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Giada Bianchi , Paul G. Richardson and Kenneth C. Anderson
Blood 2015 126:300-310; doi: https://doi.org/10.1182/blood-2015-03-575365
Giada Bianchi
LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
Paul G. Richardson
LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
Kenneth C. Anderson
LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

Introduction

Progress in medical research has enhanced our understanding of tumor biology, delineated genetic and molecular mechanisms of tumor growth and survival, and defined the impact of the microenvironment in cancer pathogenesis. As a consequence of these advances, cancers deemed rapidly fatal only a few decades ago can now be treated effectively, with prolonged survival in an increasing proportion of patients. This is particularly true for multiple myeloma (MM), in which the introduction of drugs targeting the tumor in its microenvironment, such as the proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, into initial, consolidation, maintenance, and salvage therapies has markedly improved patient outcome. In this perspective, we discuss the most promising therapies to even further improve MM treatment, with a focus on drugs inhibiting the ubiquitin-proteasome pathway; histone deacetylase (HDAC) inhibitors (HDACIs); immune therapies including IMiDs, monoclonal antibodies (mAbs), immune checkpoint inhibitors, agents targeting accessory plasmacytoid dendritic cells (pDCs), vaccines, and chimeric antigen receptor–engineered T (CAR-T) cells; drugs targeting tumor cell homing to, and exploiting hypoxia in, the bone marrow (BM) microenvironment; molecularly targeted therapies against kinesin spindle protein (KSP), v-akt murine thymoma viral oncogene homolog 1 (AKT), exportin 1 (XPO1), cyclin-dependent kinases (CDKs), bromodomain and extraterminal (BET) bromodomain 4, and serine/threonine kinase 4 (STK4); as well as delineating the impact of genomics on MM therapy. These advances in understanding the biology of MM will allow for earlier treatment of patients using rationally informed combination therapies with curative potential.

Melphalan plus prednisone treatment of MM was introduced in the 1960s and achieved median survival of 2 to 3 years. Valentino Garavani Womens Rockstud PVC Slide Sandals low shipping fee online pjAoz8
High-dose IV melphalan followed by autologous hematopoietic stem cell transplant (ASCT) was pioneered in the 1970s, with the first randomized trial of high-dose chemotherapy followed by ASCT vs conventional chemotherapy showing a 5-year overall survival (OS) rate of 52% vs 12%, respectively, in the 1990s. 2 Remarkably, over the last decade, the introduction of novel agents targeting MM in the context of the BM microenvironment has transformed the MM treatment paradigm and markedly improved patient outcome. UNDERGROUND Sneakers from china sale online FzaLYSB
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In this perspective, we focus on the targeted therapies that, in our view, hold the greatest potential to even further improve on this progress ( Table 1 outlines investigational agents in advanced clinical development).

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Essential Guide

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This article is part of our Essential Guide: Advanced data visualization guide: How visualizing data can boost BI
Nick Millman and William Gatehouse

Big data holds out big promises to drive deeper analysis and valuable insights from significantly increased repositories of information.

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and clearly show the insight.

Despite not looking as appealing as the gaudily dressed artificial intelligence and machine learning, big data is still delivering beyond the hype on many projects. We look at how Mercedes are using it on their quest for Formula 1 glory, how London councils are using data science to combat housing fraud and how the Met Office is handling its deluge of data.

That is where data visualisation tools come in. These typically offer: The ability to rapidly incorporate new data sets; removal of restrictive metadata layers; a business, as opposed to a technical, tool (ie. intuitive with minimal coding required); and high performance.

These characteristics have challenged the more traditional visualisation tools provided by the larger suppliers. As a result, over the past four to five years, niche players have started to gain market share. Their success has arisen from the ability they offer the business to show powerful insight in a matter of weeks.

As a result of their flexibility, these tools are also now taking a lead in providing a direct integration with big data platforms , such as Hadoop and Cassandra. However, we now see the established suppliers starting to move to address this gap in the stack with new products coming to market, and expect to see some consolidation of the supplier landscape over the next year or two.

High performance is a particular challenge in big data landscapes. The nature of big data volumes and the query speed where tools integrate through means that to query directly against the data will inhibit the dynamic capability of the tool.

The key use case for these tools is rapid discovery rather than the creation of standard reports. This means that the data required is transient in nature – required to support a hypothesis and then discarded. The leading practice approach to achieve high performance is to create specific data sets – through map-reduce jobs, for example – and capture these in the memory of the visualisation tools.

At the height of the blaze, about 3,500 homes and businesses at and around the site of the wildfire were without power, according to San Diego Gas Electric. Some of those addresses are served by a circuit that the utility decided to deactivate as a precaution, and the rest lost service due to fire- related equipment damage, SDGE spokesman Wes Jones said.

Devastation: Driving on Alpine Blvd. just west of Via La Mancha. Homes, land scorched. crews working non-stop on

Photo shows pickup truck and structuresgutted by the West Firein Alpine. (July 7, 2018)

Photo shows cars and structures destroyedby the West Firein Alpine. (July 7, 2018)

Photo shows structures destroyedby the West Firein Alpine. (July 7, 2018)

UPDATES: Friday, July 6, 2018

5:15 p.m . - The County of San Diego Department of Environmental Health (DEH) has issued a Boil Water Advisory and Public Notification effective immediately for the Alpine Oaks Estates located at Gabriela Hearst Tito leather ankle boots 2015 cheap online very cheap cheap online reliable online EIEkwkv
. The water system serves 66 mobile home park spaces, a club house, laundry room, and the swimming pool. As a precaution, a Boil Water Advisory has been issued due to fire damage to the water system. The Boil Water Advisory will remain in effect until water is restored and laboratory analytical results confirm the absence of bacteria in the water supply. For more information on the Boil Water Advisory, please contact Jerry Jacobson, Owner of the Alpine Oaks Estates at (619) 445-3081. More »

5:15 p.m

Boil Water Advisory issued for Alpine Oaks Estates

4:38 p.m. - No official word on the number of homes lost in the West Fire, 400 acres burned, 5% contained. An Alpine Firefighter was injured fighting the fire. He suffered slight burns to the side of his face. He remains hospitalized but will be released tomorrow.

4:38 p.m.

4:00 p.m.

HAPPENING NOW: Three alpacas evacuated and seeking shelter at grounds

Freeway is open but there’s a major traffic jam on the 8E just before Alpine because of the fire....avoid the area

2:34 PM - SDGE is reporting 3,000 people are without power due to outages related to the West Fire in Alpine.

2:34 PM

If you need assistance with large animal evacuations, contact Department of Animal Services at (619) 498-2361

Lakeside Rodeo located at 12584 Mapleview Street is now accepting livestock.

1:44 PM - Update: Two lanes closed on eastbound I-8 at West Victoria overpass east of Tavern Rd. due to #WestFire QuickMap road updates: quickmap.dot.ca.gov

1:44 PM

Update: The I-8 eastbound and westbound off-ramps to Tavern Road are closed due to the QuickMap road updates:

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