Saturday, September 30, 2017

New Jersey Gets No Respect

As usual, the NY Times has a piece degrading something, this time it is New Jersey. The writer states:

Anyone who has ever driven on the New Jersey Turnpike knows that, at a certain point in the road, the entire Manhattan skyline appears to rise from the surrounding marshland like a close-yet-so-far Land of Oz, both tempting and terrorizing with its mysterious jutting cutouts. To traverse this roadway, as ... surely did as a young man, was undoubtedly to exist in a constant state of aspiration and alienation. No matter one’s personal glories, for those who call New Jersey home, and especially those who reside in Northern New Jersey, it’s difficult to forget that one is still not from “the city,” as the landmass across the river is known. Overcompensation tends to follow. Blind arrogance is an occasional byproduct.

Now I was not born nor bred in New Jersey. It was Staten Island, and yes for those in the rest of NY City Staten Island is a Borough and is NYC! Thus I was born and bred, whatever that means, in New York City. I did spend time in New Jersey, riding my bike across the old Goethals Bridge, down to Route 1 and out to the old Newark Airport, Lockheed Constellations and all. We did have a ferry to NYC, and a ferry to Brooklyn. No one really ever went to Brooklyn, it was also a little ferry, and an ugly one at that, not the grand ferry to Manhattan.

Residing in Northern New Jersey is also interesting. You see that from the Morris County line to the California border, county by county, it voted Republican. Not saying that it was all Republican but it is interesting to note the dramatic difference.

The above mentioned article, an ad hominem attack on someone allegedly born and bred in New Jersey, Livingston I believe, it is an adjacent town but a different county, all Democrats, is also an attack on anyone in New Jersey. Now New Jersey is not that bad, in fact it can be very livable. The people are generally friendly, similar to Staten Island. We had our notables on Todt Hill, "death" hill if you read Dutch, and in my town we had a similar family, if you get my gist. So it was like home.

The only problem in New Jersey is taking a train to New York City. It was easier to travel from St Petersburg to Moscow during the Russian Revolution than getting from my town to NYC. But then they had a Communist Revolution we have Amtrak and New York State. Go figguah.

For the many who may have never been in New Jersey, or for those limited to the Turnpike or Newark Airport, try a trip west. The Delaware river, the rising hills, the forests and preserved lands, go south to the pine lands. Not too bad. And unlike NYC, one can escape from New Jersey quite easily. We have roads. At one point the Turnpike has a total of sixteen lanes, yes eight in each direction. Road maintenance is at night so as not to slow traffic. That is the opposite of Connecticut, where two lane roads are closed at random times to trim a tree, resulting in hours of delay. Or the same in Pennsylvania.

So to the writer who seems to have an inferiority complex of birth in New Jersey, give it a rest! You had no choice, I did. It sure beats Connecticut!

Oh yes, "blind arrogance", it seems that the arrogance is on the other foot, the one who wrote this piece. 

Friday, September 29, 2017

The Microbiome and Cancer

The microbiome is that collection of stuff we carry around in our guts. Most of us never really think much about this but it turns out to have significant impacts on cancers. After a bit of thought it becomes clear why.

In a recent paper by Fullbright et al they have done a wonderful job on describing some of these effects. They conclude:

The densest populations of endogenous microbes are found within the intestines and are in close proximity to the epithelium and underlying mucosal immune system. As a result, the earliest observations linking the microbiota with the hallmarks of cancer have primarily focused on gastric cancers and CRC. Nonetheless, more recent studies have also implicated the microbiota in cancers at distal sites as a potential predictor of successful response to cancer therapy and as a means to augment the efficacy of existing anticancer therapeutics. Furthermore, the well-established link between several viruses and human cancers (i.e., Human papillomavirus and cervical, genital, anal, and oral cancers; Epstein-Barr virus and lymphomas; hepatitis C virus and hepatocellular carcinoma; Kaposi’s sarcoma–associated herpesvirus and Kaposi’s sarcoma) provides a strong rationale to investigate the role of nonbacterial members of the microbiota (virus, fungi, and archaea) in modulating the hallmark capabilities and cancer development. Finally, the cancer microenvironment itself can enhance the procarcinogenic activities of the microbiota, which further demonstrates the importance of the crosstalk between host and microbe in modulating cancer progression. In summary, because of the extensive capacity of the microbiota to influence many hallmarks of cancer, treatment for a variety of cancers may soon involve personalized medicine targeting the microbiota.

This is definitely worth following as we understand more regarding this complex environment.

Trump Care?

Just a note on Taxes and Healthcare. So you thought Obamacare was bad. Try Trumpcare. Not the failed plans but the tax proposals. You see they want to eliminate deductions for medical expenses. So not only do you pay Medicare, on everything, that 3% of every transaction, selling your house etc, but no God forbid you get slammed with medical bills, you must pay the new taxes on top of that! Yep, you sick folks will really get soaked this time. If they can't fix it then tax it! Good luck in 2018!

Just an observation. The poor old folks paying high real estate taxes and state income taxes, and medical expenses will pay through the roof, but the advantage is their heirs will not have to pay tax on whatever is left! So I guess the solution is to die broke! That is one way to eliminate the estate tax. Middle Class tax cut? What moron thought this one up. Karl Marx!

Monday, September 25, 2017

CBO Latest Proposal

The CBO released their latest estimates. They contend:

Over the 2017–2026 period, CBO and JCT estimate, the legislation would reduce the on-budget deficit by at least $133 billion, the projected savings from the House-passed reconciliation bill. (The effects on the deficit were estimated relative to CBO’s March 2016 baseline, as has been done for all legislation related to the 2017 budget resolution.) Those savings would occur mainly because, under the legislation, outlays from new block grants between 2020 and 2026 would be smaller than the reduction in net federal subsidies for health insurance. Funding would shift away from states that expanded eligibility for Medicaid under the Affordable Care Act (ACA) and toward states that did not. The number of people with comprehensive health insurance that covers high-cost medical events would be reduced by millions compared with the baseline projections for each year during the decade, CBO and JCT estimate. That number could vary widely depending on how states implemented the legislation, although the direction of the effect is clear. The reduction in the number of insured people relative to the number under current law would result from three main causes. First, enrollment in Medicaid would be substantially lower because of large reductions in federal funding for that program. Second, enrollment in nongroup coverage would be lower because of reductions in subsidies for it. Third, enrollment in all types of health insurance would be lower because penalties for not having insurance would be repealed. Those losses in coverage would be partly offset by enrollment in new programs established by states using the block grants and by somewhat higher enrollment in employment-based insurance. Many of the new programs would probably cover people with characteristics similar to those of people made eligible for Medicaid by the ACA. The decrease in the number of insured people would be particularly large starting in 2020, when the legislation would make major changes to federal funding for Medicaid and the nongroup market. CBO and JCT expect that market disruptions and other implementation problems would accompany the transition to the block grants created by the legislation—despite the availability of funding specifically designated to assist with that transition—given the short time for planning and making changes between now and then.

This is a lot of effort for nothing. The major problems are:

1. Central Government control of everything.

2. An absurd Electronic Health Record system designed by people who seem in my opinion to have no clue as to how medicine functions.

3. Excess reporting of details that are useless.

4. Lack of change in key sectors such as torts etc.

5. Funding of absurd entities like PCORI.

I let you all be the judge.

Humans?

As the hurricanes swirl about the Atlantic and the under tow pulls and then throws one back upon the massive rocks the sea gulls watch as one rather dumb human sets out to surf among the waves. Now who is the smarter? Or is there a reason why there are more sea gulls than humans?

Saturday, September 23, 2017

Improved CRISPR

The use of CRISPR techniques to cleave and cut/add DNA sequences is a two step process. First the use of a CRISPR or equivalent to target the sequence and then the CAS9 to cut it.  Target and cut. However there are problems. The target may appear at multiple locations and the DSB, double stranded break cut, is often subject to faulty repairs. Thus, although CRISPER can be an elegant approach, its errors can have massive defects.

Doudna and her team have announced some improvement in Nature. They state:

The RNA-guided CRISPR–Cas9 ... has been widely repurposed for genome editing. High-fidelity (SpCas9-HF1) and enhanced specificity (eSpCas9...) variants exhibit substantially reduced off-target cleavage in human cells, but the mechanism of target discrimination and the potential to further improve fidelity are unknown. Using single-molecule Förster resonance energy transfer (smFRET) experiments, we show that both SpCas9-HF1 and eSpCas9... are trapped in an inactive state when bound to mismatched targets. We find that a non-catalytic domain within Cas9, REC3, recognizes target complementarity and governs the HNH nuclease to regulate overall catalytic competence. Exploiting this observation, we designed a new hyper-accurate Cas9 variant (HypaCas9) that demonstrates high genome-wide specificity without compromising on-target activity in human cells. These results offer a more comprehensive model to rationalize and modify the balance between target recognition and nuclease activation for precision genome editing.

As  The Scientist notes:

Tuesday, September 19, 2017

News and Fake News

In a piece in the NY Times an Irish born former Administration official bemoans the explosion of "fake news". The author states:

What exactly has changed since then to make foreign propaganda far more dangerous today? During the Cold War, most Americans received their news and information via mediated platforms.  Reporters and editors serving in the role of professional gatekeepers had almost full control over what appeared in the media. A foreign adversary seeking to reach American audiences did not have great options for bypassing these umpires, and Russian dezinformatsia rarely penetrated. While television remains the main source of news for most Americans, viewers today tend to select a network in line with their political preferences. Even more significantly, The Pew Research Center has found that two-thirds of Americans are getting at least some of their news through social media. After the election, around 84 percent of Americans polled by Pew described themselves as at least somewhat confident in their ability to discern real news from fake. This confidence may be misplaced.

 Now let's go back a bit. Remember Hearst and the Spanish American Wat? You don't you say, well you should. Had it not been for his papers we most likely would never have had the hill climbing Teddy. Strange how events turn out.

Now one should also remember Radio Moscow. I do. In 1952 I had a Hallicrafters Short Wave receiver. I listened to the BBC, to Radio Moscow, and a slew of other stations. Even at a young age one could tell Radio Moscow was propaganda, I did not need the Nuns to tell me that. But they did offer a free magazine, Soviet Life. So like a good young Catholic student I wrote a letter asking for my free subscription, doing so on my lined note paper using my best Waterman Blue Ink pen and placing the cross and "JMJ" atop the letter ans mandated by the Nuns. I unfortunately never got my Soviet Life then, perhaps it was the JMJ or perhaps it was intercepted before ever getting out of the US. But that did not stop my listening to what, even at that age, I knew was fake news. It was comedic, the Soviet exaggeration. Then of course there was Voice of America and Radio Free Europe. The list went on.

You see a rational person can readily identify "fake news". We see it everywhere today. It starts with advertising and then fills the cable news channels. Newspapers all have their own slant on what they consider news. As for social media, I have no use for it. 

Proper education is the solution. A Civics class, a real History class, reading from what the Founders based their decisions on, ie the Federalist Papers and their opposition. Then rely upon educated reason. "Confidence misplaced" is a rather snarky way to say. "I know the truth and you have no clue" Rather in a democracy people are bombarded with "facts", many contorted, many twisted and bent to meet some other objective. But that is life.

Oh, by the way, if anyone in Russia is monitoring this, any chance I can get my Soviet Life subscription? I liked the pictures and it was free. Thanks.

Thursday, September 14, 2017

CBO Healthcare Costs for those Under 65

The CBO published a report indicating the 2017 costs of Healthcare for those under 65. Note Medicaid is $300 billion plus and Medicare, for those disabled, is $100 billion plus. The dominant driver is the expended Medicaid from the ACA.

They continue:

According to CBO and JCT’s estimates, a monthly average of about 244 million noninstitutionalized civilians under age 65 will have health insurance in 2017. Almost two-thirds of them will have coverage through an employer, and about a quarter will be enrolled in Medicaid or the Children’s Health Insurance Program (CHIP). A smaller number will have nongroup coverage, coverage that is provided by Medicare, or coverage obtained from various other sources. On average, about 28 million people—10 percent of all noninstitutionalized civilians younger than 65—will be uninsured in 2017, CBO and JCT estimate (see Figure 1). Between 2017 and 2018, the number of uninsured people rises by 2 million in the agencies’ projections, mainly because premiums in the nongroup market are expected to be higher. From 2018 through 2027, the number of people with coverage is expected to grow from 242 million to 247 million. But the number of uninsured people is also expected to grow, from 30 million to 31 million, keeping the uninsured share of the under-65  population stable at 11 percent.

Now under Medicare we have an annual cost of $10,000 per person. Thus Medicare for all at 330 million people is $3.3 trillion a year! Yep, a large number.

At least when Thomas Paine made his suggestions in the 1790s, he had the courage to estimate the costs as well as the source of payment. Where are Thomas Paines when we need them?

Thursday, September 7, 2017

AI and the Academy

In a Press Release MIT announces that it has entered into a $240 million dollar effort with IBM to establish a joint AI Laboratory. They state:

IBM and MIT today announced that IBM plans to make a 10-year, $240 million investment to create the MIT–IBM Watson AI Lab in partnership with MIT. The lab will carry out fundamental artificial intelligence (AI) research and seek to propel scientific breakthroughs that unlock the potential of AI. The collaboration aims to advance AI hardware, software, and algorithms related to deep learning and other areas; increase AI’s impact on industries, such as health care and cybersecurity; and explore the economic and ethical implications of AI on society. IBM’s $240 million investment in the lab will support research by IBM and MIT scientists. The new lab will be one of the largest long-term university-industry AI collaborations to date, mobilizing the talent of more than 100 AI scientists, professors, and students to pursue joint research at IBM's Research Lab in Cambridge, Massachusetts — co-located with the IBM Watson Health and IBM Security headquarters in Kendall Square — and on the neighboring MIT campus.

This comes after much criticism of the IBM Watson venture as more hype than reality. But it does raise many major questions.

1. MIT is an academic institution and what research which is done there has always been of a public nature. MIT Lincoln Lab is an exception but that Lab, as was the Draper Instrumentation Lab, considered an off shoot, not on the main campus and not an academic department.

2. IBM one would assume is investing $240 million and expects a return to shareholder value. That must mean that IBM has not only first dibs on whatever is developed but also there is some form of proprietary ownership which seems to be antagonistic to normal academic freedom.

3. If one does a study in this "Lab" then can one take what expertise one has created and take it to a competitor?

4. Why IBM. Is IBM desperate to get something out of Watson that they would dump a quarter of a billion into this effort? Motives count.

5. MIT was a Land Grant School, and as a result had an obligation to support US industry and interests as a goal if not a primary goal. Does this enhance or subrogate that goal?

Needless to say this makes for good PR but is it good science and engineering? I wonder.

Wednesday, September 6, 2017

Over Rated?

There is an explosion of AI related products. One of the most significant is Watson, the IBM entry which continually gets great praise. STAT has published an excellent piece worth reading by anyone concerned.

The article concludes:

While not specific to Watson’s health care products, the report said potential clients are backing away from the system because of significant consulting costs associated with its implementation. It also noted that Amazon has 10 times the job listings of IBM, which recently didn’t renew a small number of contractors that worked for the company following its acquisition of Truven, a company it bought for $2.6 billion last year to gain access to 100 million patient records. In its statement, IBM said that the workers’ contracts ended and that it is continuing to hire aggressively in the Cambridge, Mass.-based Watson Health and other units, with more than 5,000 positions open in the U.S. But the outlook for Watson for Oncology is challenging, say those who have worked closest with it. ...the lead trainer at Memorial Sloan Kettering, said the system has the potential to improve care and ensure more patients get expert treatment. But like a medical student, Watson is just learning to perform in the real world. “Nobody wants to hear this,” ... said. “All they want to hear is that Watson is the answer. And it always has the right answer, and you get it right away, and it will be cheaper. But like anything else, it’s kind of human.”

 Medicine is complex, and especially cancer care. No patient is the same. It is not only the pathology but the patient's approach to the disease. Even in such centers such as MSKCC there are a multiplicity of treatments. Also even the current immunotherapy treatments may work 40% of the time. Why the 40% and why not the 60% is the question without an answer.

IBM used to be a service company, selling hardware and software services. It then morphed into a consulting company, a real service business. One wonders just what business they are in now.

This is an article well worth the reading.

Monday, September 4, 2017

We Told You So!

In a just released re-study of the PCa mortality and PSA tests the authors note:

Screening was estimated to confer a 7% to 9% reduction in the risk for prostate cancer death per year of MLT. This translated into estimates of 25% to 31% and 27% to 32% lower risk for prostate cancer death with screening as performed in the ERSPC and PLCO intervention groups, respectively, compared with no screening...After differences in implementation and settings are accounted for, the ERSPC and PLCO provide compatible evidence that screening reduces prostate cancer mortality.

And the reasons are what he had noted when these, in my opinion fatally flawed, trials were performed.

Perhaps they could now calculate how many mend died as a result.

As Eureka notes:

After differences in implementation and settings were accounted for, two important prostate cancer screening trials provide compatible evidence that screening reduces prostate cancer mortality. These findings suggest that current guidelines recommending against routine PSA-based screening may be revised. However, questions remain about how to implement screening so that the benefits outweigh the potential harms of overdiagnosis and overtreatment. 

 It is a shame!

Saturday, September 2, 2017

The FCC and Net Neutrality

It appears as if the current FCC management is about to undo what is called Net Neutrality. A while back I wrote a long piece in Internet Neutrality while still back at MIT. My point was simply that a carrier is just that, a carrier, and since the days of Elizabeth I this concept was accepted and became the element which led to the dominance of England in world trade. Now comes the FCC and the incumbents. The FCC has never been known for much more than a political equivocator depending on whose party is in charge. So one should not expect anything more than an expression, nay and echo, of what the powers to be or those in charge really want.

Wired magazine has a piece that somehow thinks this is all new. They state:

This past April, the Federal Communications Commission invited the American people to weigh in on whether the federal government should roll back the rules currently in place to protect net neutrality. By the time the online comment submission period ended last Wednesday, the agency had collected 21.9 million comments, an astounding level of participation on what at first glance appears to be a rather esoteric telecommunications policy issue. (For comparison, when the FCC received around 500,000 postcards and emails about its media ownership rule changes in 2003, it was considered a big deal. Even Janet Jackson's wardrobe malfunction at the 2004 Super Bowl garnered only about 1.4 million comments.) So what did the people say? The industry group Broadband for America, which opposes the FCC's current rules, recently commissioned an analysis of the comments from a company called Emprata. The study determined that a majority of the comments–about 60 percent–favor keeping the FCC's current rules, which classify internet service providers as "Title II" common carriers like mobile and landline phone companies and ban them from blocking or interfering with lawful content. If you look only at unique comments, as opposed to form letters using boilerplate text, those in favor of keeping the Title II rules outweigh those who want to jettison the rules 1.52 million to 23,000. The only hitch: the commenting process was such a debacle that the legitimacy of the entire body of comments is now in question.

Should one be surprised that the FCC's system  is so let us say reckless? Hardly. It is a Government controlled process. Some Beltway Bandit probably wrote the specs, then another Beltway Bandit did the software. And in the midst of this no one is really responsible for anything. So one expects rational actions from these folks.

In my experience and in my opinion I saw the FCC up close. If I went in with some issue, my opponent was in the waiting room after I finished to rebut my position. How did they find out? Simple, the Sunshine rule, the FCC tells everyone everything. In those days one filed a paper document. Yes it was cumbersome and yes form was important. But it meant that someone had to give some thought to the process and multiple filings were difficult. The on line approach allows for slamming of various types not to mention the system allows the uploading on anything, yes folks anything.

These then are the people who will control our information flow. One should understand that the main ISPs, such as Comcast, Verizon, AT&T are also  in the media business and promulgate their own interests. They carry a big stick, and they also have great carrots for FCC officials when they go out in the world. Just look at the heads of major industry lobbying groups!

So what will happen with Net Neutrality; ask the largest bidder!