Former U.S. Secretary of Labor Robert Reich vividly remembers the nausea he felt the first time he met Bill Clinton. It was 1968, and Reich and Clinton were both Rhodes Scholars aboard the ocean liner, SS United States, en route to Oxford University. "The Atlantic in the first week of October tends to be fairly turbulent, so halfway across I got dreadfully seasick," Reich recalls. "I retired to my cabin thinking I would die. There was a knock on my door and here was this tall, gangly Southerner holding chicken soup in one hand and crackers in the other and hearing that I wasn't feeling well. My first impulse at seeing the crackers and chicken soup was to vomit."
It would be years before Clinton coined his signature line, "I feel your pain." But that less-than-auspicious introduction was the start of an ongoing dialogue between the two men that would last another 30 years. In 1992, when President-elect Clinton assumed the helm of the ship of state, he brought Reich aboard to lead his economic transition team. In early 1993, Reich was appointed Secretary of Labor, a position he held until 1997. During his tenure, Reich oversaw a number of landmark initiatives to bene- fit American workers, including the Retirement Protection Act, the Family and Medical Leave Act, and the first increase in the minimum wage since 1989. He also launched significant efforts to crack down on sweatshop labor, unsafe workplaces, and pension and health-insurance fraud.
Reich, who is 58, is co-founder and editor of The American Prospect magazine and has written 10 books, including The Work of Nations, which has been translated into at least 22 languages. He is currently the Maurice B. Hexter Professor of Social and Economic Policy at Brandeis University. Last year, Reich was awarded the prestigious Vaclav Havel Prize in Prague for his contributions to global thinking and culture. Over the years, he's served as a consultant to a number of foreign governments and labor unions, and next month heads to Australia at the request of that country's Labor Council.
Reich now serves as an informal advisor to Senator John Kerry. Last week, he spoke at length with Seven Days before this week's Vermont visit, which was sponsored by the Vermont Council on World Affairs.
SEVEN DAYS: There was a time in the not-too-distant past when Vermonters felt like they were shaping the national debate because our former governor was ahead in the polls. At the time, it seemed like Howard Dean was leading a grassroots, populist movement to galvanize the Left and take back America. But once John Kerry became the presumptive nominee, it felt like the Democratic Party lurched back to the center out of fear of alienating swing voters. Do you think that was a wise decision?
ROBERT REICH: First of all, I think Governor Dean played a hugely important role in developing the Democratic message and in inspiring millions of voters, many of them young voters who had not been involved in politics before. And his influence is still felt. So I don't look upon John Kerry's nomination as repudiation in any way of the enormous contributions Governor Dean made. When it comes to nominating a candidate, parties have a tendency to move toward the center ...There are substantial differences between John Kerry and George Bush on foreign policy and domestic policy. But when Democratic voters ultimately came to make a decision, they did what they often do, and that is choose someone they believe has the best chance overall to beat the Republican.
SD: This year, the choice for president couldn't be any more stark. But with all the ammunition the Democrats have at their disposal to challenge Bush's record, are you surprised that the polls show this race as close as it is?
RR: I am a bit, although one learns to be skeptical of the polls, especially these days when it's so difficult for polling organizations to actually get through to people on the telephone, when so many people have cell phones and caller ID. And also when it's so difficult to tell whether someone is a likely voter. This election is going to be decided by turnout, by the people who are sufficiently motivated to go to the polls. So the race may not be nearly as tight as the polls are showing it to be.
SD: But even if it's somewhat close, does that reflect a failure on the part of the Democrats to deliver a clear and consistent message?
RR: Well, you can bet that if Kerry loses, there will be a lot of Monday morning quarterbacks saying the message should have been this or that. On the other hand, if he wins, the campaign will be deemed brilliant. He will be known as the greatest strategist since Bill Clinton. Much in politics is decided in hindsight. So I guess my assessment, honestly, is that, given that right-wing radio and television are so uniformly pro-Bush and so vehemently attacking John Kerry, and given the highly disciplined media machine of this White House, I'm not surprised that much of the public has bought into the deceptions of this administration, ranging from the assertion that Iraq is critical to the War on Terror to the mind-blowing assertion that the Bush tax cut has generated a surging economic recovery. George Orwell understood the principle very well: If you tell a big lie often enough, some people will start believing it.
SD: During the presidential debates, President Bush talked about addressing job loss by promoting better education for American workers. And you yourself have written that we've "underinvested in our people" and need to promote more higher education to create upward mobility. But according to the Bureau of Labor Statistics, seven of the 10 fastest-growing jobs in the next decade will require only a high school diploma and on-the-job training. Is there a point to educating American workers if the jobs being created for them pay low wages, offer no benefits and don't require a college education?
RR: Yes. The president was confused -- let's put it generously -- between the issue of the number of jobs created and a very different issue, which is how much jobs pay. This has been an anemic job recovery in terms of jobs. Education has very little to do with generating more jobs. The way you generate more jobs is you have a strong economic recovery. The way you do that is the government stimulates the economy adequately. A tax cut for the rich doesn't stimulate the economy because the rich already buy as much as they want to buy. That's the very definition of being rich. So, the Bush tax cut was a terribly inefficient way of stimulating the economy and had the unfortunate side effect of widening the budget deficit considerably.
Switch gears and focus on the quality of jobs and the amount of money a job earns. The Bureau of Labor Statistics merely extrapo-lates its predictions on the basis of who has what job now. The problem over the long term is not that Americans will lack jobs. The problem is that if you simply extrapolate from the present, most of those jobs are going to be paying very little. We need to rebuild our middle class and create good jobs in this country. You do that by providing people with adequate early childhood education, good schools, access to higher education, research and development for our universities and industries so that new fields can be developed, incentives to train workers on the job, and many other provisions. [On this issue] this administration has done little or nothing.
SD: One of Vermonters' biggest concerns on the jobs front is outsourcing. Obviously, we're living in an increasingly integrated global economy and that's not likely to change. From your perspective, should we simply accept that certain jobs won't be done in the United States anymore and that our economy and workers must adapt to this new reality?
RR: Outsourcing is part of a larger pattern that began decades ago when manufacturing jobs began moving overseas. Many of those jobs would have gone in any event. Others have been automated away. That is, if they didn't go overseas, they would have been replaced by software. The answer isn't to preserve and protect the old jobs. It's to make sure that Americans get a substantial share of the good new jobs. If you look at the Bureau of Labor Statistics' listing of jobs in 1978 and compare it to today's list, you'll see that about a quarter of the jobs today were not even dreamt of in 1978. There's constant job change. But are we preparing enough of our people for the good jobs of the future? I think not.
I'm not saying that outsourcing is not a problem, although it represents only a small fraction of today's high-technology jobs. It should be a warning bell to us that over the next 15 or 20 years, if we don't maintain our lead in research and development at our universities, our high-tech centers, our infrastructure, then we are not going to have a high proportion of the good jobs of the future.
SD: Then why has so much been made of outsourcing in recent years?
RR: When manufacturing drifted abroad over the last 25 years, much was said of it during recessions, but manufacturing workers didn't have nearly the political clout or visibility of professional and high-tech workers. Profession-al and high-tech workers during this last recession took a beating. Naturally, the movement of some of those jobs to India and China has caused a lot of worrying. But the numbers are still pretty small, relative to the total number of professional and high-tech jobs in the United States. College graduates are still earning good wages and, indeed, their median earnings continue to move upward at a rapid clip, both in absolute terms and relative to the median earnings of high school grads. I don't want to suggest that outsourcing isn't a problem at all. But it's not nearly the problem that it may seem to be from the depths of a recession that is slow to fade.
SD: Can you explain what effect the $413 billion federal deficit will have on Vermonters' quality of life?
RR: It's already affecting their lives because Vermonters are paying interest on that debt right now. A portion of the taxes they pay to the federal government goes to pay fairly wealthy Americans and foreigners who have lent the U.S. government money. Those are tax dollars that are not going to schools or roads or job training or homeland security. They're going to interest payments. Eventually, those huge deficits are going to have to be paid and Vermonters will bear part of that burden. So it's not only a tax today in terms of interest payments. It's a tax tomorrow in terms of paying that debt off one way or the other. It means we get back less for our taxes.
SD: Would you describe yourself as a free-trade advocate?
RR: Not exactly. I believe that there needs to be labor and environmental standards in trade treaties. I think we have to vigorously enforce our trade laws. But I don't believe we should provide huge subsidies to American industries in order to keep them competitive. I hope I'm not irking too many Vermonters when I say that big agricultural subsidies to large agribusiness makes very little economic or social sense. One of the problems with the current administration is that so much of the budget has gone toward corporate welfare ...The recent corporate tax bill is a scandal. And all of this means less money for education, job training, social services, low-income housing, homeland security. It's just fiscally irresponsible.
SD: Congressman Bernie Sanders has said that our current trade agreements aren't helping the working class and suggests that we repeal NAFTA and our current trade deals with China and negotiate new ones. Do you agree or disagree?
RR: I disagree. I think we do have to have labor and environmental standards in our trade agreements, but no one has shown that NAFTA is responsible for our manufacturing decline. Most of the new manufacturing jobs are occurring in China, not in Mexico. And many of those manufacturing losses are due to technology. NAFTA has had very little effect relative to these other forces.
As to China, we do need to enforce our trade agreements. So I'm not a raving free-trader by any stretch. I think protectionism is dangerous and ill-advised. It doesn't deal with the fundamental problem, which is that too many our workers are not prepared for the jobs of the future.
SD: NAFTA has been around for over a decade. Do you think it's delivered on its promises?
RR: No. NAFTA was grossly oversold. Neither the benefits its proponents projected nor the costs its opponents feared have nearly come to pass. China became a much larger manufacturing center much sooner than anyone anticipated. Partly, it's because trade doesn't either create or destroy jobs, it reallocates them. And those who said that NAFTA would create a lot of new jobs in the United States were as wrong as those who said NAFTA would destroy a lot of jobs.
SD: Besides the economic impact of outsourcing, do you have other concerns about jobs going to other countries?
RR: We used to worry a great deal about the loss of our technological edge. But if you examine the issue closely, you'll see that our technological edge depends on our own public investments in everything ranging from basic research and development to public higher education. It's not a zero-sum game, in which there's a certain number of high technologies to be parceled out around the world. There's no necessary limit on the ingenuity of the human mind. The question is, where are innovative things done around the world? If you look to the future economy of Vermont, the question is, what are Ver-monters able to do that contributes to an increasingly integrated global economy? What's the value that Vermonters will be adding to that economy?
SD: In the last four years, Vermont has lost about 10,000 manufacturing jobs, and many of the jobs we're creating in the service sector pay significantly less than the jobs we've lost.
RR: Yes, and that's a huge problem. But that's not necessarily because we've gone from manufacturing to services. There are many, many high-paying service jobs in the United States, ranging from advertising to design, marketing, people services, financial services, engineering. These are all service jobs, but they tend to pay very well. The most important distinction is not between manufacturing and service. It's between high-wage service and low-wage service.
SD: As our economy becomes more globalized and decisions about wages and working conditions are increasingly made at the international level, where do you see unions fitting in?
RR: Unions are critically important in the local service sector, and I say that because in the local service sector, workers need more bargaining leverage. At the same time, they're not competing with workers from other countries. Nor are they, in general, competing with technology. Two of the most successful unions nationally have been the SEIU (Service Employees International Union) and HERE (Hotel Employees and Restaurant Employees). Construction trades have also been quite successful in unionizing. Again, this is one very important way that local service sector workers can improve their wages.
SD: So, do you see unions becoming more or less relevant in the global economy?
RR: The trend has been downward. In 1955, 35 percent of American workers were unionized. Today, fewer than 8 percent of private-sector workers are unionized. So, if you're only looking at the trend lines, you would have to conclude that they are having less influence. But, if you look more closely at the areas where they have gained bargaining leverage, those tend to be in local service industries: Las Vegas hotels, Los Angeles hospitals, custodial and janitor services in New York. These are jobs that in the past paid very low wages and these people need more bargaining leverage. So in these sectors, unionization has been a big success story.
SD: There's been some talk in Vermont recently about the issue of corporate personhood, the ability of corporations to claim the same constitutional rights as living, breathing human beings. Do you think this is a problem that needs to be addressed?
RR: Yes. Corporations are not people. People are people. Workers and managers and investors in corporations are people. But corporations themselves should not have the rights of people. I think that we get into trouble as a country when we assign personhood rights to entities that are legal fictions. For example, the idea that corporations have a free-speech right is a mischievous one. The Supreme Court decided that they did, but that conclusion ought to be challenged ...One of the large and growing problems we have in this country is with the great concentrations of economic power. The large corporation represents one such example. Another example is the media conglomerate. If we're not careful, we could lose our democracy.
SD: As you travel internationally, have you noticed a difference in attitudes towards the United States compared to the Clinton years?
RR: Yes, a big difference. Most people I met abroad were very fond of Bill Clinton, and still are. They liked the Clinton administration. Most of the people I come in contact with outside the United States today are quite negative about the United States, and in particular, the Bush administration ...It's like night and day. Immediately after 9/11 there was a great outpouring of world support and commiseration with the United States. After the invasion of Iraq, world opinion turned very sour, and it's still very sour.
SD: Has it affected their willingness to do business with us?
RR: To some extent, yes. I've encountered a number of business executives who are involved in international business deals of various sorts who tell me they play down their American citizenship and play up their international credentials. And it's also true with several retail products. I ran into a business executive recently from a big apparel manufacturer who told me that they've changed their advertising and marketing strategy to minimize any connection with the United States ...It's going to take a very long time to undo the damage that's been done over the last four years.


We would all want to live in a home that would be attractive and good to look at as it would surely be able to make us happier. We live in our home and stay in it for a long period of time that is why we should also invest properly on how it looks. It would be great if we could have a proper design for every part of our home so that we would be able to enjoy our life in living there. There are different kinds of design that we could have in our home and it would be best if we could start on one part of it so that we can eventually have a proper design at https://www.granitecolchester.co.uk for all of the parts of our home. We could start with remodeling our kitchen or having a design that would surely be eye catching for all of us. If you want to have a kitchen that you would enjoy using, it would be best if we could invest in having materials that would have a high quality on it. We could have tiles or granite as a table top. We should know that there are a lot of wonderful materials or stones that we could use as materials for our kitchen. It may be a little bit costly but there are surely some advantages that we should get to know of.
There are a lot of people that are hesitant in buying high quality materials for their kitchen as they are expensive but we should know that the luxury that they are going to give us would surely be worth it. kitchen materials like marble and granite may cost a lot of money but we should know that they can also be very durable. Read https://www.reference.com/home-garden/explore/interior-decorating to know more about home improvement.
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Co-founding equity partner of Foster & Foster, a Legal Aid practice in Enfield, London, specialising in social welfare law and in particular debt, housing, community care and welfare benefits. Then from 1 April 2013 helped expand the firm setting up offices in Leyton, South Woodford, Tottenham and Cheshunt and specialising in housing and debt and community care after removal of welfare benefits from Legal Aid. Then from 1 September 2018 from offices in Enfield and Leyton specialising in housing and debt, community care law and public law. SQM supervisor in housing and debt.
Having obtained a Law degree in Nigeria and then a Law degree from the University of London, I then obtained a broad range of experience in relation to housing and property and legal aid work and in relation to the administration and running of a solicitor's office including at a number of leading London legal aid practices with a view upon qualification to setting up my own practice at the earliest opportunity. I am now the co-founder equity partner of Foster & Foster Solicitors where in addition to dealing with the day to day management of the practice I have specialised in housing and debt and community care and public law and earlier in welfare benefits and debt.
In my current role I advise and represent primarily tenants, homeless applicants and mortgage borrowers in relation to housing issues including defending possession proceedings, disrepair, illegal eviction and homelessness and allocations. Throughout my career as a solicitor I have successfully represented tenants, homeless applicants, mortgage borrowers, community care service users and debtors in housing, debt and community care litigation and cases using legal aid.
I am an active member of the Housing Law Practitioners Association (HLPA).
I am a member of the Association of Women Solicitors.
I am a member of the Institute of Money Advisers (IMA).
I have recently been invited to be one of the representatives for 2018/19 by The Parliamentary Review in order to share my best practice as a learning tool to individuals within the public and private sector.


text:
Morris Bullock Honored for Scientific Achievement
Morris Bullock, 2017 PNNL Exceptional Scientific Achievement Award
Congratulations to Dr. Morris Bullock on receiving Pacific Northwest National Laboratory's 2017 Exceptional Scientific Achievement Award. Presented by Laboratory Director Dr. Steven Ashby, the award recognizes Bullock's pioneering role in understanding and controlling hydrogen activation in bioinspired catalysts.
Mother Nature uses Earth-abundant metals, such as iron and nickel, to produce hydrogen, and to oxidize hydrogen as a fuel. Industry performs the same reaction, using electrons and protons to produce electricity, less efficiently and with significant cost. Taking inspiration from enzymes, natural catalysts found in plants and algae, Bullock and his co-workers have unraveled the secrets of how electrons, protons, and hydrogen move in different catalysts to create or split hydrogen molecules.
To get at these secrets, Bullock took a holistic view by conducting careful, elegant experiments, models and simulations, calculations, and theory. Morris's innovative research has changed the field of catalysis, particularly in the creation of well-defined, precisely understood catalysts that can turn hydrogen (fuel) or other chemicals into electricity and vice versa. His work has changed how the scientific community understands and controls certain catalysts with implications not only for fuel cells but also for biofuels.
Bullock is Director of the Center for Molecular Electrocatalysis, a DOE Energy Frontier Research Center led by PNNL, and an Associate Director for PNNL's Institute for Integrated Catalysis. He is a leader in the scientific community, and has presented invited talks in the U.S., Europe and Asia. He has seven U.S. patents and is the author or co-author of more than 160 publications. This award is part of a distinguished list of honors that include being named a fellow of the American Chemical Society, the Royal Society of Chemistry, the American Association for the Advancement of Science, and receiving the Royal Society of Chemistry's Homogeneous Catalysis Award in 2013.

redpajama_set_name: RedPajamaCommonCrawl


At Renee Applebaum, Ph.D., P.C. psychotherapy is provided to assist individuals in coping with emotional and behavioral effects of a brain injury or neurological disorder as well as chronic pain. Individuals with these conditions often find themselves struggling with adjustment difficulties in everyday living. Treatment is aimed to assist individuals in managing associated depression, anxiety, self esteem issues and relationship problems associated with these complex medical conditions.
Psychotherapy is also frequently offered at our clinic to assist individuals in coping with psychological trauma or a Post Traumatic Stress Disorder. Psychological trauma can be devastating and debilitating. Cognitive behavioral therapy is a well researched and effective intervention for post traumatic stress reactions that is utilized in sessions typically scheduled on a weekly basis or more frequently when necessary. The goal is to neutralize the stress reaction and relieve symptoms of psychological trauma.
Finally, psychotherapy is offered at Renee Applebaum, Ph.D., P.C. to assist individuals in dealing with chronic pain that can be debilitating and significantly detract from the quality of life of the affected individual and their loved ones. We offer education and intervention that help relieve and manage physical pain. We attempt to work closely with physicians to complement medical interventions.
Our goal via psychotherapy is to assist individuals in improving emotional adjustment and to use internal and external resources to transcend obstacles and alleviate negative emotions/behavior that may be interfering with the ability to function.


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Bad Neighbors in South Asia
Posted on February 28, 2003 by actr7928
International Herald Tribune, February 28, 2003
While world leaders are preoccupied with Iraq and North Korea, relations between South Asia's nuclear rivals are deteriorating. India recently expelled Pakistan's acting ambassador in New Delhi, accusing him of funneling money to anti-India politicians in Kashmir. Pakistan retaliated by expelling the most senior Indian diplomat in Islamabad. The two neighbors are now left with low-level diplomatic contact.
Meanwhile, Indian and U.S. officials have accused Pakistan of reviving the flow of militants into Indian-controlled territory after several months of restraint that followed the threat of war last year. If this pattern of hostility continues, it is likely that Indian and Pakistani forces will again be involved in eyeball-to-eyeball confrontation when the spring thaw in the Himalayas makes fighting possible.
The United States has periodically engaged in shuttle diplomacy to keep the two nuclear-armed rivals from going to war, most notably in 2002, when both sides mobilized more than a million troops along their 2,000-kilometer frontier after a failed terrorist attack on the Indian Parliament. But the region needs a sustained peace process. Without it, the cycle of bluster and violence could escalate to unpredictable levels.
Frustrated by its inability to secure an Indian commitment to negotiate the future of Kashmir, Pakistan could continue down the slippery slope of using Islamic militancy as an instrument of policy. Sufficiently provoked, India could decide to follow Israel's example of dealing with the Palestinians or the U.S. example of dealing with Iraq.
The problem, of course, is that Pakistan is neither as weak as the Palestinians nor as vulnerable as Iraq. It has a sizable arsenal of nuclear weapons and a demonstrated ballistic missile capability. It is also a strategically located American ally.
At the heart of the conflict is mutual suspicion that each country wants to divide and destroy the other. Pakistan lives in dread of being "erased from the world map" – a phrase used by India's defense minister recently to describe what would happen in the event of nuclear war. Both sides refuse to seek a long-term solution to their pathological antipathy.
Before initiating a peace process, the United States should try to prevent an arms race. Pakistan has re-entered the international arms market as a buyer. India wants to expand the overwhelming superiority in conventional weapons that it already enjoys.
From 1997 to 2001, India was the fifth largest importer of arms in the world, after Taiwan, China, Saudi Arabia and Turkey. India has several major deals in the works with the United States, Russia, Israel and France that could make it the second biggest arms importer. In addition, India's Defense Research and Development Organization is engaged in indigenous development of weapons and systems. Economic problems limit Pakistan's ability to match India's arsenal. Pakistan's defense budget stands at around $3.3 billion, which is $10 billion less than India's. Of course, India has security concerns beyond Pakistan, notably in relation to China, whereas Pakistan's defense is primarily India-specific.
China, which supplies one-third of Pakistan's weapons, finds it useful to help Pakistan in keeping India bogged down in South Asia.
But in the absence of dialogue or a sustained peace process, India's decision to enlarge the military imbalance is driving hard-liners in Pakistan to press for further support of Islamic militants in Kashmir.
Some experts in India have argued that India should spend Pakistan into the ground, much as the United States crippled the Soviet Union. Because Pakistan has a much smaller economy, it cannot compete with India weapon system for weapon system, so it relies on nuclear deterrence and unconventional warfare. The one area where it has competed successfully, and possibly even managed parity, is in nuclear weapons and ballistic missiles. India's secular identity and the evolution of Islamic Pakistan toward sustainable democracy are being undermined by their military rivalry and tension. Security concerns have made Pakistan's military stronger than other national institutions and independent of civilian control. Hindu chauvinism directed against religious minorities, especially Muslims, is on the rise in India.
The growing power of Islamists in Pakistan and Hindu ideologues in India makes the region more dangerous, adding to the list of reasons why the United States and other concerned powers should give it more constructive attention.


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Australia Post Tests Drone Delivery Options
Updated: March 27, 2017 Jesse Young
Australia Post and the Upcoming Drone Test
Other Innovations at Australia Post
Image: Yaymicro.com
A big change is coming to the way Australia Post, the national postal services, will be delivering packages. Drones may be flying around and bringing the boxes as early as next year. A test use of the drones will begin in early 2016, Australia Post CEO Ahmed Fahour said in an interview with Australian Financial Review.
As in the case of the Amazon Prime Air program, the drones will deliver packages of up to two kilograms to the local communities. GPS will be used to make sure packages are brought to the correct location. Each of the drones that Australia Post will utilize in the trial costs 10,000 dollars, Business Insider Australia reported.
The technology comes with a range of security features that will be used to ensure timely delivery. Backup motor engines will be available for optimal weight balancing. They will be needed in case the original installation fails.
The idea to deliver a package right on the client's doorstep has always been a goal ecommerce companies have pursued. Hiring enough deliverymen to cover all areas that the company makes deliveries to, however, happens to be a costly endeavor. With drones, fast, traffic-free and stable transportation of the packages is possible.
"We've been talking to a major customer, an e-tailer, who would like to particularly deliver to regional and rural communities," Fahour said during the interview.
He confirmed that smaller trials of the program are already underway but the new customer will make bigger trials possible in early 2016.
The postal services are predominantly focused on the safety of the packages and the recipient's overall control over the deliveries. All clients want to know what is happening with their packages. Fahour confirmed that the drone deliveries will be controlled via a shared service. Using cloud-based information, all recipients will keep track of the delivery at all times.
Australia Post is also considering the purchase of 3D printers in an attempt to give customers access to even more diversified services.
They could potentially be used to print out common items, preventing people from waiting for a delivery. Currently, Australia Post officials are looking into possibilities for bringing the idea to reality.
These are just some of the new technologies that Australia Post will add to the equipment that it already utilizes. In 2014, 500-million dollar parcel sorting machines were bought for the offices in Sydney and Melbourne. All of these transitions are happening in an attempt to boost the popularity of the postal service once again. Since people are increasingly becoming dependent on digital communication, Australia Post has been experiencing losses stemming from a decreased demand for postal services.
Jesse Young
When he´s not writing about tech, you may find Jesse flying his Mavic Mini, re-watching Battlestar Galactica or enjoying a cup of java.
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GE Thinks its AiRXOS Can Solve the Drone Air Traffic…


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GAMETES: a fast, direct algorithm for generating pure, strict, epistatic models with random architectures
Nicholas A Sinnott-Armstrong1,
Tamra Heberling1,
Geneticists who look beyond single locus disease associations require additional strategies for the detection of complex multi-locus effects. Epistasis, a multi-locus masking effect, presents a particular challenge, and has been the target of bioinformatic development. Thorough evaluation of new algorithms calls for simulation studies in which known disease models are sought. To date, the best methods for generating simulated multi-locus epistatic models rely on genetic algorithms. However, such methods are computationally expensive, difficult to adapt to multiple objectives, and unlikely to yield models with a precise form of epistasis which we refer to as pure and strict. Purely and strictly epistatic models constitute the worst-case in terms of detecting disease associations, since such associations may only be observed if all n-loci are included in the disease model. This makes them an attractive gold standard for simulation studies considering complex multi-locus effects.
We introduce GAMETES, a user-friendly software package and algorithm which generates complex biallelic single nucleotide polymorphism (SNP) disease models for simulation studies. GAMETES rapidly and precisely generates random, pure, strict n-locus models with specified genetic constraints. These constraints include heritability, minor allele frequencies of the SNPs, and population prevalence. GAMETES also includes a simple dataset simulation strategy which may be utilized to rapidly generate an archive of simulated datasets for given genetic models. We highlight the utility and limitations of GAMETES with an example simulation study using MDR, an algorithm designed to detect epistasis.
GAMETES is a fast, flexible, and precise tool for generating complex n-locus models with random architectures. While GAMETES has a limited ability to generate models with higher heritabilities, it is proficient at generating the lower heritability models typically used in simulation studies evaluating new algorithms. In addition, the GAMETES modeling strategy may be flexibly combined with any dataset simulation strategy. Beyond dataset simulation, GAMETES could be employed to pursue theoretical characterization of genetic models and epistasis.
Despite the rising quality and abundance of genetic data, epidemiologists continue to struggle to explain the known heritability of these complex phenotypes with existing genetic factors. While strategies seeking single locus associations (i.e. main effects) are often sufficient to address diseases which follow Mendelian patterns of inheritance, their application to diseases characterized as complex has yielded limited success in the pursuit of explaining heritability [1, 2]. Epistasis is one of several phenomena reviewed by [3] believed to hinder the reliable identification of predictive genetic markers in association studies. The term epistasis was coined to describe a genetic "masking" effect viewed as a multi-locus extension of the dominance phenomenon, where a variant at one locus prevents the variant at another locus from manifesting its effect [4]. In the present study we consider statistical epistasis, which is the phenomenon as it would be observed in association studies. Statistical epistasis is traditionally defined as a deviation from additivity in a mathematical model summarizing the relationship between multi-locus genotypes and phenotypic variation in a population [5]. Specifically, we focus on statistical epistasis that is both strict and pure. An n-locus model is purely and strictly epistatic if all n loci, but no fewer, are predictive of disease status. The loci in these models could be viewed as "fully masked" in that no predictive information is gained until all n loci are considered in concert.
Computational geneticists are putting significant effort into developing algorithms for the detection of complex disease associations within clinical data [6–9]. While real biological datasets serve as the gold standard for validating new techniques, the development and systematic evaluation of computational strategies calls for simulated data.
Previous genetic data simulation efforts have introduced strategies for generating different data types including: quantitative trait loci mapping [10], pedigree association [11–15], and case/control-based association [16–23]. The simulation of datasets typically involves two stages: model generation, and sample generation. While most of the strategies cited above focus on the latter stage, the generation of realistic complex disease models constitutes a key challenge.
Moore, et. al [18] noted that simple, biallelic, 1-locus or purely epistatic 2-locus models of disease can be assembled with relative ease via trial and error. [24] characterized all fully penetrant two-locus models, where genotype disease probabilities were restricted to zero and one [25], later expanded upon this to include models with continuous penetrance values [26], generated purely epistatic models using the double description method [27] (for 2-locus models) and a non-linear maximization strategy (for 3 and 4-locus models) [17] and [18], recruited an evolutionary algorithm (EA) to evolve 2 to 5-locus epistatic models encoded as binary chromosomes. Over successive generations, models evolved towards a state of pure epistasis. Most recently, [23] circumvented the typical first stage of data simulation (i.e. model generation), directly evolving the genotypes and affection status of samples in a dataset. Evolving datasets with 3 to 5 SNPs at a time, this EA strategy evolved 3 to 5-locus epistatic interactions while attempting to avoid main effects and any intermediate nested 2-locus interactions.
While EA's have offered some success in the automated discovery of complex genetic models, there are distinct drawbacks to their use. First, they are computationally expensive, limiting the order and the quantity of models that can be feasibly generated. Second, EA's are not guaranteed to find epistatic models that are either pure or strict. Finally, if researchers wish to specify other model constraints (e.g. heritability, or prevalence), the EA fitness landscape becomes multi-objective, introducing further challenges and limitations to the evolutionary process.
In this study we introduce a Genetic Architecture Model Emulator for Testing and Evaluating Software (GAMETES). This algorithm provides a direct approach for the simulation of biallelic n-locus epistatic models which may be used in conjunction with any sample generation strategy. Specifically, GAMETES generates a precise class of epistatic models that are both pure and strict. Each n-locus model is generated deterministically, based on a set of random parameters, a randomly selected direction, and specified values of heritability, minor allele frequencies, and (optionally) population disease prevalence. For valid combinations of these model constraints, GAMETES attempts to generate a population of model architectures. We use the term architecture to reference the unique composition of a model (i.e. the penetrance values and arrangement of those values across genotypes). We demonstrate that GAMETES is a fast, reliable, and flexible method for generating complex genetic models of random architecture. We evaluate GAMETES over an example simulation study using MDR [28], an exhaustive combinatorial search algorithm designed to detect epistasis.
In this section, we describe (1) relevant background in genetics and modeling, (2) the specific steps for generating n-locus epistatic models that are both strict and pure and (3) an example simulation study using GAMETES.
Single nucleotide polymorphisms (SNPs) are single loci in the DNA sequence where alternate nucleotides (i.e. alleles) are observed between members of a species or between paired chromosomes in an individual. Most characterized SNPs are biallelic, meaning that only two alleles (A or a) are observed in a population. The genotype of a SNP in a diploid organism is determined by alleles found on each chromosome of the homologous pair. A biallelic SNP can have one of three genotypes: AA, Aa, or aa. The term genotype has been used to refer both to the allele states of a single SNP, as well as the combined allele states of multiple SNPs. To avoid confusion, we refer to the latter as a multi-locus genotype (MLG) whenever necessary.
SNPs not under selective pressure within a population typically exhibit genotype frequencies that are predicted by the Hardy-Weinberg Law [29]. Like most data simulation strategies, GAMETES adopts the assumption of Hardy-Weinberg Equilibrium (HWE) such that the allele frequencies of a SNP may be used to calculate it's genotype frequencies as follows: freq(AA) =p 2, freq(Aa) =2pq, and freq(aa) =q 2, where p is the frequency of the major (more common) allele 'A', q is the minor allele frequency (MAF) of the minor allele 'a', and p + q=1. GAMETES also assumes that alleles at different loci are in linkage equilibrium.
Penetrance functions, also referred to as penetrance tables, represent one approach to modeling the relationship between genetic variation and risk of disease. Penetrance is the probability of disease, given a particular genotype or MLG. Table 1 gives a penetrance function for a simple autosomal recessive disease model (i.e. a disease that requires two copies of the same allele).
Table 1 Penetrance function providing penetrance values for three genotypes from a SNP acting under an autosomal recessive disease model
This penetrance function is fully penetrant, since disease status is completely dependent on genotype (i.e. penetrance values are either 0 or 1). For single-locus models such as this, one can quickly determine if the SNP displays any main effect. The absence of a main effect would manifest itself as equal penetrance values for all three genotypes. Penetrance functions are easily extended to describe n-locus interactions between n predictive loci using a penetrance function comprised of 3n penetrance values corresponding to each of the 3nMLGs.
Statistical models of epistasis
We classify models of statistical epistasis into pure and impure, as well as strict and nested subtypes. For each, we say that n loci interact epistatically if the heritability of the n loci together exceeds the sum of the heritabilities of each of the n loci individually. Pure refers to epistasis between n loci that do not display any main effects [8, 26, 30]. Alternatively, impure epistasis implies that one or more of the interacting loci have a main effect contributing to disease status (see §1.1 in Additional file 1). Impure epistasis should be easier for non-exhaustive data analysis strategies to detect since any main effect(s) could serve as a guide towards the correct multi-locus interaction. Strict refers to epistasis where n loci are predictive of phenotype but no proper multi-locus subset of them are. By definition, all 2-locus epistatic interactions are strict. Nested refers to epistasis in which at least one proper subset of the loci also interact epistatically. Nested epistasis should be easier for non-exhaustive data analysis strategies to detect since the nested subset of loci could serve as a guide towards the correct n-locus interaction. To the best of our knowledge, the literature has yet to consider the distinction between strict and nested epistasis. Figure 1 illustrates the distinction between pure / impure and strict / nested. The present study explores the generation of worst-case models of epistasis, that are both pure and strict. However, the methods we present can be easily extended to the other types of epistatic models just described.
Illustrations (A) – (H) indicate various types of 3-locus epistatic interactions. Each numbered circle represents a SNP (where white circles indicate a SNP with no main effect, and darkened circles represent main effects). Each solid black node, with incident edges connecting respective SNPs, represents a 2 or 3-locus epistatic interaction. Illustrations (A) – (D) exemplify pure epistasis, while (E) – (H) exemplify impure epistasis. Illustrations (A) and (E) exemplify strict epistasis, while (B) – (D) and (F) – (H) exemplify nested epistasis.
Tables 2 and 3 give examples of epistatic models that are both pure and strict. While fully penetrant models, like those found in Tables 1 and 2 are easy to interpret, they are rarely representative of real interactions. More realistic models, like the one in Table 3 and the ones typically generated by GAMETES, possess continuous penetrance values between 0 and 1. The models from Tables 2 and 3 include a penetrance function relating two SNPs to risk of disease. Each of the nine entries in these tables correspond to one of the nine possible MLGs combining SNPs 1 and 2. For instance, according to Table 2, subjects that have the MLG (AA-Bb) are certain to have disease and according to Table 3 subjects that have the MLG (aa-bb) have a 14.7% chance of having disease. What makes these penetrance functions purely epistatic is that while the genotypes of SNPs 1 and 2 are together predictive of disease status, neither is individually. Indeed, in the case of Table 3, if an individual has genotype AA and SNP 2's genotype is ignored, the probability he has disease is
. 25 · . 266 + . 5 · . 764 + . 25 · . 664 = 〈 . 25 , . 5 , . 25 〉 · 〈 . 266 , . 764 , . 664 〉 = . 614
which is the marginal penetrance associated with genotype AA. (Computations are to three decimals places.) If he has genotype Aa, the probability of disease is
〈.25,.5,.25〉·〈.928,.398,.733〉=.614
and for genotype aa it's
〈.25,.5,.25〉·〈.456,.927,.147〉=.614.
Table 2 A fully penetrant 2-locus purely epistatic penetrance function
Thus, SNP 1's genotype alone is not predictive of disease status. Similar computations (using the probabilities of SNP 1's genotypes and the columns in Table 3) give the same value of .614 for the three marginal penetrances associated with SNP 2. Therefore, SNP 2 alone is also not predictive of disease status. The equality of all six of these marginal penetrances is the mathematical definition of strict, pure epistasis for 2-locus models. Their common value equals the population prevalence of disease (K). An expanded definition for n-locus models is given in Additional file 1 (§2.3). It essentially says that an (n)-locus model is strictly and purely epistastic if all of the n 3n−1 dot products, analogous to the six just discussed, are equal.
The GAMETES algorithm
We first outline some of the main ideas GAMETES uses to generate random, pure, strict epistatic models. More detail is given in the following sections, and still more is in Additional file 1 (§2). A key part of the GAMETES algorithm is that certain choices of 2n entries of an n-way strict, pure epistatic penetrance table uniquely determine the rest of the table. Here we are assuming that the population prevalence is specified. For example, the four entries .764, .398, .733 and .456 of the penetrance table in Table 3 determine the remaining five entries via equations (1), (2) and (3), and the analogous equations involving the columns of the table. So a first attempt to generate random penetrance tables might be to randomly vary these entries or even to randomly seed the four positions in the penetrance table they occupy. Two difficulties arise with this. One is that the mere choice of these positions—the ones that would be randomly seeded—biases the resulting penetrance tables (to have, for instance, high heritabilites). The other is that varying the values, even slightly, of the four chosen entries might not produce a penetrance table. For instance, if the entry .398 of the four chosen ones is changed to .37, then the entry just below it is forced to be greater than one.
This latter difficulty is addressed by working with what we call pre-penetrance tables. These are easily converted to strict, pure, epistatic penetrance tables and are essentially such tables with all marginal penetrances equal to zero. Pre-penetrance tables were used in a somewhat different context from ours in §8 of [5]. There, they arise as the difference between the 2-locus genotypic means of a quantitative trait and the linear model which best fits these means, and so show the wealth of epistatic models. They are our starting point for generating these models, primarily because all pre-penetrance tables, unlike strict, pure, epistatic penetrance tables, are easily described: each point of ℝ 2 n , Euclidean space of dimension 2n, corresponds to a unique n-locus pre-penetrance table. So picking a random point in ℝ 2 n (only a random direction is needed) determines a random pre-penetrance table. Converting this to a penetrance table gives our notion of a random, strict, pure, epistatic penetrance table.
There is a catch here which gets back to the first difficulty: the one-to-one correspondence between points of ℝ 2 n and all pre-penetrance tables depends on the choice of the 2n positions that are randomly seeded. The GAMETES algorithm accounts for this by choosing these positions as randomly as is computationally feasible, as discussed in the next section.
We think of a variable as occupying each of these 2n positions—the ones which, when seeded, determine all the entries of a pre-penetrance table. We call these 2n variables parameters. Figure 2 (A,B,C,D) gives four sets of parameter choices out of the 81 that are possible for 2-locus tables. Parameters are independent variables for determining pre-penetrance tables since all entries can be expressed in terms of them.
Examples of our methods for generating parameters for 2-locus pre-penetrance functions. Example A, illustrates the Sudoku method and examples B, C, and D illustrate the Point Method. The a's (white boxes) are independent variables, or parameters, chosen by these two methods. The b's (grey boxes) are dependent variables, specified in terms of the a's, where the dark grey boxes highlight the last variables to be specified. The subscripts indicate one of many orders in which these dependences can be found. In A, the variables a 1, a 2and a 3are first chosen by the Sudoku method, then b 4and b 5are found in terms of these. After this, one of the four possibilities for a 6is selected. The remaining b's are then found. In B, C, and D, the circled b's represent example reference points for the Point Method.
Generating random parameters
A truly random way to pick parameters for n-locus pre-penetrance tables is to sequentially pick 2n positions at random and then check to see if these give parameters. The check, however, is computationally slow. (It requires determining if a 2n×2nmatrix is invertible.) Moreover, many such choices do not give parameters. GAMETES uses what we call the Sudoku method, a much more efficient approach to picking parameters, with only a slight loss of randomness (see Figure 2A). The Sudoku method also picks parameters sequentially. However, after each choice, it expresses as many entries as possible in terms of the chosen parameters, and these are then omitted as possible future choices. This greatly reduces the number of choices which do not lead to parameters. Another advantage of the Sudoku method is that if after 2n choices all 3n entries of an n-locus table have been expressed in terms of the chosen ones, then no check is required: the 2n choices always give parameters in this case.
The Sudoku method always produces parameters randomly when the number of loci n is 2. As n grows, two things happen: (1) some bias occurs in parameter generation, and (2) the success rate for finding parameters decreases: for n=2,…,8, these rates were 100%, 99.9%, 99%, 92.9%, 61.2%, 3.28%, and 0% based on 750,000 GAMETES runs. Because of this, GAMETES uses what we call the Point method to generate parameters when n≥6. Figure 2 (B,C,D) illustrates three iterations of the Point method in the case of two loci. For n loci, the method starts by randomly choosing any one of the 3n entries. The parameters the Point method then produces are the ones given by the 2n entries whose corresponding genotypes differ at every single SNP from the genotype corresponding to the chosen entry. The Point method always succeeds, and since it picks randomly from 3n choices of parameters, not much randomness is lost.
From parameters to penetrance functions
Any pre-penetrance function can be converted to a pure, strict, epistatic penetrance function by applying a linear scaling function S to each of its entries. This function S is defined by: the i j th entry of S(G), G being any pre-penetrance function, is S ( G ) ij = g ij − m M − m . Here g ij is the i j th entry of G, and M and m are the maximum and minimum respectively, of the entries of G. The entries of S(G) lie in the interval [0,1], with the minimum entry 0 and the maximum 1. Note that if all entries of G are multiplied by any positive constant c, giving the pre-penetrance table cG, then S(cG)=S(G). So applying the function S to all pre-penetrance tables in the direction of G, meaning all positive multiples of G, gives the same penetrance table.
Now, given a random direction of pre-penetrance tables, the function S converts it to our notion of a random, strict, pure, epistatic penetrance table. Choosing such a random direction requires an explicit description of all pre-penetrance tables. Any parameters, for instance those supplied by one of the methods discussed above, provide such a description. It takes the form of a one-to-one correspondence between all points of ℝ 2 n and all n-locus pre-penetrance tables. Specifically, given a point in ℝ 2 n , the corresponding pre-penetrance table has parameter values equal to the coordinates of the point. So, given randomly chosen parameters, picking a random direction of n-locus pre-penetrance tables now amounts to picking a random direction or, equivalently, a unit vector in ℝ 2 n . We do this using G.W. Brown's algorithm discussed on page 135 of [31].
Adjusting heritability and prevalence
Assume now that a random, pure, strict epistatic penetrance table with a specified heritability, and perhaps also a specified prevalence is desired. Then GAMETES generates a random penetrance table as above and linearly scales its entries to achieve, if possible, the specified values. Linearly scaling the entries, meaning applying a function of the form f(x)=mx + b,m>0 to each, changes the penetrance table in a relatively minor way so that randomness is preserved. If just heritability is specified, this scaling is done without changing prevalence. The required values of m and b are discussed in Additional file 1 (§2.5).
Certain values of heritability and prevalence can never be achieved as discussed in the next section. So GAMETES will always fail if these values are specified. Also, penetrance tables with certain other values of heritability and prevalence are very sparse among all penetrance tables and so are generated by GAMETES with extremely low probability. For example, there exist n-locus penetrance tables with all heritabilities ≤1 having prevalence and all MAFs equal to 1 2 . However, in both the 5 and 6-locus case, GAMETES generated none of these with heritability ≥.1 after 100,000 iterations.
Limits on heritability and prevalence
The values of heritability and prevalence which a penetrance table can have are limited. For instance, no penetrance table has heritability 1 and prevalence 1 4 . The limits are more severe if MAFs are specified. For example, there are 2-locus penetrance tables with heritability 1 and prevalence 1 2 , but none if both MAFs are 1 4 . Penetrance tables with heritability 1 only exist if the MAFs are 1 2 or 1− 1 2 . See Table 2 for an example of a penetrance table with a heritability of 1.
Culverhouse, et. al [26] summarized estimates of maximum heritabilities for 2 to 4-locus purely epistatic models over a range of MAFs and prevalence values. Figure 3 illustrates our maximum heritability estimates for pure, strict 2-locus epistatic models where both SNPs have the same MAF. Our method for estimating maximum heritability is discussed in Additional file 1 (§2.6). Generally speaking, if the prevalence K is near .5, maximum heritabilities are largest when the MAFs are either 0.5 or 1− 1 2 (≈.29), and fall off as the MAFs move away from these values. For other values of K, maximum heritabilities tend to increase with MAFs.
Plot of our maximum heritability estimates for pure, strict, 2-locus models.
Summary of the GAMETES Algorithm
The GAMETES algorithm first (1) generates random parameters and a random unit vector in ℝ 2 n , then (2) generates a random pre-penetrance table by seeding these parameters using the unit vector, and then (3) uses the function S to scale the entries of this random pre-penetrance table to generate a random penetrance table. In case a random penetrance table having a specified heritability, or heritability and prevalence is desired, it further (4) scales the entries of this penetrance table to achieve, if possible, these values. If the Sudoku method fails in step (1) or the scaling in step (4), the algorithm iterates until it either succeeds or a specified iteration limit is reached.
We give alternative descriptions, illustrated in Figure 4, of steps (2), (3) and (4) to clarify our notion of a random penetrance table. The parameters and vector given by successful completion of step (1) together determine a random direction of pre-penetrance tables. It consists of all pre-penetrance tables obtained by seeding the parameters with points in the direction of the vector. This random direction of pre-penetrance tables determines, in turn, a random class of strict, pure, epistatic penetrance tables. The members of this class consist of all penetrance functions which can be obtained from some pre-penetrance function in the random direction by linearly scaling its entries. These classes, one for each direction of pre-penetrance tables, partition the set of all strict, pure, epistatic penetrance tables. Each (successful) iteration of the GAMETES algorithm essentially picks, at random, one of these classes. The penetrance table in this class with maximum heritability is our random penetrance table. In case a random, strict, pure epistatic penetrance table with specified values of heritability and prevalence is desired, GAMETES picks the unique (if any) penetrance table from this class with these values.
A schematic depiction of our method for picking random, strict, pure, epistatic penetrance functions. Points in the parameter space, ℝ 2 n correspond to pre-penetrance functions, and points in the shaded region correspond to strict, pure, epistatic penetrance functions. The vector V → indicates a random direction in the set of pre-penetrance functions. V → determines a random class of penetrance functions, which is indicated by the line in the shaded region. The point A on the boundary of this region indicates one (of the two) penetrance functions in this class with maximum heritability. The point B indicates the penetrance function in this class having specified values of prevalence and heritability (if one exists). It may be viewed as random among all those with these values.
A GAMETES simulation study
Our evaluation of GAMETES included an assessment of run time, tracking of model generation success, and an example application of GAMETES-simulated datasets to a simulation study using Multifactor Dimensionality Reduction (MDR). MDR is a well documented combinatorial genetics algorithm that exhaustively searches for epistatic interactions [28]. MDR finds models by scanning through all possible combinations of factors up to a pre-specified order of interaction, and has the ability to identify pure, strict epistatic models. MDR was run on a spectrum of simulated datasets, generated using GAMETES. While model generation is the focus of GAMETES, we have included a simple sample generation strategy within the software (see Additional file 1, §2.7). We used GAMETES to attempt generating 5 random models for each of 48 different constraint combinations which differ by number of loci (2, 3, 4, or 5), heritability (0.005, 0.01, 0.025, 0.05, 0.1, or 0.2), and MAF (0.2 or 0.4) with prevalence allowed to vary. GAMETES successfully generated 5 random models for 40 of these constraint combinations. For each of these models, we simulated 100 replicate datasets having balanced sample sizes of 200,400,800, and 1600 (400 datasets per model). For simplicity, each dataset was generated with a total of 20 SNPs. On whole we generated a total of 200 models and 80,000 datasets, all of which were evaluated using MDR.
For every evaluation, MDR was directed to search up to one order higher than the order of the simulated model. The best model was selected based on cross validation (CV) consistency, and in the event of a CV tie, based on testing accuracy. In this study, model detection success was evaluated, referring to the proportion of datasets within which the correct underlying model was identified. Detection success was considered to be meaningful when it was greater than 0.8.
Table 4 gives the average run time required for GAMETES to make 100, 000 n-locus model generation attempts. Each average is based on 8 different runs of GAMETES in which pure, strict, epistatic models were sought with heritabilities of 0.005, 0.01, 0.025, 0.05, 0.1, 0.2, 0.3, or 0.4 (MAFs =0.5 and K 0.5). Run times were obtained running GAMETES on a 64-bit Dell PC with a 2.5GHz Intel Xeon Processor. The difference between run times for different heritabilities was negligible.
Table 4 Average n-locus run time of GAMETES
In addition to run time, we tracked the number of times a model was successfully generated having the specified set of model constraints. Table 5 indicates the frequency of successful model generation for each of the 8 specified heritabilities over all n-locus combinations explored. This frequency gives us an indication of how many iterations it takes to find a pure, strict, epistatic model with these specified heritabilities. As we approach the limits of what constraint combinations can be generated it takes GAMETES more attempts to successfully generate such models. In general, models of higher heritability take more attempts to find. This trend is exaggerated as the number of loci (n) is increased. The low likelihood of GAMETES to find models of high heritability is an expected limitation of the algorithm, since random models may only be scaled down to lower heritabilities during the model generation process.
Table 5 Model generation frequency
In Additional file 1 (§3) we give the results of an example simulation study evaluating MDR using the models and datasets generated with GAMETES as previously described. We find that GAMETES is able to generate models useful for such evaluations, i.e. models with constraints at the boundary of what MDR is able todetect.
This study introduces GAMETES, a fast and reliable strategy for the generation of complex genetic models with random architectures. Specifically, we focus on the generation of pure, strict n-locus epistatic models (considered to be the most difficult to detect). The benefits of our strategy include (1) speed; deterministic calculation of models makes our approach much faster than an EA approach, (2) randomness; models are generated using a strategy which seeks to maximize the randomness of model architecture, (3) the ability to precisely specify genetic constraints, (4) the ability to generate a large population of models from which to choose, and (5) the potential to combine the GAMETES modeling strategy with any data simulation strategy. An obvious limitation of this approach is the difficulty it has finding models of higher heritability. However, GAMETES is proficient at finding models with heritabilities typically used in evaluating and comparing new bioinformatic strategies.
While the probability is low that these types of 'extreme' epistatic interactions occur in biology by chance alone, we instead focus on the fact that they 'can' occur. With that in mind, our focus on pure strict epistasis is intended to promote the development of strategies that can accommodate even the most challenging relationships. In doing so, we make minimal assumptions about the true nature of biological interaction. Notably, the GAMETES strategy may be extended to produce impure epistatic models, as well as nested epistasic models, which are more likely to occur by chance. This extension will be a focus of future work.
The GAMETES software is open source and freely available for download. It offers an intuitive and flexible framework for the simulation of complex genetic models, and the option to generate simulated datasets from these models. This software offers both a graphical user interface, as well as command line accessibility to facilitate the quick generation of a large simulated dataset archive. The GAMETES software along with a detailed users guide is included as Additional file 2 and Additional file 3, respectively.
Availability and requirements
Project name: GAMETES
Project home page: http://sourceforge.net/projects/gametes/files/
Operating systems: Linux, Mac, PC
Programming languages: Java
Other requirements: None
License: None
RU co-developed the methodology and software, carried out experiments, and co-wrote the manuscript. JK devolped the mathematical proofs, co-developed the methodology, and co-wrote the methods and supplemental material of the manuscript. NSA co-developed the computational methodology, and carried out the run-time experiment. TH carried out experiment determining maximum heritabilities and worked on respective figure. JF co-developed the software, and programmed the GAMETES GUI software. JH co-developed software. All authors read and approved the final manuscript.
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Ryan J Urbanowicz, Jeff Kiralis, Nicholas A Sinnott-Armstrong, Tamra Heberling, Jonathan M Fisher & Jason H Moore
Nicholas A Sinnott-Armstrong
Tamra Heberling
Additional file 2: GAMETES Software Version 1.0 Beta. The graphical user interface for the GAMETES software. This software is open source and includes a User's Guide. (JAR 128 KB)
Additional file 3: GAMETES User's Guide Version 0.1.0 Beta. A reference guide for using the GAMETES software. (PDF 247 KB)
Urbanowicz, R.J., Kiralis, J., Sinnott-Armstrong, N.A. et al. GAMETES: a fast, direct algorithm for generating pure, strict, epistatic models with random architectures. BioData Mining 5, 16 (2012). https://doi.org/10.1186/1756-0381-5-16


The Best Anison Entertainment and Dance groupe of the world !
The TV show "Star Draft Kaigi" on Nippon Tv permitted to RAB to do major debut. They also gain in popularity on the japansese Niconico Douga video site in addition to the support from Anime's world who loved their video. They do performance on Ooishi Masayoshi's song : "Kimi jyanakya dame mitai" of "Gekkan Shoujo Nozaki-kun" which have more than 1.000.000 views and they also participate for "Google Rewind!?" as Japanese ambassador.
They are an unique dance perfomer unit who have charisma and popularity on internet but also in real life.


text:
FORMER WEST is a long-term, transnational research, education, publishing, and exhibition project in the field of contemporary art and theory. The project grapples with the repercussions of the political, cultural, and economic events of 1989 for the contemporary condition. It does so in the search for ways of formerizing the persistently hegemonic conjuncture that is "the West"; to be able instead to simply refer to "the west," and with it, suggest the possibility of producing new constellations, another world, other worldings.
Through the propositional imaginary "former West," the project brings forth a means by which to assess the contemporary at the intersection of two temporal constructions of "the West": one equated with the "first world" of a post-WWII, tripartite Cold War arrangement; the other, synonymous with the notion of Western ultramodernity.
If the "former East" emerged in the aftermath of the Cold War in 1989, its western geo-political counterpart—blinded by the (seemingly default) victory of neoliberal capitalism—has widely failed to recognize the impact of these massive changes upon itself. The so-called West has continued to think and act, symbolically and realistically, as "first" among what were supposed to have become equal if heterogeneous provinces of one world. One wonders precisely why then, when there is a "former East," there is no "former West"?
Yet, not in spite of their differences, the Cold War ideological rivalry of communism and capitalism could also be viewed as a competition between two variants of grand modernity, with both invested—under the guise of developmentalism—in constructing economic, technological, political, and epistemological infrastructure of power, and forcing such agendas upon others through domination and exploitation. Here, in this second temporal construction, the proposition "former West" confronts such a colonial, imperialist ultramodernity, seeking ways of undoing the resilient universalization of Western narratives.
As a research undertaking, FORMER WEST included a series of educational activities, individual research projects, research seminars and symposia, research exhibitions, and major public Research Congress events. The constantly evolving process of this research trajectory has been registered and made publicly accessible through the online platform formerwest.org.
In its culminating phase (2014–2016), the project works towards a major publication FORMER WEST: Art and the Contemporary after 1989, edited by Maria Hlavajova and Simon Sheikh (2016). This process evolves through a series of Public Editorial Meetings held in various geographical and discursive contexts, including Berlin (2013), Utrecht (2014), London, Budapest, and Warsaw (2015), and is realized by means of a collaborative effort between the project's densely-knit web of individual and institutional partners from around the world. The publication can be ordered via The MIT Press.


text:
Bahwan Tower
Suhail Bahwan Group
9/1, Burj Khalifa Street
Bahwan Tower on the map of Dubai
New projects Dubai, Downtown Dubai, Zabeel
🟧 Number of floors G+M+3P+15
🟧 Security 24 hour security and access control
🟧 Amenities Purpose-built laundry areas, Maid's room en-suite (3BR), Spacious balconies, closed plan kitchen layouts, Built-in wardrobes, Italian porcelain tiled flooring, 24 hour security and access control, CCTV in common areas
🟧 Property Type Apartment
🟧 Project № 1732
About the units
🟧 Number of units 132
🟧 Apartment area 982–2,174 SQFT
Information about the project
What is the location?
Bahwan Tower is located in the Burj Khalifa community while being surrounded by an array of outlets for shopping, recreation, and leisure. Here you can move from one place to another with ease, thanks to the availability of the metro stations at Business Bay and the Dubai Mall. At the same time, the main road arteries of Dubai are never far away, making this area one of the most central districts of Dubai. These days, Downtown Dubai is one of the most sought-after areas in the world of real estate and is popular among both home buyers and investors. This is no surprise when you look at the wide range of amenities the area boasts.
What's around The Bahwan Tower?
Nurseries/ Education: Blossom Business Bay (1 min), Learning Tree Nursery (6 min), Pinocchio Nursery (2 min), Eduscan Group (12 min), Alunoz Learning Center (2 min), Sindin Management Training Institute (SMTI Dubai) (4 min)
Shopping: Vida Souk (5 min), Dubai Mall (11 min), Mazaya Shopping Centre (15 min)
Medical Facilities: Midline Bay Medical (7 min), Zack Medical Centre (13 min), Excellency Center (10 min), Monroe Medical Center (15 min), BetterCare Medical Center, Dubai (11 min)
Café/Restaurants: Billionaire Mansion & Sumosan Dubai (6 min), Zaatar w Zeit - Bussiness Bay (7 min), Pizzaro Old Town (8 min), Yeldizlar restaurant (7 min), Sargon Dubai (8 min), At.Mosphere Burj Khalifa (7 min)
Entertainment: Burj Plaza (8 min), Dubai Ice Rink (9 min), Dubai Aquarium & Underwater Zoo (8 min), SEGA Republic (10 min), The Green Planet (13 min)
Others: Boudoir Beauty Lounge Dxb (1 min), Mansory Middle East Motors Dubai (7 min), F Mart (7 min)
The Bahwan Tower has a ground floor with a lobby and a reception while there is also a retail area. Besides the ground floor, there is also a mezzanine and 3 podium levels, providing covered parking. The building houses 44 1-bedroom apartments that range from 982-1.081 square feet. There are also 59 2-bedroom apartments with sizes varying from 1.529-1.699 square feet. When you are looking for a 3-bedroom unit, you can choose from 29 apartments that range from 2.501-2.174 square meters.
The Bahwan Tower is decorated with a contemporary facade that matches the stylish interiors. The modern and sleek design of the building provides residents with a luxurious atmosphere and the feeling of hospitality.
The Bahwan Tower offers all the amenities and facilities that are common in modern life. When you want to go for a workout, the gym and gym terrace provide you with all the materials you need. You can also opt for a swim in the enormous swimming pool. When you have children you can entertain them by going to the kid's play area, where they can find an abundance of interesting attractions. When you arrive by car, you can leave your vehicle in the secure covered parking, where there is 1 place reserved for each apartment, while the 3-bedroom units have access to 2 parking spots.
How to get around?
Bus stop: 8 Boulevard Walk Tower 1 (2 min), Clover Bay Tower 1 (3 min), Clover Bay Tower 2 (5 min)
Metro Line: Burj Khalifa / Dubai mall metro station going to Abu Dhabi (13 min), Business Bay Metro Station Exit 1 (6 min)
Road Access: Sheikh Zayed Road
Airport: Al Maktoum International Airport (44 min), Dubai International Airport (24 min)
Car Rental: Cubra Car Rental (5 min), Dubai Luxury Cars Rental (4 min), One Click Drive Portal Dubai: Rental Car, Chauffeured Car, Driver Service (7 min)
Heliport: Heli Pad AHC (9 min), Helipad MBK Tower - E11 (6 min),
Others: Lavish Yacht Rental Dubai (7 min), Cozmo Yachts (5 min)
About the apartments
The meticulous design of each unit in the Bahwan Tower has made efficient living spaces for each apartment. Besides being stylish, the units are also finished with Italian tiled flooring, modern kitchens, and ample storage facilities throughout the apartments. The units have large floor to ceiling windows that allow the sunlight to come in while also providing the opportunity to fully enjoy the stunning views. Every apartment comes with a spacious balcony, home automation, and stylish bathroom suites. In the 2- and 3-bedroom units there are also purpose-built laundry areas.
Who is the master developer?
Utmost Properties, founded in 2006, has redefined the concept of space. Over the years the company has blended form and function by creating unique residential complexes in the United Arab Emirates. The portfolio of Utmost Developers consists of exclusive apartment units and luxury villas. At the same time, the company is also active in the industrial and commercial segments. Utmost Properties is guided by the principles of integrity, trust, and commitment and as a result, has become one of the most trusted companies in the UAE. Do you want to know more about the new and upcoming projects of Utmost Properties? On their website, you can find all the latest news and launches.
Read all information
bahwantower.com
Suhail Bahwan Group's building projects
Belgravia Heights I
This project is also called Bahwan Tower Downtown.
Where is Bahwan Tower located?
9/1, Burj Khalifa Street.
According to our information in Bahwan Tower there are currently no apartments available for sale from the developer.
Who is the developer of Bahwan Tower in Dubai?
Developer Bahwan Tower – Suhail Bahwan Group.


text:
Shabani (, adjective form of شعبان (Sha'ban), the name of the eighth month of the Islamic calendar) is a Muslim surname and may refer to:

Agim Shabani (born 1988), Norwegian footballer of Albanian descent
Bujar Shabani (born 1990), Kosovar-Albanian footballer; see 2018–19 FC Drita season
Bunjamin Shabani (born 1991), ethnic Albanian footballer from the Republic of Macedonia
Hussein Shabani (born 1990), Burundian footballer
Nasser Shabani (died 2020), Iranian general
Razie Shabani (1925–2013), Azerbaijani politician and activist
Shabani Nonda (born 1977), retired DR Congolese footballer
Xhevdet Shabani (born 1986), Kosovar-Albanian footballer

Places
Shabani, Iran, village in Kurdistan Province, Iran
Shabani, Zimbabwe, mining town Zimbabwe

Other uses
Shabani (gorilla) (born 1996), a tightrope-walking western lowland gorilla at the Higashiyama Zoo in Nagoya, Japan

See also
Sha'ban (disambiguation)
Shaybanids, dynasty

Persian-language surnames
Albanian-language surnames
Swahili-language surnames

redpajama_set_name: RedPajamaWikipedia


At Alta Public Schools, we are working hard to provide our employees with best of breed educational technologies to empower you to succeed and provide a fulfilling working environment. We are in the process of rolling out a new "Digital Facilities" initiative were we all interact together with staff, students and parents with industry-leading technologies.
This Employee Portal will continue to grow and expand. Please feel free to provide us with feedback about how you think we can improve together.


text:
title: Alerting
sort_rank: 5
---

# Alerting

We recommend that you read [My Philosophy on Alerting](https://docs.google.com/a/boxever.com/document/d/199PqyG3UsyXlwieHaqbGiWVa8eMWi8zzAn0YfcApr8Q/edit)
based on Rob Ewaschuk's observations at Google.

To summarize: keep alerting simple, alert on symptoms, have good consoles to
allow pinpointing causes, and avoid having pages where there is nothing to do.

## What to alert on

Aim to have as few alerts as possible, by alerting on symptoms that are
associated with end-user pain rather than trying to catch every possible way
that pain could be caused. Alerts should link to relevant consoles
and make it easy to figure out which component is at fault.

Allow for slack in alerting to accommodate small blips.

### Online serving systems

Typically alert on high latency and error rates as high up in the stack as possible.

Only page on latency at one point in a stack. If a lower-level component is
slower than it should be, but the overall user latency is fine, then there is
no need to page.

For error rates, page on user-visible errors. If there are errors further down
the stack that will cause such a failure, there is no need to page on them
separately. However, if some failures are not user-visible, but are otherwise
severe enough to require human involvment (for example, you are losing a lot of
money), add pages to be sent on those.

You may need alerts for different types of request if they have different
characteristics, or problems in a low-traffic type of request would be drowned
out by high-traffic requests.

### Offline processing

For offline processing systems, the key metric is how long data takes to get
through the system, so page if that gets high enough to cause user impact.

### Batch jobs

For batch jobs it makes sense to page if the batch job has not succeeded
recently enough, and this will cause user-visible problems.

This should generally be at least enough time for 2 full runs of the batch job.
For a job that runs every 4 hours and takes an hour, 10 hours would be a
reasonable threshold. If you cannot withstand a single run failing, run the
job more frequently, as a single failure should not require human intervention.

### Capacity

While not a problem causing immediate user impact, being close to capacity
often requires human intervention to avoid an outage in the near future.

### Metamonitoring

It is important to have confidence that monitoring is working. Accordingly, have
alerts to ensure that Prometheus servers, Alertmanagers, PushGateways, and
other monitoring infrastructure are available and running correctly.

As always, if it is possible to alert on symptoms rather than causes, this helps
to reduce noise. For example, a blackbox test that alerts are getting from
PushGateway to Prometheus to Alertmanager to email is better than individual
alerts on each.

Supplementing the whitebox monitoring of Prometheus with external blackbox
monitoring can catch problems that are otherwise invisible, and also serves as
a fallback in case internal systems completely fail.

redpajama_set_name: RedPajamaGithub


text:
In philosophy, accidentalism denies the causal closure of physical determinism and maintains that events can succeed one another haphazardly or by chance (not in the mathematical but in the popular sense). Opponents of accidentalism maintain that what seems to be a chance occurrence is actually the result of one or more causes that remain unknown due only to a lack of investigation. Charles Sanders Peirce used the term tychism (from τύχη, chance) for theories that make chance an objective factor in the process of the Universe.

In ethics the term is used, like indeterminism, to denote the theory that mental change cannot always be ascribed to previously ascertained psychological states, and that volition is not causally related to the motives involved. An example of this theory is the doctrine of the liberum arbitrium indifferentiae ("liberty of indifference"), according to which the choice of two or more alternative possibilities is affected neither by contemporaneous data of an ethical or prudential kind nor by crystallized habit (character).

See also
 Necessitarianism
 Indeterminacy

References

Further reading

External links

Metaphysical theories
Meta-ethics


text:
Insch
Local Areas Videos Tools Guides Tweets Blog Posts
There are 31 properties in Insch
Shieldaig
Price over £200,000
4a Mayfield Terrace
Joiners Croft
15d High Street
Drumrossie Lodge
2 Simpson Street
Price around £120,000
4 Newton Of Rothmaise Steadings
1 Whitehall Crescent
Framar, 56 High Street
Show all 31 properties
Area Select area Aberdeen Aberlour Aboyne Alford Ballater Banchory Banff Bieldside Braemar Brechin Bridge of Don Buckie Bucksburn Collieston Cove Cruden Bay Cullen Cults Drumoak Dufftown Durris Dyce Edzell Ellon Fraserburgh Fyvie Gardenstown Glenlivet Gourdon Huntly Insch Inverbervie Inverurie Johnshaven Keith Kemnay Kincardine O-Neil Kingswells Kintore Laurencekirk MacDuff Milltimber Montrose Monymusk New Deer Newburgh Newmachar Newtonhill Oldmeldrum Peterculter Peterhead Portlethen Portsoy St Cyrus Stonehaven Strathdon Tarland Tarves Torphins Turriff Westhill Balmedie Strichen Chapelton
Insch is an attractive residential village in the Garioch area of Aberdeenshire. It is situated around 11 miles from Inverurie, 14 miles southeast of Huntly and within easy commuting distance of the city of Aberdeen, which is about 30 miles and less than an hour's drive away.
Insch has excellent transport links, with Insch Railway Station located on the main Aberdeen to Inverness line and serving over 100,000 passengers per year. There are also regular bus services to Huntly and Inverurie, and the village's convenient location just off the A96 provides great commuting options for those who work in the surrounding areas, such as Aberdeen, Inverurie, Huntly and Elgin.
2,150 people
Distance from Aberdeen
Regular bus and rail services
Irish School
Inverurie Academy, Inverurie
The Gordon Schools, Huntly
Alford Academy, Alford
Things to do in Insch
The village, which is located in the heart of the beautiful Aberdeenshire countryside, has a good selection of amenities for residents including a number of local shops and a post office. There's also a health and community centre in the village as well as a local library, and for the young ones, there are a number of play parks scattered throughout the village as well as a football pitch beside the leisure centre.
Additionally, the village has its own primary school, Insch School, and has easy links to secondary schools in the neighbouring areas of Inverurie and Huntly. There is also a Golf Club in the village, Insch Golf Club, which has been described as a 'hidden gem' in Grampian's crown and boasts a stunning location between the hills of Bennachie and Dunnideer.
History of Insch
The area is rich in history, and the site of the remains of Dunnideer Castle, an ancient hill fort whose origins can be traced as far back as 250 BC, can be found on the outskirts of the town. The ruins of the tower house that lie on the hill are from a larger structure which was built around the mid-13th century, giving an idea of the history that lives in the area.
Looking for houses for sale in Insch, Aberdeenshire? ASPC can help! Use our property search tool to see what's available today, and browse our comprehensive range of houses for sale in Insch online now, which range from one bedroom properties to substantial family homes.
View area localities
Auchleven
Culsalmond
Duncanstone
Old Rayne
Oyne
Premnay
Tillymorgan
Wardhouse


The author describes her New Year's Resolution... The Dreaded New Year Diet. Every year it's the same thing, and this year will be no different. With any luck, I'll stay motivated for longer than two weeks this year!
Texas toy mogul Wes Jackson is on the brink of a billion-dollar breakthroughuntil a sinister anonymous tipster reveals Wes is a dad! Suddenly his family-friendly company is in crisis and Wes's sole focus is finding the daughter he never knew. But confronting the child's mother, Isabelle Graystone, means resisting a chemistry that is as fierce as ever.
MAUREEN CHILD is the author of more than 130 romance novels and novellas that routinely appear on bestseller lists and have won numerous awards, including the National Reader's Choice Award. A seven-time nominee for the prestigous RITA award from Romance Writers of America, one of her books was made into a CBS-TV movie called The Soul Collector.


Code for Asheville is currently working on 10 projects.
A page listing the projects that Code for Asheville is working on.
Explore the city of Asheville's budget from 2007 to 2012 and learn how the money is being spent.


text:
Maine: Collins Looks Safe, From Both Left and Right
Sen. Susan Collins of Maine looks well positioned for re-election in 2014. (Bill Clark/CQ Roll Call file photo)
By Abby Livingston and Jonathan Miller
Maine Sen. Susan Collins is a Republican in a state that's not. She's moderate and bipartisan in a party that's not.
Yet it would be tough for her to be any safer, politically, as she looks toward re-election in 2014.
"She may be the strongest Republican incumbent in the country," GOP consultant Erik Potholm, who hails from Maine, wrote in an email. "She has sky high approval numbers and has become a political rock star in Maine."
"In the past she has easily crushed top tier Dem challengers like [former Rep.] Tom Allen and [now-Rep.] Chellie Pingree," he added. "I doubt any credible Dems will take her on this cycle. They would be crazy to do so."
"I think she's fine," said Maine political consultant Dennis Bailey, who is a registered Democrat. "I don't see any vulnerability."
Safe from a real Democratic challenge, Collins' vulnerability from the right also appears marginal.
One name floated as a potential Republican challenger is former state Treasurer Bruce Poliquin, who came up short in the GOP primary for Senate in 2012.
Tyler Harber, a GOP consultant who is close to Poliquin, said that the former state treasurer has been approached to run against Collins or for one of Maine's two House seats but Poliquin "hasn't made a decision yet as far as I know."
"He's so deliberate, it will probably be awhile before he makes a decision," Harber said. "I'd be surprised if he jumped in against Susan Collins, but anything is possible."
A Collins spokesman said she remained focused on her job and "not on the campaign."
There remains, of course, the possibility of any number of conservatives trying to challenge Collins from the right in a GOP primary. But Pine Tree State insiders don't see any genuine threats on the horizon, despite her moderate voting record. In 2011, in votes where a majority of Democrats opposed a majority of Republicans, Collins voted with her party only 48 percent of the time.
Longtime Maine conservative activist Mary Adams, who ran against Collins in the 1994 Maine GOP gubernatorial primary, said the senator was in good shape.
"I probably don't agree with her on 50 percent of her votes, and I can't get her to sign the Taxpayer Protection Pledge," Adams said with frustration. But, she added, when Republican primary day rolls around next year, the senator will have her vote.


text:
Brachyclados  es un género con tres especies de plantas con flores en la familia de las Asteraceae.

Taxonomía
El género fue descrito por David Don y publicado en  Philos. Mag. Ann. Chem. 11: 391. 1832.

Especies
Brachyclados caespitosus (Phil.) Speg.
Brachyclados lycioides D.Don
Brachyclados megalanthus Speg.

Referencias

Enlaces externos

Mutisieae


text:
The Vasectomy of the Future
Neil Wagner
Women take note: it's possible to plug the vas deferens so sperm can't get out. And the procedure may even be reversible.
Women take heart: birth control may no long have to be all on you.
Preparations have begun for the first human trial of a vasectomy alternative. Instead of snipping, crushing or tying, this one plugs up the vas deferens so that no sperm can get out.
It may even be reversible.
The procedure consists of injecting a gel, called Vasalgel, into the vas deferens that blocks sperm from leaving so they don't get into the semen. The gel does let some liquid (but not sperm) pass, limiting any pressure buildup inside the vas.
Researchers just completed a study of the effectiveness of the gel on rhesus macaque monkeys. Sixteen male monkeys were injected with the gel at various times and then returned to their community. They were living with from three to nine females who were known to be fertile, yet there were no pregnancies over the next breeding season (about six months). Seven of the males have been back in the community for nearly two years without any of the females becoming pregnant. Complications have been few and similar to those that occur with vasectomies.
For men, contraceptive options have remained basically unchanged for over a century. (Yes, vasectomies are that old.)
While people are naturally most interested in what this means for men, these results do suggest a use in animals. Vasectomies are a routine procedure for primate veterinarians, but the operation is more complex in other primates than it is in humans, and complications are more common. So there's definitely room for an alternate procedure.
For men, contraceptive options have remained basically unchanged for over a century (yes, vasectomies are that old). While researchers have come up with a variety of interesting alternatives that work in the laboratory, none has yet made it to market.
This study was only designed to show that the gel worked. It did not test whether its effects could be reversed later. A preliminary study did find that the gel could be easily flushed out from rabbits with a solution of baking soda, successfully restoring sperm flow. It's not clear that the same would happen in men, or even monkeys. The vas deferens are tiny and delicate vessels, and there's no guarantee that even if the gel could be flushed out, they'd be anywhere near as functional as they were before the gel was injected.
The researchers are seeking more funding to test the gel's reversibility in monkeys. The initial trial in humans will only include men who are not counting on being able to reverse the procedure.
They hope to start enrolling men by the end of 2017.
The study appears in Basic and Clinical Andrology and is freely available.
Testosterone, No Magic Bullet
Sex And Happiness
Suffering Semen