Drug resistance may make malaria parasites vulnerable to other substances

Malaria parasites that develop resistance to the most effective class of anti-malarial drugs may become susceptible to other treatments as a result, researchers at St George’s, University of London, UK have revealed in a study. The discovery could reveal potential new drug options, which would be essential in the event of resistance to the best anti-malarials.

The researchers have shown how the anti-malarials artemisinins attack the malaria parasite by inhibiting the action of a crucial protein, and that genetic mutations in this protein can reduce the effect of the drugs.

While demonstrating this, they also discovered that a mutation that gives the parasite resistance to artemisinins makes it more sensitive to attack by another substance, cyclopiazonic acid (CPA). CPA is thought to be too toxic to be a suitable anti-malarial treatment, but the findings suggest it could be worth pursuing derivatives of the acid as treatment options.

The research has been published in The Journal of Infectious Diseases.

The yeast model provides a convenient and reliable method to study anti-malarials and this particular mechanism of resistance to them

The artemisinin group of drugs are the most effective and widely used treatments for malaria – used most powerfully with other drugs as artemisinin-based combination therapies – but little is known about their mechanism of action on the malaria parasite. There are signs that the parasite is developing resistance to such therapies, meaning that further understanding of the drugs could be crucial to prevent them from becoming obsolete.

The researchers demonstrated that artemisinins work by acting on a protein within the parasite called a calcium pump, which regulates calcium levels in cells, and if it is not functioning properly the parasite dies.

In previous studies, the team saw the same effect on the calcium pump in genetically engineered malaria parasites. However, in these studies the parasites’ sensitivity to artemisinins fluctuated, so they did not give a clear indication of the drugs’ mechanism of action and the findings could not be confirmed.

To provide more consistent results, the latest study used yeast cells instead of parasite cells.

After confirming that artemisinins inhibited the calcium pump in the yeast model, the researchers mutated the pump to mimic three mutations previously observed to give parasites resistance to the drugs. When they did this, they saw similar resistance.

The latest study used yeast cells instead of parasite cells

Following this, they tested whether these mutations had any effect on the action of another five substances known to have an anti-malarial effect. They found that one particular mutation that gave the pump resistance to artemisinins made it more susceptible to CPA.

Their findings also showed that the yeast model could be used to identify other drugs that harm the parasite.

Lead author Professor Sanjeev Krishna said: ‘CPA is a compound used in science and not in clinical practice in any way. However, it points to a proof of concept that we can look for weaknesses in the more resistant strains of the parasite. The yeast model provides a convenient and reliable method to study anti-malarials and this particular mechanism of resistance to them.’

Manufacturing and Millennials : Can Manufacturing Be Sexy for Millennials?

Unemployment remains high in the U.S. and other countries, and yet manufacturers struggle to find the skilled workers they need. It’s a maddening paradox.

There’s a clear skills gap out there. Young people especially—“millennials”—aren’t gravitating towards manufacturing careers and don’t see the work as sexy.

“Manufacturing has a PR problem with young people,” said John Nesi, VP of Market Development for Rockwell Automation, speaking recently during a panel discussion at his company’s annual Automation Fair. Millennials don’t have an appreciation for the high-tech nature and diversity of careers in manufacturing today, he said.

It’s not just in the U.S., said another panelist, Tom Duesterberg, a manufacturing expert at The Aspen Institute. “In both India and China, the quality of engineers and those going into jobs as line workers and so on is not adequate. In the U.S., we’re not training enough scientists and engineers. We are going to have to focus on immigration as one solution. But also, basic literacy and numeracy skills and the basic ability to be trained are missing.”

“Skill is a combination of education and experience,” said Mary Isbister, president of the metal fabrication firm GenMet. Most younger workers she sees “don’t have experience, and they don’t have basic math and science, and even the basic work-readiness skills of arriving to work on time!”

Irving McPhail, President of the National Action Council for Minorities in Engineering, bemoaned the “Engineering Awareness Conundrum.” “There are just not enough young people aware of the excitement in STEM careers,” he said. “Not a lot of young people know people in their lives who work in these fields. And we need K-12 educators who can impart enthusiasm in these fields.”

The end result, said McPhail: “We are not producing the number of engineers required to give the U.S. the ability to participate in the flat, global world.”

Duesterberg said that the U.S. must, as Germany and Japan have, place more emphasis on technical colleges and technical tracks in high schools, with support from government and industry. (North Carolina got this message long ago, and some other states and regions are catching on as well.)

But two things stand in the way, Duesterberg said. First, the U.S. as a society places an inordinate emphasis on the “entrepreneurial” rather than the “industrial.” (Are they mutually exclusive?)

And, despite evidence to the contrary, many of our most influential thought leaders say “the future of our economy is in the service sector.” As Duesterberg and others have pointed out, successful economies need diversity—and that includes a healthy manufacturing sector.

It was an enlightening panel discussion. But making manufacturing sexy is an uphill climb. 

A better approach would be to tap into a trait that all of us, millennials included, have in spades: greed. 

If sexy just won’t work, maybe greedy will. In the National Association of Colleges and Employers (NACE) report on the best paying jobs for 2011 college graduates, engineering dominated the list. Here are the first 10: 

1.    Chemical engineering ($66,886)

2.    Computer science ($63,017)

3.    Mechanical engineering ($60,739)

4.    Electrical/electronics and communications engineering ($60,646)

5.    Computer engineering ($60,112)

6.    Industrial/manufacturing engineering ($58,549)

7.    Systems engineering ($57,497)

8.    Engineering technology ($57,176)

9.    Information sciences & systems ($56,868)

10.    Business systems networking/ telecommunications ($56,808)

These jobs top even those in finance, accounting, and human resources. The good salaries, of course, have something to do with the fact that there are not a lot of qualified candidates out there. But one would think that a starting salary of $60K and a wealth of open job positions would be enough to raise the eyebrows of even the most dour and discriminating millennials.

SaaS Business Intelligence - It Just Makes Sense

I spoke recently to the commercial leaders of a well-established pharma company who were relaying their frustrations with their current data and business intelligence environment. The complaints were ones I hear frequently – “it’s slow and inflexible,” “it doesn’t contain all of our data and we have quality issues,” “it’s inflexible, complex and expensive to maintain,” “the analytics are not relevant to the changing business.” This particular Sales Operations group was considering options for enhancing their analytic capabilities and was considering “rebuilding” portions of the company’s enterprise data warehouse to meet their needs. This was an undertaking that was projected to take almost two years to complete and would result in internal demand on technical and business resources that simply wasn’t there. In the meantime the organization would be stuck in the equivalent of the Dark Ages when it came to sales and customer analytics and intelligence. This didn’t make sense to those leaders who needed insights today, and it was difficult to rationalize business as usual when the current solution wasn’t meeting expectations.

When I asked if they had built their new CRM system from the ground up, the obvious answer was no. They had recently implemented a leading SaaS CRM solution that replaced a cumbersome in-house one and the same was true for their newly launched Closed Loop Marketing System. When I asked why they were only considering “building” their data and reporting system, their response was that they didn’t know other options existed.

There remains a deep-rooted belief in pharma that data and reporting systems need to be managed internally. It exists for a number of reasons, most of which don’t apply today.

• Security – data was once believed to be sacred; to expose it to third parties or internet accessible systems could lead to a corporate breach.
• Lack of solutions – SaaS-based business-focused commercially available data integration solutions have not been mainstream.
• Expertise – the thought that only IT and engineering teams could build and manage such complex solutions.
• Corporate hub – the idea that data could only exist in one place and serve the entire organization from the same physical system.

Security alone is not a reason to silo your data. Your organization is likely already hosting sensitive data outside of the four walls. If you deploy a SaaS-based CRM system such as Salesforce.com, your customer data is being managed in the cloud. Many HRS and ERP functions are internet-enabled and comply with the strictest data privacy laws. The security issue has largely been solved with SaaS solutions and is no longer a barrier to entry.

Traditional mainstream data and business intelligence solutions are big, cumbersome, and  difficult to maintain. Not only has there been a lack of pharma specific solutions, the ones that do exist require a monumental effort to design, customize and implement. Couple this with yearly upgrades, support teams, engineering and infrastructure, and you end up with a system that rarely meets Sales and Marketing needs. Better solutions exist today that are nimble and adaptive, pharma-centric, cost-effective and deliver more value than legacy systems. If the benefits of SaaS are appropriate for your CRM, the same is true for your commercial analytics solution.

Additionally, the SaaS era has brought with it the need for less IT expertise in your organization. All application and software upgrades and improvements are managed by the vendor, further reducing the burden on internal IT teams, and lessening the reliance on the engineering of the solution.  Complexity is removed with the productization of complex activities once thought only IT could handle. SaaS solutions remove the technology and engineering barrier and put the focus on the business and the opportunities the solution can provide. Pharma is in the business of developing and commercializing products that improve the health and wellbeing of their patients – not developing software.

While I’m a proponent of SaaS BI solutions, I’m not advocating against enterprise data warehouses (EDW); there is a time and a place for them. But I’ve seen the corporate chokehold of data cripple commercial teams in some of the most sophisticated organizations. Sales and marketing by virtue is a nimble and responsive organization that operates in real-time, competitive markets. Data and insights are the lifeblood of 

1) Decision making, 

2) Calling tactics and strategy, 

3) Understanding your customer and 

4) Determining performance cause and effect. 

Commercial teams require analytic solutions that can keep up and deliver real value through contextual and timely insight. The corporate EDW is rarely designed with these values in mind and hence rarely meets expectations.

The good news is that organizations are no longer bound to slow-moving legacy solutions that do not adapt to the ever-changing life sciences business. SaaS technology has brought remarkable improvements in the speed and agility in which pharma can process data and deliver insights. For an industry in need of flexible, intuitive, cost-effective BI solutions, it just makes sense.

Pharma CRM: The Good and the Bad

When deploying or upgrading Customer Relationship Management (CRM) systems, pharmaceutical companies have experienced varying degrees of success. At its most basic level, the primary function of a CRM system is to make your sales force successful in developing and maintaining strong relationships with customers. In today’s dynamic environment, where the focus is on a customer centric business approach, Pharma companies should have a solid understanding of what their CRM systems can and cannot deliver.

Achieving the unified customer view is essential to enabling your sales force and ultimately product success - but thinking it can be done with CRM alone is wishful thinking. It is worth exploring the good and bad virtues of CRM and the opportunities it could provide as the life science industry continues to evolve.

THE BAD:

Low success rate: The success rate for CRM implementations is horribly low. Studies by Gartner have shown that less than 50% of CRM initiatives meet their intended goals. This is a statistic that has not changed since 2001 when enterprise and mid-market companies were asked if there CRM efforts had met expectations. The primary force at play here is the lack of a clear strategy and understanding of how to calculate true ROI for CRM. Traditional CRM deployments have generally been led by the IT function (can you get any further from the customer?) further disconnecting the objectives from the corporate and functional strategy the system was meant for. The key take-away here is to go into your CRM initiative with your eyes wide open and a clearly articulated strategy that aligns to business objectives (not your vendor’s spec sheet).

Good data gone bad: Historically the data housed in a Pharma CRM system has not been of the highest quality. This can often be the case for systems that rely heavily on user entered data. Incorrect data involves misspelled names, bad addresses, and at its worse – fabricated data. There are also cases when data becomes outdated or misaligned and is no longer an accurate reflection of the relationship you have with your customer. Poor data quality leads to poor analytics and ultimately poor execution and decisions.  

Don’t let the name fool you: Today’s CRM systems are missing the primary component – the customer. Yes, they house and track customer information and activity but they lack any substantive collaboration tools to engage your customer. The term “customer” often has different meanings and definitions to various departments creating a distorted or overly simple view of the customer. Traditional CRM is very much based on data collection all of which is used to better target various customers. This leads to one-way communication between a brand and the customer. Reps will continue to maintain the relationships (e.g. trust and rapport) with physicians and ultimately drive engagement. CRM is a support mechanism for this activity - not a replacement.

THE GOOD:

Critical piece to the puzzle: CRM systems are a critical part of the commercial solution ecosystem and provide a number of high valued functions. When deployed correctly they can maintain your customer master of accounts. They provide home-office with critical real-time information and activity from the field allowing your company to be more responsive to your customers. CRM can result in deeper relationships with your key customers, increased sales, more effective and targeted marketing, and better determination of sales force ROI.

Enriching CRM data: Enriched multi-dimensional customer data is the most important tool you can provide your field when enabling value-added interactions with your customers. The data stored in your CRM system plays a large part in understanding your customer influences, local and personal prescribing characteristics, and overall relationship strength with your customer. By integrating your CRM data with information across an increasing number of channels – including IMS®, Verispan®, Wolters Kluwer®, closed loop marketing systems, managed markets, contracting, and incentive compensation – Sales Operations teams can create timely, accurate, and targeted insights tailored to your sales force and home office users. 

Social CRM model: Customer relationship management is evolving. The current trends in Pharma put a premium on physician access and rely on a change in rep to physician engagement focused on value creation. We also live in a more social environment, which enables more collaboration, transparency and engagement. Advocacy and experience are crucial components of maintaining a relationship, which all revolve around the customer. In the social CRM model, the customer is the focal point of how an organization operates. Instead of marketing or pushing messages to customers, brands now talk to and collaborate with customers to solve problems, empower customers to shape their own experiences and build relationships with your company, with the goal of turning them into customer advocates.

The point here is, while there is certainly huge value to your CRM system, it is not meant to be an end point. It is a critical functional asset to the sales process and an entry point to engaging your customers. Your CRM data is invaluable and by enriching it you create a better understanding of your customer, leading to more compelling, local and personalized interactions.

Lots of Exercise May Boost Kids' Grades

Lots of Exercise May Boost Kids' Grades

A Dutch review of prior research reveals that the more physically active school-aged children are, the better they fare in the classroom.

Most of the studies in the review had been conducted in the United States, while one came out of Canada and the other out of South Africa.

The findings are published in the January issue of the Archives of Pediatrics & Adolescent Medicine.

"We found strong evidence of a significant positive relationship between physical activity and academic performance," the researchers, led by Amika Singh of the Vrije Universiteit University Medical Center at the EMGO Institute for Health and Care Research in Amsterdam, the Netherlands, said in a journal news release.

"The findings of one high-quality intervention study and one high-quality observational study suggest that being more physically active is positively related to improved academic performance in children," the authors noted.

Fourteen studies were analyzed; they ranged in size from about 50 participants to as many as 12,000 and involved children between the ages of 6 and 18.

The investigators noted that increases in blood and oxygen flow to the brain that accompanies exercise may play a role in improving classroom performance. The suggestion is that the dynamic prompts an increase in levels of hormones responsible for curtailing stress and boosting mood, while at the same time prompting the establishment of new nerve cells and synapse flexibility.

The Dutch team cautioned, however, that more rigorous work is needed to confirm the connection.

"Relatively few studies of high methodological quality have explored the relationship between physical activity and academic performance," they acknowledged. "More high-quality studies are needed on the dose-response relationship between physical activity and academic performance and on the explanatory mechanisms, using reliable and valid measurement instruments to assess this relationship accurately."

Red wine makes cancer drug more potent

Red Wine can make Cancer Drugs even moreEffective

Resveratrol, a compound which gives red wine its colour, makes breast cancer drug rapamycin more potent.

Lab tests found the ingredient can prevent cancer cells from developing resistance to the drug.

Resveratrol is a potent antioxidant produced by plants such as grapes, raspberries, cranberries and peanuts to fight off fungal and bacterial infections, the journal Cancer Letters reports.

Scientists have been exploring its potential in reducing the risk of heart disease, Alzheimer's and even the ageing process, according to the Daily Mail.

Prof Charis Eng from Cleveland Clinic's Lerner Research Institute in Ohio, said: "Rapamycin has been used in clinical trials as a cancer treatment. Unfortunately, after a while, the cancer cells develop resistance to rapamycin.

"Our findings show resveratrol seems to mitigate rapamycin-induced drug resistance in breast cancers, at least in the laboratory."

Resveratrol is also available in supplement form. In high doses it causes side effects such as insomnia, joint pain, diarrhoea and acne.

Ibuprofen could treble stroke risk

Ibuprofen 'trebles the risk of a stroke' doctors warn

Large regular doses of ibuprofen and similar painkillers could treble the risk of stroke and up the likelihood of heart attacks, scientists warn.

Researchers have found that high doses of ibuprofen may carry health risks similar to painkillers withdrawn from the market several years ago on safety grounds.

Up to eight million Britons are prescribed so-called anti-inflammatory drugs every year, usually to combat arthritis or back pain, the British Medical Journal reports.

Doctors stress that stroke and heart risks only exist for those taking high doses of ibuprofen over long periods and that there is no danger in the odd pill for a headache, according to the Daily Mail.

Researchers from the University of Bern in Switzerland looked at more than 31 clinical trials involving 116,429 patients.

They had each taken one of seven commonly-used painkillers. The study found that those who had taken ibuprofen over a long period of time were almost three times as likely to suffer a stroke.

Professor Peter Jüni of the University of Bern said: "We looked at patients taking these drugs three to four times a day."

"In terms of stroke, ibuprofen doesn't look very good. If I was in chronic pain, I would not take it as the risks are just too high. I would look at the different options."

The painkiller was also shown to raise significantly the risk of heart attacks and deaths caused by heart disease.