• MPs are reportedly planning to change House of Commons rules to seize control of the Brexit process.
• Theresa May has warned MPs that failure to deliver Brexit would be an "catastrophic and unforgivable breach of trust in our democracy" ahead of the meaningful vote on her deal.
• May is almost certain to lose that vote. Potentially by a margin of over 100 MPs.
• A cross-party group of MPs are reportedly planning to exploit parliamentary arithmetic to weaken the prime minister and give greater powers to backbench MPs who want to soften, delay and stop Brexit.
• MPs will vote on the Withdrawal Agreement on Tuesday. 

LONDON — Theresa May has warned that failure to deliver Brexit would be a "catastrophic and unforgivable breach of trust in our democracy" has MPs plot to sideline the prime minister and take control of the process.

Writing for the Sunday Express today, May says that the meaningful vote on her Brexit deal on Tuesday would be the "biggest and most important decision that any MP of our generation will be asked to make."

She adds that MPs "cannot — and must not — let you (voters) down" and urged MPs "to forget the games and do what is right for our country" ahead of the historic House of Commons vote on her deal with the European Union."

The prime minister is almost certain to lose that vote with MPs on all sides opposed to the Withdrawal Agreement.

The margin of victory could be over 100 MPs, with tens of Conservative MPs and the Democratic Unionist Party that props up May's government set to join all opposition parties in voting against the Brexit deal.

The prime minister is set to return to the Commons within days of a defeat to lay out what she'll do next, with MPs calling for a range of options including a softer Brexit, an extension to Article 50, and a new referendum.

Staunch Brexiteers want May to ditch the controversial backstop for Northern Ireland and negotiate a cleaner break from Brussels, with some calling for a no-deal Brexit.

READ MORE: Conservative MPs blame Theresa May's 'dysfunctional' leadership for looming Brexit deal defeat

According to a report in The Sunday Times, a cross-party group of MPs including pro-second referendum Conservative MP Dominic Grieve is planning to take greater control of the Brexit process.

MPs will reportedly try to re-write long-standing parliamentary rules to make motions proposed by backbench MPs take precedent over government business, therefore putting what happens next in the hands of MPs.

10 Downing Street fears that this "very British coup" will give pro-Remain MPs greater power to delay Britain's exit from the EU or even put the issue back to the public via another referendum, the report suggests.

A government source is quoted as saying: “Without control of the order paper, the government has no control over the House of Commons and the parliamentary business and legislation necessary to progress government policies.

"The government would lose its ability to govern."

It goes on to add that Grieve — who has been behind a number of amendments designed to stifle May's Brexit plan — met with House of Commons Speaker John Bercow earlier this week. Bercow infuriated the government this week when he upended constitutional convention to let MPs vote on amendment to a usually unamendable motion.

Grieve refused to deny the reported plans, telling The Sunday Times: "I have no doubt that lots of people may be looking at all sorts of ideas since we are in a deepening national political crisis."

On Friday, Grieve told an anti-Brexit rally that he would do everything in his power to stop a no-deal Brexit, telling campaigners: "Parliamentarians have a responsibility to prevent national suicide and a no deal Brexit would be just that."

His Conservative party colleague, Nick Boles MP, has confirmed that he is working on an amendment that if passed would make it illegal for the government to take the country out of the EU without an exit deal.

SEE ALSO: Exclusive: Second Brexit referendum campaign fear it's 'game over' unless Corbyn backs a People's Vote

Join the conversation about this story »

NOW WATCH: MSNBC host Chris Hayes thinks President Trump's stance on China is 'not at all crazy'

• Analysts at Credit Suisse think smartphone production levels are in free-fall, and the bottom is nowhere near in sight.
• The investment bank said smartphone production levels will drop to their lowest level since 2013 in the first three months of 2019.
• People are happier to hang on to their handsets for longer and breakout innovation is becoming harder to come by, with many phones capable of doing similar things.

Apple is far from alone in feeling the pain of falling demand for new smartphones.

After its earnings warning shook Wall Street earlier this month, new figures show that all manufacturers are increasingly struggling to get customers to upgrade or buy new phones.

In a note to clients, Credit Suisse published estimates showing that global smartphone production is in free-fall, and the bank's analysts warned that the "bottom not yet in sight."

Credit Suisse revised down its smartphone production forecast for the final three months of 2018, predicting it will fall by 3% quarter-on-quarter to 357 million units. It said first-quarter output will fall 19% to 289 million units.

Read more: Apple is reportedly cutting iPhone production by 10% after one of the darkest weeks in its history

Put another way, Credit Suisse thinks smartphone production levels will drop to their lowest level since 2013 in the first three months of 2019. This graph says it all:

If Credit Suisse's forecasts prove accurate, it means that first-quarter smartphone production will have fallen for five consecutive years. "It is too early to say whether this news is already fully discounted in share prices, or will continue to have an impact," it added.

Apple, Samsung, and companies like Huawei — the second biggest phone manufacturer in the world — are all feeling the squeeze. People are happier to hang on to their handsets for longer and breakout innovation is becoming harder to come by, with many phones capable of doing similar things.

As James Cordwell, a tech analyst at Atlantic Equities, told Business Insider this month, the smartphone market has "become a bit boring."

SEE ALSO: Apple's brutal sales warning sparked a Wall Street debate on whether tech stocks will be dragged into a disastrous downturn

Join the conversation about this story »

NOW WATCH: China made an artificial star that's 6 times as hot as the sun, and it could be the future of energy

• China is facing international pressure over its crackdown on its Muslim ethnic minority, the Uighurs.
• Chinese authorities are accused of arbitrarily imprisoning Uighurs in prison-like camps and making them renounce their religion.
• More and more activists and countries, including those with Muslim majorities, are condemning Beijing over these actions.
• Pakistan, a major economic ally of China, was first to censure Beijing. But over the past few months, it started toeing the Chinese line.
• Experts say it illustrates the power of Chinese money.

Pakistan, China's largest economic ally in the Muslim world, abruptly stopped censuring Beijing over its unprecedented crackdown on Muslims.

The shift clearly illustrates the power of Chinese money, activists and critics say.

China is facing international pressure over its treatment of the Uighurs, a majority-Muslim ethnic minority who live mainly in the northwestern region of Xinjiang.

Activists accuse Chinese authorities of imprisoning up to 1 million Uighurs in prison-like camps, where detainees are reportedly forced to sing hymns to President Xi Jinping and renounce their religion.

Beijing justifies these measures as counterterrorism, and routinely calls the camps "free vocational training," meant to turn Uighurs into "normal persons."

After an initial period of silence, Muslim nations have started to speak out about the treatment, which has been condemned by the UN and the US, as well as by dozens of human rights groups.

Read more:A wall of silence around China's oppression of its Muslim minority is starting to crumble

But Pakistan — where Islam is the state religion and where Muslims make up more than 90% of the population — has increasingly muted its voice on China's human rights record in recent months.

In September, it was the first country in the Muslim world to censure Beijing over its treatment of the Uighurs. 

Pakistan's federal minister for religious affairs, Noorul Haq Qadri, said that China's intensive regulation of Uighur activity is fuelling extremism, rather than countering it. Beijing's response was to deny that the criticism even happened.

Since then, Pakistan has dramatically changed its tune.

'The Chinese have been a breath of fresh air for us'

In December, Pakistan's foreign ministry toed the Chinese line, accusing the media of "trying to sensationalize" the Xinjiang issue, according to Agence France-Presse.

Mohammad Faisal, a spokesman for the ministry, echoed China on the detention camps, saying that some Pakistanis detained in Xinjiang were "undergoing voluntary training" instead.

Pakistani Prime Minister Imran Khan this week claimed "I don't actually know much" about the situation of Muslims in Xinjiang. He discussed his country's economic partnership with China instead.

Pakistan is one of the largest recipients of Chinese aid and infrastructure contracts. Loans and infrastructure contracts have been a lifeline to the Pakistani economy, which faces a growing mountain of national and foreign debt.

"In this doom and gloom which we inherited, the Chinese have been a breath of fresh air for us," Khan told Turkey's TRT World news channel. "They have been extremely helpful to us ... we have these plans of reviving our economy, [and] China is going to play a huge part."

China is 'buying the silence of Pakistan'

Experts have made an explicit link between Pakistan's increasingly tepid response and its reliance on Chinese investment.

Many Muslim countries have refrained from criticizing China over its treatment of Uighurs in the past, likely to keep Chinese investments coming, or to avoid charges of hypocrisy over their own human rights record.

Pakistan is a major part of the Belt and Road Initiative, a major Chinese project that aims to link the country to more than 70 countries via infrastructure.

The China-Pakistan Economic Corridor (CPEC) — a massive, $62 billion partnership between the two countries consisting of transport and energy projects — passes directly through Xinjiang.

Simone van Nieuwenhuizen, a Chinese politics researcher at University of Technology Sydney, told INSIDER: "From the Pakistani government's perspective, it would be wary of raising concerns about human rights in Xinjiang in case this might jeopardize further negotiations.

"It's possible that Pakistan has moved towards tacit endorsement of China's 're-education' facilities in Xinjiang because it considers the Chinese Communist Party's justification of its Xinjiang policy — in terms of counter-terrorism and stability maintenance — as being beneficial to the security and longevity of the CPEC project," she added.

Peter Irwin, a project manager at the World Uyghur Congress in Munich, said China was "buying the silence of Pakistan."

He told INSIDER: "Khan's statement this week was incredibly worrying, but very much expected.

"Khan is trying to stabilize the Pakistani economy and he knows that with unreliable American support under Trump, China remains the much more appealing choice — he knows he simply needs to keep his mouth shut."

"Someone like Khan has a very good idea of the balance of power in their relationship with China," he said.

• Read more on the Uighurs:
• A wall of silence around China's oppression of its Muslim minority is starting to crumble
• US clothing company cuts ties with Chinese factory that reportedly used forced labor to make college sportswear
• China is locking up its Muslim minorities, and pushing Islamophobia to get Europe to do it too

SEE ALSO: A wall of silence around China's oppression of its Muslim minority is starting to crumble

Join the conversation about this story »

NOW WATCH: North Korea's leader Kim Jong Un is 35 — here's how he became one of the world's scariest dictators

• The high-fat, low-carb keto diet can be great for shedding weight, but it presents distinct challenges.
• Jennifer Still writes that though the keto diet has been a "godsend" for her, there are several things she wishes she'd known before starting.

Having been overweight for years, I've tried every diet in the proverbial book in the hopes of shedding pounds and getting healthy.

Like with many people, any success I found in dieting was usually short-lived, and I always ended up frustrated and right back where I started — that is, until I discovered the keto diet four years ago.

While following a diet high in fat, moderate in protein, and very low in carbohydrates has been a godsend for me, it has come with its fair share of difficulties.

Here are a few things I wish I'd known before I started the keto diet:

SEE ALSO: 10 surprisingly filling foods you can eat on the keto diet

A lot of people really won't get it.

The idea that you can eat a large amount of fatty foods — bacon, steak, whole milk, cheeses, etc. — and not only lose weight but increase energy tends to surprise people.

You'll soon lose count of the number of people who insist you need carbs to live. Ignore them. As the saying goes, KCKO. Keep calm and keto on.

You still need to count calories.

You may lose more weight more quickly on the keto diet than on other diets, but you can't eat with abandon just because you're cutting out carbs.

Calories still count, so it's important to determine your basal metabolic rate, which is how many calories your body burns daily by simply existing, as well as the deficit you should be eating at to lose weight.

Going "off plan" for even a day could make you gain weight.

It's pretty disheartening to wake up a few pounds heavier than you were the day before just because you had to have a cheat meal at McDonald's.

While this change is may just be water weight that you can shed after going back to the keto diet for a day or two (it flushes water from your system), some people will find that such an interruption is not worth the trouble.

• Lonely Planet named Sri Lanka the number one country in the world to visit in 2019.
• Vast tea terraces, an abundance of wildlife, and stunning beaches (and much more) make Sri Lanka a truly unforgettable destination.
• I had the pleasure of visiting Sri Lanka in 2018 and I can't recommend it enough.
• Here's why you simply can't miss it.

Travel guide company Lonely Planet recently named Sri Lanka the number one country in the world to visit in 2019.

The South Asian country was chosen because of a diversity of experiences, incredible food, and burgeoning tourism industry.

I had the pleasure of visiting this extraordinary country for two and a half weeks last year, and I honestly can't recommend it enough.

During my stay, I was lucky enough to take part in multiple safari tours, travel through the country's central highlands via one of the most beautiful train journeys in the world, and much, much more.

Scroll down for 15 stunning images and reasons why you can't afford to leave Sri Lanka off your bucket list for much longer.

It has the highest density of elephants in Asia.

Sri Lanka has around 5,800 wild elephants wandering around its national parks. One of the best places to witness these gentle giants is Udawalawe National Park, which is home to about 600 elephants that roam in herds of up to 50.

You may even see elephants on the roads, where they often interrupt traffic — it's usually best to let them pass.

Be warned: There are a number of so-called elephant orphanages and sanctuaries that are very popular with tourists. However, some have been highlighted by PETA for animal abuse as the elephants are often chained up and controlled by a mahout wielding a bullhook.

Basically, anywhere that allows you to ride the elephants should be a no-go.

Views don't get much better than sunrise over Adam's Peak.

I defy you to find a better view than this — it's not possible.

Adam's Peak (Sri Pada) climbs 2,243 metres (7,359 feet) into the air and is known for its depression at the peak, which Buddhists believe to be the footprint of the Buddha.

The climb itself should take you around 2-4 hours depending on your level of fitness and is best done first thing for an incredible sunrise view.

This shot was taken from the monastery, which is located right on the top of the peak.

Historic Galle Fort is great for shopping and dining.

While the city of Galle now stretches far beyond the ramparts, the fort itself (built up by the Dutch in the 17th century) has been painstakingly maintained and is now a UNESCO World Heritage Site.

There are plenty of historical monuments to visit, but its also a great place to peruse shops at leisure and stop off at cafés and restaurants for refreshments.

It is also home to some of the country's best boutique hotels like Fort Bazaar and 41 Lighthouse Street.

This is a preview of a research report from Business Insider Intelligence, Business Insider's premium research service. To learn more about Business Insider Intelligence, click here. Current subscribers can read the report here. 

If we're living through a “retail apocalypse” that spells doom for brick-and-mortar retail, as many have suggested, why are e-commerce leaders like Amazon, Alibaba, and JD.com so focused on building their own brick-and-mortar networks?

It's because they want to revitalize physical stores by introducing features associated with online shopping like personalization — and a whopping 65% of consumers said personalization and promotions are most important to their shopping experiences, according to a report from Oracle cited by Chain Store Age.

Brick-and-mortar retailers have the opportunity to reap the same benefits of personalization that e-tailers do, like repeat visits and impulse purchases, but they need to invest in the right technologies and techniques to do so because they currently don’t meet shoppers’ expectations. For example, 41% of consumers expect sales associates to know about their previous purchases, but just 19% have experienced this, according to a report from Segment.

In this report, Business Insider Intelligence analyzes how physical retail’s personalization is being outperformed by e-commerce’s, and examines the value personalization holds for brick-and-mortar in particular. We also look at what techniques and technologies are available to help retailers identify and track consumers in-store, and how they can be used to bolster their personalization capabilities. Finally, we examine the different channels through which retailers can reach consumers with their personalized offerings in-store.

The companies mentioned in this report are: Amazon, Alibaba, JD.com, Intel, Mastercard, Target, Velocity Worldwide, RetailMeNot, b8ta, Nordstrom, Saks Fifth Avenue, Sitecore, Oak Labs, Calabrio, and Alegion.

Here are some of the key takeaways from the report:

• Consumers say that a personalized shopping experience can inspire loyalty and increases in spending.
• But brick-and-mortar retailers aren't meeting consumers’ in-store personalization expectations.
• The nature of online shopping gives e-commerce the upper hand when it comes to personalization.
• Physical retailers can close the gap in personalization by identifying consumers when they enter, tracking them throughout their journey, and then using that information to inform individualized offerings.
• To make the most of personalized offerings, retailers must consider how content is being presented to consumers in-store, and what the strengths of each channel are.
• If physical retailers fail to improve their in-store personalization, they risk losing sales and market share to e-commerce companies, both online and in-store.

In full, the report:

• Identifies the values of personalization to physical retailers.
• Details the reasons e-tailers currently offer better personalization than brick-and-mortar stores.
• Outlines the technologies and processes that can bolster in-store personalization.
• Discusses how retailers can best present personalized offerings in-store.

Join the conversation about this story »

• Billion-dollar deals from the drug giants Eli Lilly & Co. and Bristol-Myers Squibb could set the tone for a year full of healthcare acquisitions, analysts and investors say.
• Factors like biotech companies' slumping stocks and last year's tax cuts could drive the trend, compared with last year's competitive nature and high premiums.
• These are the drugmakers to watch and what they've said so far about M&A.

Headline deals by the drug giants Eli Lilly & Co. and Bristol-Myers Squibb could be just the beginning of mergers-and-acquisitions activity in healthcare this year.

Deal fever has been building among investors and analysts, many of whom gathered at this week's J.P. Morgan Healthcare Conference, a major industry event held in San Francisco each year.

January's banner $74 billion BMS-Celgene merger and $8 billion Lilly-Loxo deal could set a tone for the year, they say, especially in biopharma. That's something of a reversal from expectations that dealmaking would slow this year after hitting a record in 2018.

"Anytime you start the year with a bellwether biotech company like Celgene being acquired, it gets everyone excited for deal activity," Mike Gaito, JPMorgan global co-head of healthcare investment banking, said. 

"We're extremely busy coming into the new year," he said. There's "a lot going on in the M&A world and financing world."

There could be more big pharma deals in 2019

Big companies also hinted in recent days that hopes for more deals were justified.

"I think the fact that you haven't seen a large deal coming out of Merck recently is not a reflection of the fact that we're not looking at those," Merck CEO Kenneth Frazier said during the JPMorgan conference.

"We are active," he said, adding, "I think with the valuations coming down, it creates more possibilities."

Deal activity could be higher than in 2018 because of a confluence of factors, according to a sector sales commentary from Stifel. Those include the underperformance of many small- to mid-cap biotech companies, last year's tax cuts, and a desire to pull ahead of any possible 2020 political changes.

Subscribe to Business Insider's weekly healthcare newsletter Dispensed for all the biggest news from the J.P. Morgan Healthcare Conference.

'First and foremost, we're focused on M&A'

Steve Elms' venture-capital firm has benefited from this year's dealmaking. His company, Aisling Capital, made about $470 million when Lilly agreed to acquire Loxo this week. And he told Business Insider he expected to see more deals.

"With the market selling off from the highs, yes I do believe 2019 is going to be an M&A year," Elms said.

Read more:Here's why Bristol-Myers Squibb's record-breaking $74 billion biotech deal is facing investor backlash

Drugmakers with large cash holdings have been clear targets for questions about M&A. They include Amgen and Gilead, which "both have well over $30B in cash," the Cantor Fitzgerald analyst Alethia Young pointed out.

Amgen "may be much more active in M&A this year," Young predicted.

Robin Washington, the chief financial officer of the biotech giant Gilead, said at the conference that when it came to spending the company's cash pile, "first and foremost, we're focused on M&A."

Wall Street is watching Biogen and J&J too

Another company Wall Street has its eye on is Biogen. Some of the company's most promising experimental drugs are intended for Alzheimer's disease — an area with high unmet need, where drug development is notoriously high-risk, prompting calls for more diversification.

The biopharmaceutical company has typically bought earlier-stage companies, translating to relatively smaller price tags, including paying $27.5 million upfront when acquiring two drugs, one in phase 1a and one preclinical, from AliveGen in July, and its $75 million upfront acquisition of a phase 2b ready drug from Pfizer in April.

See more:A $63 billion biotech is returning to the scene of its worst failure in search of new treatments for a deadly muscle disorder

But the company raised eyebrows with recent comments about having $13 billion in financing capacity — prompting "several" questions about M&A during a recent hourlong meeting at the JPMorgan conference, the Mizuho analyst Salim Syed observed.

By Syed's math, Biogen's purchasing power is $17 billion to $18 billion. Even so, the analyst said he didn't expect a large deal in the immediate future.

Johnson & Johnson, meanwhile, seemed to signal its interest in smaller deals during a JPMorgan presentation. CEO Alex Gorsky described the company's best deals as "the tuck-ins, the bolt-ons."

"Bigger is always more complicated," he said. "It's always more challenging, just more disruption. We're willing to take a look as we did with Actelion, and we think that that's been an important addition to us. But it does raise the bar in terms of your thought process and the capabilities that you need to bear."

Deals don't always work out, and some companies are cautious

Of course, M&A is also notoriously difficult to predict, Aisling Capital's Elms pointed out.

Last year, for example, a few acquisitions were announced early in the year "and then it was kind of quiet," he said. "Pharma companies continue to need pipelines. But you also just saw AbbVie write off their Stemcentrx acquisition — that must have been painful."

Read more: AbbVie just admitted that a cancer drug it acquired in 2016 is a $4 billion flop

Big drugmakers, health insurers, and care providers agreed to a record high of about $421 billion in transactions in 2018, Business Insider previously reported.

Notable biopharma deals included Sanofi's $11.6 billion bid for Bioverativ, Celgene's $9 billion acquisition of Juno, and Roche's $1.9 billion acquisition of Flatiron Health.

But, by contrast, companies were also "paying high premiums ... as competition drives prices higher," according to an Informa Pharma Intelligence report from 2018, raising concerns about too-high valuations.

Read more:

• Healthcare deals hit an all-time record in 2018. See the 7 biggest tie-ups that could change how we buy drugs and treat diseases.
• A biotech is proposing a plan to pay for its pricey rare-disease treatment the same way you'd buy a TV or dishwasher. Here's the inside story.
• A top investor who just made $470 million on buzzy biotech Loxo's $8 billion takeover told us where he might place his next bets

Join the conversation about this story »

NOW WATCH: I stopped eating breakfast for 2 weeks and I'm never doing it again

• Biotech company Bluebird Bio proposed a five-year installment plan for its pricey gene therapy at a major healthcare conference on Tuesday.
• The company hasn't put out a price tag for the experimental product, which hasn't yet been approved, but capped it at $2.1 million a treatment.
• Bluebird CEO Nick Leschly told Business Insider the inside story of how the plan came about and what challenges it could face.

Installment plans are used for big-ticket items like dishwashers and TVs — and now, for medical treatments?

That's exactly what the biotech Bluebird Bio is suggesting for its cutting-edge, experimental gene therapy, LentiGlobin, which is intended as a one-time treatment for the rare blood disorder beta thalassemia.

The idea works like this: Patients get the treatment, and their health insurer or employer will then pay Bluebird over five years. The company hasn't yet said how much the treatment will cost, but capped it at $2.1 million.

A key difference from other payment plans is that Bluebird will get paid in years two through five only if the treatment works for patients. Medicines are usually paid for as the patient takes them — whether or not the drug works.

It's a bold proposal, one that puts substantial financial risk on Bluebird itself, and there are still problems left to be ironed out, CEO Nick Leschly acknowledged in an interview late Tuesday with Business Insider.

But the decision was ultimately about the nearly 30-year-old Cambridge, Massachusetts-headquartered biotech's principles and its belief in doing the right thing, Leschly said. In that sense "the die was cast long ago," he said.

In developing the model, he told employees, "Don't limit yourself to what the system can't digest," Leschly said. "Do not feel that we should be penalized because we came up with something that provides value over time."

Metallica and caffeine

Leschly put the new pricing proposal out on Tuesday at the J.P. Morgan Healthcare Conference, the biggest industry event of the year.

Before presenting to a packed room, Leschly psyched himself up with four cups of coffee and by listening to Metallica, he told Business Insider.

LentiGlobin won't cost more than $2.1 million total, according to Bluebird — the amount of value that the biotech estimates its treatment should provide to patients by allowing them to live longer and with a better quality of life.

The plan has evolved significantly over time, Leschly said. The biotech originally considered a 10-year payment timeline, he said, but decided against it as because of the heavy administrative burden. In the current plan, health insurers can choose to distribute their payments over less than five years, he said.

Read more:From the gene therapy that spurred a $9 billion acquisition to a CBD medication for rare types of childhood epilepsy, here are the 12 promising drugs to watch in 2019

The plan will face serious challenges, including: What happens if a patient switches insurers? What if the individual becomes uninsured?

But Leschly is confident that Bluebird can get through them. For one, beta thalassemia — which is caused by a genetic mutation and can require regular blood transfusions and lifelong medical care, according to the National Organization for Rare Disorders — affects about one in 100,000 individuals, a relatively small patient population.

Individuals with "very severe conditions like this have a tendency to not change payers as often," Leschly said.

Payers can also check in to see if the treatment is working by looking at their claims data to see if, say, the patient suddenly needed new blood transfusions, he said.

Another key part of the plan is that Bluebird won't make any price increases beyond a measure of inflation, an interesting commitment that comes at a time when pharmaceutical price increases have prompted controversy.

Read more:Trump may have shamed Pfizer for increasing drug prices, but that isn't stopping drugmakers from doing more of the same

Bluebird has been criticized for not yet disclosing its price tag.

Leschly told Business Insider that there's "more work to be done on what the price exactly ought to be."

LentiGlobin hasn't yet been approved. The company expects a decision in Europe this year and could get a decision in the US as early as next year.

Gene therapies challenge the health system

Gene therapies like LentiGlobin are challenging the status quo and the limits of what the medical system can and will pay for.

To large extent, that's because the sums talked about when it comes to gene therapy are astronomical.

Read more:Bill Gates warns that nobody is paying attention to gene editing, a new technology that could make inequality even worse

Drugmakers say that's because their products are for rare, often deadly conditions with few or no other options. Moreover, they say, gene therapies could have lifelong benefits for patients and are expected to save the medical system money on things like hospitalizations.

That hasn't lessened the sticker shock: Swiss drug giant Novartis' suggestion that its new gene therapy for a deadly, rare disease would be cost-effective at $4 million to $5 million per patient encountered substantial resistance last fall, for example.

Join the conversation about this story »

NOW WATCH: Mistletoe is actually a tree-killing parasite — here's how it became a Christmas icon

• John, who runs the personal finance blog ESI Money, has spent the past few years interviewing millionaires.
• He found that building wealth involves a four-step process: Growing income, controlling spending, investing in index funds, and finding additional investment sources — namely, real estate.
• The first three steps are all about simplicity, whereas investing in real estate requires more complexity — but the financial advantages are worth it, according to real estate investors.

At the end of the day, building wealth is relatively simple: Earn good money, save, and invest. 

But there's a fourth, additional step millionaires often take once that's all said and done: Investing in real estate.

"Investing in real estate seems like a natural result once the basics are covered and excess cash is generated," John, who retired early at the age of 52 with a $3 million net worth and writes personal finance blog ESI Money, wrote in a blog post.

John would know — he spent the past few years interviewing 100 millionaires. Here, he breaks down the four-step process many of the millionaires he spoke with used to build wealth:

• "Person/couple begins with normal job, then works to grow income and/or advance, generating additional, strong career income.
• While doing this they keep their spending under control, creating an ever-widening financial gap between what they make and what they spend.
• They invest in index funds to add even more growth to their finances.
• As this cycle continues and feeds itself, they look for additional sources of investment and real estate seems a natural fit for this extra cash."

The first three steps involve tried and true principles to becoming a millionaire. 

Most millionaires are goal-oriented and hard workers — they commit to increasing their skill set to build wealth for a long-term plan, according to author Chris Hogan, who studied 10,000 millionaires. This leads to the strong career income John spoke of.

They also have enough perseverance to avoid "lifestyle creep"— the tendency to spend more whenever one earns more. By spending below their means, millionaires are able to commit to saving that well-earned income, which is the heart of building any wealth.

William D. Danko, the coauthor of the best-seller "The Millionaire Next Door," recently said in a Q&A with The Washington Post, that you should create a lifestyle off of 80% of your income and save the remaining 20%. 

Read more: Most people believe 6 myths about millionaires, and it can keep them from building their own wealth

A portion of this 20% goes to millionaires' favored investing strategy: Low-cost index funds, which are rcommended by experts like legendary investor Warren Buffett for their minimal risk and cheap costs.

It's then that millionaires can begin to move beyond simplicity and look for additional investment opportunities like real estate.

Seasoned investors build wealth through real estate

"It's an interesting result since real estate is not known to fit the other investment criteria millionaires prefer (simple, easy, etc.) but there's certainly something about it that draws them," wrote John.

Just ask Dana Bull, a realtor and real-estate investor based in Massachusetts. After becoming a landlord in her early 20s when she bought a condo and rented it out for extra income, she now owns more than a dozen rentals — and thinks that real estate is one of the best ways to build wealth.

"What I love about real estate is that you can build your own strategy," she wrote in a post for Business Insider. "My bread and butter has been purchasing small multifamilies with two to four units per building. This is a great entry-level strategy, especially for those looking to live in one apartment while renting out the rest to offset a mortgage."

The financial advantages of investing in real estate are plentiful, according to Bull: Positive cash flow, appreciation in terms of housing values, leverage, and tax advantages.

But the reward doesn't come without the effort, she says. Like building wealth, investing in real estate takes patience and hard work.

SEE ALSO: A researcher who studied more than 600 millionaires found the same 2 qualities helped them get rich

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• America operates on a progressive tax system. That means as a person earns more and progresses through tax brackets, their tax rate increases for each level of income.
• Rep. Alexandria Ocasio-Cortez of New York has touted a plan that would tax Americans earning more than $10 million at a rate as high as 70%.
• Under America's progressive tax system, that means Americans earning more than $10 million wouldn't owe 70% of their total income on taxes; they would owe 70% of the income they earned only after a certain point.
• The highest tax bracket is 37% for single filers earning more than $510,301 and married filers earning more than $612,351.

Rep. Alexandria Ocasio-Cortez of New York appeared on "60 Minutes" Sunday night and touted a plan that would tax the richest Americans at a rate as high as 70%.

"Once you get to the tippy-tops, on your 10 millionth dollar, sometimes you see tax rates as high as 60% or 70%," Ocasio-Cortez said. "That doesn't mean all $10 million are taxed at an extremely high rate. But it means that as you climb up this ladder, you should be contributing more."

As Dion Rabouin of Axios said, some people believe Ocasio-Cortez is proposing a flat tax rate of 70%, but that's not how it works under our progressive tax system.

Read more: Alexandria Ocasio-Cortez's plan to tax the wealthiest Americans 60-70% could bring in billions of extra dollars for the federal government

How much you pay in taxes depends on several factors, including whether you're single or married, and, of course, how much you earn. President Donald Trump's tax plan went into effect in January 2018, mandating new income tax brackets for nearly all American taxpayers. The IRS has released new tax brackets for income earned in 2019, updated for inflation.

If you earn $40,000 a year as a single filer, that puts you in the 22% tax bracket in 2019 — but while 22% of $40,000 is $8,800, you're not paying $8,800 in taxes.

Your tax bracket applies to only the amount you earn above the minimum income threshold for that bracket. For income below that limit, you pay the same amount of federal income taxes as everyone else, even if they earn less overall.

Here's how the calculation works for a single taxpayer in 2019:

1. Figure out your taxable income: annual salary minus deduction(s).
2. Everyone pays a 10% federal-income tax rate on their first $9,700 of taxable income.
3. Everyone pays a 12% federal-income tax rate on their next $9,701 to $39,475 of taxable income.
4. Everyone pays a 22% federal-income tax rate on their next $39,476 to $84,200 of taxable income.
5. And so on and so forth.

One notable thing about this kind of tax setup is that the amount of taxes owed by someone steadily increases as that person's amount of income increases. It's not a monumental change when people jump from one tax bracket to another.

Read more: Everything you should be doing to prepare for tax season

Let's run through how this would work for an imaginary person: John, who earns $40,000. To keep it simple, let's say he makes all his money from his work salary and has no dependents.

For his 2019 taxes, John would subtract the standard deduction ($12,200) and take zero personal exemptions, since they were eliminated with the GOP tax law.

That makes his taxable income $27,800, putting him in the 12% tax bracket.

Here's how to estimate how much he would owe in taxes:

• The first $9,700 of his $27,800 total taxable income is taxed at a 10% rate, yielding $970 in taxes.
• Then, his income between $9,700 and $27,800 — a total of $18,100 — is taxed at a 12% rate, yielding $2,172 in taxes.
• So, adding $970 to $2,172, John might owe about $3,141 in taxes, rather than the $3,336 he would owe if his entire taxable income were evaluated at the 12% rate.

Elena Holodny contributed to an earlier version of this article.

SEE ALSO: The IRS can't pay out tax refunds during the partial government shutdown, and it's the biggest problem for people who need it the most

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• On Monday, a new drug for depression got a big lift from positive clinical trial results. Stocks surged on the news.
• The drug is made by Sage Therapeutics, a Cambridge-based pharmaceutical company that focuses on brain disorders.
• Nearly all existing antidepressants, from Celexa to Zoloft, work on the brain's serotonin network. But the drugs fail for as many as 1 in 3 people and take 4-6 weeks to have an effect.
• Sage's new drug targets a different brain system than these antidepressants. As a result, it appears to work faster and last longer.

A drug that works differently than all existing antidepressants just got a big boost. 

In results from its latest clinical trial on Monday, the drug, called Sage 217, appeared to relieve symptoms of post-partum depression in a sample of roughly 150 women. Made by pharmaceutical company Sage Therapeutics, the new drug candidate acts on the brain’s gaba system, in stark contrast to all current medications for depression. Those drugs are called SSRIs (selective serotonin reuptake inhibitors) and effect the brain’s serotonin network.

Sage's stock surged accordingly, rising from roughly $97 per share to almost $150 per share.

Some early research suggests it may even be possible for patients to go several weeks without taking the drug — as opposed to being tied to a daily pill. And analysts say the results suggest the drug would also be a good candidate for people with regular depression, also known as major depressive disorder, as well as those with post-partum depression or PPD.

Experts who study depression told Business Insider they'd been cheered by earlier study results on the drug, which suggested it could offer patients relief in a different way from current treatments.

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The latest results bolster that analysis, they say, making the new drug potentially appealing for many patients.

However, although the drug appears to be a big innovation in several ways, those experts say it's worth noting that it would likely not work as a sort of one-and-done treatment in the way Sage CEO Jeff Jonas described over the summer. 

Why Sage's new drug could be a game changer for people with depression

Analysts, scientists, and clinicians agree that Sage's new drug could be a game-changer for the millions of people who live with depression and don't get results with current treatments.

For its latest study, researchers concluded that Sage-217 worked fast and well, noting that most patients observed a relief in symptoms as early as three days into the treatment. Those results were maintained for at least a month.

"In our view, these data not only provide a more commercially viable product for post-partum depression, but should also further increase investor confidence in the ongoing Phase 3 trial in the broader population of patients [with major depression]," JPMorgan analyst Cory Kasimov wrote in a note

A drug that works fast and lasts is something that most patients with depression have never seen. For all of the hope that drugs like Celexa and Prozac have inspired, they don't work for as many as one in every three patients. 

In addition, the drugs — which target the brain's serotonin system and are thus known as SSRIs (selective serotonin reuptake inhibitors) — take roughly 4-6 weeks to work.

That's not quick enough for patients with severe depression and suicidal thoughts, according to Cristina Cusin, a psychiatrist at Massachusetts General Hospital and an assistant professor at Harvard University who specializes in severe depression. 

By contrast, Sage's drug appears to take an effect as quickly as two weeks into treatment — not as fast as rapid-fire anesthetic drug ketamine, but significantly quicker than all existing approved antidepressants.

Read more:A 'party drug' with potential to be the next blockbuster antidepressant is edging closer to the mainstream, but it could set you back $9,000

Wall Street analysts say they see a huge market potential for the new drug.

Latest results are 'a best case scenario' for the new drug

The results the company released this morning "represent essentially a best case scenario," for the drug, wrote JPMorgans' Kasimov.

Others agreed.

"The possibility of having something that impacts the Gaba system is attractive because if you were to launch it tomorrow, there’s likely going to be lots of patients who’ve failed with anything that’s available,"Paul Matteis, the managing director of biotech research with brokerage firm Stifel, told Business Insider in December.

Plus, the drug may not require patients to take it daily, at least according to both the latest study and a series of preliminary results from the company's clinical trials.

That's something that Matteis said sounds like it would be "preferred by most patients than having to take something indefinitely."

That optimism is what Sage CEO Jonas was likely alluding to when he made his comments about Sage-217 over the summer, Matteis said. 

In June, Jonas said Sage-217 had the potential for patients with depression "to feel well within days, with just a two week course of treatment — similar to how antibiotics are used today."

Shortly after he made that statement, the company's stock surged.

Yet instead of taking the drug only once, most experts say patients would likely need to take it "episodically"— meaning as frequently as once a month. That's still a big change from the way current antidepressants are administered, and could be a significant boost for patients, said Matteis.

"Any paradigm-shifting drug is going to have some nuances that, I don’t wanna say are scary, but are counterintuitive to the current therapy model."

SEE ALSO: A Silicon Valley VC in the hottest area of healthcare explains what it looks for in new startups aiming to disrupt the $35 billion addiction market

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• Companies ordered 43% fewer semi-trucks in December 2018 year-over-year, according to ACT Research. 
• A slump in truck orders typically forebodes an economic turndown because it shows retailers and manufacturers plan to move fewer goods. 
• But four trucking insiders told Business Insider that they still have a rosy outlook for freight in 2019. 
• 2018 was a red-hot year for trucking, and 2019 is forecasted to be a smaller, but still healthy, market. 
• The industry will cool slightly in the second half of the year.

The last few weeks of December were tumultuous times on the market — to put it lightly. Christmas Eve saw the deepest plunge in stocks in that day's history, indicating that the Dow and S&P 500 would have its worst performance in 2018 since the financial crisis.

Two days later, markets shot up for its best day in a decade, only to slump again the day after. 

A slowing global economy, the US government shutdown, and uncertain trade talks between the US and China are all making investors uneasy, and manyhave saida recession is in the works for 2019. 

Read more:Shipping boomed in 2018 — but transportation companies' stocks plunged this year

Yet analysts in the exact areas where one would expect rampant fretfulness are oddly calm. Traders in Europe, for instance, are betting that European companies will flourish, despite dipping consumer confidence and industrial output in France, Germany, and others.

Issues seem to be arising in trucking, too

New truck orders plunged by 43% in December 2018 year-over-year, according to ACT Research. Orders sank last month by 24% from November 2018. Cancellations were also higher than expected, according to a note by Morgan Stanley freight analysts. That ends 2018, one of the hottest years in trucking, on a sour note and appears to foretell trouble in 2019. 

Read more:Household staples from Hershey's chocolate to Crest toothpaste will get more expensive next year, and executives are partially blaming the 'overrun' trucking industry

A dip in truck orders is particularly foreboding as it indicates manufacturers are producing less and that retailers assume they'll be moving fewer goods in the coming months. Steve Tam, vice president of ACT Research, called truck orders a leading indicator. 

"Because trucking participates in all phases of manufacturing, it increases as manufacturing starts to ramp up, giving it leading indication on economic growth," Tam told Business Insider.

Major trucking stocks including FedEx and XPO Logistics faltered last month, too. 

Still, trucking analysts mostly have a cheery outlook for 2019 

Tam of ACT Research said he forecasted that 335,000 trucks will be produced in 2019, up 5% from 2018's production of 320,000. 

"A lot of the predictions are maintaining that there will be some momentum coming out of 2018 and seeing if it can hold in 2019," Michael DiCecco, who is executive managing director of Huntington Bank's asset finance sector, told Business Insider. Part of Huntington's $6.5 billion asset finance business includes lending to trucking companies to buy new trucks and equipment.

Read more:Walmart's trucking fleet used to be as selective as Harvard, but a truck driver shortage has changed how Walmart hires 

Morgan Stanley freight analysts wrote that year-over-year orders in 2019 will sink below 2018's record numbers. But analysts like Tam said production will increase. The industry is expected to be healthy in the first half of 2019, then cool.

"Company executives may slow from a flat out sprint to a jog, but they might not stop or start walking backwards at this point," Tam said. 

Orders are down because the production backlog is severe 

As 71% of America's freight is moved on trucks, the fact that companies foresee that they'll need fewer trucks is typically an omen for an economic downtown.

But there's one explanation for why orders are down that doesn't spell economic doom. So many companies ordered trucks last year that there's a huge backlog of trucks. Those transportation companies are still waiting for their orders, and understandably not ordering more. 

DiCecco said freighters are waiting seven to eight months for truck orders — even though they take only 10 weeks to produce in a normal circumstance. In the third quarter of 2018, the wait was as long as a staggering nine months. 

Tam said there's around 300,000 orders in the backlog. In a normal year, that's around 80,000 to 100,000 units.

Watch out for production slowing

Because of healthy truck production numbers, insiders like Don Ake, vice president at freight-equipment research group FTR, are doubting there will be a devastating slowdown in trucking or the economy as a whole in 2019. The industry will cool slightly in the second half of the year.

"Right now, if somebody came to me and said to me, 'Hey, these people are saying recession in 2019,'" Ake told Business Insider, "I'm going back to numbers from the equipment market and I'm going to say, 'No recession in 2019 under normal circumstances.'"

If production slows, though, Ake said he'll start to to "watch the economy like a hawk." 

"That means that there could be a significant change on the way," Ake said. 

SEE ALSO: Here's why a little-known autonomous trucking company is beating Tesla and Waymo in the race for driverless big rigs

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• Microsoft President Brad Smith penned a blog post on LinkedIn about the 10 biggest issues tech is sure to tackle in 2019. 
• Artificial intelligence, he mentioned, will play a powerful role in how the economy functions, whether it leads to job growth or decline, and how tech companies work with law enforcement to implement facial recognition. 
• And with no mention of President Donald Trump, Smith echoed concerns made by other tech giants over the trade relationship between China and America. 

The tech industry is still reeling from a tumultuous 2018, as growing privacy concerns, cyber security threats and online disinformation campaigns have caused many people to reassess their relationship with technology.

Things are only going to get more complicated as new innovations like artificial intelligence and voice recognition become increasingly commonplace in our lives. 

Microsoft President Brad Smith outlined some of the biggest tech issues in store for us this year in a sobering blog post he recently published on LinkedIn.  Another year of public 'tech-lash' seems probable, Smith writes, as society debates the roles that technology, and tech companies, play in our lives. But there's also an opportunity for us to confront the challenges head on, and to take steps that will help us reap the benefits of innovation while avoiding the pitfalls. 

Here's what Microsoft's President believes the top 10 tech issues will be in 2019: 

First priority: Privacy

Smith believes privacy protection is set to gain traction in 2019, both in Europe and the United States. 

Businesses in Europe will have to continue to find ways to interpret the General Data Protection Regulation — a 2016 law guarding the data and privacy of all those within the European Union. And California's new Consumer Privacy Act means the issue is becoming more widespread. 

"Look to the next few months for the spread of privacy legislation to several other state capitals, all of which will set the stage for an even bigger debate on Capitol Hill," Smith says. 

Fakes News and 'Disinformation'

Social media platforms have become a preferred means for nation-states to spread disinformation campaigns. And last year marked a "sea change" in our understanding of the problem, Smith says. 

"The big question now is what will be done to address the problem," he writes.

While social media companies have begun to acknowledge their responsibilities and accountability, Smith suggests that new laws could be used to ensure that social media companies take the issue seriously. He mentions a white paper by Virginia Senator Mark Warner to "impose a duty on social media platforms to determine the origin of accounts or posts, identify bogus accounts and notify users when bots are spreading information." 

The US/China relationship

The tech sector could be in for a bumpy ride this year when it comes to trans-Pacific trade, Smith says.

"Across the American political spectrum there is greater appreciation of China’s momentum in artificial intelligence and other technology and heightened concern about its economic and national security implications," writes Smith. 

Smith likened the December arrest of Meng Wanzhou, the chief financial officer of Chinese smartphone maker Huawei, to a "Netflix drama."  Talk of export controls on emerging tech like AI, and the potential for protectionist rules limiting acquisitions by foreign companies in Europe will become increasingly important stories to follow. 

• The government shutdown just became the longest on record, entering into a 23rd day on Sunday.
• Past government shutdowns have not typically had a meaningful impact on the stock market or economic growth, Wall Street economists and market strategists say.
• But a partial shutdown dragging on could delay trade talks between the US and China, and contribute to an element of uncertainty that could upset markets.

The government shutdown won't impact the stock market or the economy — until it does.

That was the crux of Wall Street's outlook this week as the partial US government shutdown over funding for President Donald Trump's proposed wall on the southern border was on track to become its longest on record. The shutdown broke the record on Saturday, and extended to a 23rd day on Sunday.

Experts say while past shutdowns have indeed had a benign impact on stocks and economic growth, risks around US-China trade talks, consumer sentiment, and the market's performance are not off the table.

"We think a deal will be reached to reopen the government, but only after economic, financial and/or political pain is felt," Bank of America Merrill Lynch economists led by Michelle Meyer told clients on Thursday. "Every two weeks of a shutdown trims 0.1pp from growth; additional drag is likely due to delays in spending and investment."

Now read: China and the US just agreed to a fresh set of trade-war negotiations — but the government shutdown threatens to derail any progress

Looking back to prior shutdowns, Bank of America found the "general rule of thumb" is that the direct impact felt by a shutdown is roughly a 0.1 to 0.2 percentage-point drag on growth per week. That led them to lower their own forecast for fourth-quarter GDP to 2.8% from 2.9%. 

"Additional drag could be felt if the shutdown generates uncertainty shocks in the economy leading to a decline in business and consumer sentiment and/or a decline in US equity markets."

To be sure, it's well documented that stocks tend to take government shutdowns in stride. Rarely has a shutdown pushed stocks down in a meaningful way, according to an analysis from LPL Financial Research. Shutdowns have corresponded with a flat median return in the previous 20 shutdowns going back over 40 years, LPL found. Since the shutdown began on December 22, the S&P 500 has gained 7.4%.

An ongoing shutdown could even influence the Federal Reserve's interest-rate hiking path at a time when uncertainty persists around future rate hikes.

"With economic growth set to hold up fairly well in the near term we continue to expect up to two more rate hikes in the first half of this year," Nikhil Sanghani, assistant economist at Capital Economics, told clients earlier this week. "But a renewed plunge in the stock market or more serious disruption resulting from the government shutdown would probably take any further hikes off the table." 

Now read: From airport lines to food inspections, here are all the ways the government shutdown is impacting the lives of average Americans

More granularly, the manufacturing and services sector could feel the pain as a result of the shutdown. The shutdown negatively impacting the purchasing manager's index (PMI) — a widely followed economic indicator — was among Fundstrat Global Advisors' eight listed risks to the firm's otherwise bullish 2019 outlook. 

Others view the shutdown as more a more benign event. Economists at UBS do not view it as a major macroeconomic risk, they told clients in a note out Friday.

"In the past two major government shutdowns, private employment and consumer spending were unaffected," a team led by Samuel Coffin wrote. "There were some increases in initial jobless claims in states with a lot of Federal employees, but they did not spill into longer deterioration." 

Even still, the current shutdown will have "larger effects the longer it goes on."

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This is a preview of a research report from Business Insider Intelligence,  Business Insider's premium research service. Current subscribers can read the report here.

Until now, healthcare was the only remaining industry that had yet to feel the rapid impact of digitization endured by retail, banking, and media. But consumer adoption of digital tech, regulatory overhauls, and a shifting reimbursement model are forcing healthcare players' hands.

Digital health innovation offers market incumbents new opportunities to combat constricting margins, labor shortages, and rising costs.

But it also poses a threat to slow movers, as new entrants lean on their digital prowess and lack of legacy infrastructure to cut costs and remain nimble. As such, incumbents are turning to acquisitions, partnerships, and new investments to strengthen their digital health services.

The first Digital Health Ecosystem Report from Business Insider Intelligence explores the current healthcare ecosystem, industry trends that are driving digital transformation, and where the industry is headed.

We outline the role of each of the industry's major players — including payers, providers, and manufacturers — and how they're affected by healthcare's digital disruption. 

Here are some of the key takeaways from the report:

• Digital health is at the forefront of transformation in the healthcare industry — both as a driver of and an answer to the challenges industry players are grappling with.
• All of the industry's major players — including payers, providers, and manufacturers — are affected by healthcare's digital disruption.
• A confluence of forces induced healthcare's embrace of digital health, including changing consumer expectations, a new and disruptive reimbursement model, and rising healthcare costs
• Tech-focused entrants are also breaking into healthcare, acting as catalysts for change and threatening legacy players' bottom lines.
• Key digital health solutions like EHRs, digital therapeutics, telehealth, AI, wearables, and blockchain are the foundation of the industry's digital awakening.
• Early evidence that digital health can address many of the industry's myriad challenges has fueled a vibrant US digital health funding market in 2018, with overall funding hitting $6.8 billion at the end of Q3. 

 In full, the report:

• Details the US healthcare landscape by the role that payers, providers, manufacturers, and distributors play in the healthcare ecosystem.
• Gives an overview of how digital health is enabling incumbents to overcome industry challenges.
• Outlines how tech-focused healthcare entrants are pressuring incumbents and accelerating healthcare's digital transformation
• Identifies promising digital health funding areas to illustrate what the future of digital health will look like.

Interested in getting the full report? Here are two ways to access it:

1. Purchase & download the full report from our research store. >>Purchase & Download Now
2. Subscribe to a Premium pass to Business Insider Intelligence and gain immediate access to this report and over 100 other expertly researched reports. As an added bonus, you'll also gain access to all future reports and daily newsletters to ensure you stay ahead of the curve and benefit personally and professionally. >>Learn More Now

The choice is yours. But however you decide to acquire this report, you've given yourself a powerful advantage in your understanding of the fast-moving world of the Digital Health.

The companies mentioned in this report are: Aetna, Alphabet, Amazon, American Well, AmerisourceBergen, Anthem, Apple, Arizona Care Network, Arterys, Babylon Health, Beth Israel Deaconess Medical Center, Bay Labs, Blue Cross and Blue Shield Association, Blue Mesa Health, Bright Health, Cardinal Health, Cedars-Sinai, Cleveland Clinic, Clover Health, CVS, DePuy Synthes, Devoted Health, Dexcom, Doctor on Demand, Express Scripts, Fitbit, Fresenius Medical Care, GE Healthcare, Geisinger, Glooko, GSK, healthfinch, IBM, IDx, Johnson & Johnson, Mass General, McKesson, Medtronic, Merck & Co., Merck KGaA, Microsoft, NewYork-Presbyterian, Northwell Health, Novartis, Olive, Omada Health, Optum Rx, Oscar Health, Pear Therapeutics, Pfizer, Philips, PillPack, ResMed, Rite Aid, Roche, Samsung, Sanofi, Senseonics, Suki, Tallahassee Memorial Hospital, T-Mobile, UnitedHealth Group, Verily, Viant, Walgreens, Walmart, Wellpepper, Zocdoc

SEE ALSO: Patients are transforming from passive recipients of healthcare services to active participants in their own health

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• I rode in a self-driving car for the first time at this year's International Consumer Electronics Show (CES) in Las Vegas.
• The car was operated by Yandex, the Google of Russia.
• If I hadn't been making a point of paying attention to the vehicle's performance, I likely would have forgotten that it was driving without human assistance.

Yandex is the Google of Russia, known for running a search engine that, by some measures, is more popular than Google in its home country. Like Google (via a spin-off company, Waymo), Yandex is also developing autonomous driving technology.

The company operates an autonomous ride-hailing service in two Russian cities and demonstrated its software at this year's International Consumer Electronics Show (CES) in Las Vegas. I rode in a converted Toyota Prius on a 4.3-mile loop, my first experience riding in a self-driving car. The car was outfitted with three lidar sensors, five cameras, and eight radars.

Here's what my ride was like.

SEE ALSO: These are the 5 leaders in the self-driving-car race

This is what the car, a converted Toyota Prius, looked like.

It had three lidar sensors, which emit pulses of light to detect objects and determine how far they are from the car.

The car had five cameras, like the one pictured below.

• A one-time treatment for a devastating rare disease could be paid for with an installment plan as soon as this summer in Massachusetts. 
• Novartis's AveXis unit is involved in the discussions. Its gene therapy could cost up to $5 million per treatment. 
• Organizers hope the plan will ensure patients can access a potentially life-changing treatment.
• Business Insider is the first to report on the discussions and the interest from AveXis. 

In recent years, no treatments were even available for the rare, devastating disease known as spinal muscular atrophy.

Now, in a matter of months, an experimental one-time therapy designed to address the disease's underlying genetic cause could treat the disorder. First though, someone has to pay for its potential multimillion-dollar pricetag. 

A new effort is underway in Massachusetts to figure out how to do that. The idea is to let health insurers pay for the treatment over several years. If it succeeds, organizers hope that it could prove to be a viable model for the entire US. 

Novartis's AveXis unit, which makes the gene therapy, Zolgensma, and has suggested a price tag of up to $5 million could be appropriate, is in talks to participate. Business Insider is the first to report both the plan and interest from Novartis's AveXis. 

Americans have long paid for big-ticket items like houses and cars in a similar manner. But the plan — if it is finalized — would mark one of the first such approaches for a medicine. And Novartis would only receive each of its payment if the treatment is effective.

Paying for drugs on an installment plan

"Think of it as installment plan that’s then tied to how well the therapy works. This would be a car loan but you’ve still got to see if the car is going to work,"Mark Trusheim, strategic director of the MIT Center for Biomedical Innovation's NEWDIGS program, told Business Insider.

NEWDIGS brings organizations together to discuss how the US health system will be able to pay for costly cures, and the Massachusetts initiative came out of that, Trusheim said.

That work has become increasingly important as more gene therapies are likely to become available in coming years for different diseases, according to experts interviewed for this story. Gene therapies are typically administered in a single treatment and can have very high price tags compared to other types of pharmaceuticals. That could impose massive costs and challenges for an unprepared health system

Read more:From the gene therapy that spurred a $9 billion acquisition to a CBD medication for rare types of childhood epilepsy, here are the 12 promising drugs to watch in 2019

Doing the unthinkable, at an exceptional price

Gene therapy is a cutting-edge technology with the potential to cure diseases by tinkering with the body's genetic material. Drugmakers have cited the value these new products could bring to patients and the medical system to justify their high prices.

Spinal muscular atrophy is a rare genetic condition that affects muscle movement in children and is the leading genetic cause of mortality in infants.

About 10,000 to 25,000 individuals in the U.S. are thought to have SMA, according to the SMA Foundation. But far fewer individuals would likely be treated with Zolgensma, since it's thought that only newborns would be eligible.

In Massachusetts, only one or two dozen patients are expected each year at most, according to Trusheim. A US approval decision Zolgensma, is expected in May, and Novartis isn't likely to release a precise price tag until then.

An independent group that evaluates drug prices has said the treatment could merit a price of $1.6 million to $5 million, Novartis Pharmaceuticals CEO Paul Hudson told Business Insider this week, noting that the cost of ventilators and another expensive therapy for the rare disease over a five-year period were, in total, comparable.

AveXis plans to explore `creative' ways to get paid for its new treatment

Hudson heads up the business that oversees AveXis's SMA gene therapy. AveXis would not comment specifically about its participation in the Massachusetts program, but said in a statement that gene therapies require new approaches in the US health system.

"Our objective is to ensure patients get access to this therapy, so we can make a meaningful difference in their lives," the AveXis statement said. "We are working closely with payers to ensure we establish appropriate prices reflecting the value of gene therapy and explore creative options for payers, including installment payment options, as well as outcomes-based arrangements."

As the Massachusetts pilot currently stands, the price of Zolgensma would be paid by health insurers in five annual installments, spread out over four years. It is similar to a plan unveiled by biotech Bluebird Bio earlier this week, MIT's Trusheim said. 

Read more:A biotech is proposing a plan to pay for its pricey rare-disease treatment the same way you'd buy a TV or dishwasher

The program is starting with the Novartis product, but intends to add other gene therapies over time. Many but not all health insurers in Massachusetts are involved in the discussions, Trusheim said, and others could eventually join. Its organizers hope to launch it by this summer, and they believe they have addressed many of the challenges of this type of approach. 

'We shouldn't let cost get in the way'

One crucial challenge for these types of installment plans is what happens when patients switch health insurers. In this case, the insurers that intend to participate in the Massachusetts pilot have agreed to pick up the remaining payments left on the installment plan.

"If you believe these are likely to be life-changing to the people who need them, then we shouldn't let cost get in the way," Dr. Michael Sherman, chief medical officer of the nonprofit health insurer Harvard Pilgrim, told Business Insider. If the program gets off the ground, Harvard Pilgrim intends to be a part of it, he said. 

The planners are still working out other details. For instance, even though the payment structure and performance metrics for the gene therapy would be the same across insurers, each individual health plan would negotiate its own price for Zolgensma.

Insurers will also have to work out with Novartis what happens if a patient moves to another state. That might include continuing to make the payments or potentially making a one-time exit payment.

Another challenge is a legal requirement that the government Medicaid program get the "best price" on a drug. That could complicate this type of installment plan, since a failed treatment in which only one installment is paid could be interpreted as violating that "best price" guarantee. 

Read more: Bill Gates warns that nobody is paying attention to gene editing, a new technology that could make inequality even worse

Because spinal muscular atrophy is so rare, health insurers haven't expressed concerns about Zolgensma's price tag specifically, Hudson told Business Insider this week. Instead, they'd like the flexibility to pay in installments if needed, according to Hudson. 

"What they're not saying is, 'We're worried about the price.' What they are saying is, 'We may have concerns about staging payments,'" Hudson said. 

Additional reporting by Lydia Ramsey

Read more about pharmaceutical innovation: 

The CEO of $230 billion pharma giant Novartis explains why he's not scared of buying biotechs at an earlier — and riskier — stage

Big drugmakers are sitting on billions of cash — and top pharma executives are hinting about big M&A to come in 2019

One of the biggest drugmakers in the world thinks it has 26 billion-dollar drugs in the pipeline — here's what they aim to treat

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• Trucking moves 71% of the freight in the United States.
• Most of the basic functions of society wouldn't be effective if truckers were to stop working.
• And naturally, your Amazon Prime packages would be delayed. 

Trucking moves 71% of the freight in the United States. And if it were to suddenly cease, the effects would be more drastic than you might expect.

In May 2018, truck drivers in Brazil went on strike for a week, and it "paralyzed" the country in unexpected ways. As gas stations ran out of fuel, for instance, public transit halted. 

"Without trucking, we would be naked, starving, and homeless," Mike Robbins, a longtime trucker and leader of trucker strike group Black Smoke Matters, told Business Insider. 

A study by the American Trucking Associations outlined what would happen if truckers were to stop working. The effects would hit hospitals, gas stations, ATMs, grocery stores, and even your garbage can.

And, of course, your Amazon Prime packages would be delayed. 

Within the first day

Basic medical supplies, like syringes and catheters, would be at risk of running out. Medication for cancer patients that use radiopharmacuticals, which only have a life span of a few hours, would expire. 

During the 2018 truck strike in Brazil, a lack of medical supplies was a key choke point for the country. Government security forces escorted trucks with supplies to hospitals and doubled fines against striking truckers who were carrying medical cargo. 

Are you a truck driver with a story about the industry? Email the reporter at rpremack@businessinsider.com.

Read the full report from the American Trucking Associations here.

SEE ALSO: Thousands of truck drivers are organizing a strike in a Facebook group called 'Black Smoke Matters' — here's the origin of the provocative name

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• Worm toilets require no traditional flushing and aren't hooked up to a sewer system — instead, worms compost human waste.
• More than 4,000 such "Tiger Toilets" have been installed to date across India, in homes of people who were previously defecating in the open.
• The worm toilets smell a lot better than a pit latrine, and don't breed mosquitoes either.
• Here's how a $350 toilet powered by worms could change the world and save lives. 

Worms may not have spines, but they're doing some back-breaking sewer work in more than 4,000 toilets across India. 

Since 2015, a creative new type of toilet called the Tiger Toilet has been popping up outside homes and schools around the country. From the outside, this toilet looks like any other pit latrine. But it doesn't smell like one. Instead, it comes with a built-in population of tiger worms. 

"Their natural breeding, natural habitat is in cow dung heaps, or horse sh*t heaps, that kind of thing," Ajeet Oak, director of the Tiger Toilet company, told Business Insider. "Poop. That’s where they like to live."

The toilets involve no traditional flushing and aren't hooked up to a sewer system. Instead, the worms are contained in a container below the toilet, and they feast on feces. The creatures' activity leaves behind a mix of water, carbon dioxide, and a small amount of wormy compost (that's technically the worms' poo, though it's much less toxic and more nutrient-rich than ours).

The resulting water isn't clean enough to drink, but it "can go into the ground and it sort of gets filtered naturally from there on," Oak said. No wastewater treatment plant needed. 

To get the worm system to market, The Bill and Melinda Gates Foundation awarded at least $4.8 million in grant money to the London School of Hygiene and Tropical Medicine to perfect the technology. Tiger Toilets also received $170,000 for initial testing in India, Myanmar and Uganda from USAID. Now, after years of development and field testing around the world, the technology is finally reaching people who need it most.

"These are people who are getting toilets for the first time," Oak said, adding that before getting a Tiger Toilet, "they would go out in the field." 

Bill Gates recently told a crowd in Beijing that he's ready to spend an additional $200 million developing technology for next-generation toilets like these that can operate without mainframe sewer systems. 

"We estimate that by 2030, the opportunity here is over $6 billion a year," Gates said.

Read More: Bill Gates is so obsessed with redesigning the world's toilets, he brought a jar of poop onstage in Beijing to prove it

How worms clean excrement

Tiger worms, or Eisenia fetida if you prefer the scientific term, are animals that love to eat waste. This makes them a perfect composting solution, and they especially love what falls into their Tiger Toilet compartment. 

"These worms, they won’t escape on their own, because they won’t survive in just soil," Oak said. They need our human waste to live.

The Tiger Toilet system costs about $350 USD to install and requires no connection to drainage pipes or a mainline sewer.

Once a person does their business in the toilet, they send their waste down into the worm-filled compartment below using a pour-flush system, usually with a little bucket of water. (There are no handles or automatic flushing devices in the Tiger Toilet.)

The toilet's cleaning stats are impressive: they process feces, remove 99% of the pathogens, and leave behind no more than 15% of the waste by weight, in the form of compost material. The rest becomes water (around 60-70%) and carbon dioxide. That's better performance than a septic tank.

Plus, the leftover byproduct makes for "excellent fertilizer," Oak said, because its mix of nitrogen, phosphorous, carbon, and potassium is good for growing plants. 

Tiger Toilets (and Tiger worm-powered treatment plants, like the one pictured below) also don’t breed mosquitoes or attract other flying menaces.

"Users find the toilets preferable to traditional latrines,” USAID wrote of the toilets during field testing in 2015. "Because the worms break down the solid waste, the toilets emit fewer odors and attract fewer flies than traditional latrines."

The earliest editions of Tiger Toilets are now more than five years old and their worm compartments haven't needed any maintenance yet — the slimy creatures are still chomping away. Eventually, after about eight to 10 years, the company expects some toilet maintenance to be required. At that point, the worm bin, which isn't visible to toilet users, must be emptied.

It's not a terrible job — "you don’t have to handle sludge," Oak said. 

Simply remove the lid of the toilet, exposing the top layer of worm castings — their leftovers from years of hard work. Then shovel it out and use it in a garden as fertilizer. Then the worm population will be ready to work again. 

Why people need worm toilets

The tiny worms that make their home in filth are performing a lifesaving task for humans. 

Across the developing world, people without a safe place to go to the bathroom can die because of unsanitary conditions. Diarrhea kills 525,000 children under five annually around the world "as a result of poor hygiene," according to the World Health Organization. 

Improper hygiene also causes the global economy to miss out on an estimated $223 billion USD per year.

Additionally, open defecation can be a dangerous situation for women. A 2016 study in India found that women who defecate in the open are twice as likely to be sexually assaulted by a stranger as those who have a toilet in their house.

In India, millions of people relieve themselves outdoors on a daily basis — 40% of the country's population, according to the World Bank’s estimate from 2015.

The country has set a"Swachh Bharat Mission" goal of becoming open-defecation free this year, but it's unlikely to be fully successful, since even people who can access a toilet don’t always use it. A 2018 survey of more than 9,800 people and 150 local government officials across India found that one in four people in rural northern provinces have access to latrines but don’t use them. 

Some people choose to relieve themselves in the open for compelling reasons. An Indian woman identified only as "Veer" told Meenakshi Dalal, a program and communications specialist with USAID/India, that men block the way to her community toilet, taunting and harassing women.

"They dress up as women, they get in line with us, they might touch us,"Dalal recalled Veer telling her. "Every few days someone is raped. On one side of the toilet is where we live and on the other side it’s jungle. They can pull us there."

Tiger toilets is testing out some options for crowded slums like Veer's — a kind of downsized, city-friendly version of the worm toilet — but they’re not ready yet.

"The challenge is to have something for a family which can be put in a very small house," Oak said. "We’re calling it the Urban Tiger Toilet." 

India's government has also started offering cash incentives to people who install toilets in their homes, which makes a Tiger Toilet even more affordable for families who are getting their first toilet. 

Bringing worm toilets to the world

Lixil Group, the parent company that owns toilet-industry giants American Standard and Grohe, is also interested in Tiger Toilets. The company recently signed a letter of intent to bring Tiger Toilets to scale.

"Eventually we want to have something that’s really sleek and you can place anywhere,"Daigo Ishiyama, Lixil's  marketing and technology director, told Business Insider.

But he said that will take some time: "We’re dealing with living creatures — you know, worms."

Still, this kind of game-changing new invention — a toilet that requires no traditional sewer system — is an exciting prospect for Gates. He has even compared it to the invention of the personal computer. 

"A whole new product category is being introduced here," he said.

SEE ALSO: Bill Gates is so obsessed with redesigning the world's toilets, he brought a jar of poop onstage in Beijing to prove it

Join the conversation about this story »

NOW WATCH: Bill Gates is backing the waterless toilet of the future — here's how it works

• Bed Bath & Beyond's effort to clean up its stores is taking shape as it follows through on a plan to "show more, carry less."
• The stores have been called "a mess" by at least one analyst in the past.
• The company said in 2018 that its stores would look "noticeably different" beginning in March of last year, as it would start cramming less core merchandise onto shelves and adopt a more curated look.
• A new survey of customers by Morgan Stanley implies that this change is beginning to take root in customers' minds.

Bed Bath & Beyond's effort to clean up its stores seems to be making headway.

Its stores have been criticized in the past for being crammed with product, which has lead at least one analyst to call them a "mess."

"They are a hodge-podge of product, tightly crammed into a space that is largely devoid of inspiration. This makes them hard and sometimes unpleasant to shop," analyst Neil Saunders, managing director of GlobalData Retail, told CNBC in an email in 2018.

The company announced plans to make some changes in the form of what CEO Steven Temares called "show more, carry less initiatives" during a call with analysts in 2017, according to Retail Dive. He said the chain's stores would look noticeably different starting in March 2018, with less cramming of core merchandise on shelves and adopting a more curated look.

The effects of that change are apparently starting to take root in customers' minds. In a November survey of 1,350 furniture buyers by Morgan Stanley's Alphawise, analysts wrote that responses from customers "implies a perception of [Bed Bath and Beyond's] selection is moderating" in a note to investors.

In the survey, only 42% customers said that "selection of merchandise" prompted shopping at Bed Bath and Beyond, down from 55% in 2016.

The analysts were quick to point out that this could be due to the store's announced plans coming to fruition, but that it's too soon to say whether the change in perception is a good or a bad thing for the retailer.

On the other hand, citing "quality of merchandise" as a reason for shopping at Bed Bath and Beyond, grew from 43% in 2016 to 47%, while "store atmosphere and layout" fell from 26% to 23%.

Read more: Bed Bath & Beyond customers are starting not to care about the best reason to shop there

Morgan Stanley also said that customers seem to be relying less on the retailer's famous 20% off coupons, which may reflect success with its Beyond+ program, which gives permanent 20% off every purchase for a $29 annual fee.

SEE ALSO: Bed Bath & Beyond's stores have been slammed as 'devoid of inspiration' and 'a mess.' We went shopping there and found it completely overwhelming.

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