Pediatric leukemia ‘super drug’ could be developed in the coming years


Northwestern Medicine scientists have discovered two successful therapies that slowed the progression of pediatric leukemia in mice, according to three studies published over the last two years in the journal Cell, and the final paper published Dec. 20 in Genes & Development. When a key protein responsible for leukemia, MLL, is stabilized, it slows the progression of the leukemia, the most recent study found. The next step will be to combine the treatments from the past two years of research into a pediatric leukemia “super drug” to test on humans in a clinical trial.

The survival rate is only 30 percent for children diagnosed with MLL-translocation leukemia, a cancer that affects the blood and bone marrow. Patients with leukemia have a very low percentage of red blood cells, making them anemic, and have approximately 80 times more white blood cells than people without cancer.

“These white blood cells infiltrate many of the tissues and organs of the affected individuals and is a major cause of death in leukemia patients,” said senior author Ali Shilatifard, the Robert Francis Furchgott Professor of Biochemistry and Molecular Genetics and Pediatrics, the chairman of biochemistry and molecular genetics and the director of Northwestern’s Simpson Querrey Center for Epigenetics. “This is a monster cancer that we’ve been dealing with for many years in children.”

There are several types of leukemia. This research focused on the two most common found in infants through teenagers: acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL).

For the past 25 years, Shilatifard’s laboratory has been studying the molecular function of MLL within its complex known as COMPASS (Complex Proteins Associated with Set1). Most recently, it was demonstrated that COMPASS components are one of the most frequently identified mutations in cancer. The next step of this work will be to bring the drug to a clinical trial setting, which Shilatifard said he hopes will happen in the next three to five years.

“I’ve been working on this translocation for more than two decades, and we’re finally at the point where in five to 10 years, we can get a drug in kids that can be effective,” Shilatifard said. “If we can bring that survival rate up to 85 percent, that’s a major accomplishment.”

Earlier work from Shilatifard’s laboratory published in Cell in 2018 identified compounds that could slow cancer growth by interrupting a gene transcription process known as “Super Elongation Complex” (SEC). It was the first compound in its class to do this.

This MLL stabilization process discovered in the most recent paper could potentially work in cancers with solid tumors, such as breast or prostate cancer, said first author Zibo Zhao, a postdoctoral research fellow in Shilatifard’s lab.

“This opens up a new therapeutic approach not only for leukemia, which is so important for the many children who are diagnosed with this terrible cancer, but also for other types of cancers that plague the population,” Zhao said.

“The publication of these four papers and the possibility of a future human clinical trial could not have happened if it weren’t for the cross-disciplinary collaboration at Northwestern,” Shilatifard said.

Zhao Z, Wang L, Volk AG, Birch NW, Stoltz KL, Bartom ET, Marshall SA, Rendleman EJ, Nestler CM, Shilati J, Schiltz GE, Crispino JD, Shilatifard A.

Regulation of MLL/COMPASS stability through its proteolytic cleavage by taspase1 as a possible approach for clinical therapy of leukemia.

Genes Dev. 2018 Dec 20. doi: 10.1101/gad.319830.118.

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Former S T Industries VP Friesen Passes Away 2018 12 24

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FDA approves first treatment for rare blood disease

FDA approves first treatment for rare blood disease


FDAThe U.S. Food and Drug Administration today approved Elzonris (tagraxofusp-erzs) infusion for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients, two years of age and older.

“Prior to today’s approval, there had been no FDA approved therapies for BPDCN. The standard of care has been intensive chemotherapy followed by bone marrow transplantation. Many patients with BPDCN are unable to tolerate this intensive therapy, so there is an urgent need for alternative treatment options,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

BPDCN is an aggressive and rare disease of the bone marrow and blood that can affect multiple organs, including the lymph nodes and the skin. It often presents as leukemia or evolves into acute leukemia. The disease is more common in men than women and in patients 60 years and older.

The efficacy of Elzonris was studied in two cohorts of patients in a single-arm clinical trial. The first trial cohort enrolled 13 patients with untreated BPDCN, and seven patients (54%) achieved complete remission (CR) or CR with a skin abnormality not indicative of active disease (CRc). The second cohort included 15 patients with relapsed or refractory BPDCN. One patient achieved CR and one patient achieved CRc.

Common side effects reported by patients in clinical trials were capillary leak syndrome (fluid and proteins leaking out of tiny blood vessels into surrounding tissues), nausea, fatigue, swelling of legs and hands (peripheral edema), fever (pyrexia), chills and weight increase. Most common laboratory abnormalities were decreases in lymphocytes, albumin, platelets, hemoglobin and calcium, and increases in glucose and liver enzymes (ALT and AST). Health care providers are advised to monitor liver enzyme levels and for signs of intolerance to the infusion. Women who are pregnant or breastfeeding should not take Elzonris because it may cause harm to a developing fetus or newborn baby.

The labeling for Elzonris contains a Boxed Warning to alert health care professionals and patients about the increased risk of capillary leak syndrome which may be life-threatening or fatal to patients in treatment.

The FDA granted this application Breakthrough Therapy and Priority Review designation. Elzonris also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted the approval of Elzonris to Stemline Therapeutics.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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Custom Software for Energy and Utilities

Custom Software for Energy and Utilities


Software is great until it isn’t. How many times have you found the perfect software solution that looks like it will solve 100% of your needs? And then you realize it only solves 70%.

You then try to justify how you can do without the last 30% for now, and maybe cover the gap with a manual process — all while waiting for the software provider to “add that capability to the roadmap.”

The truth is, most packaged software solutions will never perfectly match your unique business processes because pre-built software applications cater to the lowest common denominator of the problem they solve. Specialty solutions will only get you part of the way there. And when it comes to your unique way of doing business, you ultimately find yourself having to fit your processes to the software, and not the other way around. So how do you make software work for you?

At Trackvia, we hear this story all the time. Our energy and utilities customers tell us about their issues with massive, inflexible ERP (Enterprise Resource Planning) systems, or point solutions that are overly simplistic. In every case, the business has implemented a 70% solution that doesn’t map to their company’s unique business processes.

As the 90/90 rule humorously states, the last 10% of the code takes 90% of the work. Luckily that’s where a low-code platform like TrackVia really shines.

We recently worked with KS Industries (KSI), a single-source service provider in the energy sector, which was struggling with tracking their work in the field. Data collection was slow and inconsistent, leading to mistakes in work and errors in reporting. They were spending upwards of seven hours every week managing data in Microsoft Excel. KSI’s ERP solution lacked a true mobile capability, and way too much time was spent re-entering data to keep it up to date. KSI evaluated several pre-built software solutions, but none offered both the flexibility they needed and an easy way to integrate with the ERP.

To stop the drain of time and money, managers realized they needed to do three things:

  • Improve the accuracy and consistency of data collected in the field
  • Reduce the amount of time needed to get data into the ERP system
  • Keep the ERP system up-to-date with current, accurate, consistent information

How did KSI solve these problems and make software work for them? They built a custom application that addressed all of the above and supported their unique business processes within a matter of weeks.

How did they do that so quickly and easily? With TrackVia’s low-code application platform, building a TrackVia app involves no programming and no coding of any kind. To create its TrackVia app, KSI simply started by importing their existing spreadsheets, then built the rest of their workflows and reports using our drag and drop tools.

The best part: The app KSI built followed almost the exact same process as their manual one (just automated), letting them avoid massive change management efforts to roll the app out to the field. The team already knew the workflow. And, because using the app is so easy, the field service professionals quickly adopted it and use it more than any previous tool. The result? Vast improvements in the consistency and accuracy of data communicated and collected in the field. To learn more about how KSI uses TrackVia, read KS Industries Boosts Margins and Improves Safety.

Utilities Software

Because data in TrackVia is available in real time, managers can quickly capture information and keep tighter tabs on what is happening. For example, they can get notifications and alerts when conditions change or things aren’t right. Just as important, TrackVia helps management keep the ERP up-to-date with the data from the field, giving them visibility all the way to the front lines of the business.

ERP systems are great at managing resources, but as anyone in energy and utilities industries can tell you, these solutions can’t come close to solving all the problems that can arise with delivering quality field services, managing assets and equipment, and meeting safety and compliance requirements.
In this and many other stories, TrackVia integrates with and extends legacy systems. Because TrackVia is a complementary solution, there is never any need to rip and replace large systems. Unless of course your current solution is MS Excel – but that’s another story.

We’d like to hear from you. What solution gaps are you experiencing with your current ERP or other systems and how are you managing them?

For more information on how TrackVia can help your organization, read Business Applications for Your Operations at the Speed of Now.


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Constructing the Case for Digitization

Constructing the Case for Digitization


I recently had the opportunity to attend the Advancing Construction Technology conference in Chicago. While I’m not an expert, I’ve been learning a thing or two lately about the construction industry so I was excited to see all the new, innovative technologies on display. In preparation for the show, I set some goals for my time at the conference.

My first goal — understand more about the challenges the construction industry is facing when it comes to digitization. At a roundtable discussion, I spoke with several attendees about the challenge of maintaining internet connectivity on the job site. This basic detail prevented companies from going digital in the field. It was great to share that TrackVia had thought of this by incorporating offline mobile capability into its platform.

Additional digitization challenges at the forefront were end-user adoption, building a business case, and measuring the ROI. With the margins so thin in the construction industry, they needed to show digitization could drive top and bottom line results. This was case with our customer KS Industries, which significantly improved their margins by automating field operations.

My second goal — share customer stories with attendees about how gaining speed, control, and visibility can improve their operations. To showcase this, TrackVia solutions architect Brandon Gill shared how our customer, Cascade.Build, grew its business 520% over the last 5 years by automating several processes with TrackVia. This story really lit up the crowd with new ideas about creating a data ecosystem instead of relying on a variety of different point solutions, and the power that comes from un-siloing your data.

Constructing Technology

With respect to point solutions, there seem to be so many software choices out there for construction — construction management, project management, time tracking, incident management, and daily site notes to name just a few. Honestly, I don’t know if TrackVia is right for your business, but I do know that point solutions may only accomplish 70% of what is needed in your business.

This was the issue our customer RP Construction Services (RPCS) ran into with point solutions — none of them did exactly what they needed, there were either too many features or not enough functionality, and would require extensive integrations to connect all these tools together. That’s why RPCS selected the TrackVia platform — one platform that could be customized according to its unique workflows, multiple use cases, and requirements.

During the conference, many people also mentioned that their legacy systems were getting in the way of going digital, particularly silo-ing data and inability to go mobile in the field. That’s why TrackVia looks to extend that legacy system and un-silo that data.

I’m curious to hear about the challenges you might be facing with digitizing your firm and how you might be overcoming them?


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Artificial intelligence and machine learning in information management

Artificial intelligence and machine learning in information management


Information management has changed from pure document management and archiving into a real business enabler. Today’s intelligent information management solutions offer ways to automate the time-consuming and often boring document-driven processes within a business.

One of the key drivers in this automation is the use of artificial intelligence and machine learning. AI and machine learning have the ability to reason and discover meaning as well as learn from past experience. Moreover, artificial intelligence systems can easily churn through lots of information to recognize patterns and categories in the data. That ability is put to work to enable new ways to search, find, use and manage information, and add automated workflows to document management processes.

But, artificial intelligence and machine learning mean very different things to different organizations and people. To us, they mean something that really drives the development of the industry but is at the same time very simple and easy for the end users to use and benefit from. Our objective is to allow customers to intelligently find and manage the critical data they need to make smart decisions.

Jayson deVries, our artificial intelligence expert in the Product Management team, lists three major, emerging themes related to AI and machine learning:

Artificial intelligence should not be complicated for the user

We believe in providing intelligence services out of the box, so that you or anyone in your organization do not need to be a data scientist to use it in your business.

The thing that differentiates M-Files AI from others is the usage of machine learning behind the scenes. The users do not need to change how they do things or take extra steps to train the system.  Just by observing what the users are doing, M-Files AI will then begin to assist them automatically and will continue to improve the more it is used. We have worked hard to provide a tool with this self-learning capability, so that even an SME can benefit from AI without needing to hire expensive data analysis expertise.

Some products offer fantastic, powerful AI capabilities, but they require a deep understanding on how to carefully train, test, tune …and repeat.  If you attempt to implement this without the correct skills, it can turn into an expensive endeavor that doesn’t end well, with the product taking the blame.  Then there are products that offer out-of-the-box by delivering pre-trained “canned” AI.  These do have merit but must only be used in their intended contexts – a fact that, if overlooked or misunderstood, will cause disappointing results.

AI needs to be tested with your data

There has been a recent onslaught of “intelligent” products and services on the market, however some of these are not really that intelligent at all. It is important for customers to be able to see what’s behind the scenes and ideally understand how well an AI solution really works with their own data, not just demo data.

To be able to execute testing with real data before the decision to buy, the AI solution needs to be easy enough to implement. If it takes too much effort to get the artificial intelligence to work, it can be totally impossible to try it out with real data.

On the surface, an AI feature can sometimes appear rather mundane or obvious to a user.  All the clever algorithms and mechanisms are invisible to them and they just see something happen automatically.

Jayson explains:  “I’ve recently been using the classic duck analogy: ducks are swimming around calmly, but a lot of impressive work is happening below the surface to make sure the duck gets to where it needs to go.  Extending that analogy further, some vendors are now selling ‘rubber duckies’. They look and quack like a duck – if you squeeze them just right – but they’re actually hollow with nothing below the surface.”

Cloud leads the way, but on-premises AI is an opportunity

Cloud services and SaaS have been around for some time now, but certain customers and industries have not yet embraced them fully. As long as AI services are only available in the cloud, there can be significant dollars left on the table. So, even though it might look like a bit of an old-fashioned way, there is a real opportunity for premium, fully on-premises AI backend solutions.

A related, emerging technology is so called Edge AI where AI is executed directly on the device so that the data never even leaves.

We at M-Files have taken a cloud-first approach but are also working toward offering many AI tools for on-premises installations.

M-Files intelligence services

We are launching a new tool, M-Files Smart Classifier, as an add-on feature in November. M-Files Smart Classifier is based on the approach described above, where the product learns while it is used, and it provides suggestions for what type of a document a certain document is.

In addition to the new M-Files Smart Classifier, we offer other intelligence services, for example M-Files Repository Sensor, which helps crawl through large amounts of data and identify business critical information, such as personally identifiable information, from clutter.

These services are all part of offering increased automation and improved efficiency in office work.

Our aim is to develop the services so that we have three steps towards intuitive, intelligent information management:

Step 1: Provide meaningful metadata suggestions

  • Use AI to analyze and understand the content users are managing.

Step 2: Separate business critical data from dark data

  • Crawl through data repositories.
  • Find relevant data, make it visible, and attach it to business processes.
  • Remove information clutter.

Step 3: Offer users data that is relevant for them now

  • Understand who the user is.
  • Provide proactive information that is relevant today (not yesterday or tomorrow).
  • More relevant search for the user.

In case you wish to learn more about intelligent information management, contact us for more details.

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