Genomic analysis of liver cancer reveals unexpected genetic players – Medical Xpress

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June 16, 2017 Cancer cell during cell division. Credit: National Institutes of Health

Liver cancer has the second-highest worldwide cancer mortality, and yet there are limited therapeutic options to manage the disease. To learn more about the genetic causes of this cancer, and to identify potential new therapeutic targets for HCC, a nation-wide team of genomics researchers co-led by David Wheeler, Director of Cancer Genomics and Professor in the Human Genome Sequencing Center (HGSC) at Baylor College of Medicine, and Lewis Roberts, Professor of Medicine at the Mayo Clinic, analyzed 363 liver cancer cases from all over the world gathering genome mutations, epigenetic alteration through DNA methylation, RNA expression and protein expression. The research appears in Cell.

Part of the larger Cancer Genome Atlas project (TCGA), this work represents the first large scale, multi-platform analysis of HCC looking at numerous dimensions of the tumor. "There have been large-cohort studies in liver cancer in the past, but they have been limited mainly to one aspect of the tumor, genome mutation. By looking at a wide variety of the tumor's molecular characteristics we get substantially deeper insights into the operation of the cancer cell at the molecular level," Wheeler said.

The research team made a number of interesting associations, including uncovering a major role of the sonic hedgehog pathway. Through a combination of p53 mutation, DNA methylation and viral integrations, this pathway becomes aberrantly activated. The sonic hedgehog pathway, the role of which had not been full appreciated in liver cancer previously, is activated in nearly half of the samples analyzed in this study.

"We have a very active liver cancer community here at Baylor, so we had a great opportunity to work with them and benefit from their insights into liver cancer," Wheeler said. Among the many critical functions of the liver, hepatocytes expend a lot of energy in the production of albumin and urea. It was fascinating to realize how the liver cancer cell shuts these functions off, to its own purpose of tumor growth and cell division.

"Intriguingly, we found that the urea cycle enzyme carbamyl phosphate synthase is downregulated by hypermethylation, while cytoplasmic carbamyl phosphate synthase II is upregulated," said Karl-Dimiter Bissig, Assistant Professor of Molecular and Cellular Biology at Baylor and co-author of the study. "This might be explained by the anabolic needs of liver cancer, reprogramming glutamine pathways to favor pyrimidine production potentially facilitating DNA replication, which is beneficial to the cancer cell."

"Albumin and apolipoprotein B are unexpected members on the list of genes mutated in liver cancer. Although neither has any obvious connection to cancer, both are at the top of the list of products that the liver secretes into the blood as part of its ordinary functions," explained Dr. David Moore, professor of molecular and cellular biology at Baylor. "For the cancer cell, this secretion is a significant loss of raw materials, amino acids and lipids that could be used for growth. We proposed that mutation of these genes would give the cancer cells a growth advantage by preventing this expensive loss."

Multiple data platforms coupled with clinical data allowed the researchers to correlate the molecular findings with clinical attributes of the tumor, leading to insights into the roles of its molecules and genes to help design new therapies and identify prognostic implications that have the potential to influence HCC clinical management and survivorship.

"This is outstanding research analyzing a cancer that's increasing in frequency, especially in Texas. Notably, the observation of gene expression signatures that forecast patient outcome, which we validate in external cohorts, is a remarkable achievement of the study. The results have the potential to mark a turning point in the treatment of this cancer," said Dr. Richard Gibbs, director of the HGSC at Baylor. The HGSC was also the DNA sequence production Center for the project.

Wheeler says they expect the data produced by this TCGA study to lead to new avenues for therapy in this difficult cancer for years to come. "There are inhibitors currently under development for the sonic hedgehog pathway, and our results suggest that those inhibitors, if they pass into phase one clinical trials, could be applied in liver cancer patients, since the pathway is frequently activated in these patients," added Wheeler.

Explore further: Study identifies a role for the metabolism regulator PPAR-gamma in liver cancer

More information: Adrian Ally et al. Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma, Cell (2017). DOI: 10.1016/j.cell.2017.05.046

Journal reference: Cell

Provided by: Baylor College of Medicine

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Genomic analysis of liver cancer reveals unexpected genetic players - Medical Xpress

Gene therapy by the numbers – BioPharma Dive

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Gene therapies have been in clinical development for decades, a winding, stop-and-start path toward transforming science's understanding of the genome into commercial therapies. Strimvelis, a gene therapy made by the British pharma GlaxoSmithKline and approved in Europe last year, will be a high-profile test of the viability of selling cures to a tiny handful of patients.

A broader pipeline, though, backs up an emerging field that could soon begin delivering new therapies to patients in need. Biotechs like Spark Therapuetics and BioMarin have promising gene treatments in late-stage development, and big pharmas like Pfizer and GlaxoSmithKline are active in exploring market opportunities in the space.

Only two gene therapies for inherited diseases have been approved for commercial sale in the Western world, both in Europe.

UniQures Glybera was the first to market, authorized under a five-year conditional approval for treatment of an ultra-rare genetic disorder known as familial lipoprotein lipase deficiency. Yet, Glyberas $1 million price tag and low demand (only one patient was ever treated) meant the therapy never gained any traction. In April, UniQure decided against seeking renewal of its marketing authorization when it lapses this October.

Gene therapy got some new momentum after GlaxoSmithKline won approval from the European Commission in May 2016 for Strimvelis, an ex-vivo stem cell gene therapy for a disease called ADA-SCID, perhaps better known as the "bubble boy" disease.

GlaxoSmithKline

Strimvelis is considered the first outright cure for a genetic disease, although its not known if the 100% survival rate seen in clinical trials will persist over a lifetime. Median duration of follow-up at the time of approval was seven years.

The cost of Strimvelis.

Cures dont come cheap. GlaxoSmithKline priced Strimvelis at 594,000 ($669,000), which after Glyberas $1 million pricetag and Strimvelis' better efficacy profile, was actually lower than what some had expected.

With more gene therapies in development, pricing will be a critical problem to solve for drugmakers seeking to commercialize genetic fixes particularly against the backdrop of the ongoing debate over how to price and value drugs.

One-time treatments that promise to deliver cures will clearly be priced higher than existing therapeutics. But its not just the high cost that will be an issue. If a drugmaker markets a cure with all costs paid upfront, the insurer and patient will hold the risk if the gene therapy stops working after, say, 10 years.

In addition, when patients in the U.S. are free to move from insurer to insurer as they change jobs and move through life, why would one insurer pay $500,000 or $1 million upfront if that patient is free to change insurance?

Estimated number of patients affected by ADA-SCID in Europe each year.

ADA-SCIDs ultra-rare nature underscores the challenge of successfully marketing a gene therapy. While some rare diseases have a sizable enough patient population to support a product commercially, others like ADA-SCID occur so infrequently that even a cure like Strimvelis might not actually make much money for GlaxoSmithKline.

The shelf life of freshly transduced cells for treatment with Strimvelis.

With Strimvelis, stem cells are taken from a patients bone marrow, inserted with a correct copy of the ADA gene using a viral vector, and then infused back into the patient, who has received low dose chemotherapy to improve engraftment.

Due to the limited window of time for infusion, GlaxoSmithKline only offers Strimvelis at the San Raffaele Hospital in Milan, Italy, which is near a cell processing laboratory.

While production and dosing procedures for other gene therapies will be different, manufacturing and logistical challenges are weightier than with small molecules or even biologics.

Since the drug is a patients own modified cells, chain of custody and supply chain visibility are crucial. Managing treatment at its own center simplifies things, but also makes it more difficult for patients to access treatment.

In 2003, the Food and Drug Administration temporarily halted 27 gene therapy trials amid safety concerns.

While Strimvelis and a full pipeline of gene therapies in testing have buoyed optimism in the field, progress from gene therapies hasnt been a straight line.

The FDA decided to suspend the 27 studies, which represented around 15% of the total number of gene therapy trials then underway, after two children developed leukemia-like symptoms in a French study. The new concern followed the 1999 death of Jesse Gelsinger, who had reacted to a gene therapy he received for a metabolic disorder.

The number of worldwide clinical trials for gene therapy or gene-modified cell therapy, according to numbers cited by the Alliance for Regenerative Medicine (ARM) in an annual report.

Thirty-one are in Phase 3, reflecting the progress in clinical development. Spark Therapeutics, for example, recently completed an application submission for U.S. approval of voretigene neparvovec in patients with a type of inherited retinal disease. The therapy, developed in collaboration with Pfizer, is one of the most high-profile candidates in the U.S.

Other well-known names such as BioMarin and Bluebird Bio are also making progress on treatments for beta thalassemia and hemophilia A, respectively.

Total amount of global financing for gene and & gene modified cell therapy companies raised last year, according to ARM.

That figure includes sums raised by a variety of means such as upfront payments, IPOs, venture rounds and partnerships.

Much of the work developing gene therapies has been driven forward by biotech companies, but big pharmas are starting to notice too.

Last summer, Pfizer put down $150 million upfront to acquire Bamboo Therapeutics, with another $495 million in milestones to shareholders lined up. More recently, the pharma giant paid $70 million upfront with $475 million in milestones to work with Sangamo Therapeutics on its hemophilia A gene therapies.

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Newly Designed Viral Vectors Could Lead to Improved Gene Therapies – Bioscience Technology

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For many patients, participating in gene therapy clinical trials isnt an option because their immune system recognizes and fights the helpful virus used for treatment. Now, University of Florida Health and University of North Carolina researchers have found a solution that may allow viruses used for gene therapy to evade the bodys normal immune response.

The discovery, published in the Proceedings of the National Academy of Sciences, is a crucial step in averting the immune response that prevents many people from taking part in clinical trials for various disorders, according to co-author Mavis Agbandje-McKenna, Ph.D., a professor in the University of Florida College of Medicine department of biochemistry and molecular biology and director of the Center for Structural Biology.

During gene therapy, engineered viruses are used to deliver new genes to a patients cells. While the recombinant adeno-associated virus, or AAV, is effective at delivering its genetic cargo, prior natural exposure to AAV results in antibodies in some people. As many as 70 percent of patients have pre-existing immunity that makes them ineligible for gene therapy clinical trials, Agbandje-McKenna said.

The findings provide a road map for designing virus strains that can evade neutralizing antibodies, said Aravind Asokan, PhD, an associate professor in the department of genetics at the University of North Carolina School of Medicine, who led the study.

University of Florida first identified the structural footprints where pre-existing antibodies interact with the virus, using an cryo-electron microscope. The UNC researchers then evolved new viral protein shells. Using serum from mice, rhesus monkeys, and humans, the researchers showed that the redesigned virus can slip past the immune system.

This is the blueprint for producing AAV strains that could help more patients become eligible for human gene therapy. Now we know how to do it, Agbandje-McKenna said.

While the findings prove that one variation of AAV can be evolved, further study in preclinical models is needed before the approach can be tested in humans. Next, the immune profile of one particularly promising virus variant will need to be evaluated in a larger number of human serum samples, and dose-finding studies are needed in certain animal models. Researchers may also need to study whether the same virus-manipulating technique can be used in a broader range of gene therapy viruses, Agbandje-McKenna said.

Although human gene therapy remains an emerging field and has yet to reach patients on a wide scale, researchers elsewhere have used AAV therapy to successfully treat hemophilia, a blood-clotting disorder, in a small trial. It has also been or is now being studied as a way to treat hereditary blindness, certain immune deficiencies, neurological and metabolic disorders, and certain cancers.

The latest findings are the result of more than 10 years of studying the interactions between viruses and antibodies and a long-standing collaboration with Asokan, who heads the synthetic virology group at the UNC Gene Therapy Center.

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Saturday’s letters: Hit-and-run, Frontier, gene therapy, Braves – Sarasota Herald-Tribune

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Hit-and-run story makes police look really inept

You have got to be kidding me.

A serious crime is committed (hit and run) with substantial bodily injury and property damage. When reporting the accident, the injured party says the person responsible has fled the scene, and the dispatcher asks: Do you still want an officer to respond?

Really? That must have instilled great confidence that a professional investigation was under way.

The initial responding officer fails to collect and protect physical evidence. Fortunately, the family of the injured party does. That's the extent of it for 16 days, until a complaint is made to the mayor.

The next officer on the case is able to identify the owner of the other vehicle. That person does not cooperate. So that's the end of it. Really? You can't bring him in for questioning?

Put Tom Lyons on the case and he will get it done really.

John Corning, Venice

Frontier not profiting from 'bogus billing'

The implication in Tom Lyons June 12 column that Frontier Communications somehow profits from customer billing issues is untrue and unjustified.

As with any company, our customers are our lifeblood. Our intent, in every interaction, is to provide reliable communications services.

When we let a customer down, we are accountable and do our best to fix the problem as quickly as possible. We offer sincere apologies and remedy the issue, making the customer whole. Often this includes credits for the customer quite the opposite of benefiting from bogus billing.

Frontier has made solid improvements over the past year and we will continue to sharpen our service. We live in and support the communities we serve, and our only goal is to be better.

Melanie Williams, Senior Vice President-Operations, Florida, Frontier Communications

Gene therapy article strikes home for reader

Regarding the June 6 article on the gene therapy of Stefanie Joho:

This article is very close to my heart. My husband Steve was diagnosed with cancer in 2005 and has been a patient since 2009 of Dr. Richard Brown, an oncologist at Florida Cancer Specialists in Sarasota.

In November 2015, Steve's chemotherapy was no longer effective. We were fearful and feeling desperate. Ironically, Jimmy Carter's remarkable life-saving treatment with a new immunology drug Keytruda (Merck pharma) was in the forefront of the news.

At Steve's next appointment, we told Dr. Brown that we had learned through a friends son, a breast cancer researcher, that Merck wanted to test Keytruda on other cancers. Dr. Brown, always Steve's advocate, told us that the practice had already discussed Steve. He would contact Merck.

It was determined Steve was a candidate and would qualify for the trial. He enrolled immediately. The rest is history!

The drug "suppressed a mutation" in his DNA. It attacked the cancers growth. Steve is no longer in the trial. He continues to receive an infusion treatment every three weeks and so far, so good!

Happily, life goes on and we owe a debt of gratitude to all the selfless researchers who have opened a new frontier in cancer treatment. Dr. Brown revealed that more options will be coming as they make new discoveries.

Good luck and long life to Stefanie!

Donna Jablo, Lakewood Ranch

Atlanta Braves play with taxpayers' money

In their quest for a cushy deal on their spring training facility, the Atlanta Braves were rebuffedby Palm Beach County and twice by Collier County, but have been welcomed with open arms by the easy marks in Sarasota County.

The pending deal will be another screw job unleashed on taxpayers by politicians offering huge subsidies to billionaire owners and multimillionaire players.

According to reports in the Herald-Tribune and elsewhere, the amount of public taxpayer money potentially allocated is:

$20 million from the Florida Sports Foundation, which, thanks to the Legislature and governor, is taxpayer-supported and hands out grants to special-interest groups like the Braves.

$22 million from the county tourism tax, which is paid by guests who stay in hotels and motels and largely used to fund special-interest groups rather than go into general revenues to benefit overburdened taxpayers. According to the Herald-Tribune, the requested amount is below the amount that would require public-referendum approval.

$300,000 a year paid by North Port for maintenance.

Also, West Villages is donating land worth $7 million to $9 million and paying for improvements.

Now, as reported in the Herald-Tribune, the county administrator and financial management officer suggest that a millage increase may be in store.

They play and you pay.

William Allen, Longboat Key

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Saturday's letters: Hit-and-run, Frontier, gene therapy, Braves - Sarasota Herald-Tribune

Judicial Review In To Futurist Decision Refused – Yorkshire Coast Radio

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The High Court in Leeds has refused Permission for a Judicial Review of the Borough Councils decision to demolish the Futurist Theatre.

The save the futurist campaign group has started legal action against the council seeking a review of the decision which was take in January but the high court dismissed the action on Friday afternoon.

The Save the futurist group say they will be speaking to their legal team next week in light of the decision.

Councillor Janet Jefferson, who has been heavily involved in the campaign to save the building, gave us her reaction today's judgement.

The save the Futurist group issued legal proceedings against Scarborough Borough Council on On 7th April 2017seeking permission to judicially review its decisions of 9th January and 17th January 2017 to demolish Scarboroughs Futurist Theatre.

In order to take the legal actionThe Save The Futurist group was required to become a legal entity and reformed as Save The Futurist Theatre (Scarborough) Ltd.

The group engaged solicitors, Squire Patton Boggs LLP of Leeds to work on the action together with a leading London public law QC. A fund raising campaign was started to help fund the legal action.

Speaking in May,Debi Silver from Save the Futurist explained why they were taking the action.

"The reason we're taking legal action against Scarborough Borough Council is because we're not happy with how the whole thing has been dealt with.

At the end of the day, we don't feel what they've done has been done correctly and it's left us with no other option.

I can't tell you the amount of work that's gone into bringing this case forward, presenting it to our solicitors.

This is a huge undertaking that's gone on, it's not been done lightly.

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Elon Musk Just Published His Plan to Colonize Mars – Futurism

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A New Plan

They say everythings sweeter the second time around, and that seems to be the casefor SpaceXs plans to colonizeMars. Last year, Musk unveiled his plans to colonize the Red Planet and make it fit for human habitation. Now, that version of the plan has been published and madeavailable for freewith a few notable updates.

In the paper, the focus is on affordability, as that is the primary factor in making life on Mars a reality. As Musk notes, You cannot create a self-sustaining civilization if the ticket price is $10 billion per person. In order for it to be viable, Musk asserts that the cost should be about $200,000equivalent to the median price of a house in the United States. In the paper, Musk outlines the steps he considers essential to ensuring this relative affordability.

But this is just the beginning.Musk posted a tweet today hinting that this version one is already being reviewedand version 2 is on its way.

According to Musk, the version one has one fundamental flaw, which is the cost of developing and operating giant rockets. While SpaceX has been specializing on reusable rockets, getting to Mars would still be costly due to the size of the rockets needed. According to V1 of the plan, getting to Mars depends on a reusable rocket-and-spaceship tandem, which Musk has called the Interplanetary Transport System (ITS). Reducing the costs to developing the ITS is crucial, especially since Musk himself has already put a cap on how much a trip to Mars should be.

Musk asserts that he envisions 1,000 or soITS spaceships, each of which are carrying 100 or more people, leaving Earth orbit during Mars windows, the point in time when Earth and Mars align favorably, which happens once every 26 months.

Outlining the importance of making this information freely available, New Space editor-in-chief Scott Hubbard asserts that publishing this paper provides not only an opportunity for the spacefaring community to read the SpaceX vision in print with all the charts in context, but also serves as a valuable archival reference for future studies and planning.

There is a huge amount of risk. It is going to cost a lot,Musk wrote. There is a good chance we will not succeed, but we are going to do our best and try to make as much progress as possible. By giving everyone access to this information, our chances of success are greatly improved.

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Head Transplant Doctor Reports Successful Repair of Spinal Cord in Rats – Futurism

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In BriefA head transplant doctor claims to have made advance towardrealizing the medical procedure, but the scientific communityremains skeptical. The team claims to have used a proprietary"glue" to repair the severed spines of rats and achieved fullrecovery. Head Transplants?

Sergio Canavero, a man who has made the goal of his lifes work to transplant a human head onto a donor body, is claiming a success. He and his team have reported seemingly positive results from a technique called the Gemini Protocol. They used the protocol to repair severed spinal cords in rats, and their findings indicate that their methodology works across the board.

The researchers severed thespinal cords of 15 rats. Nine then received the actual Gemini Protocol, while the remaining six served as controls.

After the team severed the spinal cords, they applied adrenaline and a cooled saline to reduce bleeding. The rats treated with the experimental process received a polyethylene glycol (PEG) substance Canavero simply refers to as glue, which he says repairs and seals nerve cells in damaged spinal cords. The wounds were closed and the rats received antibiotics for three days.

Fourteen of the 15 rats survived for a month following the operation. According to the researchers, the experimental rats treated with PEG mixture recovered motor function steadily and were about to walk again by day 28. In fact, two of them were basically normal by that time.

However, most in the scientific community joined by most in the gaming community for totally different reasons are as highly skeptical about these alleged outcomes as they have been all along.

Scientists are doubtful for several reasons. First, the team didnt describe their methods well enough for other researchers to be sure about them. Case Western Reserve University Professor of Neurosciences Jerry Silver said in an interview with Newsweek that its not clear whether they severed only the dorsal spinal chord or the entire spinal chord.

He also points out an overall lack of evidence: they show no evidence for regeneration. There is no histology [the microscopic study of tissue structure], which is the only way to assess what is really going on here, Silver added.

Moreover, the characterization and scoring of motor function in the experimental rats is, according to Silver, unrealistic. The study reported that two of the treated animals recovered nearly normal locomotor skills (scoring of 19 and 20 points out of a possible 21 total) and that the treated rats had average a score of 12, which means that, on average, they could take multiple weight-bearing steps.

[This is] unbelievable, Silver said in the interview. Too good to be true in my opinion, which mandates that these results will have be independently verified and properly analyzed before this work can be accepted as scientifically valid.

Gamers are also skeptical because this appears to many to be a viral marketing scheme for Metal Gear Solid. The games creator and Canavero both deny this.

The team is now moving on to experimentation on dogs apparently horrifying many potential consumers is not a concern for them. They hope this next stage will provide indisputable proof that the technique works across the board. The first human head transplant remains scheduled in December of this year; the patient will be a Chinese national.

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Amazon CEO Jeff Bezos Needs Your Ideas For a New Philanthropic Endeavor – Futurism

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In Brief Amazon and Blue Origin CEO Jeff Bezos is asking help over Twitter for a new philanthropy strategy that's focused on helping people in the here and now. Though obviously an innovator, Bezos believes he needs to do something more immediate.

Serial entrepreneur Jeff Bezos needs your help. He recently took to Twitter to post a message about a predicament hes currently facing; he is crowdsourcing for a new philanthropic idea.

Im thinking I want much of my philanthropic activity to be helping people in the here and now short term at the intersection of urgent need and lasting impact, Bezos wrote in the tweet. It seems like the Amazon CEO was inspired by the philanthropic work done at Marys Place in Seattle.

Bezos admitted that much of his time is currently occupied by long-term innovation, as can be seen in his work with Blue Origin. His private space company is currently working on improving its rocket technology as it builds the New Glenn, its biggest one yet. The plan, Bezos revealed previously, is to colonize the SolarSystem, which is obviously a long-term endeavor.

Bezos also has projects that bring long-term ambition into the here and now. One example of this is how Amazon is redefining the retail experience with its unmanned stores. Its a product of how Amazon has been usingartificial intelligence (AI), an advanced and quickly developing technology, to influence business in the present.

As for Bezos new philanthropic idea, one can say that whatever positive changes it could make in the here and now could give people a shot at a better future. And hey, you can even get involved and pitch in an idea or two.

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Toshiba Has Unveiled a Swimming Robot to Assist in the Fukushima Cleanup – Futurism

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In Brief Toshiba has developed a robot to help survey highly radioactive waters at the site of the Fukushima nuclear power plant. The robot will help find lost fuel rods and gauge the structural integrity of the facility to ensure safe removal.

The 2011 meltdown of the Fukushima Da-Ichi nuclear power plant was a disaster of outrageousproportions. Triggered by a massive earthquake, the meltdown forced tens of thousand of people to evacuate their homes. The cleanup effort is ongoing and has been employing robots to help remove the radioactive fuel still trapped within the ruins of the facility.

Past robots used in the effort have consistently run into issues given the intense radiation on the site. Tokyo Electric Power Co (Tepco) has made progress in the removal of some of the spent fuel rods, but some melted fuel rods have managed to evade detection.

A new remote-controlled robot, however, is hoping to help locate those melted rods while also surveying the structural damage to the facility. Once the rods are located, the team will have to study the best way to safely remove them. The robot is about the size of a loaf of bread.

Radiation levels in the plant continue to make it impossible for humans to complete the cleanup. One robot, known as the scorpion probe, was exposed to radiation levels of 1,000 Sievert, which would kill a human in a matter of seconds. Robotics give humans control in these impossible conditions.

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Hawaii Becomes the First State to Pass a Bill in Support of Universal … – Futurism

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In BriefThis month has shown that Hawaii may be the U.S.'s mostforward-thinking state. Earlier in June, it became the first stateto formally accept the provisions of the Paris Climate Accord, andnow, the state congress has passed a bill that puts Hawaii on thepath to universal basic income. Eyes on the Future

Innovation and forward-thinking may beHawaiis two biggest exports in 2017. Earlier this month, the state earned the distinction of being the first in the U.S.to formally accept the provisions of the Paris Climate Agreement after President Donald Trump decided to withdraw the nation from it, and now, Hawaii is taking the lead in embracing yet another innovative idea: universal basic income (UBI).

Today, Hawaii state representative Chris Lee wrote a Reddit post aboutHouse Concurrent Resolution 89, a bill he says he introduced in order to start a conversation about our future. According to Lee, After much work and with the help of a few key colleagues, it passed both houses of the State Legislature unanimously.

Lee also mentioned the development via Twitter:

The bill has two major provisions. First, it declares that all families in Hawaii are entitled to basic financial security. As far as Im told, its the first time any state has made such a pronouncement, wrote Lee. The second provision establishes a number of government offices to analyze our states economy and find ways to ensure all families have basic financial security, including an evaluation of different forms of a full or partial universal basic income.

The congressman thanked redditors in his post, as he said the site became his first resource in considering UBI, and added a Reddit-standard TL;DR at the end: The State of Hawaii is going to begin evaluating universal basic income.

Under a UBI program, every citizen is granted a fixed income thats not dependent on their status in life. Despite the current focus on the concept, itactuallyisnt particularlynew. In fact, former U.S. President Richard Nixon actually floated the idea back in 1969.

However, the benefits of such a program havebecome more appealing in light of recent technological advances, specifically, the adoption ofautomated systems that could result in widespread unemployment.

Proponents of UBI have highlighted how it would be an improvement on existing social welfare programswhile mitigating the effects of the joblessness expected to follow automation. Critics think that UBI would encourage a more lax attitudeabout workand argue thatfunding such a system would be difficult, if not impossible.

Existing pilot programs, however, seem to indicate otherwise.

Hawaii may be the first U.S.state to pass any sort of UBI-positive legislation, but several countries around the globe are already testing the system. Finland began its two-year UBI pilotin 2016, and Germany has one as well. Canada plans to start trialsin Prince Edward Island (PEI) and Ontario, while India is currently debating the merits of UBI. Several private UBI endeavorsare also in the works, including one that uses blockchain and cryptocurrency.

Of course, the implementation of any major UBI program requires a great deal of political will. As Lee wrote, Planning for the future isnt politically sexy and wont win anyone an election []. But if we do it properly, we will all be much better off for it in the long run.

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Elon Musk in Talks to Bring Electric Cars to India – Futurism

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Tesla CEO Elon Musk said hes in talks with Indias government to sell electric cars in the country, which is currently the fourth-largest auto market in the world.

Musk said on Twitter Thursday that he is currently negotiating a relief on import penalties until Tesla can build a local factory. This isnt the first time Musk has announced he intends to enter the Indian market Musk said in February he was hoping to launch in the country this summer.

India could become one of the most important markets for Tesla given the countrys massive population size and focus on reducing emissions.

Vehicle adoption in India is expected to growrapidly. At its current pace,the country is set to become the third-largestauto market in the world by 2020, according to a May report by the India Brand Equity Foundation, the Indian governments resource center for economic information.

Indias passenger vehicle segment witnessed the most growth in the 2016 fiscal year, but two-wheelers still secure the most widespread adoption.

But some foreign automakers have so far struggled to increase sales in India, driven partially by a crackdown on diesel vehicles. General Motors putits $1 billion planned investment in India on hold last summer due to poor sales and the regulatory environment, Reuters reported at the time.

What could give Tesla an edge is that India islooking topromote electric and hybrid vehicle sales through its National Electric Mobility Mission Plan. The initiative aims to have 6-7 million electric and hybrid vehicles on the road by 2020 by offering manufacturing and purchasing incentives. The country, however, will need to invest heavily in a charging infrastructure to make that vision a reality.

As Musk explores India, Tesla is also looking to further tap into theChinese car market, the largest in the world, asthe government pushes battery-powered vehicle adoption.

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Elon Musk in Talks to Bring Electric Cars to India - Futurism

Renewable Energy in the US Broke Energy Records for the First Time – Futurism

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In Brief Renewable energy sources, particularly solar and wind, have broken records in the U.S. electricity market. According to a report by the EIA, solar and wind combined generated 10 percent of the nation's total energy, the highest percentage yet.

A new report shows that earlier this year, renewables brokeenergy records in the United States for the first time. The data from the U.S. Energy Information Administrations (EIA) Electric Power Monthlydemonstrated that the monthly electricity generation from solar and wind sources made up10 percent of the countrystotal generation in the U.S.during the month of March.

The date from the EIA showed that around 8percent of the total electricity generated during that month came from wind, and the other 2 percent was from solar sources, including residential and utility-scale solar panels. The EIA noted these two renewable sources are highly seasonal: wind generates increasedin electricity during spring and solar output reaches its highest numbersin the summertime.

The agency saidits likely when they review the data for April, the trend will have continued: Based on seasonal patterns in recent years, electricity generation from wind and solar will probably exceed 10% of total U.S. generation again in April 2017, then fall to less than 10% in the summer months, according to a press release by the EIA. Renewable energy is clearly stirring things up, as it continues to break records andnot just in the U.S. These record-breaking quarters arent surprising, sincethe price of renewables has decreased considerablycompared to traditional coal-based sources. Renewables are also disrupting the U.S. job scene: more people are now employed by solar power than all fossil fuel employers combined. Renewable employees also outnumber those working at huge companies likeGoogle, Facebook, and even Apple.

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Renewable Energy in the US Broke Energy Records for the First Time - Futurism

US bishops vote to make religious freedom committee permanent – Crux: Covering all things Catholic

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INDIANAPOLIS The U.S. bishops voted on Thursday to make their Ad Hoc Committee on Religious Liberty a permanent committee of the national bishops conference.

The very idea of religious freedom and its root in human nature is challenged today, said Archbishop Lori, chair of the ad hoc committee, at a meeting of the U.S. bishops Thursday.

He added, how important it is that we remain in the public square through advocacy for the freedom of religious institutions to fight poverty, provide health care and education, serve immigrants, and protect human life.

In 2011, the ad hoc committee was formed for a period of three years, as the bishops were deeply concerned about a broad trend of threats to religious freedom on the local and national level, Lori noted, speaking at the annual spring general assembly of the U.S. Conference of Catholic Bishops in Indianapolis.

Pope Benedict XVI, in his address to U.S. bishops in January of 2012 during their ad limina visit, warned of grave threats to the Churchs public moral witness presented by a radical secularism where there were certain attempts being made to limit that most cherished of American freedoms, the freedom of religion.

Many of you have pointed out that concerted efforts have been made to deny the right of conscientious objection on the part of Catholic individuals and institutions with regard to cooperation in intrinsically evil practices, the pope said. Others have spoken to me of a worrying tendency to reduce religious freedom to mere freedom of worship without guarantees of respect for freedom of conscience.

The U.S. bishops voted in 2014 to extend the committee for another three-year period. Then on Thursday, they voted to make the committee permanent by a vote of 132-53, with five bishops abstaining.

Most notably, the committee established the annual Fortnight for Freedom, a two-week campaign of prayer, penance, and advocacy for the Churchs continued freedom to serve in the public square, starting on June 21, the eve of the feasts of Sts. Thomas More and John Fisher, and ending on July 4, Independence Day.

One of the most notable threats the ad hoc committee warned of was the contraceptive mandate. The Department of Health and Human Services, interpreting the Affordable Care Act, had issued rules under the Obama administration that employer health plans had to cover sterilizations, contraceptives, and drugs that can cause abortions.

While churches and their immediate auxiliaries were exempt from the mandate, many religious institutions, including hospitals, universities, and charities, were not. Changes to the regulation offered by the Obama administration still violated the religious beliefs of the Catholic organizations, bishops and Church leaders contended.

In May, President Donald Trump promised regulatory relief from the mandate for religious non-profits like the Little Sisters of the Poor.

The struggle against the HHS mandate is not over, Lori warned on Thursday. Victory is not assured.

The promised relief could change with another presidential administration who could again enforce the mandate against religious groups, the archbishop said.

And other threats to religious freedom persist, he said, like the legalization of same-sex marriage, which could pose problems for religious institutions that uphold the Churchs teaching on marriage.

The archbishop cited then-Solicitor General Donald Verrilli, who admitted during oral arguments in Obergefell v. Hodges, the 2015 Supreme Court case that legalized same-sex marriage in all 50 states, that there could be an issue with the tax-exempt status of religious universities teaching that marriage is between one man and one woman, if same-sex marriage were the law of the land.

Some bishops voiced their strong support for the committee on Thursday, including Cardinal Timothy Dolan of New York, who chaired the USCCB when the committee was formed, and Cardinal Donald Wuerl of Washington, D.C. The most recent president of the USCCB, Archbishop Joseph Kurtz of Louisville, also supported making the committee permanent.

The bishops of the world look to us, Dolan told his fellow bishops, to be the real quarterbacks in defense of religious freedom.

A few bishops voiced objections to making the committee permanent in the discussions before the vote on Thursday.

Several were concerned about how it would appear to make the religious liberty committee permanent at the same time that the bishops working group on immigration, begun in November, finished its formal work.

However, Archbishop Jose Gomez of Los Angeles, vice president of the conference, clarified later on Thursday at an afternoon press conference that the working group will continue, although Cardinal Daniel DiNardo of Houston-Galveston, president of the conference who had begun the working group last November, had not specified a timeline for how long it would continue.

Furthermore, Lori stressed, the conference already has a standing Committee on Migration. The important thing is that as the sun sets, theres a permanent committee in place, because we understand the questions of migration are permanent, he said.

Bishop Christopher Coyne of Burlington, Vermont also voiced concerns that funding for the religious freedom committee could eventually dry up, while Cardinal Joseph Tobin of Newark said that domestic religious freedom concerns can be handled by the domestic policy committee, referring to the USCCB Committee on Domestic Justice and Human Development.

I am not convinced that there is a need at this time for it, he said of the religious freedom committee.

Bishop Francis Kalabat of the Chaldean Eparchy of St. Thomas the Apostle in Detroit strongly supported extending the committee, however.

There are currently 60 million refugees in the world, he said. What percentage of them came as a result of a lack of religious freedom?

Who you back up, or who backs you up, is who gives you the strength in the Middle East, he said, noting that if the U.S. shows strong support for religious freedom, it also shows support for persecuted Christians elsewhere.

Religious freedom, Lori stressed, covers a wide spectrum of ministries, a wide spectrum of advocacy, and there is need for some consistency for a clearing house and a clear voice.

Religious liberty is a concept that really relates to ones fundamental stance towards God, he said, that first and primal relationship towards God. As Dignitatis Humanae states, he noted, religious freedom is rooted in human nature and granted by God as a fundamental human endowment.

On Thursday, the bishops also voted to approve new guidelines for the celebration of the sacraments of persons with disabilities.

The new guidelines were said to pay deeper attention to allergy problems, for example the gluten intolerance or alcohol intolerance of a communicant. They encouraged parishes to be more aware and accommodating of persons with disabilities in the distribution of the sacraments.

Kurtz tweeted on Thursday that the National Catholic Partners on Disability were excited about the revised guidelines.

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US bishops vote to make religious freedom committee permanent - Crux: Covering all things Catholic

The North Korea detainee’s final moments of freedom – New York Post

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Newly released images show former North Korea detainee Otto Warmbier smiling with his tour group and throwing snowballs, before he was taken prisoner by the hermit nation.

A short video clip, released Thursday by Warmbiers brother, shows the 22-year-old University of Virginia student playing in the snow with friends in North Korea sometime in January 2016.

I wanted to share one final thing today before we take time to be alone as a family. This is the last video we have of Otto enjoying life before his imprisonment.

It was taken in North Korea with members of his tour group, Warmbiers younger brother Austin said as he released the video, according to The Daily Mail.

This is the Otto I know and love. This is my brother.

The video is believed to be the last clip of the Wyoming native before he was jailed for removing a propaganda poster from a hotel in 2016 and left comatose after 18 months in a North Korean prison.

Warmbier was released from the rogue country on Tuesday.

His father, Fred Warmbier, said his son had been brutalized and terrorized by Kim Jong Uns regime.

Doctors at a Cincinnati hospital where Warmbier is being treated said the young man is suffering from severe brain injuries.

He is in a state of unresponsive wakefulness, his doctors said.

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The North Korea detainee's final moments of freedom - New York Post

Freedom Caucus Conservatives Break from Trump, Want More Surveillance Reform – Reason (blog)

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PhotojogtomThe White House and several prominent Senate Republicans want to keep the scope of federal surveillance powers intact, but there's a rebellion afoot. The House Freedom Caucus has said it does not want to renew some federal snooping powers unless there's reform that better protects Americans from unwarranted data collection.

Earlier this month, such Republican senators as Tom Cotton of Arkansas, Marco Rubio of Florida, John McCain of Arizona, and Susan Collins of Maine, among others, announced they were introducing a bill to make permanent some temporary surveillance powers granted by amendments to the Foreign Intelligence Surveillance Act (FISA). The White House has formally declared its support for this bill.

The powers under dispute fall under Section 702 of FISA amendments. Section 702 is intended to allow the National Security Agency (NSA) to snoop on the communications of foreign targets. But this surveillance often ends up drawing in data and records and communications from United States citizens as well, all collected without a warrant.

While there's a "minimization" process intended to protect U.S. citizens' privacy and due process rights, there's also an "unmasking" procedure government officials have used to investigate domestic crimes beyond threats of terrorism and espionage. Such a process appears to run afoul of the Fourth Amendment's protections, and civil rights advocates across the political spectrum want to reform Section 702 to protect against these "backdoor" searches.

Section 702 wll expire at the end of the year if Congress does nothing (or is unable to get enough votes to pass something). So this short announcement from House Freedom Caucus Chairman Mark Meadows (R-N.C.) is a warning to President Donald Trump, Sen. Cotton, and others that the party is not in total agreement:

Government surveillance activities under the FISA Amendments Act have violated Americans' constitutionally protected rights. We oppose any reauthorization of the FISA Amendments Act that does not include substantial reforms to the government's collection and use of Americans' data.

If this conflict within the party sounds familiar, it's because it played out after Edward Snowden's leaks too. At that time, several privacy-minded Republicans resisted efforts to renew a part of the Patriot Act that was being used to justify the mass collection of Americans' private phone call and online activity metadata.

The end result of that fight was that part of the Patriot Act was allowed to sunset and was replaced by the USA Freedom Act, which formalized but also put some restrictions on how the government was able to access that metadata.

I noted earlier in the week that the pro-surveillance senators who support the unchanged renewal of Section 702 were in a difficult situation because they did not have a lot of leverage: All opponents have to do to make them fail is nothing at all. This warning by the Freedom Caucus, which has about three dozen members, will let the Senate and the White House know that Republican control over Congress doesn't mean reauthorization is going to be easy. This may be the first step in a USA Freedom Actstyle compromise.

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Freedom Caucus Conservatives Break from Trump, Want More Surveillance Reform - Reason (blog)

With freedom and prosperity for all – Inquirer.net

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One concrete output from the Philippines Asean hosting is the recently launched, business-sector-driven Prosperity for All Alliance. With GoNegosyo as its secretariat, the alliance includes groups like AmCham, Bankers Association, Filipino Chinese Chamber of Commerce, Financial Executives of the Philippines, Indian Chamber, Makati Business Club, Management Association of the Philippines, Philippine Chamber of Commerce and Industry, Semi-Conductor and Electronics Industries in the Philippines Foundation, among others. I understand the alliance now has 18 of the most influential business groups in the country, so apologies to the others I did not name. You are all doing Gods work!

The alliance will focus on micro, small and medium enterprises, or MSMEs.

Focus is actually not precise as MSMEs comprise 99.5 percent of all registered businesses in the country today. Combined they employ almost 62 percent of the workforce. They account for 25 percent of the countrys total export revenue and comprise 60 percent of all Philippine exporters. So our focus is actually a humongous one. The key implication, therefore, is that achieving positive and far-reaching impact on MSMEs will almost surely bring us closer to realizing our shared goals of inclusive growth and zero poverty.

Leading the effort to finally make the private and public sectors more aligned in addressing MSME development and sustainability is Joey Concepcion, presidential adviser for entrepreneurship and chair of the Asean Business Advisory Committee (BAC). But Joey has always attributed his and GoNegosyos successes to very effective people on the ground, like former trade undersecretary Merly Cruz and Sulu initiatives dynamo Ginggay Hontiveros. It certainly was Joeys leadership in the Asean BAC that convinced big business in the region to adopt a prosperity-for-all agenda on the Philippines Asean hosting year. And it was his calls and viber messages that brought together the 18 business groups to unite on a common purpose to help MSMEs.

Worth highlighting is the fact that this very young alliance has mobilized to support not only the Marawi evacuees but also the soldiers and policemen on the frontline, who are risking life and limb to liberate the city from terrorists. The fallen heroes now number 58 and the alliance has made a commitment to recognize their supreme sacrifice by at least taking care of the families left behind.

But it doesnt stop there. The soldiers and policemen need what has been dubbed as care packages to help them cope with the terrible conditions in the battle zones. The packages even include messages from children and youth who need to understand at a very young age that securing their freedom does come at significant costs and with much sacrifice.

Once the freedom of Marawi is regained, the alliance is committed as well to help rebuild the city together with the government. What programs have been launched and sustained in Sulu will be replicated in Marawi so that families can quickly recover from the ravages of war. It will not be easy, but the commitment to roll out projects and programs soon after our troops accomplish their mission will be key to ensuring that there will be no more left behind.

On the ground, we will have to rely on initiatives like the public-private Kapatid Program and groups like the Philippine Business for Social Progress, which incidentally is now being steered by former education secretary Br. Armin Luistro. To honor the soldiers who made the supreme sacrifice, scholarships for their children through the Hero Foundation will be the best vehicle to ensure a future of prosperity for the orphaned. There are many groups ready to bring the proper and well-calibrated response on the ground, and the business community must help them deliver and scale up their efforts. These can be done through funds as well as mentorship, technical assistance and logistics support, not to mention the mobilization of employees as volunteers.

There can be no better way to secure freedom in Marawi and the rest of the country than to ensure prosperity for all.

Peter Angelo V. Perfecto is executive director of the Makati Business Club and vice president of Integrity Initiative Inc.

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With freedom and prosperity for all - Inquirer.net

The Personal Freedom Index – Inquirer.net

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The latest global compilation of statistics for advocacy to come my way is The Human Freedom Index 2016 by Ian Vsquez and Tanja Porcnik, published by the CATO Institute, Fraser Institute, and Friedrich Naumann Foundation for Freedom.

The Human Freedom Index merges the Economic Freedom Index and a Personal Freedom Index. The first is an older construction by the Fraser Institute (The Economic Freedom Index, Opinion, 11/21/15); the second is my topic today. Both indexes are instrumental to the state of democracy (see The Democracy Index, Opinion, 11/15/14).

The Personal Freedom Index (PFI) has seven dimensions, as listed in the table here, with figures for the six major Asean countries as of 2014, the latest available data point. The scores are on a scale from 0 to 10, or the range from no freedom to full freedom; I would read a score of 5.0 as half-free.

The Philippine PFI of 6.05 in 2014 ranks 113th of the 159 countries that were indexed; the average PFI for all countries is 7.01. Over time, the Philippine score rose at first, but later fellit was 7.37 in 2008. 7.37 in 2010, 7.77 in 2011, 6.75 in 2012, 5.75 in 2013, and 6.05 in 2014. The world average PFI also fell steadilyit was 7.18 in 2008, 7.13 in 2010, 7.13 in 2011, 7.06 in 2012, 7.04 in 2013, and 7.01 in 2014. These are alarming trends, calling for serious assessment.

Within Asean, as of 2014, the Philippine PFI is in fourth place, behind Singapore, Indonesia and Thailand, and ahead of Vietnam and Malaysia. The Philippines is fifth with respect to Rule of Law, and sixth in Security and Safety; these first two dimensions have half the weight of the PFI. Much of the basic data for these dimensions is from the same sources as the WJP Rule of Law Index (see Opinion, 4/8/17). Other sources are the UN Office on Drugs and Crime, the Uppsala Conflict Data Program, the Economic Intelligence Unit, the CIRI Human Rights Data Project, and the University of Marylands Global Terrorism Database.

The other half of the PFI is made up of the scores on the next five dimensions, pertaining to specific freedoms. The Philippines is tied for second, with Indonesia and Singapore, in freedom of Movement. It is second to Indonesia in freedom of Religion. Third in freedom of Association, behind Indonesia and Thailand. Second to Indonesia in freedom of Expression. And tied for third, with Indonesia, in freedom of Relationship, behind Vietnam and Singapore.

The scores for the specific freedoms are from many sources, among them the OECD (Organization for Economic Cooperation and Development), the Committee to Protect Journalists, the French Development Agency, Freedom House, and the International Lesbian and Gay Association. What they have in common is advocacy for certain aspects of personal freedom, and an understanding of the role of statistics in pursuing their mission.

Contact mahar.mangahas@sws.org.ph.

(Editors note: This has been updated to reflect the Personal Freedom countries of major Asean countries in 2014. Our apologies for the oversight.)

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The Personal Freedom Index - Inquirer.net

Buying Whole Foods could complete an Amazon ecosystem a decade in the making – Popular Science

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Yesterday, Amazon unveiled the second generation of its Dash Wand, an Alexa-enabled home barcode scanner that adds grocery items to an AmazonFresh cart. Yesterday, the Dash was a promotional tool, a way for Prime members in five urban markets (New York, Philadelphia, Seattle, and Northern and Southern California) to get back-doored into the $15/month AmazonFresh grocery delivery service.

Did we mention that was yesterday?

Today, Amazon announced a $13.7 billion deal to buy the Whole Foods grocery chain, which includes 461 stories across the U.S., Canada, and the U.K. Today, the Amazon Dash Wand got a lot more interesting.

Most Americans live within an hours drive of a Whole Foods, and many are a half-hour or less from one. Thats good news for a company like Amazon, whos been slowly but surely building out the necessary logistics for on-demand grocery delivery, but has yet to expand outside major metro areas.

AmazonFresh debuted a decade ago, in 2007. The Prime Now one- or two-hour delivery service has been steadily expanding since it launched in New York City in 2014. Whats more, Prime Now got an Alexa-integration upgrade in March of this year. The updated Dash Wand, which takes up the mantle of its defunct and limited predecessor and a cluttered array of Dash Buttons, is a key piece in this on-demand delivery puzzle.

Ask for eggs, and ye shall receive.

From a shoppers standpoint, building a grocery list via voice assistant is a lot more impactful than asking Alexa to buy, say, a pair of sneakers. Interacting with Alexabe it through the Dash Wand, an Echo device, or Amazon appcould become as natural an experience as saying Honey, we need eggs.

The key difference: When you say that to Amazon, the eggs could just arrive. Fresh, organic, and straight off the shelves of the nearest Whole Foods store. Or so we hope.

On the backend, Amazon has been developing an infrastructure to support such an enterprise for years. The Seattle company has deals with many delivery contractors, and also runs a network of independent gig couriers through a program called Amazon Flex. All this is in service of making the last mile of the delivery chain move as quickly and efficiently as possible.

It makes perfect sense that all this infrastructure can support a growing e-commerce grocery business. Though services like Instacart, Fresh Direct, and Google Express make good business delivering sundries, online grocery retail is a mere fraction (1.2 percent, to be precise) of the entire food-shopping market, according to research firm Euromonitor. At the same time, online grocers are projected to grow more than four times as quickly as their brick-and-mortar counterparts.

Order up!

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Buying Whole Foods could complete an Amazon ecosystem a decade in the making - Popular Science