nobody knows exactly how old some of the children are. Many don’t have birth certificates and don’t know their own age themselves.

Abdul (not his real name) is now about 17-18 years old. He is very soft-spoken and painfully shy, but spoke English very well. He has big brown eyes and a wonderful, broad smile. He was very thin, but so shy he wouldn’t take the food offered to him at lunch.

We were very sensitive to the trauma he had experienced at the hands of the terrorists. The staff briefed us about the abuse he endured. In our limited time with Abdul, we were careful not to ask him anything that might upset him so we focused only on speaking about his future, and how he has adapted to life after Sabaoon.

Abdul is a great success story. One of the first graduates of the program, he excelled academically at Sabaoon. Shortly after his repatriation to his home village, he won a scholarship to university. He chose to defer his admission to take care of his mother and younger brother.

He occasionally comes back to Sabaoon to visit the staff and also to talk to the younger students about how the program has changed his life.

He is one of Sabaoon’s role models.

Although addressing the children’s needs and reducing the risk of re-engagement in terrorism are Sabaoon’s most pressing objectives, its staff are not unaware of the seemingly insurmountable obstacles that face the children when the leave the program.

For Sabaoon, so far it appears that recidivism is not the problem, though with any such program, we may have to wait a bit longer to see if someone returns to the fight. No terrorism risk-reduction program has a 100% success rate, or even close to that. When such claims are made, it doesn’t take long to realize that there are significant questions surrounding definitions and measurement of “success” or “re-engagement.”

Such questions need to be answered if programs like these are to be supported as creative approaches to counterterrorism. Knowing why they work is as important as knowing if they work. A few high profile instances of recidivism may spell the death-knell for such initiatives.

As academic researchers who study violent extremism, we have a great deal of hope for such programs, and Sabaoon in particular has been the shining ray its name implies. Battling immense odds, Sabaoon’s staff remain infectiously optimistic and dedicated, and that’s one of the reasons we will return later this year.

But time is not on their side.

A few years ago, research conducted by Dr. Mia Bloom highlighted the changing nature of women’s involvement in terrorism. Today a similar argument could be made for the involvement of young children. Both in Pakistan and Afghanistan, the child suicide bomber has come to represent a routine terrorist profile.

Children are easier to manipulate, and like female operatives, they can penetrate security checkpoints without raising the normal levels of suspicions. A 2012 report from Afghanistan suggested that almost 100 would-be child suicide bombers had been ‘intercepted’ in the preceding 12-month period. Many of those boys were recruited in Quetta.

What the rising tide of child militants means for the development of counter-terrorism initiatives, or even child protection, is unclear.

Sabaoon alone will certainly not solve this problem, but it, and programs like it must continue to develop if we are to truly prevent the next generation of militants.

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Child suicide bombers find safe haven

Yelp releases a free new revenue estimation tool for local businesses available starting today

130444745 520x245 Yelp releases a free new revenue estimation tool for local businesses available starting today

Yelp announced today the launch of a new revenue estimation tool for local businesses. With this tool, any shop owner can determine just how much of their business coming from Yelp compares to the national averages based on a Boston Consulting Group Study released last week. Available for free, Yelp says all businesses will be able to access the tool beginning today.

In a post announcing the news, Matt Halprin, Yelp’s Vice President of Revenue & Analytics, says that the revenue estimation tool will be beneficial to all business owners for two reasons:

  • It will help to quantify the revenue opportunities Yelp believes it is sending to each business
  • It will establish a revenue baseline for prospective advertisers, which can be used to help evaluate the impact of their investment in Yelp Ads

So how does this service handle the calculations to determine how a particular business stacks up against the national average? According to Yelp, it will multiply customer leads sent by the service each month by the business’s average revenue per customer lead. It will also include the average spend per customer for each business category, as a matter of reference and based on the BCG study.

Yelp currently has 39,800 active business accounts, which is a 68 percent growth from 2011, according to its Q4 2012 financial earnings. At the end of last year, the company said that it had more than 36 million reviews in its system. At the time, Yelp’s CEO Jeremy Stoppelman said that he believed 2013 would be a “tipping point for our brand in Europe as Yelp continues to become a trusted local resource.” He also said that not only would mobile be a top priority, but Yelp would continue to focus on the business owners, “creating more ways to measure the value of Yelp leads.”

The revenue estimation tool appears to be just the latest innovation Yelp has for the business owner. With thousands of businesses utilizing Yelp, some might be thinking about how exactly it’s beneficial for them. At some point, they might even wonder how they would know if being on Yelp actually produced a sale — this new tool will hopefully answer that question and make the business owner feel comfortable with using the service.

6a00d83452b44469e2017d424a5617970c 730x519 Yelp releases a free new revenue estimation tool for local businesses available starting today

Photo credit: Spencer Platt/Getty Images

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Yelp releases a free new revenue estimation tool for local businesses available starting today