Listen carefully it's fast.
The link
Tuesday, February 27, 2018
Friday, February 23, 2018
Apalutamide Increases Metastasis-Free Survival in Prostate Cancer
From practice update.
Background
Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis.
Methods
We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death.
Results
A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%).
Conclusions
Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo.
Background
Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis.
Methods
We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death.
Results
A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%).
Conclusions
Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo.
Sunday, February 18, 2018
Crime, Deterrence, and Right-to-Carry Concealed Handguns
If you want to know the facts about concealed handguns, take a look at this.
Lott, John R. and Mustard, David B., Crime, Deterrence, and Right-to-Carry Concealed Handguns. Journal of Legal Studies, Vol. 26, No. 1, 1997.
Here is the abstract.
Using cross-sectional time-series data for U.S. counties from 1977 to 1992, we find that allowing citizens to carry concealed weapons deters violent crimes and it appears to produce no increase in accidental deaths. If those states which did not have right-to-carry concealed gun provisions had adopted them in 1992, approximately 1,570 murders; 4,177 rapes; and over 60,000 aggravated assaults would have been avoided yearly. On the other hand, consistent with the notion of criminals responding to incentives, we find criminals substituting into property crimes involving stealth and where the probabilities of contact between the criminal and the victim are minimal. The largest population counties where the deterrence effect on violent crimes is greatest are where the substitution effect into property crimes is highest. Concealed handguns also have their greatest deterrent effect in the highest crime counties. Higher arrest and conviction rates consistently and dramatically reduce the crime rate. Consistent with other recent work, the results imply that increasing the arrest rate, independent of the probability of eventual conviction, imposes a significant penalty on criminals. The estimated annual gain from allowing concealed handguns is at least $6.214 billion.
Lott, John R. and Mustard, David B., Crime, Deterrence, and Right-to-Carry Concealed Handguns. Journal of Legal Studies, Vol. 26, No. 1, 1997.
Here is the abstract.
Using cross-sectional time-series data for U.S. counties from 1977 to 1992, we find that allowing citizens to carry concealed weapons deters violent crimes and it appears to produce no increase in accidental deaths. If those states which did not have right-to-carry concealed gun provisions had adopted them in 1992, approximately 1,570 murders; 4,177 rapes; and over 60,000 aggravated assaults would have been avoided yearly. On the other hand, consistent with the notion of criminals responding to incentives, we find criminals substituting into property crimes involving stealth and where the probabilities of contact between the criminal and the victim are minimal. The largest population counties where the deterrence effect on violent crimes is greatest are where the substitution effect into property crimes is highest. Concealed handguns also have their greatest deterrent effect in the highest crime counties. Higher arrest and conviction rates consistently and dramatically reduce the crime rate. Consistent with other recent work, the results imply that increasing the arrest rate, independent of the probability of eventual conviction, imposes a significant penalty on criminals. The estimated annual gain from allowing concealed handguns is at least $6.214 billion.
Friday, February 16, 2018
Exercise and Cardiovascular Risk
From www.practiceupdate.com
Objectives
We investigate the independent and interacting long-term associations of occupational physical activity (OPA) and sport physical activity (SpPA) with the incidence of coronary heart disease (CHD) and cardiovascular diseases (CVD; CHD plus ischaemic stroke) in North Italian male workers.
Methods
3574 employed men aged 25–64 years, free of CVD at baseline, recruited in three population-based and one factory-based cohorts, were included in the analysis. The Baecke Questionnaire was used to assess OPA and SpPA in ‘minutes per week’ of moderate or vigorous PA. We estimated the associations between different domains of PA and the endpoints, adjusting for major CVD risk factors, using Cox models.
Results
During a median follow-up of 14 years, 135 and 174 first CHD and CVD events, fatal and non-fatal, occurred. Compared with the intermediate OPA tertile, the HRs for CHD among low and high OPA workers were 1.66 (95% CI 1.06 to 2.59) and 1.18 (0.72 to 1.94), respectively (P value=0.07). Decreasing trends in CHD and CVD rates across increasing levels of SpPA were also found, with an HR for CVD of 0.68 (0.46 to 0.98) for intermediate/recommended SpPA compared with poor SpPA. We also found a statistically significant SpPA-OPA interaction, and the protective effect of SpPA was only found among sedentary workers, for both endpoints. Conversely, high OPA workers with intermediate/recommended SpPA levels had increased CHD and CVD rates compared with the poor SpPA category.
Conclusions
Our results provide further evidence on the health paradox of OPA, with higher CVD rates among workers with intense PA at work. Moreover, the protective effect on CVDs of SpPA is prominent in sedentary workers, but it attenuates and even reverses in moderate and strenuous OPA workers.
Objectives
We investigate the independent and interacting long-term associations of occupational physical activity (OPA) and sport physical activity (SpPA) with the incidence of coronary heart disease (CHD) and cardiovascular diseases (CVD; CHD plus ischaemic stroke) in North Italian male workers.
Methods
3574 employed men aged 25–64 years, free of CVD at baseline, recruited in three population-based and one factory-based cohorts, were included in the analysis. The Baecke Questionnaire was used to assess OPA and SpPA in ‘minutes per week’ of moderate or vigorous PA. We estimated the associations between different domains of PA and the endpoints, adjusting for major CVD risk factors, using Cox models.
Results
During a median follow-up of 14 years, 135 and 174 first CHD and CVD events, fatal and non-fatal, occurred. Compared with the intermediate OPA tertile, the HRs for CHD among low and high OPA workers were 1.66 (95% CI 1.06 to 2.59) and 1.18 (0.72 to 1.94), respectively (P value=0.07). Decreasing trends in CHD and CVD rates across increasing levels of SpPA were also found, with an HR for CVD of 0.68 (0.46 to 0.98) for intermediate/recommended SpPA compared with poor SpPA. We also found a statistically significant SpPA-OPA interaction, and the protective effect of SpPA was only found among sedentary workers, for both endpoints. Conversely, high OPA workers with intermediate/recommended SpPA levels had increased CHD and CVD rates compared with the poor SpPA category.
Conclusions
Our results provide further evidence on the health paradox of OPA, with higher CVD rates among workers with intense PA at work. Moreover, the protective effect on CVDs of SpPA is prominent in sedentary workers, but it attenuates and even reverses in moderate and strenuous OPA workers.
Monday, February 12, 2018
Aerobic exercise and Alzheimer’s
From practiceupdate.com
OBJECTIVES
To examine the effects of exercise training on cognitive function in individuals at risk of or diagnosed with Alzheimer's disease (AD).
DESIGN
Meta-analysis.
SETTING
PubMed, Scopus, ClinicalTrials.gov, and ProQuest were searched from inception until August 1, 2017.
PARTICIPANTS
Nineteen studies with 23 interventions including 1,145 subjects with a mean age of 77.0 ± 7.5 were included. Most subjects were at risk of AD because they had mild cognitive impairment (64%) or a parent diagnosed with AD (1%), and 35% presented with AD.
INTERVENTION
Controlled studies that included an exercise-only intervention and a nondiet, nonexercise control group and reported pre- and post-intervention cognitive function measurements.
MEASUREMENTS
Cognitive function before and after the intervention and features of the exercise intervention.
RESULTS
Exercise interventions were performed 3.4 ± 1.4 days per week at moderate intensity (3.7 ± 0.6 metabolic equivalents) for 45.2 ± 17.0 minutes per session for 18.6 ± 10.0 weeks and consisted primarily of aerobic exercise (65%). Overall, there was a modest favorable effect of exercise on cognitive function (d+ = 0.47, 95% confidence interval (CI) = 0.26-0.68). Within-group analyses revealed that exercise improved cognitive function (d+w = 0.20, 95% CI = 0.11-0.28), whereas cognitive function declined in the control group (d+w = -0.18, 95% CI = -0.36 to 0.00). Aerobic exercise had a moderate favorable effect on cognitive function (d+w = 0.65, 95% CI = 0.35-0.95), but other exercise types did not (d+w = 0.19, 95% CI = -0.06-0.43).
CONCLUSION
Our findings suggest that exercise training may delay the decline in cognitive function that occurs in individuals who are at risk of or have AD, with aerobic exercise possibly having the most favorable effect. Additional randomized controlled clinical trials that include objective measurements of cognitive function are needed to confirm our findings.
OBJECTIVES
To examine the effects of exercise training on cognitive function in individuals at risk of or diagnosed with Alzheimer's disease (AD).
DESIGN
Meta-analysis.
SETTING
PubMed, Scopus, ClinicalTrials.gov, and ProQuest were searched from inception until August 1, 2017.
PARTICIPANTS
Nineteen studies with 23 interventions including 1,145 subjects with a mean age of 77.0 ± 7.5 were included. Most subjects were at risk of AD because they had mild cognitive impairment (64%) or a parent diagnosed with AD (1%), and 35% presented with AD.
INTERVENTION
Controlled studies that included an exercise-only intervention and a nondiet, nonexercise control group and reported pre- and post-intervention cognitive function measurements.
MEASUREMENTS
Cognitive function before and after the intervention and features of the exercise intervention.
RESULTS
Exercise interventions were performed 3.4 ± 1.4 days per week at moderate intensity (3.7 ± 0.6 metabolic equivalents) for 45.2 ± 17.0 minutes per session for 18.6 ± 10.0 weeks and consisted primarily of aerobic exercise (65%). Overall, there was a modest favorable effect of exercise on cognitive function (d+ = 0.47, 95% confidence interval (CI) = 0.26-0.68). Within-group analyses revealed that exercise improved cognitive function (d+w = 0.20, 95% CI = 0.11-0.28), whereas cognitive function declined in the control group (d+w = -0.18, 95% CI = -0.36 to 0.00). Aerobic exercise had a moderate favorable effect on cognitive function (d+w = 0.65, 95% CI = 0.35-0.95), but other exercise types did not (d+w = 0.19, 95% CI = -0.06-0.43).
CONCLUSION
Our findings suggest that exercise training may delay the decline in cognitive function that occurs in individuals who are at risk of or have AD, with aerobic exercise possibly having the most favorable effect. Additional randomized controlled clinical trials that include objective measurements of cognitive function are needed to confirm our findings.
Tuesday, February 06, 2018
Don Boudreaux: A letter to his parents
Here is Don Boudreaux's letter to his parents.
DB is on target. His parents were wise - a lot wiser than most pseudo-intellectual media types, politicians, and, yes, academics.
A nice test to see if you may be one of these pseudo intellectuals is if you think "unfettered capitalism" is worse than Socialism.
------------------------------------------
DB is on target. His parents were wise - a lot wiser than most pseudo-intellectual media types, politicians, and, yes, academics.
A nice test to see if you may be one of these pseudo intellectuals is if you think "unfettered capitalism" is worse than Socialism.
------------------------------------------
Dear Mom and Dad:
I suppose I’m typical: not until my own child came along did I reflect seriously on the sacrifices you made and on the challenges you confronted in raising my siblings and me.
There’s so much to thank you for. But here I focus on what is surely your most precious gift to each of your four children: through example and through words you taught us those rules of living that make us fit to live in a free society.
I know that you never consciously thought of your goal in quite these terms. You just straightforwardly taught us right from wrong, good from bad, decent from indecent. But it’s in learning these vital distinctions—in having them etched into one’s very being—that a child grows into a respectable, responsible, productive, and decent adult. And a free society depends upon such adults.
Here’s what you taught my siblings and me.
There’s no excuse for taking other people’s things. I recall when I was about five years old and returned home with Mom from a short visit to a neighbor’s house. Mom, you discovered in my hand a fistful of rubber bands. “Where did you get these?” you asked. “From Miss Jane’s house,” I replied.
I suppose I’m typical: not until my own child came along did I reflect seriously on the sacrifices you made and on the challenges you confronted in raising my siblings and me.
There’s so much to thank you for. But here I focus on what is surely your most precious gift to each of your four children: through example and through words you taught us those rules of living that make us fit to live in a free society.
I know that you never consciously thought of your goal in quite these terms. You just straightforwardly taught us right from wrong, good from bad, decent from indecent. But it’s in learning these vital distinctions—in having them etched into one’s very being—that a child grows into a respectable, responsible, productive, and decent adult. And a free society depends upon such adults.
Here’s what you taught my siblings and me.
There’s no excuse for taking other people’s things. I recall when I was about five years old and returned home with Mom from a short visit to a neighbor’s house. Mom, you discovered in my hand a fistful of rubber bands. “Where did you get these?” you asked. “From Miss Jane’s house,” I replied.
“Did she give them to you?” you inquired.
“No, but they’re only rubber bands. And she has plenty of them.”
After sternly assuring me that this excuse was worthless, you marched me back across the street to return my pilfered booty. I was ashamed of myself when I confessed to Miss Jane my offense and apologized to her. It’s an excellent thing that I felt that shame then, and that I remember it to this day.
I remember also your reaction to the philosophy of a newly ordained Catholic priest who came to our parish. While having coffee at our home one evening, he assured you that, in God’s eyes, it’s okay to take someone else’s things if that other person is wealthier than you and if the things taken are of little value.
You were appalled! Despite your immense respect for men of the cloth, despite the priest’s being more schooled than you, and despite our family’s very modest income, not for a moment did you countenance this nonsense. For years afterward I heard you recount to friends and acquaintances how, with all the respect you could muster, you replied to the priest that “stealing is wrong, period.”
We are each responsible for our lot in life. Often, each of your children would try to blame others for his or her misfortune. “The teacher is mean” and “the teacher is unfair” were favorite excuses for bad grades or for being punished at school. Not once did these excuses work.
Looking back, perhaps there were times when you suspected our teachers of incompetence or of unfairness. If so, you never let on to your children. I remember envying friends whose parents would readily side with them when they accused their teachers of unfairness or some other treachery. But your children learned early on that no such excuses had the slightest hope of causing you even tentatively to forgive a poor grade or a school punishment. The lesson for us was clear: excuses don’t work. Each of us, individually, must accept responsibility for his actions and not blame others.
Life has promise for those who work hard and are honest. I cannot tell you how pleased I am that, after the many years that each of you spent working in a shipyard, you are now retired and finally have the time and resources to relax and travel a bit. How you stretched our family’s meager income to make a comfortable and happy home is beyond me—but you did.
Not once did I ever hear you complain that others were wealthier than we were. Indeed, although all of us were aware that our family was not rich, not once did you act or speak in a way implying envy or bitterness. Nor did you ever suggest to my siblings and me that the social or economic deck was stacked against us. You expressed nothing but assurances that if we worked hard and were honest, no amount of success would be out of reach.
These last points might appear to be especially trite. I’d bet my last dollar that you never even thought to be envious or bitter or hopeless.
Resentful of Wealth?
But having now spent the bulk of my adult life in academia, I tell you that most academics think that blue-collar workers, such as you, inevitably envy more highly paid white-collar workers. In the opinion of the professionally opinionated, you are supposed to resent your lot in life; you are supposed to see others’ greater material wealth as being stolen from you and other working-class families (particularly given that neither of you ever belonged to a labor union); you are supposed to believe that without special assistance from government, you and your children are doomed to continued oppression by heartless employers as well as by devious merchants who beguile you with crass marketing gimmicks into wasting your money on worthless trinkets.
None of what you are “supposed” to believe do you believe. Thankfully so, because it is all untrue. It’s a hodgepodge of hallucinations by people obsessed with money—people who believe that the most important thing is how much money each of us has relative to others—people who believe that those with above-average wealth get it by unsavory means and will inevitably use it to crush workers of modest means unless the state intervenes—people who believe that ordinary men and women can have no happiness or hope without income redistribution and other forms of government assistance.
I’d caught not a whiff of class antagonism until, as an adult, I first met people from the academic class. But this antagonism wasn’t held by any of the working-class families that our family knew so well; it is merely assumed by the academic class to describe the attitudes of the working class. What a mistaken assumption!
In fact, Mom and Dad, you taught your children well that our society rewards hard work, good education, and honesty. You taught us to be proud of what we earn and never to envy what others earn or possess. You taught us to be responsible, truthful, and civil.
In short, you taught us how to be good citizens of a free society. For that, and for much else, I thank you from the bottom of my heart.
“No, but they’re only rubber bands. And she has plenty of them.”
After sternly assuring me that this excuse was worthless, you marched me back across the street to return my pilfered booty. I was ashamed of myself when I confessed to Miss Jane my offense and apologized to her. It’s an excellent thing that I felt that shame then, and that I remember it to this day.
I remember also your reaction to the philosophy of a newly ordained Catholic priest who came to our parish. While having coffee at our home one evening, he assured you that, in God’s eyes, it’s okay to take someone else’s things if that other person is wealthier than you and if the things taken are of little value.
You were appalled! Despite your immense respect for men of the cloth, despite the priest’s being more schooled than you, and despite our family’s very modest income, not for a moment did you countenance this nonsense. For years afterward I heard you recount to friends and acquaintances how, with all the respect you could muster, you replied to the priest that “stealing is wrong, period.”
We are each responsible for our lot in life. Often, each of your children would try to blame others for his or her misfortune. “The teacher is mean” and “the teacher is unfair” were favorite excuses for bad grades or for being punished at school. Not once did these excuses work.
Looking back, perhaps there were times when you suspected our teachers of incompetence or of unfairness. If so, you never let on to your children. I remember envying friends whose parents would readily side with them when they accused their teachers of unfairness or some other treachery. But your children learned early on that no such excuses had the slightest hope of causing you even tentatively to forgive a poor grade or a school punishment. The lesson for us was clear: excuses don’t work. Each of us, individually, must accept responsibility for his actions and not blame others.
Life has promise for those who work hard and are honest. I cannot tell you how pleased I am that, after the many years that each of you spent working in a shipyard, you are now retired and finally have the time and resources to relax and travel a bit. How you stretched our family’s meager income to make a comfortable and happy home is beyond me—but you did.
Not once did I ever hear you complain that others were wealthier than we were. Indeed, although all of us were aware that our family was not rich, not once did you act or speak in a way implying envy or bitterness. Nor did you ever suggest to my siblings and me that the social or economic deck was stacked against us. You expressed nothing but assurances that if we worked hard and were honest, no amount of success would be out of reach.
These last points might appear to be especially trite. I’d bet my last dollar that you never even thought to be envious or bitter or hopeless.
Resentful of Wealth?
But having now spent the bulk of my adult life in academia, I tell you that most academics think that blue-collar workers, such as you, inevitably envy more highly paid white-collar workers. In the opinion of the professionally opinionated, you are supposed to resent your lot in life; you are supposed to see others’ greater material wealth as being stolen from you and other working-class families (particularly given that neither of you ever belonged to a labor union); you are supposed to believe that without special assistance from government, you and your children are doomed to continued oppression by heartless employers as well as by devious merchants who beguile you with crass marketing gimmicks into wasting your money on worthless trinkets.
None of what you are “supposed” to believe do you believe. Thankfully so, because it is all untrue. It’s a hodgepodge of hallucinations by people obsessed with money—people who believe that the most important thing is how much money each of us has relative to others—people who believe that those with above-average wealth get it by unsavory means and will inevitably use it to crush workers of modest means unless the state intervenes—people who believe that ordinary men and women can have no happiness or hope without income redistribution and other forms of government assistance.
I’d caught not a whiff of class antagonism until, as an adult, I first met people from the academic class. But this antagonism wasn’t held by any of the working-class families that our family knew so well; it is merely assumed by the academic class to describe the attitudes of the working class. What a mistaken assumption!
In fact, Mom and Dad, you taught your children well that our society rewards hard work, good education, and honesty. You taught us to be proud of what we earn and never to envy what others earn or possess. You taught us to be responsible, truthful, and civil.
In short, you taught us how to be good citizens of a free society. For that, and for much else, I thank you from the bottom of my heart.
Monday, February 05, 2018
New water-splitting method could open path to hydrogen economy
From www.sciencedaily.com
This seems a bit overstated - how do you store the hydrogen in a manner that does not require energy?
-------------------------------------------
Using inexpensive nickel and iron, the researchers developed a very simple, five-minute method to create large amounts of a high-quality catalyst required for the chemical reaction to split water.
They describe their method in the February issue of the journal Nano Energy.
Energy conversion and storage is a key to the clean energy economy. Because solar and wind sources produce power only intermittently, there is a critical need for ways to store and save the electricity they create. One of the most promising ideas for storing renewable energy is to use the excess electricity generated from renewables to split water into oxygen and hydrogen. Hydrogen has myriad uses in industry and could be used to power hydrogen fuel-cell cars.
Industries have not widely used the water splitting process, however, because of the prohibitive cost of the precious metal catalysts that are required -- usually platinum or ruthenium. Many of the methods to split water also require too much energy, or the required catalyst materials break down too quickly.
In their work, the researchers, led by professor Yuehe Lin in the School of Mechanical and Materials Engineering, used two abundantly available and cheap metals to create a porous nanofoam that worked better than most catalysts that currently are used, including those made from the precious metals. The catalyst they created looks like a tiny sponge. With its unique atomic structure and many exposed surfaces throughout the material, the nanofoam can catalyze the important reaction with less energy than other catalysts. The catalyst showed very little loss in activity in a 12-hour stability test.
"We took a very simple approach that could be used easily in large-scale production," said Shaofang Fu, a WSU Ph.D. student who synthesized the catalyst and did most of the activity testing.
The WSU researchers collaborated on the project with researchers at Advanced Photon Source at Argonne National Laboratory and Pacific Northwest National Laboratory.
"The advanced materials characterization facility at the national laboratories provided the deep understanding of the composition and structures of the catalysts," said Junhua Song, another WSU Ph.D. student who worked on the catalyst characterization.
The researchers are now seeking additional support to scale up their work for large-scale testing.
"This is just lab-scale testing, but this is very promising," said Lin.
This seems a bit overstated - how do you store the hydrogen in a manner that does not require energy?
-------------------------------------------
Using inexpensive nickel and iron, the researchers developed a very simple, five-minute method to create large amounts of a high-quality catalyst required for the chemical reaction to split water.
They describe their method in the February issue of the journal Nano Energy.
Energy conversion and storage is a key to the clean energy economy. Because solar and wind sources produce power only intermittently, there is a critical need for ways to store and save the electricity they create. One of the most promising ideas for storing renewable energy is to use the excess electricity generated from renewables to split water into oxygen and hydrogen. Hydrogen has myriad uses in industry and could be used to power hydrogen fuel-cell cars.
Industries have not widely used the water splitting process, however, because of the prohibitive cost of the precious metal catalysts that are required -- usually platinum or ruthenium. Many of the methods to split water also require too much energy, or the required catalyst materials break down too quickly.
In their work, the researchers, led by professor Yuehe Lin in the School of Mechanical and Materials Engineering, used two abundantly available and cheap metals to create a porous nanofoam that worked better than most catalysts that currently are used, including those made from the precious metals. The catalyst they created looks like a tiny sponge. With its unique atomic structure and many exposed surfaces throughout the material, the nanofoam can catalyze the important reaction with less energy than other catalysts. The catalyst showed very little loss in activity in a 12-hour stability test.
"We took a very simple approach that could be used easily in large-scale production," said Shaofang Fu, a WSU Ph.D. student who synthesized the catalyst and did most of the activity testing.
The WSU researchers collaborated on the project with researchers at Advanced Photon Source at Argonne National Laboratory and Pacific Northwest National Laboratory.
"The advanced materials characterization facility at the national laboratories provided the deep understanding of the composition and structures of the catalysts," said Junhua Song, another WSU Ph.D. student who worked on the catalyst characterization.
The researchers are now seeking additional support to scale up their work for large-scale testing.
"This is just lab-scale testing, but this is very promising," said Lin.
Get rid of income taxes in favor of a value added tax
From John Cochrane's blog.
JC is on target.
These kind of shenanigans are not possible with a value added tax. A value added tax with no exceptions and that everyone pays
------------------------------------------
From Richard Rubin at WSJ:
The new tax law’s treatment of deductions gives people more reasons to concentrate giving in certain years, both inside and outside donor-advised funds.
A donor-advised fund is an investment account held for charitable purposes. Donors take tax deductions when they put money in, then recommend grants to charities over time.
Mr. Young,...added $30,000 to a donor-advised fund run by the Los Altos Community Foundation. His plan: alternate years between taking the standard deduction and donating to his fund and claiming itemized deductions.
How very clever. The tax law allows a $24,000 per year standard deduction. Arrange things so that in some years you have zero actual deductions, and get $24,000 free deduction. Pile all the real deductions into other years.
In economics we call this "convexification". There are lots of clever ways to draw lines through a stair step.
Of course, you can also just give $50,000 to charity in alternate years, and let the charity put it in the bank. Donor-advised funds are useful if you think your local charity's endowment investment policy isn't that smart. If they invest in obscure high-fee hedge funds and private equity deals and you'd rather they invested your money in transparent low-fee assets, then set up a donor-advised fund.
In a rare moment of sanity and good government from my ex-home state, Marc Levine, chairman of the Illinois state board of investment, pulled all of Illinois' pension assets out of high-fee obscure hedge funds.
Industry “experts” suggested we keep these investments to diversify our holdings and reduce overall risk. Yet we already owned bonds for that purpose. Our Procter & Gamble bonds made sense to us. I’m pretty sure my children will brush their teeth tonight. But I don’t have a clue about that long-lumber, short-sugar trade.
Did anyone at the table really understand what these hedge funds were doing? Should we be putting the retirement funds of Illinois state employees into investments that not a single trustee, consultant or staffer could explain?
Donor-advised funds are also a great way to give money to your favorite charity if you think their own investment
The article includes more clever advice:
... Donors who give appreciated assets get an added benefit: They avoid paying capital-gains taxes when they make the donation, and they get a deduction against their income taxes for the full value of the asset.
If you paid $50 for stock, now worth $100, give the stock to your favorite charity (Hoover!). The charity gets $100, you take $100 off your taxes, but you don't pay capital gains taxes on the $50. Essentially you get to take $100 plus the capital gains tax as a deduction.
It gets better though. Give a non-market asset to your favorite charity. You can see both you and the charity have every incentive to report fanciful values for the asset. If it's really worth $100, well, call it $200 for the IRS. The charity still gets $100 for free.
Now you can actually make money out of donations. Conservation easement syndications (here, here and most fun here are even better. Buy land cheap, declare a huge value, put the land in a conservation trust, promising not to build houses on it -- actual operating golf courses are ok, and too bad if sometime in 2050 building some houses is a good idea -- and deduct the high value against other income.
the former Millstone golf course outside Greenville, S.C. Closed back in 2006, it sat vacant for a decade...In 2015, the owner put the property up for sale, asking $5.8 million. When there were no takers, he cut the price to $5.4 million in 2016.
Later in 2016, however, a pair of promoters appeared. They gathered investors who purchased the same parcel at the market price and, with the help of a private appraiser, declared it to be worth $41 million, nearly eight times its purchase price. Why? Because with that new valuation and a bit of paperwork, the investors were suddenly able to claim a tax deduction of $4 for each $1 they invested. ..
...A preliminary IRS analysis of syndicated partnerships this summer showed investors claimed an average of $9 in tax deductions for every dollar they invest.
There are lots of ways to interpret all this. One can celebrate the creativity of the American tax lawyer and wealthy investor. Who said innovation has fled the US?
Obviously, I'm not such a fan. Even if you take a benign view -- the US likes to pass very high taxes for symbolic purposes, and then allows all sorts of shenanigans on the side so people don't actually have to pay the taxes -- much of the economic damage is done. Aside from the fact that marginal disincentives are high, the cost of all this stuff is not trivial either. From the first article
The funds linked to investment firms such as Fidelity and Vanguard typically charge administrative fees... The funds are often invested in vehicles managed by those firms and generate fees for the for-profit business.
And the lawyers who set up conservation trusts, and the lobbyists who keep them in the tax code, are all taking their cut too.
But even that is not the most annoying part. Now, on top of everything else, a wise taxpayer needs to set up a donor advised fund, sign a bunch of papers, and manage it each year. Already, perfectly normal citizens have to have trusts to manage estates, and hundreds of pages of tax forms each year. The needless complexity of life in the Republic of Paperwork is, to me, the most annoying part. We need a grand simplification of our public life. If this is what it leads to, the whole charitable deduction thing should get tossed overboard.
JC is on target.
These kind of shenanigans are not possible with a value added tax. A value added tax with no exceptions and that everyone pays
- Provides voters with an incentive to reduce the size of Government.
- Frees up hordes of tax lawyers, tax accountants, and bureaucrats to do something useful.
- Raises our standard of living
------------------------------------------
From Richard Rubin at WSJ:
The new tax law’s treatment of deductions gives people more reasons to concentrate giving in certain years, both inside and outside donor-advised funds.
A donor-advised fund is an investment account held for charitable purposes. Donors take tax deductions when they put money in, then recommend grants to charities over time.
Mr. Young,...added $30,000 to a donor-advised fund run by the Los Altos Community Foundation. His plan: alternate years between taking the standard deduction and donating to his fund and claiming itemized deductions.
How very clever. The tax law allows a $24,000 per year standard deduction. Arrange things so that in some years you have zero actual deductions, and get $24,000 free deduction. Pile all the real deductions into other years.
In economics we call this "convexification". There are lots of clever ways to draw lines through a stair step.
Of course, you can also just give $50,000 to charity in alternate years, and let the charity put it in the bank. Donor-advised funds are useful if you think your local charity's endowment investment policy isn't that smart. If they invest in obscure high-fee hedge funds and private equity deals and you'd rather they invested your money in transparent low-fee assets, then set up a donor-advised fund.
In a rare moment of sanity and good government from my ex-home state, Marc Levine, chairman of the Illinois state board of investment, pulled all of Illinois' pension assets out of high-fee obscure hedge funds.
Industry “experts” suggested we keep these investments to diversify our holdings and reduce overall risk. Yet we already owned bonds for that purpose. Our Procter & Gamble bonds made sense to us. I’m pretty sure my children will brush their teeth tonight. But I don’t have a clue about that long-lumber, short-sugar trade.
Did anyone at the table really understand what these hedge funds were doing? Should we be putting the retirement funds of Illinois state employees into investments that not a single trustee, consultant or staffer could explain?
Donor-advised funds are also a great way to give money to your favorite charity if you think their own investment
The article includes more clever advice:
... Donors who give appreciated assets get an added benefit: They avoid paying capital-gains taxes when they make the donation, and they get a deduction against their income taxes for the full value of the asset.
If you paid $50 for stock, now worth $100, give the stock to your favorite charity (Hoover!). The charity gets $100, you take $100 off your taxes, but you don't pay capital gains taxes on the $50. Essentially you get to take $100 plus the capital gains tax as a deduction.
It gets better though. Give a non-market asset to your favorite charity. You can see both you and the charity have every incentive to report fanciful values for the asset. If it's really worth $100, well, call it $200 for the IRS. The charity still gets $100 for free.
Now you can actually make money out of donations. Conservation easement syndications (here, here and most fun here are even better. Buy land cheap, declare a huge value, put the land in a conservation trust, promising not to build houses on it -- actual operating golf courses are ok, and too bad if sometime in 2050 building some houses is a good idea -- and deduct the high value against other income.
the former Millstone golf course outside Greenville, S.C. Closed back in 2006, it sat vacant for a decade...In 2015, the owner put the property up for sale, asking $5.8 million. When there were no takers, he cut the price to $5.4 million in 2016.
Later in 2016, however, a pair of promoters appeared. They gathered investors who purchased the same parcel at the market price and, with the help of a private appraiser, declared it to be worth $41 million, nearly eight times its purchase price. Why? Because with that new valuation and a bit of paperwork, the investors were suddenly able to claim a tax deduction of $4 for each $1 they invested. ..
...A preliminary IRS analysis of syndicated partnerships this summer showed investors claimed an average of $9 in tax deductions for every dollar they invest.
There are lots of ways to interpret all this. One can celebrate the creativity of the American tax lawyer and wealthy investor. Who said innovation has fled the US?
Obviously, I'm not such a fan. Even if you take a benign view -- the US likes to pass very high taxes for symbolic purposes, and then allows all sorts of shenanigans on the side so people don't actually have to pay the taxes -- much of the economic damage is done. Aside from the fact that marginal disincentives are high, the cost of all this stuff is not trivial either. From the first article
The funds linked to investment firms such as Fidelity and Vanguard typically charge administrative fees... The funds are often invested in vehicles managed by those firms and generate fees for the for-profit business.
And the lawyers who set up conservation trusts, and the lobbyists who keep them in the tax code, are all taking their cut too.
But even that is not the most annoying part. Now, on top of everything else, a wise taxpayer needs to set up a donor advised fund, sign a bunch of papers, and manage it each year. Already, perfectly normal citizens have to have trusts to manage estates, and hundreds of pages of tax forms each year. The needless complexity of life in the Republic of Paperwork is, to me, the most annoying part. We need a grand simplification of our public life. If this is what it leads to, the whole charitable deduction thing should get tossed overboard.
Does supplementation with marine-derived omega-3 fatty acids have any associations with reductions in fatal or nonfatal coronary heart disease in people at high risk of cardiovascular disease?
From jamanetwork.com.
Here is a link to the article.
The article pertains to people at high risk of developing cardiovascular disease.
Here are some excerpts.
-----------------------------------------------------
This meta-analysis of 10 trials involving 77 917 participants demonstrated that supplementation with marine-derived omega-3 fatty acids for a mean of 4.4 years had no significant association with reductions in fatal or nonfatal coronary heart disease or any major vascular events.
The results provide no support for current recommendations to use omega-3 fatty acid supplements for the prevention of fatal coronary heart disease or any cardiovascular disease in people who have or at high risk of developing cardiovascular disease.
Of the 77 917 high-risk individuals participating in the 10 trials, 47 803 (61.4%) were men, and the mean age at entry was 64.0 years; the trials lasted a mean of 4.4 years. The associations of treatment with outcomes were assessed on 6273 coronary heart disease events (2695 coronary heart disease deaths and 2276 nonfatal myocardial infarctions) and 12 001 major vascular events. Randomization to omega-3 fatty acid supplementation (eicosapentaenoic acid dose range, 226-1800 mg/d) had no significant associations with coronary heart disease death (rate ratio [RR], 0.93; 99% CI, 0.83-1.03; P = .05), nonfatal myocardial infarction (RR, 0.97; 99% CI, 0.87-1.08; P = .43) or any coronary heart disease events (RR, 0.96; 95% CI, 0.90-1.01; P = .12). Neither did randomization to omega-3 fatty acid supplementation have any significant associations with major vascular events (RR, 0.97; 95% CI, 0.93-1.01; P = .10), overall or in any subgroups, including subgroups composed of persons with prior coronary heart disease, diabetes, lipid levels greater than a given cutoff level, or statin use.
Here is a link to the article.
The article pertains to people at high risk of developing cardiovascular disease.
Here are some excerpts.
-----------------------------------------------------
This meta-analysis of 10 trials involving 77 917 participants demonstrated that supplementation with marine-derived omega-3 fatty acids for a mean of 4.4 years had no significant association with reductions in fatal or nonfatal coronary heart disease or any major vascular events.
The results provide no support for current recommendations to use omega-3 fatty acid supplements for the prevention of fatal coronary heart disease or any cardiovascular disease in people who have or at high risk of developing cardiovascular disease.
Of the 77 917 high-risk individuals participating in the 10 trials, 47 803 (61.4%) were men, and the mean age at entry was 64.0 years; the trials lasted a mean of 4.4 years. The associations of treatment with outcomes were assessed on 6273 coronary heart disease events (2695 coronary heart disease deaths and 2276 nonfatal myocardial infarctions) and 12 001 major vascular events. Randomization to omega-3 fatty acid supplementation (eicosapentaenoic acid dose range, 226-1800 mg/d) had no significant associations with coronary heart disease death (rate ratio [RR], 0.93; 99% CI, 0.83-1.03; P = .05), nonfatal myocardial infarction (RR, 0.97; 99% CI, 0.87-1.08; P = .43) or any coronary heart disease events (RR, 0.96; 95% CI, 0.90-1.01; P = .12). Neither did randomization to omega-3 fatty acid supplementation have any significant associations with major vascular events (RR, 0.97; 95% CI, 0.93-1.01; P = .10), overall or in any subgroups, including subgroups composed of persons with prior coronary heart disease, diabetes, lipid levels greater than a given cutoff level, or statin use.
Have your heart attack Monday to Friday from 0700 to 2300
From www.practiceupdate.com
------------------------------------
Background
Survival after in-hospital cardiac arrest (IHCA) is lower during nights and weekends (off-hours) compared with daytime during weekdays (on-hours). As overall IHCA survival has improved over time, it remains unknown whether survival differences between on-hours and off-hours have changed.
Objectives
This study sought to examine temporal trends in survival differences between on-hours and off-hours IHCA.
Methods
We identified 151,071 adults at 470 U.S. hospitals in the Get with the Guidelines–Resuscitation registry during 2000 to 2014. Using multivariable logistic regression with generalized estimating equations, we examined whether survival trends in IHCA differed during on-hours (Monday to Friday 7:00 AM to 10:59 PM) versus off-hours (Monday to Friday 11:00 PMto 6:59 AM, and Saturday to Sunday, all day).
Results
Among 151,071 participants, 79,091 (52.4%) had an IHCA during off-hours. Risk-adjusted survival improved over time in both groups (on-hours: 16.0% in 2000, 25.2% in 2014; off-hours: 11.9% in 2000, 21.9% in 2014; p for trend <0.001 for both). However, there was no significant change in the survival difference over time between on-hours and off-hours, either on an absolute (p = 0.75) or a relative scale (p = 0.059). Acute resuscitation survival improved significantly in both groups (on-hours: 56.1% in 2000, 71% in 2014; off-hours: 46.9% in 2000, 68.2% in 2014; p for trend <0.001 for both) and the difference between on-hours and off-hours narrowed over time (p = 0.02 absolute scale, p < 0.001 relative scale). In contrast, although post-resuscitation survival also improved over time in both groups (p for trend < 0.001 for both), the absolute and relative difference persisted.
Conclusions
Despite an overall improvement in survival, lower survival in IHCA during off-hours compared with on-hours persists.
------------------------------------
Background
Survival after in-hospital cardiac arrest (IHCA) is lower during nights and weekends (off-hours) compared with daytime during weekdays (on-hours). As overall IHCA survival has improved over time, it remains unknown whether survival differences between on-hours and off-hours have changed.
Objectives
This study sought to examine temporal trends in survival differences between on-hours and off-hours IHCA.
Methods
We identified 151,071 adults at 470 U.S. hospitals in the Get with the Guidelines–Resuscitation registry during 2000 to 2014. Using multivariable logistic regression with generalized estimating equations, we examined whether survival trends in IHCA differed during on-hours (Monday to Friday 7:00 AM to 10:59 PM) versus off-hours (Monday to Friday 11:00 PMto 6:59 AM, and Saturday to Sunday, all day).
Results
Among 151,071 participants, 79,091 (52.4%) had an IHCA during off-hours. Risk-adjusted survival improved over time in both groups (on-hours: 16.0% in 2000, 25.2% in 2014; off-hours: 11.9% in 2000, 21.9% in 2014; p for trend <0.001 for both). However, there was no significant change in the survival difference over time between on-hours and off-hours, either on an absolute (p = 0.75) or a relative scale (p = 0.059). Acute resuscitation survival improved significantly in both groups (on-hours: 56.1% in 2000, 71% in 2014; off-hours: 46.9% in 2000, 68.2% in 2014; p for trend <0.001 for both) and the difference between on-hours and off-hours narrowed over time (p = 0.02 absolute scale, p < 0.001 relative scale). In contrast, although post-resuscitation survival also improved over time in both groups (p for trend < 0.001 for both), the absolute and relative difference persisted.
Conclusions
Despite an overall improvement in survival, lower survival in IHCA during off-hours compared with on-hours persists.
Thursday, February 01, 2018
China weighs slowing or halting purchases of U.S. Treasuries
The headline read “China weighs slowing or halting purchases of U.S. Treasuries”.
Some perspective.
This is the best of all possible worlds. The US gets useful stuff and the Chinese get pieces of paper. Too bad China wouldn’t do this for long.
The excess dollars are worthless to China. The US Treasury does not get them, hence cannot spend them. The US loses the (questionable) benefit of the excess dollars spent by Government but avoids deficit spending. If the US could be sure that China would never cash in the excess dollars, the US Government could simply print new dollars in the amount of the excess dollars and continue to spend as before.
China buys other US debt, e.g., Corporate bonds.
Corporations probably would use the money in a way that benefits US citizens more than what Government spending would – this is good.
The US Government may be forced to reduce spending to avoid inflation – this is good.
The US Government could issue the same amount of debt as it would have to China, but sell it to others – this could lead to the same undesired outcomes the US faces now, e.g., Government wasteful spending and growing Government debt and inflation.
Most likely, the US would be better off because the US Government might be forced to control spending.
China buys other countries’ debt.
This reduces the problem to what the other countries’ do with the excess dollars, which is the same problem as what China would do with them.
China buys US products, including those exported to China and others that are not, e.g. real estate.
The US is worse off than before. China gets worthwhile goods and services and the US get pieces of paper.
Some perspective.
- The US imports (buys) more things from China than China imports (buys) from the US, a trade deficit for the US.
- The US sends more dollars to China to pay for its imports from China than China sends to the US to pay for its imports from the US.
- China uses the excess dollars to buy US Treasuries (pieces of paper) (to keep it simple, I am ignoring China’s purchases of US things that do not get sent to China, e.g., real estate).
- The US Treasury spends the excess dollars on things that are consumed in the US, e.g., pays government bureaucrats and others who buy consumer goods.
- The US gets the benefit of the excess dollars in the form of worthwhile products and services (except, to some extent, Government “products and services”). China gets pieces of paper.
China keeps them in a vault.
This is the best of all possible worlds. The US gets useful stuff and the Chinese get pieces of paper. Too bad China wouldn’t do this for long.
The excess dollars are worthless to China. The US Treasury does not get them, hence cannot spend them. The US loses the (questionable) benefit of the excess dollars spent by Government but avoids deficit spending. If the US could be sure that China would never cash in the excess dollars, the US Government could simply print new dollars in the amount of the excess dollars and continue to spend as before.
China buys other US debt, e.g., Corporate bonds.
Corporations probably would use the money in a way that benefits US citizens more than what Government spending would – this is good.
The US Government may be forced to reduce spending to avoid inflation – this is good.
The US Government could issue the same amount of debt as it would have to China, but sell it to others – this could lead to the same undesired outcomes the US faces now, e.g., Government wasteful spending and growing Government debt and inflation.
Most likely, the US would be better off because the US Government might be forced to control spending.
China buys other countries’ debt.
This reduces the problem to what the other countries’ do with the excess dollars, which is the same problem as what China would do with them.
China buys US products, including those exported to China and others that are not, e.g. real estate.
The US is worse off than before. China gets worthwhile goods and services and the US get pieces of paper.
Government Safety Regulations can cause net deaths
There is a tradeoff between safety and cost, the latter measured
both in dollars and foregone opportunities.
The more safety, the higher the dollar cost and the more valuable the
foregone opportunities. Moreover, there
is no way of achieving complete safety.
Balancing safety, cost, and the value of foregone opportunities
can be thought of as an optimization problem (not that we know the
optimum). The more constraints added in
the form of Government Safety Regulations (GSR) that reflect a focus on only part of the problem, the less
likely the optimum is a feasible solution.
The problem with GSRs is that
tradeoffs seldom are taken into proper account.
GSRs too often reflect a focus on reducing the probability of obvious
adverse events without considering adequately their less obvious adverse consequences. There is a reason for this – most voters,
media talking heads, and politicians are aware of the former and unaware or
less aware of the latter. Therefore,
they clamor for GSRs protecting them from the former – and Government obliges. The result is a high probability that GSRs
are too restrictive – in the sense that an informed populace would choose less
restrictive GSRs. A reasonable assumption
is that GSRs are too restrictive and often cost lives by failing to consider
all aspects of safety.
Example: Drugs
Drug safety is paramount in most people’s minds. The last thing Politicians and Bureaucrats
want is an angry public reaction to a drug killing people. Consequently, GSRs focus on assuring safety. But the only way safety can be assured is by
not using drugs. GSRs try to accomplish safety
by requiring a huge amount of expensive and time-consuming testing and
approving only “safe” drugs. This
assures a large measure of safety, but at the cost of unnecessarily expensive
drugs that reach the market long after they could have, the failure to develop
drugs with possible serious side-effects for diseases where no effective drugs
currently exist, and the failure to develop drugs that would have been
effective for serious rare diseases where the potential market cannot justify the
expense of going through the approval process.
Safety is necessarily achieved at the cost of excess deaths – a tradeoff
that is largely ignored in the analysis leading to the GSRs.
The potential excess deaths can be large. To illustrate, suppose a drug is delayed one
year and that it can reduce the death rate from a serious disease by 50% from
20% to 10% relative to existing drugs.
If the disease’s incidence in the population is 0.01%, then about 30,000
people in the US will contract it annually. Of
these, 6,000 people will die if the new drug is not available and 3,000 will
die if it is available. Excess deaths
are 3,000 for each year delayed. But
this is only part of the story, because subsequent even newer drugs each will
be delayed, too. Thus, the total of
excess deaths over time far exceeds 3,000 with a drug approval process that
takes one year longer than the optimum.
Cancer 'vaccine' eliminates tumors in mice
From www.sciencedaily.com
So, should we wait many years for all the human trials to be completed or give short-timers the opportunity to try them now?
--------------------------------------------
Injecting minute amounts of two immune-stimulating agents directly into solid tumors in mice can eliminate all traces of cancer in the animals, including distant, untreated metastases, according to a study by researchers at the Stanford University School of Medicine.
The approach works for many different types of cancers, including those that arise spontaneously, the study found.
The researchers believe the local application of very small amounts of the agents could serve as a rapid and relatively inexpensive cancer therapy that is unlikely to cause the adverse side effects often seen with bodywide immune stimulation.
"When we use these two agents together, we see the elimination of tumors all over the body," said Ronald Levy, MD, professor of oncology. "This approach bypasses the need to identify tumor-specific immune targets and doesn't require wholesale activation of the immune system or customization of a patient's immune cells."
One agent is currently already approved for use in humans; the other has been tested for human use in several unrelated clinical trials. A clinical trial was launched in January to test the effect of the treatment in patients with lymphoma.
Levy, who holds the Robert K. and Helen K. Summy Professorship in the School of Medicine, is the senior author of the study, which will be published Jan. 31 in Science Translational Medicine. Instructor of medicine Idit Sagiv-Barfi, PhD, is the lead author.
'Amazing, bodywide effects'
Levy is a pioneer in the field of cancer immunotherapy, in which researchers try to harness the immune system to combat cancer. Research in his laboratory led to the development of rituximab, one of the first monoclonal antibodies approved for use as an anticancer treatment in humans.
Some immunotherapy approaches rely on stimulating the immune system throughout the body. Others target naturally occurring checkpoints that limit the anti-cancer activity of immune cells. Still others, like the CAR T-cell therapy recently approved to treat some types of leukemia and lymphomas, require a patient's immune cells to be removed from the body and genetically engineered to attack the tumor cells. Many of these approaches have been successful, but they each have downsides -- from difficult-to-handle side effects to high-cost and lengthy preparation or treatment times.
"All of these immunotherapy advances are changing medical practice," Levy said. "Our approach uses a one-time application of very small amounts of two agents to stimulate the immune cells only within the tumor itself. In the mice, we saw amazing, bodywide effects, including the elimination of tumors all over the animal."
Cancers often exist in a strange kind of limbo with regard to the immune system. Immune cells like T cells recognize the abnormal proteins often present on cancer cells and infiltrate to attack the tumor. However, as the tumor grows, it often devises ways to suppress the activity of the T cells.
Levy's method works to reactivate the cancer-specific T cells by injecting microgram amounts of two agents directly into the tumor site. (A microgram is one-millionth of a gram). One, a short stretch of DNA called a CpG oligonucleotide, works with other nearby immune cells to amplify the expression of an activating receptor called OX40 on the surface of the T cells. The other, an antibody that binds to OX40, activates the T cells to lead the charge against the cancer cells. Because the two agents are injected directly into the tumor, only T cells that have infiltrated it are activated. In effect, these T cells are "prescreened" by the body to recognize only cancer-specific proteins.
Cancer-destroying rangers
Some of these tumor-specific, activated T cells then leave the original tumor to find and destroy other identical tumors throughout the body.
The approach worked startlingly well in laboratory mice with transplanted mouse lymphoma tumors in two sites on their bodies. Injecting one tumor site with the two agents caused the regression not just of the treated tumor, but also of the second, untreated tumor. In this way, 87 of 90 mice were cured of the cancer. Although the cancer recurred in three of the mice, the tumors again regressed after a second treatment. The researchers saw similar results in mice bearing breast, colon and melanoma tumors.
Mice genetically engineered to spontaneously develop breast cancers in all 10 of their mammary pads also responded to the treatment. Treating the first tumor that arose often prevented the occurrence of future tumors and significantly increased the animals' life span, the researchers found.
Finally, Sagiv-Barfi explored the specificity of the T cells by transplanting two types of tumors into the mice. She transplanted the same lymphoma cancer cells in two locations, and she transplanted a colon cancer cell line in a third location. Treatment of one of the lymphoma sites caused the regression of both lymphoma tumors but did not affect the growth of the colon cancer cells.
"This is a very targeted approach," Levy said. "Only the tumor that shares the protein targets displayed by the treated site is affected. We're attacking specific targets without having to identify exactly what proteins the T cells are recognizing."
The current clinical trial is expected to recruit about 15 patients with low-grade lymphoma. If successful, Levy believes the treatment could be useful for many tumor types. He envisions a future in which clinicians inject the two agents into solid tumors in humans prior to surgical removal of the cancer as a way to prevent recurrence due to unidentified metastases or lingering cancer cells, or even to head off the development of future tumors that arise due to genetic mutations like BRCA1 and 2.
"I don't think there's a limit to the type of tumor we could potentially treat, as long as it has been infiltrated by the immune system," Levy said.
The work is an example of Stanford Medicine's focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.
So, should we wait many years for all the human trials to be completed or give short-timers the opportunity to try them now?
--------------------------------------------
Injecting minute amounts of two immune-stimulating agents directly into solid tumors in mice can eliminate all traces of cancer in the animals, including distant, untreated metastases, according to a study by researchers at the Stanford University School of Medicine.
The approach works for many different types of cancers, including those that arise spontaneously, the study found.
The researchers believe the local application of very small amounts of the agents could serve as a rapid and relatively inexpensive cancer therapy that is unlikely to cause the adverse side effects often seen with bodywide immune stimulation.
"When we use these two agents together, we see the elimination of tumors all over the body," said Ronald Levy, MD, professor of oncology. "This approach bypasses the need to identify tumor-specific immune targets and doesn't require wholesale activation of the immune system or customization of a patient's immune cells."
One agent is currently already approved for use in humans; the other has been tested for human use in several unrelated clinical trials. A clinical trial was launched in January to test the effect of the treatment in patients with lymphoma.
Levy, who holds the Robert K. and Helen K. Summy Professorship in the School of Medicine, is the senior author of the study, which will be published Jan. 31 in Science Translational Medicine. Instructor of medicine Idit Sagiv-Barfi, PhD, is the lead author.
'Amazing, bodywide effects'
Levy is a pioneer in the field of cancer immunotherapy, in which researchers try to harness the immune system to combat cancer. Research in his laboratory led to the development of rituximab, one of the first monoclonal antibodies approved for use as an anticancer treatment in humans.
Some immunotherapy approaches rely on stimulating the immune system throughout the body. Others target naturally occurring checkpoints that limit the anti-cancer activity of immune cells. Still others, like the CAR T-cell therapy recently approved to treat some types of leukemia and lymphomas, require a patient's immune cells to be removed from the body and genetically engineered to attack the tumor cells. Many of these approaches have been successful, but they each have downsides -- from difficult-to-handle side effects to high-cost and lengthy preparation or treatment times.
"All of these immunotherapy advances are changing medical practice," Levy said. "Our approach uses a one-time application of very small amounts of two agents to stimulate the immune cells only within the tumor itself. In the mice, we saw amazing, bodywide effects, including the elimination of tumors all over the animal."
Cancers often exist in a strange kind of limbo with regard to the immune system. Immune cells like T cells recognize the abnormal proteins often present on cancer cells and infiltrate to attack the tumor. However, as the tumor grows, it often devises ways to suppress the activity of the T cells.
Levy's method works to reactivate the cancer-specific T cells by injecting microgram amounts of two agents directly into the tumor site. (A microgram is one-millionth of a gram). One, a short stretch of DNA called a CpG oligonucleotide, works with other nearby immune cells to amplify the expression of an activating receptor called OX40 on the surface of the T cells. The other, an antibody that binds to OX40, activates the T cells to lead the charge against the cancer cells. Because the two agents are injected directly into the tumor, only T cells that have infiltrated it are activated. In effect, these T cells are "prescreened" by the body to recognize only cancer-specific proteins.
Cancer-destroying rangers
Some of these tumor-specific, activated T cells then leave the original tumor to find and destroy other identical tumors throughout the body.
The approach worked startlingly well in laboratory mice with transplanted mouse lymphoma tumors in two sites on their bodies. Injecting one tumor site with the two agents caused the regression not just of the treated tumor, but also of the second, untreated tumor. In this way, 87 of 90 mice were cured of the cancer. Although the cancer recurred in three of the mice, the tumors again regressed after a second treatment. The researchers saw similar results in mice bearing breast, colon and melanoma tumors.
Mice genetically engineered to spontaneously develop breast cancers in all 10 of their mammary pads also responded to the treatment. Treating the first tumor that arose often prevented the occurrence of future tumors and significantly increased the animals' life span, the researchers found.
Finally, Sagiv-Barfi explored the specificity of the T cells by transplanting two types of tumors into the mice. She transplanted the same lymphoma cancer cells in two locations, and she transplanted a colon cancer cell line in a third location. Treatment of one of the lymphoma sites caused the regression of both lymphoma tumors but did not affect the growth of the colon cancer cells.
"This is a very targeted approach," Levy said. "Only the tumor that shares the protein targets displayed by the treated site is affected. We're attacking specific targets without having to identify exactly what proteins the T cells are recognizing."
The current clinical trial is expected to recruit about 15 patients with low-grade lymphoma. If successful, Levy believes the treatment could be useful for many tumor types. He envisions a future in which clinicians inject the two agents into solid tumors in humans prior to surgical removal of the cancer as a way to prevent recurrence due to unidentified metastases or lingering cancer cells, or even to head off the development of future tumors that arise due to genetic mutations like BRCA1 and 2.
"I don't think there's a limit to the type of tumor we could potentially treat, as long as it has been infiltrated by the immune system," Levy said.
The work is an example of Stanford Medicine's focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.
Long-Term Outcomes of Laser Prostatectomy for Storage Symptoms
From practiceupdate.com
------------------------------------
PURPOSE
To compare long-term outcomes for storage symptoms between PVP-120W-HPS and HoLEP, and to find factors influencing postoperative improvement of storage symptoms in the long term.
MATERIALS AND METHODS
A total of 266 men (PVP-120W-HPS group, 165; HoLEP group, 101), for whom 60-month follow-up data were available, were included in our study. Outcomes were assessed serially at 6-, 12- 24-, 36-, 48-, and 60-months postoperatively, using the IPSS, uroflowmetry, and serum PSA level. Postoperative improvement in storage symptoms was defined as a reduction by ≥ 50% of subtotal-storage-symptom-score at each follow-up visit after surgery compared to baseline.
RESULTS
Improvements of frequency, urgency, nocturia, subtotal-storage-symptom-scores, and QOL index were maintained up to 60-months after PVP-120W-HPS or HoLEP. There was no difference in degree of improvement in storage symptoms or percentages of patients with postoperative improvement of storage symptoms between the two groups throughout the long-term follow-up period. However, HoLEP group showed greater improvement in voiding symptoms and QOL than PVP-120W-HPS group. On logistic regression analysis, the higher baseline subtotal-storage-symptom-score and the higher bladder-outlet-obstruction index (BOOI) were the factors influencing the improvement of storage symptoms at 5-years after PVP-120W-HPS or HoLEP.
CONCLUSIONS
Our serial follow-up data suggest that improvement of storage symptoms was maintained throughout the long-term postoperative period for both PVP-120W-HPS and HoLEP, without any difference between the two surgeries. Also, more severe storage symptoms at baseline and more severe degree of BOOI are predictors of improvement of storage symptoms in the long-term after PVP-120W-HPS or HoLEP.
------------------------------------
PURPOSE
To compare long-term outcomes for storage symptoms between PVP-120W-HPS and HoLEP, and to find factors influencing postoperative improvement of storage symptoms in the long term.
MATERIALS AND METHODS
A total of 266 men (PVP-120W-HPS group, 165; HoLEP group, 101), for whom 60-month follow-up data were available, were included in our study. Outcomes were assessed serially at 6-, 12- 24-, 36-, 48-, and 60-months postoperatively, using the IPSS, uroflowmetry, and serum PSA level. Postoperative improvement in storage symptoms was defined as a reduction by ≥ 50% of subtotal-storage-symptom-score at each follow-up visit after surgery compared to baseline.
RESULTS
Improvements of frequency, urgency, nocturia, subtotal-storage-symptom-scores, and QOL index were maintained up to 60-months after PVP-120W-HPS or HoLEP. There was no difference in degree of improvement in storage symptoms or percentages of patients with postoperative improvement of storage symptoms between the two groups throughout the long-term follow-up period. However, HoLEP group showed greater improvement in voiding symptoms and QOL than PVP-120W-HPS group. On logistic regression analysis, the higher baseline subtotal-storage-symptom-score and the higher bladder-outlet-obstruction index (BOOI) were the factors influencing the improvement of storage symptoms at 5-years after PVP-120W-HPS or HoLEP.
CONCLUSIONS
Our serial follow-up data suggest that improvement of storage symptoms was maintained throughout the long-term postoperative period for both PVP-120W-HPS and HoLEP, without any difference between the two surgeries. Also, more severe storage symptoms at baseline and more severe degree of BOOI are predictors of improvement of storage symptoms in the long-term after PVP-120W-HPS or HoLEP.
Combination medication reduces stroke by 44% in patients with only moderate risk profile
January 25, 2018—Los Angeles, California—A combination of an angiotensin receptor blocker, a diuretic, and a statin may reduce the risk of having a first stroke by up to 44% among patients with only an intermediate cardiovascular risk profile, according to a study presented at the 2018 International Stroke Conference, taking place here from January 24 – 26.
“Blood pressure lowering [BP]and cholesterol lowering, in those with elevated values, have been shown to reduce heart attacks and strokes,” presenter Jackie Bosch, MD, of McMaster University in Hamilton, Ontario, Canada, told PracticeUpdate. But “only about one-third of those who have a first stroke report a history of hypertension, have elevated cholesterol, or are considered ‘high risk’. It was not clear if [BP] or cholesterol lowering in those who are not considered to have elevated values would be effective in preventing stroke, and yet this is a large proportion of those who are having stroke.”
Dr. Bosch and colleagues included in their analysis 12,705 participants from 21 countries who had what they defined as an “intermediate risk” of cardiovascular disease but what many would see as quite low risk. That is, they had to be ineligible for the medications being studied, based on the protocols used by the centers where they were treated, and have at least one of the following risk factors: elevated waist-to-hip ratio, smoking, low HDL cholesterol, prediabetes/diabetes, mild renal dysfunction, or a family history of coronary heart disease. None of the participants had any overt signs of cardiovascular disease.
The participants were randomized to one of four groups: 1) candesartan 16 mg/hydrochlorothiazide (HCTZ) 12.5 mg daily plus placebo, 2) candesartan/HCTZ plus rosuvastatin 10 mg daily, 3) placebo plus rosuvastatin, or 4) placebo plus placebo.
The participants’ mean age was 66 years, and 46% were women. The mean baseline BP was 138/82 mm Hg.
During a median follow-up period of 5.6 years, 166 strokes occurred. The BP difference between the treatment groups during follow-up averaged 6.0/3.0 mm Hg. Participants who received candesartan/HCTZ and rosuvastatin had a 44% reduction in stroke risk (confidence interval 0.36 - 0.87; P = .009), compared with patients who received only a placebo.
In addition, stroke was reduced by 20% (confidence interval 0.59 - 1.08, P = .14) among the patients taking candesartan/HCTZ, compared with placebo, and 30% (confidence interval 0.52 - 0.95, P = .02) among patients taking rosuvastatin, compared with placebo.
Pre-specified subgroup analyses revealed that stroke reduction with candesartan/HCTZ was seen only among patients with a baseline systolic BP in the upper third quadrant (> 143.5 mm Hg). Stroke reduction with rosuvastatin was seen regardless of baseline cholesterol level, however. While the risk of hemorrhagic strokes did increase with rosuvastatin, the effect was not significant, and the total number of hemorrhagic strokes was low.
Dr. Bosch pointed out, “there was a consistent effect on fatal or disabling strokes too, meaning that we did not just prevent people from dying from stroke, we also prevented them having the most disabling strokes.”
Questions remain. Dr. Bosch pointed out that there were not enough stroke events during the trial to reliably assess the impact on stroke subtype. Also, there were not enough participants over the age of 75 to be sure if the findings apply to older patients.
“The results of this study need to be considered in the larger context of the available evidence and with consideration of health care systems,” she noted. “The study demonstrates the efficacy of easily administered and low-risk interventions in an intermediate risk population, but the implementation of such information needs to be considered by guideline committees.”
Subscribe to:
Posts (Atom)