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Study Testing Repurposed Drugs with Resistant Bacteria

C. difficile bacteria

Yellow-green fluorescence of C. difficile bacteria (Centers for Disease Control and Prevention)

21 August 2017. A university team is investigating two current drug compounds for their ability to take on a new task, fighting bacteria becoming resistant to antibiotics. The five-year project led by Mohamed Seleem, a professor of microbiology at Purdue University, is funded by a $1.6 million grant from National Institute of Allergy and Infectious Diseases, part of National Institutes of Health.

Seleem and colleagues from Purdue’s veterinary medicine school in West Lafayette, Indiana are looking into expediting the search for new ways of treating three bacterial diseases becoming more resistant to existing antibiotics. One of the bacteria is Clostridium difficile or C. difficile. According to Centers for Disease Control and Prevention, almost a half-million C. difficile infections occurred in the U.S. in 2011, leading to 29,000 deaths within 30 days of diagnosis. The infections are often contracted in health care facilities, such as clinics and hospitals, causing inflammation in the colon, and symptoms including watery diarrhea, abdominal pain, nausea, loss of appetite, and fever.

Another particularly troublesome bacterium is methicillin-resistant Staphylococcus aureus or MRSA, implicated in outbreaks found both in community and health care settings, leading to sepsis, pneumonia, and bloodstream infections. CDC says MRSA infections in health care settings are declining, but remain a major threat to patients. The agency does not have data on MRSA infections acquired in community settings.

The third bacterium is vancomycin-resistant enterococcus, or VRE, also found in health care settings. Enteroccocci bacteria are often found in the intestines and the female genital tract, with many current strains now resistant to the antibiotic vancomycin, a first-line treatment for infections from this bacterium.

The Purdue team already screened some 4,000 current drugs that graduated from patent protection for potential antimicrobial activity, to find compounds that can be repurposed against these three bacteria. The main goal in this project is to short-cut the drug-development process, with compounds whose safety are proven. “It can take 15 years or longer to move a new drug through the approval pipelines,” says Seleem in a university statement. “The solution is to find drugs that we already know are safe.”

The two drugs being investigated are auranofin and ebselen. Auranofin is currently approved by FDA as a treatment for rheumatoid arthritis, while ebselen is a promising antioxidant compound, but not yet approved by FDA. The researchers say their tests in lab cultures and animals show the two compounds are superior against the three target bacteria than current antibiotics of choice.

The new project is expected to validate the team’s earlier studies of thee compounds for systemic, superficial, and intestinal infections. The researchers note that FDA granted orphan drug status to auranofin as a treatment for two other bacteria causing intestinal infections, which also validates their approach.

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AstraZeneca, Biotech Partner on Messenger RNA Therapies

RNA illustration

RNA illustration (University College London, Flickr)

21 August 2017. Global drug maker AstraZeneca is acquiring an option to license the rights to a technology based on genetic material transcribed from DNA, for new respiratory disease treatments. The deal with MedImmune, AstraZeneca’s biologics subsidiary is expected to bring Ethris GmbH, a biotechnology company in Munich, an immediate payment of €25 million ($US 29.3 million).

Ethris develops therapies for respiratory and metabolic disorders based on engineered messenger ribonucleic acid or mRNA, a single strand of nucleic acid related to DNA with the instructions used by cells to produce the amino acids in proteins for carrying out functions in the body. Messenger RNA, however, is highly unstable and can induce an immune reaction, which makes it difficult to use directly in therapies. In addition, mRNA needs a mechanism for crossing cell membranes to take effect.

To overcome these obstacles, Ethris developed its Stabilized Non-Immunogenic mRNA, or SNIM-RNA technology. The company says SNIM-RNA modifies the chemical building blocks in mRNA to remove components invoking immune reactions, as well as stabilizing the mRNA so it can be taken repeatedly as a medication. Ethris says these modifications make it possible to design treatments with mRNA for hereditary diseases and in regenerative medicine that replace missing or boost non-functioning proteins. The company also devised a carrier for mRNA to cross cell membranes.

In Ethris’s pipeline are treatments for inherited respiratory diseases including cystic fibrosis and ciliopathies, genetic disorders that result in abnormal formation or function of cilia, tiny fragments on cells, including in the lungs and respiratory system. The agreement calls for Ethris and MedImmune in Gaithersberg, Maryland to use SNIM-RNA technology for identifying new respiratory disease targets including asthma, chronic obstructive pulmonary disease or COPD, and idiopathic pulmonary fibrosis.

In the 5-year deal, AstraZeneca, based in London, and MedImmune have an option to acquire a worldwide exclusive license for each target once research plans are completed. Ethris is receiving an initial fee of €25 million and unspecified research funding during the collaboration. Ethris will also be eligible for future R&D milestones and royalties on sales for therapies that reach commercialization stage.

The collaboration with Ethris adds to AstraZeneca’s profile with mRNA therapies. As reported in Science & Enterprise, AstraZeneca in 2013 licensed mRNA technology from Moderna Therapeutics in Cambridge, Massachusetts to develop treatments for heart disease, metabolic disorders, and cancer. That deal, valued as high as $420 million for Moderna, released its first product candidate for clinical trials in July 2016, a treatment for cardiometabolic diseases encoding the protein vascular endothelial growth factor-A. In August 2016, AstraZeneca announced it would invest another $140 million in Moderna.

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Five Ways Science and Technology are Changing Transport

– Contributed content –

Locomotive

Locomotive (Michael Gaida, Pixabay)

21 August 2017. Scientific and technological advancements are changing the world around us. In day to day life, we are constantly connected, working on the go, and using apps and programs to help us plan and arrange every part of our lives. Industries are changing too. The advent of robotics, lasers and electronic systems have revolutionized the health care sector, and more and more people are working solely online. Another industry which is quickly developing with new technologies is transport. Here are 5 ways technology and science are changing the field of transportation.

Model based systems engineering

Transport companies and providers are using model based systems engineering (MBSE) to modernize every part of the design, manufacture, and maintenance of their services and vehicles. MBSE uses models to help engineers with requirements analysis, validation, and verification, functional analysis, performance analysis, trade studies, and system architecture specifications to result in higher quality designs, less human error and a more productive workforce. This will mean systems are developed faster, easier and more cheaply without the risk of expensive mistakes, allowing companies to spend more time and money on futuristic designs and developments.

Driverless

The development of driverless cars is quickly upon us and constant disputes between train drivers and employers over hours and pay mean that driverless trains won’t be far behind. The only thing standing in the way of progress when it comes to driverless vehicles is our general mistrust and fear of robotics. However, most road traffic accidents are caused by human error, which driverless eliminates entirely.

Booking systems

Long distance travel has utilized the internet and apps for a long time now. For years you’ve been able to check flights and trains, book online and monitor incoming times and other details. Shorter trips, however, are a little behind. In the future, you’ll be able to book all journeys on an app and never need lose change for the bus. You’ll also be able to check their locations live instead of having to put your faith in unreliable, out of date time tables.

No more getting lost

Map on iPad

(William Iven, Pixabay)

Getting lost, not knowing where you’ve left your car or not knowing where you are, are quickly becoming a thing of the past. Thanks to GPRS and WiFi signals in public locations, while you might not know where you are, your phone, and even your car, do. This means you never need to worry about getting lost, emergency services can always find you in the event of an accident and, your car is much harder to steel as you can watch its movements via an app on your phone.

Electric cars

Car charger sign

(Paul Brennan, Pixabay)

Electric cars are becoming more popular all over the world. There are many perks to owning an electric car including, cheaper tax and insurance and preferred parking spaces in public car parks. Many countries are now starting to implement strategies which meant that by 2040 no gasoline cars will be produced and some car manufacturers are aiming to stop long before them. Electric cars mark a huge step in the fight against climate change.

Thirty years ago, people may have thought we’d all be jetting around in flying cars by now. While we might not be quite there, important advancements are being made and the future of the transport industry is starting to look very different.

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Small Business Grant Funds Blood-Brain Barrier Model

ParVivo chip

ParVivo chip platform (Nortis Inc.)

18 August 2017. A spin-off company from University of Washington is developing a chip device emulating the blood-brain barrier that prevents many drugs from treating neurological disorders. The device is a creation of Nortis Inc. in Seattle, the recipient of a $688,000 Small Business Innovation Research grant from National Institute of Neurological Disorders and Stroke,or NINDS, part of National Institutes of Health, extending the project into a third year.

Blood vessels in the brain form a support network for brain functions, with tightly-packed cells lining blood vessels that allow nutrients to pass through, but keeping out foreign substances. This barrier also keeps out drugs to treat neurological conditions, such as Parkinson’s or Alzheimer’s disease, and its impaired functioning is also implicated in these disorders. So far, no efficient method is available to penetrate this barrier that prevents some 98 percent of current drugs from reaching the brain or central nervous system.

Because the blood-brain barrier represents a special challenge to developing treatments for neurological diseases, drug makers need better tools for addressing this problem. Nortis proposed to NINDS creating a model of the blood-brain barrier that provides drug makers with a means of reliably testing potential neurological treatments, before human clinical trials or even preclinical animal tests.

“Understanding how drugs are transported across the blood-brain barrier and interact with the brain presents a significant scientific challenge,” says Thomas Neumann, Nortis’s CEO in a company statement. “More predictive preclinical models based on human tissue are urgently needed to reduce costs and minimize clinical trial failures.”

The model, based on the company’s ParVivo platform, is a microfluidics or lab-on-a-chip plastic device made with fine channels and tissue cells representing blood vessels arrayed in an architecture like that in the brain. The channels have endothelial cells lining blood vessels supported by pericyte cells that control the flow of blood through the vessels. In addition, astrocytes that form the glial support network in the brain are part of the model. The company says the endothelial cells, pericytes, and astrocytes can self-assemble in the model.

Nortis is first developing a version of the model for a mouse blood-brain barrier that the company will use to test basic blood-brain functions, including transfer of proteins. A second stage, still with a mouse model, will test for more complex functions, such as the transfer of lipopolysaccharides, large molecules found on the membranes of Gram-negative bacteria, causing serious infections. The project’s third stage, a human blood-brain model, will be based on the lessons derived from the first two stages, and optimized for relevance to clinical outcomes.

Nortis was founded in 2012 by faculty at University of Washington to develop lab-on-chip devices representing tissues and organs to advance preclinical research on treatments for disease, and limit the use of animal testing.

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Cryptography Technique Boosts Genomic Privacy

Data and person graphic

(Gerd Altmann, Pixabay)

18 August 2017. A team of geneticists and computer scientists developed a technique of analyzing disease-causing mutations in a human genome without revealing other genetic data. The findings of Stanford University researchers led by developmental biologist Gill Bejerano and computer security professor Dan Boneh appear in today’s issue of the journal Science (paid subscription required).

The Stanford team is seeking a solution to address privacy concerns of people who offer their genomic data for diagnostics or analysis by researchers. While the main focus may be on one or a few genes in the genome, offering one’s genome for analysis opens up the entire set of data for inspection for anyone with access to those data, which could eventually include employers or insurance companies. These concerns are often cited as factors discouraging people from genomic analysis, even without sharing the data.

Up to now, genomic analysis means analyzing sequences of genes through the entire genome and comparing those sequences to large numbers of people with and without the suspected disease. “There is a general conception that we can only find meaningful differences by surveying the entire genome,” says Bejerano in a university statement. “But these meaningful differences make up only a very tiny proportion of our DNA.”

Bejerano adds, “There are now amazing tools in computer science and cryptography that allow researchers to pinpoint only these differences while keeping the remainder of the genome completely private.” One of those tools is a cryptographic method called Yao’s protocol. This technique addresses the so-called millionaire’s problem, where two millionaires are discussing which one is richer, but neither wants to disclose specific incomes. Solutions with Yao’s protocol involve disclosing the presence or absence of specific values, in this case variations in certain genes.

In the researchers’ solution, an individual genome is encrypted in a way that indicates the presence or absence of variations in the target genes, but does not reveal other genomic sequences. While Yao’s protocol is designed for two-party transactions, genomic analysis will likely involve more than two parties. To address this added complexity, the data for analysis are uploaded to the cloud, where the parties use secure multi-party computation to protect the data. Multi-party computation makes it possible for more than two parties to engage in a joint activity, while maintaining the privacy of the data inputs.

To prove the concept, the team applied their solution to three medical scenarios. In the first scenario, small numbers of unrelated individuals use the data-sharing and encryption techniques to reveal genomic data indicating the presence of rare diseases. Another scenario analyzes a family of mother, father, and child with the child expressing a rare inherited abnormality. The third scenario describes data from two different hospitals, each with hundreds of patients, looking for 5,000 rare genetic variations.

Their analyses show the techniques could process the desired genomic sequences, while still protecting from 97 to more than 99 percent of the individuals’ remaining genetic data. The data crunching itself took anywhere from a few seconds to a few minutes in lower-power systems. The team plans to extend the technique to cover diseases resulting from multiple genomic variations, as well as apply the methods of large-scale genome-wide association studies.

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Telemedicine Shown Feasible for Parkinson’s Care

Stethoscope and iPhone

(Pexels.com)

17 August 2017. Findings from a one-year clinical trial show individuals in the U.S. with Parkinson’s disease can receive quality care through telemedicine comparable to persons with the disorder receiving the usual care from neurologists alone. Results of the trial appear in yesterday’s early issue of the journal Neurology (paid subscription required).

The study, led by neurologist Ray Dorsey at University of Rochester in New York, is part of a program known as Connect.Parkinson evaluating the delivery of multi-disciplinary care required for people with Parkinson’s disease, but with video conferencing in the individuals’ homes. Parkinson’s disease occurs when the brain produces less of the substance dopamine, a neurotransmitter that sends signals from one neuron or nerve cell to another. As the level of dopamine lowers, people with Parkinson’s disease become less able to control their bodily movements and emotions.

Symptoms include tremors, i.e. shaking, slowness and rigidity in movements, loss of facial expression, decreased ability to control blinking and swallowing, and in some cases, depression and anxiety. According to Parkinson’s Disease Foundation, some 60,000 new cases of Parkinson’s disease are diagnosed in the U.S. each year, with more than 10 million people worldwide living with the disease.

The clinical trial evaluated the addition of telemedicine to the usual care given individuals with Parkinson’s disease. Nearly 200 people with Parkinson’s disease were randomly assigned to receive the usual care, plus either additional literature from National Parkinson Foundation or a series of 4 virtual visits from a neurologist that was not yet treating the participants. Participants were recruited throughout the U.S., through the National Parkinson Foundation, the advocacy group PatientsLikeMe, and Michael J. Fox Foundation.

Dorsey and colleagues were looking primarily at changes in participants’ quality of life, as determined by a standard 39-item rating scale covering 8 different dimensions administered by independent evaluators at the beginning of the study and after 1 year. The study team also gauged the feasibility of virtual visits, determined by the successful completion of at least 1 virtual visit. In addition, the researchers tracked a number of other factors, such as overall health and cognition indicators.

The results show persons receiving virtual visits seemed to take part in sessions with little difficulty. Nearly all people in the virtual visits group (98%) took part in at least 1 session, and the vast majority of virtual house calls (91%) were successfully completed. And the quality of life scores for individuals receiving virtual visits, and those receiving the usual care, remained about the same from before the study to a year later.

In addition, the team estimates participants in the virtual visits saved a median of 38 miles and 88 minutes of time for each session. “Virtual house calls for chronic diseases like Parkinson’s,” says Dorsey in a university statement, “are not only as effective as in-person care  but broader adoption of this technology has the potential to expand access to patient-centered care.”

The trial was funded by the Patient-Centered Outcomes Research Institute, or PCORI, and National Parkinson Foundation. Dorsey tells more about the project in this PCORI video.

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Five Lessons Everyone In Business Needs To Learn

– Contributed content –

Lecture room

(Pexels.com)

17 August 2017. Being successful in business requires one skill above all others: the ability to learn. That is how to keep moving forward. It doesn’t matter if you do your research ahead of time to prevent yourself from making a mistake, or whether you learn the hard way and bounce back from that. So long as you keep learning, you’ll stand yourself in good stead.

Of course, learning from other people’s lessons is a great way to move forward too, which is why we have come up with a list of business lessons you should make note of as early as possible and remember from now until the day you retire.

You can’t go it alone

There is not a person on the planet that can run a business alone (or a country for that matter, Mr. Trump). That is what makes building a solid team so essential when it comes to securing success. Exactly how far you can go it alone will depend on you, your experience and your other obligations, but the end game should be to create a team that can continue even when you are not there.

User feedback is key

Your judgment is clouded. It is biased. That’s why you need to ignore what your head and heart are saying and listen to the feedback of your clients, customers, and users more closely. Basically, what we are saying is, you won’t know how great or how bad your product is until it has been released to the market. So release early and release often, and then listen to what the consumer is saying and then make the tweaks they recommend.

Outsourcing is not a bad word

Outsourcing has become more beneficial than ever, especially for smaller companies. Yes, the big boys in your industry may be able to do it all in-house, but you can’t, so why bother trying. Whether it be outsourcing entire areas of your business, like telecommunications services or IT support, or just certain tasks, such as graphic design or copywriting, the benefits are impossible to ignore. Cheaper, less risky, better quality and delivered faster.

Cheap is not sustainable

You can’t be the cheapest. You need to realize that. In this day and age where the internet is so epic, a quick Google search will find someone – somewhere – that is cheaper. That is a fact. So instead of harming your business that way, start focusing on how you can compete on quality and expertise. After all, people want good value not cheap as chips. It’s why we all read an average of five reviews and look at three different products before clicking the buy now button.

People leave managers

The cost of high-employee turnover can be an absolute business killer, which is why you need to know just how to keep your employees happy. On that note, it is worth knowing that over 80% of employees don’t leave a business because of the work; they leave because of the management. People want to feel important, valued and listened too, so if you aren’t allowing this then you will start to see people leave. Not good financially.

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Tracking Algorithms Devised to ID Human Traffickers

Bitcoin graphic

(Gerd Altmann, Pixabay)

17 August 2017. Computer scientists developed techniques that help identify the people placing sexual service advertisements by tracing the bitcoin payments for those ads. The technology is described in a paper delivered this week at the Conference on Knowledge Discovery and Data Mining in Halifax, Nova Scotia, by a team from University of California in Berkeley and San Diego, as well as New York University.

The scale of forced sexual exploitation is global and substantial. International Labor Organization estimates 4.5 million individuals worldwide are forced into commercial sex services, about 1 in 5 of all 21 million people forced into slavery-like working conditions. In the U.S. the National Center for Missing and Exploited Children says in 2016 1 in 6 runaway children, all under the age of 18, were forced into prostitution rings, including girls, boys, and LGBTQ youth.

Authorities seeking to break these sexual exploitation businesses are often stymied by the anonymous nature of their transactions, even when the traffickers advertise openly in online publications. Among the ways traffickers evade detection is by paying for the ads with bitcoins, a private peer-to-peer exchange technology that enables funds transfers between anonymous accounts, which online publications accepted for sex ads at the time of the study. Bitcoin is based on blockchain, a technology linking online transactional ledgers or registries exchanging encrypted blocks of data that establish a form of trust between the parties.

The team led by UC-Berkeley doctoral candidate Rebecca Portnoff developed algorithms to unmask individuals placing the ads in online publications for so-called adult services. One algorithm analyzes text in the ads using a technique called stylometry that statistically measures factors such as sentence length and word frequency to reveal writing style signatures to identify, for example, plagiarists. In this case, the researchers employed stylometry in a machine learning routine to highlight ads written by the same person.

A second set of algorithms finds and exploits leaks in the bitcoin exchange system to trace financial transactions paying for the ads. In this case, the leaks are time stamps on transactions appearing in an intermediate public bitcoin confirmation mechanism called mempool. The researchers discovered that Backpage, one of the leading online media for escort and other prostitution services, posted new ads at almost the exact time of the transaction reaching the mempool. By matching the time stamps of Backpage ads with the mempool, the team could possibly match the bitcoin transaction identifiers to the Backpage ads.

Portnoff and colleagues then devised techniques for matching ad buyers with the time stamps of the ads and mempool appearance. One method the team calls “hard identifiers” maps the bitcoin wallet, or account, identifier to individual ad with the fewest number of nodes crossed, no more than 2, to get from the wallet to the ad. Another technique the researchers call “persistent bitcoin identity” tracks bitcoin traffic linked to the ads, when the wallet identifier is adjacent to the ad purchasing transaction.

To test their techniques, the team placed a series of phony escort ads in Backpage that enabled the researchers to trace transactions they initiated to ads appearing in the publication by matching the respective time stamps. The researchers also collected a month’s worth of adult ads from Backpage, some 10,000 in all, where they found the stylometric algorithm accurately found the same author nearly 90 percent of the time. However, the team could not consistently identify individual ad buyers to individual bitcoin transactions, but the ability to highlight suspects and narrow the search could benefit law enforcement authorities and non-government organizations fighting human trafficking.

Since the study, Backpage removed its adult advertising section, but the researchers say that ads for sex services still appear in other sections of the site.

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Trial Testing Engineered Virus as Cancer Treatment

Vesicular stomatitis virus

Vesicular stomatitis virus (CDC.gov)

16 August 2017. A clinical trial is underway testing a genetically engineered virus to kill cancer cells, then stimulate the immune system to treat solid tumor cancers. The study’s first site is Sanford Health, a health care system in Sioux Falls, South Dakota and other states and cities.

The clinical trial is testing a therapy developed by biopharmaceutical company Vyriad in Rochester, Minnesota. Vyriad is a spin-off enterprise from the Mayo Clinic, founded by physicians and researchers from the institution. The company licenses discoveries from Mayo Clinic by molecular medicine professor Stephen Russell — a company founder and its CEO — and colleagues, including treatments for cancer derived from the vesicular stomatitis virus, a virus shaped something like a bullet that affects cattle, but can also infect human cells.

In its natural state, the vesicular stomatitis virus rarely causes serious illnesses in humans, but the Vyriad technology engineers the organism, adding two genes to turn the virus into a cancer therapy. One of the genes adds a natural anti-viral protein to protect healthy human cells from infection, while the second gene adds a protein from the thyroid gland that allows physicians to track the virus as it works in tumor sites.

Vyriad says the engineered virus works first by infecting and killing some tumor cells, then inducing the immune system to kill the remaining cells. The virus initially seeds an infection in the tumor that infects and kills some of the cancer cells. As the infected tumor cells die, they invoke the immune system to respond, attacking any remaining uninfected tumor cells. The virus is also engineered to spread to other tumor sites, where the process is repeated.

The early-stage clinical trial, conducted by Vyriad, is primarily testing the safety of the treatments, including tolerated dosage levels. The study team is recruiting 42 individuals diagnosed with malignant solid tumors that are not responding to conventional cancer treatments. Participants will receive a single dose of the engineered virus, injected into the tumor, and will be tracked for 6 weeks, monitoring any reactions to the virus as well as clinical benefits. In addition to Sioux Falls, the trial is being held at sites in Miami and Dallas.

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Is There A Science To Attracting Consumers?

– Contributed content –

Laptop close-up

(Pixabay, Pexels.com)

16 August 2017. The short answer is: yes. Humans are complicated, of course, but there are certain trends and patterns that ring true for the majority of consumers. In a sense, there is a science to attracting potential customers in the marketplace based on the industry in which your company is based and the service or product you’re trying to sell to them. Here are some pieces of advice which might just help you better attract customers to your business in the future.

Do your research

The best way to figure out what the average customer wants from a business like yours is to do research into consumers within your industry. Find out what other businesses are doing to drive sales from your target market, and figure out what your company is doing well already. You might want to consider a user testing agency if you feel as if your company doesn’t have all the information it should have on its existing customers or the marketplace full of potential customers out there.

Companies in the user testing industry can help you improve your digital marketing approach if your business doesn’t fully know how, say, its web site fares in terms of impressing the average consumer in your target market. There’s no universal answer as to the best way to market your business through a website or other means, of course, but it certainly doesn’t hurt to conduct research into the methods which often work well in terms of impressing consumers and converting traffic into sales.

Make a personal connection

It’s so important to connect with customers. You can’t just be the one-dimensional corporate entity trying to force products on them. You have to show your human face if you want to attract consumers in the modern age. This means you need to utilize platforms such as social media to answer questions and solve problems that people may have; you need a team that’s available all around the clock to respond to consumers almost instantaneously.

You should also do all that you can to keep customers interested once they’ve bought from your company. Give people an incentive to come back. Perhaps you could offer a loyalty program which involves better deals, discounts, and points that can add up as a sort of currency to buy things from your business. That’ll definitely incentivize people to stick around with your business in the long-run in order to save money, rather than going to your competitors.

Contests

This is one of the most clever ways of marketing. People love to win things, as implied when we discussed loyalty programs earlier. Consumers are happy to spend money or invest in a business if there’s the chance of winning something great at a discounted price or perhaps even getting something for free. If you want to drive interest for your business then your marketing needs to be full of information about contests and prizes that your company is offering. Make people turn heads when they see your marketing campaign on a web site.

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