Baby gadgets pose risk of paranoia

Baby gadgets pose risk of paranoia

From the desk of Zedie.

Harvard book bound in human skin

Harvard book bound in human skin

From the desk of Zedie.

Sleep’s memory role discovered

Sleep’s memory role discovered

From the desk of Zedie.

In a First, Test of DNA Finds Root of Illness –

From the desk of Zedie.

The Ice Diet: Why It’s Bad For You And You Shouldn’t Try It

From the desk of Zedie.

Pouring Saltwater Over Graphene Generates Electricity

From the desk of Zedie.

The Grim Prospect Of Life Without Antibiotics .

It was not until the years just after World War II when streptomycin, the first truly broad-spectrum antibacterial agent, came onto the market, and penicillin began to be widely available that the Golden Age of antibiotic therapy really began.  Before that, even seemingly trivial infections of the skin, lungs or other organs could lead to sepsis and death.  We may now be on the verge of returning to a pre-antibiotic era, a prospect that public health experts find terrifying.

Bacteria are champions of Darwinian selection: As we try to kill them with antibiotics, they mutate in myriad ways in order to survive.  And they have quite a repertoire: Among other tricks, they develop less permeable walls to keep the antibiotics out, create ways to degrade or extrude them or alter the intracellular targets so that the antibiotics no longer work on them.  Bacteria can even transfer these evolutionary adaptations from one species to another, making it ever more imperative for us to come up with new antibiotics that work through novel mechanisms.  It’s a never-ending escalating arms race, and the harsh reality is that the bacteria are winning it.

Increasingly, microorganisms are developing resistance not only to single antimicrobial agents, but to several.  These latter organisms are called multidrug-resistant, or MDR, strains.  In some cases, the microorganisms have become so resistant that no available antibiotics are effective against them.  This led Dr. Arjun Srinivasan, assistant director of the Centers for Disease Control and Prevention (CDC), to paint this dire picture last year:

We are quickly running out of therapies to treat some of these infections that previously had been eminently treatable. There are bacteria that we encounter, particularly in health-care settings, that are resistant to nearly all — or, in some cases, all — the antibiotics that we have available to us, and we are thus entering an era that people have talked about for a long time. . . We’re in the post-antibiotic era.  There are patients for whom we have no therapy, and we are literally in a position of having a patient in a bed who has an infection, something that five years ago even we could have treated, but now we can’t.

Methicillin-Resistant Staphylococcus aureus (MRSA)

Methicillin-Resistant Staphylococcus aureus (MRSA) (Photo credit: NIAID)

According to the CDC, in 2011 there were approximately three quarters of a million hospital-acquired infections in U.S acute care hospitals, and about 75,000 patients died during their hospitalizations.  This daunting tally excludes people who acquire infections in other health-care settings, such as outpatient surgery centers, where more than 60% of all operations are now performed, and long-term care facilities.  As pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) have moved beyond health-care facilities, drug-resistant infections have become common in the community at large.

Drug resistance has important implications.  People infected with drug-resistant organisms are more likely to have longer and more expensive hospital stays and are more likely to die as a result of the infection.  When the first-line drug of choice for treating an infection won’t work, physicians must resort to second- or third-choice drugs that may be less effective and more toxic.

At the same time that bacterial resistance to antibiotics is increasing, the number of drug and biotech companies developing new antibacterials isshrinking.  This decline is due to a number of factors, including lack of industry productivity, the low return on investment of antibacterials compared with other therapeutics, difficulty in identifying new compounds with traditional discovery methods, regulatory requirements that require large and complex clinical trials for approval, and initiatives that encourage antibiotics to be used as sparingly as possible (to minimize the spread of resistance).

Neither the federal government nor private scientific philanthropy is adequately supporting research on antibiotics and antibiotic resistance.  The National Institutes of Health’s National Institute of Allergy and Infectious Diseases is “funding and conducting research on many aspects of antimicrobial (drug) resistance, including basic research on how microbes develop resistance, new and faster diagnostics, and clinical trials designed to find new vaccines and treatments effective against drug-resistant microbes.”  And another agency within the U.S. Department of Health and Human Services, the Biomedical Advanced Research and Development Authority(BARDA), funds antibiotics R&D, including costly late-stage (Phase III) clinical trials, at some of the few pharmaceutical companies still in the field.  Since 2010, BARDA has partnered with six drug makers and has sponsored nine molecular candidates in Phase II/III clinical trials to test the drugs’ efficacy against biothreats (e.g., plague) and some of the worst bacterial pathogens now threatening society.

A 2002 change in FDA requirements for the clinical testing of antibiotics helped to create the shortage of new antibiotics.  To enhance the statistical power – and therefore, the confidence level — of Phase III antibiotic clinical trials, FDA more than doubled the number of patients required.  As antibiotics researchers David Shlaes and Robert Moellering observed in that same year, because in the pharmaceutical industry business considerations play a critical part in setting R&D priorities, corporate

programs with modest potential markets and large costs are automatically deprioritized unless there is some other, overriding strategic issue to be considered.  Thus, one unintended result of promulgating these guidelines will be a decrease in the number of companies performing antibacterial research.

Their prediction was accurate: Since 2002 all but a handful of the major pharmaceutical companies have abandoned their antibiotics R&D programs.

From 2009 to 2012, in part at the urging of members of Congress who had strong opinions but little understanding of the clinical testing of antibiotics, FDA’s policy toward antibiotics testing became so risk-averse and punitive that clinical trials of new antibiotics virtually ground to a halt.  FDA evenproposed that patients enrolled in clinical trials for hospital-acquired pneumonia would be ineligible if they had received another antibiotic within 30 days prior to their participation, making such studies virtually impossible to conduct in the United States.

In July 2013, however, the FDA released new draft guidelines for the conduct of antibiotic clinical trials – part of a self-described “reboot” of policy at the agency.  The new guidelines may help, but some experts, such as UCLA Professor of Medicine Brad Spellberg, have warned that the new guidelines don’t represent significant change, and that much more improvement is needed for trials to become feasible again.

FDA should adopt a promising concept originally proposed by the Infectious Diseases Society of America (IDSA) known as the Limited Population Antibacterial Development (LPAD) pathway, via which “a drug’s safety and effectiveness would be studied in substantially smaller, more rapid, and less expensive clinical trials” — similar to the way “orphan drugs” are developed for rare diseases. Once approved, LPAD-type products would be labeled for use in small, well-defined populations of patients for whom the drugs’ benefits had been shown to outweigh their risks.  In this model, studies of potential new antibiotics would need to enroll hundreds of patients instead of the thousands now required and could be carried out relatively quickly.

However, as Shlaes and Moellering have pointed out, to revive antibiotic R&D, along with regulatory reform we will also need “value-based” pricing, so that return on investment from antibiotic development is comparable to that of other drug classes.

Consequently, we should expect LPAD-style antibiotics to cost as much as$20,000-30,000 per course.  This is not unreasonable, given that many marginally effective cancer drugs cost many times that amount; a new two-drug regimen, sofosbuvir and ribavirin to treat Hepatitis C, is about $84,000 wholesale; and Truvada, the drug combination of emtricitabine and tenovir for HIV prophylaxis, costs $15,000 per year.  In 2010, Forbes compiled a listof nine little-used drugs whose cost for the average patient exceeded $200,000 per year.

One proposed legislative fix for the market failure in antibiotics development is the bipartisan “Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms (DISARM) Act of 2014,” which would require the Centers for Medicare and Medicaid Services (CMS) to reimburse significantly more for LPAD-like antibiotics.  Currently, hospitals may actually lose money because reimbursements fail to cover the cost of the drugs.  (Hospitals would not be encouraged to over-use the drugs, however, because reimbursement would cover only their cost, but no profit-margin.)

Another possible stimulus to R&D on antibiotics derives from a 2007 law — a transferable “priority review voucher” awarded by FDA upon approval of a new drug for a neglected tropical disease.  This PRV would entitle the drug developer to move a new product of its choice to the head of the FDA review queue, or it could be sold to another company.  The company that ultimately redeems the voucher with the FDA could cut months from the review time of a New Drug Application, which could be worth hundreds of millions of dollars to a company eager to begin marketing a potential blockbuster.  This voucher program should be expanded to include drugs for any infection.

Another incentive to encourage companies to undertake antibiotics R&D was recommended in a 2009 analysis from the London School of Economics: a guaranteed government purchase of a defined supply of the antibiotic that would go into a national stockpile. A precedent for this is drugs developed for pandemic influenza and anthrax.

With more enlightened regulation and improved return on investment, which are necessary to make antibiotic development attractive, perhaps we can avoid the extinction of the antibiotic era – and the reversal of our species’ increasing longevity. Perhaps.


NASA’s Top-10 Innovations.


NASA has been synonymous with innovation since the agency’s founding in 1958. Program after program has demonstrated this, but perhaps no period was as fiercely inventive as the space race years, from 1961 to 1972. As the seventies progressed, already diminishing budgets took a toll, and the layoffs that began both within NASA and at the aerospace contractors in the late 1960s accelerated. The agency’s budget declined from a high point of almost 5 percent of the national budget in 1966 to roughly 1 percent during the 1970s, 1980s and 1990s, to the current 0.5 percent — the lowest percentage ever. [How Innovation Will Get U.S. to Mars 2020 (Op-Ed)]

Nonetheless, NASA has continued to lead the way among national space agencies and space exploration with a continuous stream of new and innovative programs and technologies. While the space shuttle had an entirely different mandate than Apollo — i.e. to make access to space (theoretically) cheaper and more efficient — the program was really about innovation being backed into ever-tighter budgets. [‘Innovation the NASA Way’ (US 2014): Book Excerpt]

The International Space Station has been a case of innovation within a global context, involving numerous primary and secondary partnerships with countries across the globe.

And then there is the Jet Propulsion Laboratory (JPL), marching to a different beat, exploring robotically. Always at the narrow end of the funding pipeline, JPL has consistently exceed both the world’s expectations and their own, with spectacular deep-space voyages of exploration that continue for decades after the conclusion of their primary missions.

Here then are ten of NASA’s prime innovations, some of their “finest hours.”

From the desk of Zedie.

Physicists Debate Finding of Ripples from Big Bang

The physics world was agog in March over the announcement that astronomers had possibly found ripples in space-time from the earliest moments of the universe. But some scientists now question whether the findings may be nothing more than galactic dust.

If the finding of these ripples, or primordial gravitational waves, is confirmed, it would represent the best evidence yet for inflation, the idea that the universe underwent an explosive burst in size in the earliest fractions of a second after the Big Bang. If the findings are discounted, inflation could still be correct, but scientists must provide other evidence.

A panel of well-known cosmologists debated the discovery and the model of cosmic inflation itself at an event here on Friday (May 30) at the World Science Festival, moderated by theoretical physicist Brian Greene of Columbia University in New York. [The Big Bang to Now in 10 Easy Steps]

Infographic: How Inflation expanded the early universe.
Inflation is the mysterious force that blew up the scale of the infant universe from sub-microscopic to gargantuan in a fraction of a second. See how cosmic inflation theory for the Big Bang and universe’s expansion works in this infographic.
Credit: By Karl Tate, Infographics Artist

A rapid expansion

One of the panelists, cosmologist Alan Guth of MIT, developed the hypothesis of inflation in 1980 to explain the large-scale structure of the universe. Another panelist, cosmologist Andrei Linde of Stanford University, helped develop the model of inflation.

The Big Bang left behind remnant heat, known as the cosmic microwave background (CMB). Radio astronomer Robert Wilson, who was in the audience, discovered the CMB along with physicist Arno Penzias in 1964. The CMB contains tiny temperature variations, but is remarkably uniform, which might be expected if the universe expanded from a very small region.

If inflation occurred, scientists suspect it might have left an imprint on the CMB, produced by gravitational waves, which would appear as a swirly pattern in the CMB. John Kovac, an astronomer at Harvard University — another of the panelists — and colleagues claimed to have detected this pattern in March using the BICEP2 instrument at the South Pole.

Controversy brewing

But since Kovac’s team announced its findings, the results have come under fire from scientists who question whether the team had ruled out other possible sources that would produce the same swirly signature, such as galactic dust. In fact, two independent analyses of the data now suggest it could be accounted for by dust in the Milky Way.

In the panel discussion, Kovac admitted some uncertainty, but defended the findings. “The pattern is not there by random chance,” Kovac said. His team has further analyzed their data and feels “very confident” the results were not spurious, he said.

But not everyone took the controversy lightly, including cosmologist Paul Steinhardt of Princeton University, who helped develop the model of inflation but now believes in an alternative model of the universe that suggests the existence of higher dimensions. Steinhardt took issue with how Kovac’s team characterized their findings in March, saying that they were too confident in their statements at the time.

Other groups are also looking for these ripples from the Big Bang, including balloon-based and space-based telescopes. The European Space Agency’s Planck satellite is expected to release its own data very soon, possibly in the next three weeks, and should offer strong evidence one way or the other.

Gravitational waves explained.
Moving masses generate waves of gravitational radiation that stretch and squeeze space-time. See how gravitational waves work in this infographic.
Credit: By Karl Tate, Infographics Artist

Exciting times

Despite having helped develop it, Steinhardt now questions inflation itself. He said the theory was in some ways not falsifiable, which veers closer to the realm of metaphysics.

But inflation is still the most widespread theory for how the universe began, Alan Guth said. Andre Linde compared inflation to democracy, which has been called “the worst form of government there is, except for all the other forms.”

As the evening panel concluded, Linde steered the discussion to a more hopeful note, about what it means to be a part of the endeavor to understand the universe in these times.

“There’s something very exciting happening right now,” he said.

Use the Triangle Technique to Make Engaging Eye Contact

Eye contact is crucial to appear engaging, but too much eye contact is creepy. The Daily Muse recommends using the triangle technique to lock your target without being awkward, especially in job interviews.

Use the Triangle Technique to Make Engaging Eye Contact

Before you try this out, you might want to ask a few colleagues and friends whether you make enough eye contact in conversations to usually appear engaging or not. If you are already doing the right things, there’s no reason to change to this “triangle technique”:P

Draw an imaginary inverted triangle on the other person’s face around their eyes and mouth. During the conversation, change your gaze every five to 10 seconds from one point on the triangle to another. This will make you look interested and engrossed in the conversation.P

Alternatively, look at their eyes long enough to register their color. Apparently this feels natural enough to not be awkward, plus it has the added advantage of helping remember names.P