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Tuesday, 22 May 2018

When Deportation Becomes A Matter of Life And Death in America

Written by By Dan Gorenstein, Kaiser Health News

What happens when an undocumented immigrant has a life-threatening diagnosis? Much depends on where the person lives. And even in states with generous care for a dire illness, a patient can face difficult life-and-death choices.

Illustration by Ella Trujillo for WHYY and KHN

“Dear the most highly respected judge and court, I’m writing this because I love my mom. My mom is very important to me. I have no idea what to do without her. Even though my mom’s afraid, she’s not giving up.”

This is the beginning of a plea written by a 13-year-old girl to the Department of Homeland Security. The goal: to get her mother the insurance coverage she would need to enter a clinical trial.

Two years ago, the girl’s mother learned she had advanced stomach cancer. Undocumented and uninsured, the mother received free treatment at Bellevue Hospital in Manhattan through New York’s emergency Medicaid program, which undoubtedly prolonged her life.

Then, last fall, her doctor identified her as a good candidate for a medicine that has been remarkably effective for some lung cancers. Would it work for her disease? The researchers were eager for patients like J. to help them answer that question. (Kaiser Health News is identifying the patient by her first initial only, because of the threat of deportation.)

“You look at these clinical trials — there are some patients who just forget to die,” said Dr. Steve Lee, J.’s oncologist. “She could be one of these long-term survivors.”

But it would not be a simple process for J. to enter a clinical trial. She emigrated from China 18 years ago on a visa that had long since expired. Her husband’s visa also expired years ago. The Queens couple have three children who are U.S. citizens, ages 13, 12 and 4.

To be accepted into the trial, J. needed the more complete coverage traditional Medicaid offers. And to get that meant declaring herself to Homeland Security and asking the agency not to act on its standing deportation order against her. That would call attention to herself and her status — and provide the agency with her address and the names of everyone she lived with.

“Before getting sick, legal status was clearly important,” J. said through a translator. “Now, both legal immigration status and my ability to continue to live are intertwined, because I can only get good treatment if I obtain legal status.”

The family faced this dilemma under President Donald Trump’s growing threat of deportations. Federal figures show arrests of undocumented people living in the U.S. were up 40 percent in the first four months of 2017 compared with the same period in 2016. The administration also is considering a change that would penalize legal immigrants if they use public benefits like Medicaid.

Up to the point of the clinical trial, J. got care very similar to what anyone with private insurance might get. And that is a function of residence. Each state covers care for undocumented immigrants through its emergency Medicaid program differently, and New York has one of the most generous programs in the country.

“In some states, they say giving you dialysis is keeping you from dying. We are going to put you on emergency Medicaid,” said Steven Wallace, a health professor at UCLA, who has studied immigrant health care in the U.S. “In other states — Georgia comes to mind — they will not put you on emergency Medicaid until you are in diabetic shock.”

By the time J. learned of the drug trial, she’d had chemotherapy and separate surgeries to have her ovaries and part of her stomach removed. As comprehensive as New York’s emergency Medicaid program is, it does not cover the costs associated with drug trials, even in dire situations.

For context, some estimates suggest that stomach cancer treatment for one year costs about $100,000. Costs vary by hospital, and Medicaid pays hospitals less.

Bellevue did not provide a tally of J.’s medical bills. The limited research available on care for very sick, undocumented immigrants shows that the treatment can vary even by county within a state. More often than not, Wallace said, when beset by a life-threatening illness such as stomach cancer, undocumented women and men miss out on the tests, procedures and drugs that could extend their lives.

By virtue of living in New York, J. did receive good care. But was the chance at the drug trial worth the risk of her or her husband being deported?

For most of an interview with a reporter, J. spoke Mandarin through a translator because of her limited English skills. But when asked whether she was more afraid to die or be deported, she answered directly, in English.

“Yeah, I [am] afraid to die, more than be deported,” J. said. “Of course. Because my family need[s] me. My children need me.”

Domna Antoniadis, a senior staff attorney at the New York Legal Assistance Group, works just across the hall from Dr. Lee at Bellevue. Her job is to help patients jump through bureaucratic hoops to get health coverage, and she said J. had a compelling case.

“She’s been here for almost 20 years. She has three young U.S. citizen children. She’s never been arrested; no criminal history. She’s worked. And right now, she has a very aggressive form of cancer,” Antoniadis said. “She’s saying, ‘Here I am. This is what’s going on with me, but please don’t remove me.’”

J.’s husband said his wife did everything she could to battle her disease, including changing her diet, walking up hills for exercise and following doctor’s orders. The decision on the drug trial was clear, he said.

“Life is more important than anything else. You have to face the cancer,” he said, speaking through a translator. “You have to face the pressures. You just have to do whatever it takes so that you can keep on living.”

J. submitted the application, and Antoniadis advised the family to be cautious. She told them if federal agents show up at the house, before opening the door the family should make sure the officials have a warrant. Her attorney gave J. a guide outlining her rights in Mandarin.

Over the fall, J.’s husband said the family felt vulnerable.

“We watch the news,” he said. “We see the things Donald Trump says, and we see that he’s been tough on immigration and has tried to make a lot of changes. So, for sure, we’re more worried.”

As they waited to hear from Homeland Security, a kind of balled-up fear settled over the family. J. talked less. Their 13-year-old daughter took over doing the dinner dishes. Their 12-year-old son set the table and played fewer video games, trying to make his mom happy. Their kid sister, age 4, asked why everything was different.

Before Homeland Security could respond, J. got word from New York’s traditional Medicaid program that she was accepted. The application to delay deportation was enough for the state to open the program to J. She had her first drug trial treatment last December. She tried to savor life.

“Now I’m not nearly as strict with my kids. I sort of just let them be kids. Before, I’d give them extra homework on top of what’s assigned at school. Now, I just want them to be happy,” she said. “Between my husband and me, we care a lot less about money. Before, we only go out to dinner once a month. Now we treasure every moment we have.”

Almost as soon as J. was in the drug trial, she was out. Her oncologist, Lee, said J. “had rapid growth of her cancer” and couldn’t remain in the trial. By early January, J. had started hospice. Her husband said it was a very difficult month for her, and on Feb. 6, J. died.

Asked if he thought the trial was worth all the risk and stress it caused the family, Lee said: “I think it’s easier to say that going on the drug trial was a waste of time, in retrospect. But the alternative for cancer like this is that she would invariably die. So I think that the opportunity to give her a shot at long-term survival was one worth putting a lot on the line for.”

Lee said what the trial really gave J., and her family — for a time at least — was hope.

Dan Gorenstein is the health care reporter for Marketplace. This story was produced in partnership with WHYY’s The Pulse and Kaiser Health News. This article was originally published on Kaiser Health News.
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Monday, 21 May 2018

Can Corporate AI Adoptions Ever Address Labor And Human Rights Concerns?

Written by Emre Eren Korkmaz, Department of International Development, Oxford University

Artificial intelligence is rapidly transforming business models, but labor rights and other human rights issues are often lost amidst these quick changes. Can we teach machines to incorporate human rights concerns?

Corporations are increasingly benefitting from digital expertise to manage their supply chains. Pic: EPA/DUC THANH

Rapid technological progress in artificial intelligence (AI) is about to transform existing business models. Companies are beginning to use AI to help manage their human resources, attract and promote the loyalty of clients and customers, and increase transparency in their supply chains. Companies are also using AI to automate decision-making processes about their employees, customers, and suppliers.

This process began with companies using big data analytics to increase transparency in supply chains and continued with companies using cloud-based systems and artificial intelligence to process the enormous amount of data collected globally from thousands of workplaces. For instance, Segura offers a cloud-based supply chain solution that allows its clients to track every component in real time. Another company, Accenture, asserts that such programs will improve efficiency and allow corporations to react to supply chain issues more quickly. 

Corporations are increasingly benefitting from digital expertise to manage their supply chains by tracking all the moves within the supply chain in real time, as well as intervening in the production and delivery processes immediately because of data collected from workplaces. Application of AI by companies to their operations provide better visibility and predictability; however, these efforts do not yet include human rights in their design. Although Segura claims that its supply chain solution helps companies to tackle modern slavery within their supply chains, there is no detail about how exactly this would work.

The threat from AI…

As technology companies involved in the development of AI target global corporations as their clients, they are not necessarily focusing on the interests and expectations of workers or local businesses. The use of AI to monitor supply chains could massively increase the power of corporations vis-a-vis their suppliers and workers, resulting in potential surveillance of workers by their employers. UNI Global Union’s The Future World of Work Initiative offers 10 principles for ethical artificial intelligence and informs AI designers and companies of the importance of worker inclusion with the aim of safeguarding workers’ interests and maintaining a healthy balance of power in workplaces.

In addition, if algorithms (focusing on visibility and traceability, based on real-time information, being received from thousands of workplaces operating in various countries) begin to manage suppliers in an increasingly competitive market, the constant comparison of different countries and workplaces to increase profits might be likely to increase the pressure over prices, delivery times and productivity. This would create enormous stress and vulnerability for those suppliers. Local business (suppliers) would then transfer all that pressure onto their workers, who would be the real losers of the process.

…mitigating the threat…

The current mainstream business model of profit-driven business where companies seek to lower prices at any cost to be competitive has caused “a race to the bottom” for their suppliers, who are generally located in the global South, by increasing the productivity of the labor force and decreasing wages. This model has intensified the exploitation of children through child labor, enabled instances of modern slavery, and undermined health and safety conditions.

As a result, unions and NGOs have taken many steps to support sustainable and fair business and increase respect for human rights in supply chains. Human rights due diligence, promoted by the UN Guiding Principles on Business and Human Rights, is one expectation of companies as part of their responsibility to respect human rights. This approach allows all stakeholders to collaborate in order to determine the actual and potential risks that harm employees within a workplace or an industry. Instead of a one-sided decision-making process, this approach is action-oriented and calls on all parties to negotiate to address potential and actual risks and to resolve and mitigate the harms caused by them. Some multinational corporations also collaborate with global trade unions to enhance safety in the workplaces, such as through the Bangladesh Accord, and promote a living wage, such as through the ACT Initiative.

These models offer important lessons for companies utilizing AI to manage their supply chains. If technology companies developing algorithms and training machines to deal with supply chain management ignore all the accumulated experiences in this field, they risk destroying the existing relationship between global corporations, suppliers and workers and erase human rights by offering unimaginable power to corporations.

…and how it can have a positive impact

The expected results of technological progress depend on the approaches of users, and the use of AI to manage supply chains could have a positive impact. It is important that companies and civil society consider two questions:

  1. How can we teach machines about human and labor rights?
  2. How can suppliers and workers/trade unions influence the machine learning process?

The answers to these two questions will determine the content of “ethics by design”. If AI internalizes accumulated knowledge about “business and human rights” and allows workers and local businesses to track its decision-making process, then it could promote labor rights.

Technology companies developing programs for supply chain traceability should understand the debates on business and human rights. For instance, one of the demands of the UNI Global Union is that workers must have the right to access, influence, edit and delete data that is collected on them and via their work processes. Also, global trade unions and corporations should include “the role of artificial intelligence” into their areas of collaboration. Additionally, multi-stakeholder initiatives which are alliances of global corporations, trade unions and NGOs, should pioneer this process to act as watchdogs for AI practices.

The recent report of The House of Lords on “AI in the UK” states that, “It is important that members of the public are aware of how and when artificial intelligence is being used to make decisions about them, and what implications this will have for them personally”. This statement is equally valid for sustainability policies of corporations towards their supply chains as well.

Emre Eren Korkmaz is a post-doctoral fellow at the University of Oxford’s Department of International Development. He is a research fellow of St Edmund Hall, Oxford. This article was originally published on Open Global Rights.
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Saturday, 19 May 2018

Why U.S. Should Follow South Korea's Lead And Apologize For Jeju Massacre

Geoffrey Fattig, Foreign Policy in Focus

To help make peace in Korea, the U.S. should follow South Korea's lead and apologize for its role in the devastating Jeju massacre.

South Korean president Moon Jae-in at a memorial for the victims of the Jeju massacre. (Photo: Blue House Photo Pool)

Singapore has been chosen to host the unlikely summit between U.S. president Donald Trump and North Korean leader Kim Jong-un in early June. The choice for the summit venue went against Trump’s preference for the meeting to take place at the Peace House in Panmunjeom, where the world had been captivated just weeks before by the amicable scenes of Kim walking hand-in-hand across the Military Demarcation line with South Korean President Moon Jae-in.

Given that Panmunejom embodies of the division of the Korean Peninsula, it is regrettable that U.S. and North Korean negotiators opted for the southeast Asian city-state instead. This is because the root of the nuclear issue stems largely from the decision by American military officers to divide the Peninsula at the 38th Parallel in the aftermath of World War II. The arbitrary divide led to a devastating war, decades of hostility between a previously unified people, and heartbreak for families forever separated from loved ones.

One of the most tragic results of the division was the 1948 Jeju Uprising, which began on April 3 of that year and resulted in the deaths of over 10,000 of the island’s inhabitants — many of whom were civilians, including an estimated 770 children under the age of five.

The primary cause of the uprising was the 1948 constitutional assembly election, which was organized under the auspices of the United Nations with the aim of establishing a national government for Korea. Due to fears that it would exacerbate the existing division, the election was boycotted by the North Korean side and leading South Korean politicians, including Kim Gu, who had served as president of the Korean Provisional Government during the Japanese colonial period.

The Workers’ Party of South Korea (WPSK), a communist group which had been banned by the U.S. military government in Seoul, also opposed the election and had a strong base of support on Jeju. Tensions had been running high on the island after police fired on a rally to commemorate the March 1 Independence Movement, killing five civilians and a six-year-old child. In the months prior to the uprising, roughly 2,500 of the island’s residents were jailed, with many subjected to torture. On April 3, one month prior to the national election, the WPSK launched an armed revolt targeting police stations across the island.

The U.S. military government responded to the uprising by blockading the island, sending in Korean national guard reinforcements, and using American advisors to coordinate counterinsurgency efforts. In August 1948, meanwhile, Syngman Rhee became the first president of the newly declared Republic of Korea, thus cementing national division.

Backed by the U.S., Rhee authorized a scorched-earth campaign in Jeju during which villages were burned and thousands of suspected guerrillas summarily executed without trial. Hundreds more were rounded up and sent to prisons across the country following dubious convictions of rebellion. Rhee also deployed a paramilitary force, the Northwest Youth League, which consisted on anti-communists who had fled North Korea and were responsible for some of the worst atrocities.

Conscious of this past, South Korean President Moon Jae-in recently visited Jeju on the 70th anniversary of the uprising and delivered a powerful speech at the island’s April 3 Peace Park, which houses grave markers for thousands of victims whose bodies were never recovered. In his address, Moon apologized “for the pain stemming from state violence” and resolved to provide compensation for the victims’ family members and restore the reputations of those wrongly convicted by military courts. He also spoke of needing to “avoid being trapped in a worn-out ideological framework.”

Of course, the Korean Peninsula is still trapped in an ideological framework, the seeds of which were sown in part due to the tragic events on Jeju. One clear manifestation of this conflict is the standoff over the North Korean nuclear program and the long-standing hostility between that country and the United States. At the heart of this animosity is the blame which the North Korean regime assigns the American government for its role in dividing the Peninsula in 1945.

When the leaders of these two sides sit down in Singapore next month, Trump and Kim will be burdened not just with the complex issue of North Korean denuclearization, but also with historical grievances that go back decades. Establishing a sense of trust and goodwill should thus be the first issue on the agenda.

Apologies can go a long way toward fostering these qualities, and perhaps nowhere does this hold truer than in Korea. After all, this is a country where hundreds still gather every Wednesday outside of the Japanese embassy to demand an apology over the issue of Korean comfort women forced to serve in brothels for the Japanese military during World War II.

By following the lead of President Moon and offering an apology for the United States’ role in facilitating the bloodshed on Jeju and the worn-out ideological framework on the Korean Peninsula, Trump would be signaling his acknowledgement of a problem that goes far beyond the nuclear issue. Such a gesture would be warmly welcomed by Koreans on both sides of the DMZ.

Most importantly, it would provide a highly effective means of putting his summit with Kim Jong-un on the path to success.

Geoffrey Fattig is an independent research analyst based in Seoul. He has a master’s degree in International Affairs from UC San Diego and previously worked as a speechwriter for the U.S. Department of State. This article was originally published on Foreign Policy in Focus.
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Friday, 18 May 2018

Islamic State Is Reinventing Itself in South East Asian Countries

Written by Greg Barton, Deakin University

Even after the recent arrests and deaths of dozens of its members, the Islamic State-linked network of militant groups in Indonesia organised under the umbrella Jemaah Ansharut Daulah (JAD) clearly remains a potent force.

Jakarta night shot. Pic: Pixabay

In the past week, five bombings have rocked the island of Java, killing at least 26 people and injuring more than 50 – the deadliest series of terrorist attacks in the country since the Bali bombings in 2002. These attacks included the bombings of three churches in the city of Surabaya, carried out by a family that used its children as suicide bombers.

The latest attack came on Wednesday when four assailants wielding swords stormed a police station in Sumatra. One officer was killed and two others were injured. The alleged militants were shot dead.

Formed in 2015, JAD achieved notoriety in January 2016 with a military-style attack in the centre of Jakarta that resulted in the deaths of four people and four attackers. Dozens of other potential attacks were foiled in the two years that followed, but several smaller ones were carried out, directed largely against the elite Detachment 88 counter-terrorism police unit – the arch-nemesis of JAD.

Formed in the wake of the 2002 Bali bombings, with assistance from the Australian Federal Police, Detachment 88 has emerged as one of the world’s most effective counter-terrorism units, having arrested more than 1,000 militants.

Last year, 172 suspected terrorists were apprehended and 16 shot dead, following 163 arrests in 2016 and 73 in 2015. Most of the militants recently arrested have been linked with JAD and the related Islamic State support network of Mujahidin Indonesian Timur (MIT).

Returning fighters

Since it declared its caliphate in Syria and Iraq in 2014, the Islamic State has perversely given special attention to planning and inspiring terrorist attacks during the Muslim fasting month of Ramadan, which began this week.

This is the first Ramadan since the group lost control of large swathes of its territory centred around Raqqa in Syria and Mosul in Iraq. As the Islamic State is clearly desperate to maintain its brand and prove its continuing potency around the globe, there are now concerns the recent attacks in Indonesia are a sign the group has extended its reach eastward to the world’s largest Muslim-majority nation.

Ever since the Islamic State shot to prominence with the fall of Mosul in 2014, there have been fears about its potential to reenergise the decades-old jihadi network in Indonesia.

Since 2013, it’s estimated between 600 and 1,000 Indonesians have travelled to Syria and Iraq to join the conflict, most drawn to the Islamic State and its fabled caliphate. (Others were aligned with al-Qaeda affiliates such as Jabhat al-Nusra.)

Indonesian police estimate 400-500 of these fighters subsequently returned home, either from Syria and Iraq, or from Turkey on their way to join the conflict. Many have been met at the airport by authorities and taken into rehabilitation programs. But others returned unannounced. With a lack of appropriate laws in Indonesia, these returning fighters cannot be prosecuted for travelling overseas to join the Islamic State.

Embed from Getty Images

After the recent JAD attacks in Indonesia, local police have spoken of sleeper cells of returnees from the Middle East and their associates, who lay low and give the appearance of having no inclination to violence, even while they prepare for an attack at an opportune time.

Initially, it was reported by the respected head of the Indonesian police, General Tito Karnavian, that a family of six involved in the bomb attacks on the churches in Surabaya had returned from the Middle East. Later reports suggested this was not the case. Nevertheless, they and the other two families involved in the attacks were close associates of Islamic State returning fighters.

Defeat in the Middle East

The world rejoiced when Raqqa, the de facto capital of the Islamic State caliphate, was finally liberated in October 2017, following a four-month siege. With the fall of the city, the last holdout of its tens of thousands of local and foreign fighters was also defeated.

Months earlier, Mosul, the last city held by the Islamic State in Iraq, fell after nine months of the most brutal urban warfare since the second world war. With the caliphate destroyed, it was believed the Islamic State itself had been eliminated, too.

As it turns out, the fall of Raqqa did not see the final destruction of the Islamic State army. Rather, under a secret deal brokered by the Kurdish-led, and American-backed, Syrian Democratic Forces who led the campaign to liberate Raqqa, thousands of Islamic State fighters and their families were allowed to leave the city in convoys of busses and trucks.

Many made their way to Turkey, where it seems some remain. But thousands more drove into the desert of eastern Syria, occupying territory along the Euphrates River and linked to others across the border in rural northern Iraq.

Many Islamic State fighters, especially local Arabs, have gone to ground, blending into villages and Sunni desert communities. Even in liberated Mosul, which is largely Sunni, many locals still express support for the militant group.

The election of a Shia-dominated government in Baghdad and the failure to rebuild Mosul and other destroyed Sunni cities, mean that in Iraq, as in Syria, all the social and communal grievances that supported the emergence of al-Qaeda in Iraq (AQI) and the Islamic State of Iraq (ISI) remain in place.

Even as the Islamic State was losing territory in Iraq in recent years, its leaders spoke with the conviction of an apocalyptic cult, confidently asserting that even if they lost the caliphate, the insurgency would rebuild.

Today, the group has active affiliates and supporters across the Muslim world, including in the southern Philippines, and a “virtual insurgency” throughout the many Western countries that contributed around one-quarter of the group’s total of 40,000 foreign fighters in Iraq and Syria.

The insurgency is far from over, and in Indonesia it may well be that the worst is yet to come.

Greg Barton, Chair in Global Islamic Politics, Alfred Deakin Institute for Citizenship and Globalisation; Co-Director, Australian Intervention Support Hub, Deakin University. This article was originally published on The Conversation
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Wednesday, 16 May 2018

As Pakistan Gears Up For Elections Later This Year, Will Democracy Prevail?

Written by By Abrahim Shah, Foreign Policy in Focus

Can Pakistan definitively put the era of military rule behind it?

Image Pakistan election 2008 (Wikimedia Commons)
The significance of Pakistan’s elections later this year lies in the fact that this will only be the second time a democratic transition of power will occur in the country. The first peaceful transition was in 2013, when Asif Ali Zardari’s Pakistan People’s Party (PPP) handed the reins of government over to Nawaz Sharif’s Pakistan Muslim League (PML-N). Prior to 2008, no democratic government had completed its five years in office.

The fragility of democracy in Pakistan owes much to its history – a diverse population, an overly centralized authority, fear of neighboring India, and excessive reliance on the military. The transition that took place in 2013 was doubly remarkable considering the economic crises gripping the country. Since 2013, Pakistan has been in the throes of a severe fiscal and current account deficit, with reserves barely enough to cover two months of imports. The incumbent government’s struggles are only further compounded by a vigorous form of judicial activism and by the landmark Supreme Court verdict in the Panama Papers case in July 2017 that disqualified then-Prime Minister Nawaz Sharif.

The court ruled in the case that Sharif had been dishonest for not revealing the United Arab Emirates work permit he held. This dissimulation, the court argued, violated Articles 62 and 63 of Pakistan’s constitution—which stipulate that a person has to be “truthful” and “trustworthy” to be a part of Pakistan’s parliament. Ironically, the infamous military dictator Zia-ul-Haq inserted these clauses into the constitution, and Nawaz Sharif had never actually withdrawn any salary based on that work permit.

The verdict in the Panama Papers case is just one element of the judicial activism currently gripping Pakistan. Since 2007, Pakistan’s judiciary has been increasingly active in influencing decisions of public policy even to the point of encroaching on what should be the parliament’s area of work.

This clash of institutions is in fact endemic to Pakistan’s democracy and highlights the potential pitfalls that could mar the elections. The greatest threat to democratic rule in Pakistan has historically emerged from state institutions such as the military that have always made their presence felt on Pakistan’s political landscape.

Military Influence

This influence has taken both direct and indirect forms, with direct influence in the form of military coups that overthrew democratic rule in 1958, 1977, and 1999. Today, however, public opinion seems to have turned against direct military rule and now acts as a significant bulwark against a possible military takeover.

The military’s indirect influence on the electoral process, however, remains a potential threat. This indirect influence stems from the present paradigm of Pakistan’s politics where several local and national level parties vie for seats in the National Assembly. This panoply of contesting parties usually results in no single party gaining enough votes to form the government. Local parties and independent legislators, therefore, carry significant influence primarily because larger parties use them to form government. It is these candidates and local parties that the military has historically manipulated to influence electoral outcomes in the country.

Pakistan’s history, in fact, is replete with examples of the military doing just that. The most blatant of these incidents was the Mehran Bank Scandal that rocked Pakistan in the early 1990s. The scandal involved the army chief of staff and the head of the intelligence agency secretly channelling funds to politicians through the now defunct Mehran Bank. These funds were then used to create the conservative coalition Islami Jamhoori Ittehad (IJI), which stood in opposition to Benazir Bhutto and prevented her re-election in the 1990 elections. The IJI won those elections by a large margin and was thus able to form the government.

Political maneuvring on the eve of any election in Pakistan, therefore, suggests the army’s involvement. It thus does not bode well for the upcoming elections that similar political scheming has emerged as political loyalties begin to shift. Most of this maneuvring has been aimed at weakening the PML-N’s hold on power.

A few months ago, for instance, several PML-N legislators in the province of Balochistan inexplicably left the party. The PML-N which initially governed the province was forced to relinquish the post of chief minister to a party with far fewer seats in the provincial assembly. Similarly, PML-N parliamentarians hailing from South Punjab also broke away from the PML-N and have formed an independent splinter group. These machinations mere months before election season are an attempt to marginalize the PML-N and wreak havoc in its ranks. It is only a matter of time before the uncertainty surrounding the PML-N in Balochistan and southern Punjab spreads throughout the party as legislators ponder their chances of winning the elections on a PML-N ticket.

Establishing the army’s culpability in these developments, however, is difficult because of the surreptitious nature of these events. Yet the army stands to gain the most from a weakened PML-N. After coming to power in 2013, the current government has locked horns with the army over key issues such as relations with India, overseeing the military operation against the Taliban in northwest Pakistan, and the annual defense budget. Thus, if the army is successful in side-lining the PML-N and in bringing to power a party that relies on the military’s patronage, it will better be able to influence domestic and foreign policy.

Other Undemocratic Influences

Pakistan’s democracy, thus, continues to be haunted by the ominous presence of undemocratic forces and outside influence. The electoral process, moreover, is also plagued by problems that challenge the veracity of electoral outcomes. Pakistan only recently adopted electoral reforms, and parliament was unable to place a cap on campaign spending. The Election Commission of Pakistan—the body responsible for overseeing the elections—also suffers from a dearth of trained staff that can be influenced by political actors.

Another significant challenge in the upcoming elections is the narrow political spectrum and the complete lack of left-wing progressive parties taking part in the election. The two main contenders—the PML-N and Imran Khan’s Pakistan Tehreek-e-Insaf (PTI) are conservative parties that adhere to a neoliberal model of development. There is currently no party promoting reforms that could help Pakistan ameliorate the staggering levels of poverty in the country. This narrowing of the political spectrum has in fact become characteristic of Pakistan’s political culture since Zia-ul-Haq’s authoritarian rule in the 1980s and his firm belief in an ideology that blended religious conservatism with neoliberal planning.

Despite the presence of challenges like the role of the military, a lack of electoral reforms, low levels of literacy, and the marginalization of left-wing movements, Pakistan’s obstinate adherence to democracy is a testament to the country’s resilience and belief in the power of elections. A smooth transition of power, thus, will be a major step in cementing democracy in Pakistan.

Abrahim Shah holds Bachelor’s degrees in economics and history from Cornell University. This article was originally published on Foreign Policy in Focus.
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Tuesday, 15 May 2018

70 Years Of Palestinian Struggle Against Israeli Occupation

Written by Yara Hawari, Open Democracy

This month marks not only 70 years since the establishment of Israel and the Palestinian Nakba, but 70 years of ongoing Palestinian resistance.

Wounded protester evacuated in Gaza. Since the beginning of the protests on March 30 more than 90 Palestinians have been shot dead by Israeli snipers, and over 10 000 thousand more have been injured. Picture by Khaled Omar/Xinhua News Agency/PA Images. All rights reserved.

The Great March of Return in the Gaza Strip has reminded the world of Palestinian resistance and the Palestinian struggle for rights. Since March 30, Palestinians in Gaza have engaged in peaceful, grassroots mass protests at the Israeli military fence that imprisons them, calling for an end to the dire conditions in the Strip as well as for the right to return to the land from which they were expelled 70 years ago this month – what Palestinians call the Nakba, or catastrophe. The protestors are literally placing their bodies on the line risking being shot by Israeli snipers. Before the US embassy move today, more than 40 Palestinians had been shot dead by Israeli snipers, and thousands had been seriously injured. Today saw the bloodiest day, with over 52 Palestinians killed at the demonstrations and again thousands injured. The brutal cost that Palestinians in Gaza are paying is because of their resistance to Israel- a resistance that began over seven decades ago.  

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In 1948, the Nakba (catastrophe in Arabic) saw the state of Israel established, 750,000 Palestinians forced into exile, and over 500 Palestinian villages and towns destroyed. Palestinian society was torn apart and Palestinians were geographically fragmented. Yet not only did the Palestinian people survive, they also demonstrated remarkable resistance to the attempt to erase them through sumud (steadfastness), collective action, and defiance. The Great March of Return is the latest manifestation of this legacy. 

In the first few years after 1948, thousands of Palestinian refugees attempted to return to their homes, only to be shot by the Israeli military along the new borders. The Israeli state called them “infiltrators” and passed the Prevention of Infiltration Law to legislate its practice of preventing them from returning. Meanwhile, Israel placed the 150,000 Palestinians who managed to stay within the borders of the new state – the Palestinian citizens of Israel – under a severe military regime and politically repressed them. 

Under this atmosphere the Palestinian citizens of Israel survived and even developed their own spaces of political, social, and cultural agency. In 1958, for example, a group established the Al Ard Movement, whose platform connected the struggles of all Palestinian people, no matter their geographic location, whilst also developing a pan-Arab tone. It called for a secular and democratic state in Palestine, as well as the right of return for the refugees. Israel frequently arrested its members and placed them under surveillance, and shut down its publishing operations. The movement was banned in 1964.  

Although Al Ard had a short existence, it paved the way for other Palestinian politics inside Israel, such as the movement known as Abnaa al Balad, which is still active today. Abnaa al Balad grew out of the student movement and also initially presented a mandate for the development of a Palestinian democratic and secular state. The movement was at its height in the 1970s and gained further momentum after the event known as Land Day. 

Land Day took place in 1976 following the Israeli government’s announcement that it would appropriate huge swathes of Palestinian land in the Galilee, in northern Israel. Palestinian citizens organised a mass collective action in resistance not only to the theft of the land but also to overall settler colonial policies of erasure. Protests in solidarity took place in other areas of Israel as well as the West Bank. Israeli authorities placed six villages in the Galilee under curfew, and met protestors there with serious violence: In addition to six killed, hundreds were injured.

Palestinian resistance doesn’t only take place in the occupied territories or in Israel proper

A decade later, Palestinians in the West Bank, Gaza Strip, and Israel joined together during the First Intifada. The uprising, which lasted from the late 1980s until the Oslo Accords of 1993, was the result of years of grassroots organising that built the foundation for political mobilisation. Palestinian left-wing factions took the lead during the 1970s, including by establishing popular committees, women’s committees, workers’ unions, student organisations, and volunteer groups. These groups took inspiration from other Third World anti-imperial struggles and were run in a decentralised, democratic, and collective fashion. Important to this struggle was the establishment of a self-reliant economy; as such, the movement explored economic models based on cooperatives that would not be subservient to the occupation and would serve the national and social Palestinian agenda. These models laid the foundation for current initiatives that aim to build economic resistance, such as Amoro, Palestine’s first mushroom farm. 

Palestinian resistance doesn’t only take place in the occupied territories or in Israel proper. Palestinians in Yarmouk camp in Syria – home to over 25,000 Palestinian refugees in the 1970s and 80s – engaged in left-wing ideas of liberation and resistance, such as Marxist theories of revolution, during the time of the First Intifada. Many organised within the camp despite the dangers of doing so under the Hafez al Assad regime. Yarmouk was also home to youth organisations that would often rally in response to events in Palestine. Since the Syrian civil war, many of the refugees have fled the camp as it has suffered an ISIS invasion as well as siege and in the last weeks a severe bombing campaign that left the camp mostly destroyed by the current Assad regime. 

A more recent act of resistance occurred in the summer of 2017, when Israeli authorities installed security cameras, turnstiles, and electric metal detectors at the Haram al-Sharif compound following an attack on Israeli soldiers by three Palestinian citizens of Israel. In response, the Islamic Waqf (trust) called for mass civil disobedience. Thousands of Palestinians from Jerusalem and around the country responded to the call, abstaining from entering the compound to protest Israel’s attempt to further control the space. Instead, they prayed in nearby streets and checkpoints. Israel met them with brute force, killing three Palestinians and injuring hundreds. Nonetheless, the perseverance of the protesters and their clear, tangible goal led to Israeli capitulation: The electronic metal detectors were removed. 

This month thus marks not only 70 years since the establishment of Israel and the Palestinian Nakba, but 70 years of ongoing Palestinian resistance – only a fraction of which is outlined above. This discourse of resistance and survival must be the focal point of the Nakba narrative. It emphasizes that the settler colonial project has not succeeded in Palestine and that the indigenous Palestinians have long fought for their rights to and existence on the land.

Yara Hawari is an Al-Shabaka Policy Analyst and Member. She is a British Palestinian scholar-activist, whose writing continues to be informed by her commitment to decolonisation. Originally from the Galilee, Yara has spent her life between Palestine and the UK. She is currently a final year PhD Candidate at the European Centre for Palestine Studies at the University of Exeter. Her thesis focuses on oral history projects and initiatives in the Galilee, and more widely on oral history as an indigenous form of knowledge production. Yara is also a post-graduate teaching assistant and works freelance as a journalist publishing for various media outlets, including the Electronic Intifada and the Independent. This article was originally published on Open Democracy.
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Monday, 14 May 2018

Filling The Talent Gap Between Cybersecurity And AI With Blockchain Technology

Written by Christina Comben, Coin Central

Cybersecurity is big business. And it costs big businesses a lot of money every year (not to mention a few panic attacks and sleepless nights). But as hackers get more inventive and data is increasingly digitized, it’s only logical that cyber threats will rise. Artificial Intelligence (AI) may be able to prevent attacks from happening. Blockchain could make our systems more secure. But beyond our current weak spots, we have another problem–an overwhelming talent gap in cybersecurity and AI.

No offense to the professionals already working in these areas. Hats off to you–you’re doing a great job, make no mistake. But with an EY report finding that 56 percent of senior AI professionals see lack of talent as the biggest barrier to implementing AI, and unemployment in cybersecurity practically nonexistent, there just aren’t enough qualified people to go around.

That leaves a talent gap in cybersecurity and AI that places businesses in a tight spot. The technology is there, but they’re stuck in their tracks. Those with the desired skill sets are of course laughing all the way to the bank, with so many job offers they don’t know what to do. But companies are biting their nails with important positions almost impossible to fill–and the end consumer has to brunt the prices.

“This year, as businesses strategized how to integrate AI into their operations,” said EY Global Innovation Technologies Leader and Global Chief Analytics Officer, Chris Mazzei, “they were hampered by a shortage of experts.”

So how can blockchain help?

Decentralizing Cybersecurity Solutions

When most people think about consumer cybersecurity, they think of antivirus, firewall, or maybe ransomware protection. But in the enterprise space, there are a multitude of tools used to protect companies The average consumer, of course, has no access to them.  

For example, can your antivirus tell you if you logged into your Gmail in the UK, and then someone entered your Dropbox account in Argentina? No. But, enterprise cybersecurity can. HEROIC is using the blockchain to decentralize and democratize cybersecurity solutions, making them available to the masses.

“Our mission is to protect the world’s information—of all individuals—not just the biggest businesses,” says Chad Bennett, founder and CEO of HEROIC. “The future of cybersecurity is decentralized and democratized—utilizing AI and the blockchain.”

The HEROIC ecosystem will be open to developers and businesses alike so that they can build their own intelligent solutions. And as the network grows, it naturally becomes more secure.

Gamifying the Bug Bounty Market

HEROIC’s model allows anyone around the world to join the network, which acts as a bridge over the talent gap in cybersecurity and AI. They can unlock important skills from people and places that were previously off the radar. This is the premise of PolySwarm, as well, another decentralized marketplace for cybersecurity experts and enthusiasts to build anti-malware engines.

Former McAfee Antivirus CIO Mark Tonnesen is on the advisory board. He says, “Blockchain could be the answer to the perpetual shortage of security talent.” Polyswarm aims to invite anyone–even cybercriminals–to the table to work on solutions to threats. And they will use cryptocurrency to gamify the bug bounty markets for white hat hackers, making it competitive as well as rewarding.

Jim Bursch, Director of the DASH Bug Bounty Program, served as a virtual sheriff in the wild, wild west that is cryptocurrency with his “Bug bounty” program developed for DASH. The program offers monetary incentives for hackers to identify points of weakness in the security of DASH’s digital currency. This allows for improvements to be made faster, without lack of access to the right individuals. A problem shared is a problem halved. Or broken down into minute fractions with potentially thousands of people on the case.

You can break down threats into microtasks, allowing a collective to work faster to provide the solution. Most cybercriminals are after the money. So, compensate them for their brilliant work and suddenly a very shallow talent pool becomes a vast lake of resources.

Scott Schober, Author of Hacked Again and President/CEO of BVS Systems says, “An incentivized basis for making things happen is extremely effective. Blockchain is a fundamental disrupter and game-changing technology, and by having incentives, it changes the way we make the connections on a much faster scale.”

Access to Education & Verification of Credentials

There are plenty of solutions coming up to fill the talent gap in cybersecurity, but what about AI? Blockchain can be instrumental in this area too, in a couple of ways. Providing access to education and teaching the skills people need in this new world is one.

The Institute of the Future and ACT Foundation released Edublocks, for example, which are essentially one-hour chunks of learning from virtually any source, shared via a blockchain.

Blockchains can also help recruiters to find the right candidates more easily. Thanks to blockchain’s ability to verify documents and ensure that they cannot be tampered with, recruiters will no longer have to spend time verifying credentials.

Mario Milicevic, IEEE Member and Staff Communication Systems Engineer at MaxLinear Inc says, “Blockchain technology relies on cryptography to validate that previous transactions in the chain are authentic, prior to adding a new transaction to the latest block.”

So an IT company seeking to hire AI personnel can utilize blockchain to maintain confidence that the candidates’ ‘badges/certs’ have not been tampered with.

Freeing up Time

“A lot of cybersecurity jobs are very niche,” says Schober, “it has become a very wide area, so how do you find the right person within these extremely narrow disciplines? When you can align people quickly to fill in those gaps, the talent gap in cybersecurity and AI closes faster by applying blockchain smarts.”

Bursch believes that blockchain is fundamental at the application layer as well. “If blockchain apps have security baked in from the beginning, then less work is required from separate, dedicated cybersecurity professionals who can focus on systems that pose a greater risk.”

The Talent Gap in Cybersecurity and AI May Be Closing

With decentralized initiatives to share resources with consumers, the ability to procure talent from around the globe, and bug bounty programs to unite hackers to their own fight, there will be more experts on the cause. At least for cybersecurity.

AI presents rather more challenges. It seems, for now, that blockchain can help free up time to learn the skills we need and focus on more creative tasks before the robots outsmart us all.

Christina Comben is a B2B writer and MBA, specializing in fintech, cybersecurity, blockchain, and other geeky areas. When she's not at her computer, you'll find her surfing, traveling, or relaxing with a glass of wine. This article was originally published on Coin Central.
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Friday, 11 May 2018

How Body Clock Disruption Can Lead To Cancer and How Same Can Be Used To Cure It

Written by By Elie Dolgin, Knowable Magazine

Chi Van Dang generally declines to discuss the science that made him famous. A leading authority on cancer metabolism, he routinely is asked to speak about how tumors reprogram biochemical pathways to help them slurp up nutrients, and how disrupting these noxious adaptations could be a powerful approach to treating cancer.

Instead, Dang uses his soapbox at every research meeting, every invited lecture and every blue-ribbon panel to advocate for something else entirely: a simple yet radical tweak to how oncologists administer cancer drugs.

The approach, known as chronotherapy, involves timing the delivery of drugs so as to minimize the side effects of treatment while maximizing the treatment’s effectiveness. The idea is to synchronize therapy with the body’s natural 24-hour rhythms — the so-called circadian clock — striking either when cancer cells are most vulnerable to assault or when healthy cells are least sensitive to toxicity (or, ideally, both).

“It’s just always been on the fringe. There weren’t that many card-carrying cancer biologists like me getting into it.” Chi Van Dang

Dang didn’t set out to become a global ambassador for this field. But as scientific director of the Ludwig Institute for Cancer Research, a nonprofit that funds hundreds of cancer labs worldwide, and chair of the board of scientific advisors at the US National Cancer Institute, he finds himself in a powerful position to reshape the research agenda — and he believes chronotherapy’s time has come.

It is not an entirely new concept. The idea of time-stipulated therapy dates back decades, with some randomized trials in the 1980s and 1990s showing dramatic reductions in toxicities and extended survival times among cancer patients treated in a clock-optimized fashion. But for the most part, “it’s just always been on the fringe,” says Dang. “There weren’t that many card-carrying cancer biologists like me getting into it.”

Until now.

The concept of chronotherapy got a major boost last year when the Nobel Prize in Physiology or Medicine went to three biologists who first uncovered the inner workings of our bodies’ daily rhythms. Scientists who study the interface of circadian biology and cancer say there’s been an uptick in interest in their work since the prize was announced last October.

But arguably, Dang’s own efforts to spread the gospel about the cancer-clock connection and its therapeutic implications have been even more important in revitalizing the field. “It’s capturing people’s interest,” he says — with a growing number of cancer researchers now beginning to explore the ways in which circadian rhythms shape tumor development.

They are finding not only new ways of administering old drugs but also clever tactics for rewiring aberrant clocks. And they are transforming a therapeutic strategy long dismissed as complementary or alternative medicine into a rigorous science.

“Time is an inconvenient truth” — one that oncologists and cancer researchers alike, Dang says, can no longer afford to ignore.

Timing is of the essence

A slender and bespectacled 63-year-old with the confident and unhurried voice of a seasoned physician, Dang cites his father — Chieu Van Dang, Vietnam’s first neurosurgeon and former dean of the University of Saigon School of Medicine — as a role model for how he approaches positions of leadership in academic medicine. His father’s death from liver cancer in 2004 remains a lasting inspiration to develop better treatments. And family, again, was a driving factor behind a fortuitous career move that prompted Dang’s recent zeal for circadian biology.

He had spent nearly 25 years on faculty at Johns Hopkins University, during which he rose through the ranks to become vice dean for research of the medical school; he figured he’d never leave. But in 2011, after his older brother Bob died of metastatic cancer of the soft tissues, Dang thought to himself: “As a medical oncologist and researcher, I need to do more.” So when the University of Pennsylvania approached him with an offer to become director of its cancer center — home to the original discovery that abnormal chromosomes can cause cancer, and where a new generation of lifesaving T-cell therapies were being developed — he jumped at the opportunity.

As luck would have it, Penn also is home to one of the largest assemblages of chronobiology researchers in the country, and Dang soon found himself chatting with — and then collaborating with — clock researchers from across the Philadelphia campus. Those interactions, he says, prompted an academic epiphany: If cancer is a disease of runaway cellular growth, and circadian rhythms are what normally keep the cell cycle in check, then disruption of the internal clock must be, as Dang puts it, a “missing link” of tumor development and growth.

Researcher Chi Van Dang is convinced that cancer treatments will be more effective and less toxic if we factor in the body's circadian rhythms. Pic The Wistar Institute

The circadian clock is a complex biological circuit that controls the daily rhythms of sleep, eating habits, body temperature and many other important physiological functions. The body has a master clock in the brain and many secondary clocks in other organs, as well as individual clocks in each and every cell, all controlled by an intricate network of oscillating genes and proteins.

When the various clocks are in sync, the body operates like a well-oiled machine. But when certain clock genes are mutated or thrown out of alignment by chronic jet lag, these systems can get out of whack, creating prime conditions for tumors to grow and spread.

“If I was still in Baltimore, I would probably be working on something else,” says Dang (who last year moved his lab again, this time just half a mile away to the Wistar Institute, an independent research center on the Penn campus, where he is a professor in the molecular and cellular oncogenesis program). And by extension, if Dang hadn’t started extolling the virtues of this research to officials at the National Cancer Institute, it’s unlikely that the agency — the largest funder of cancer research in the world — would ever have lined up behind the idea. It did so last year, putting out a call for grant applications from scientists seeking to better understand how circadian processes affect tumor development and responses of patients to therapy.

According to Dan Xi, a program director at the NCI, there’s now talk of creating a “human circadian rhythm atlas” to bring systems-level understanding to the study of clock disruption in cancer, immunity, psychiatry and general well-being. “The major challenge for the field is understanding how the function and regulation of clock genes contribute to health and diseases,” she says.

Some of the first hints that a disrupted clock could lead to cancer came in 2001, when two teams of epidemiologists working with independent datasets came to the same conclusion: that women who regularly worked the night shift had an increased chance of developing breast cancer. Later studies established a link between graveyard shifts and cancers of the colon, prostate and endometrium — which prompted the World Health Organization’s International Agency for Research on Cancer in 2007 to designate night-shift work involving circadian disruption as a probable carcinogen.

Researchers now generally think that nocturnal light, by decreasing the body’s natural synthesis of the clock-regulating hormone melatonin, explains such a cancer link — which suggests that taking melatonin pills or modulating ambient lighting could help mitigate the risk among shift workers. But prospectively testing that idea would be difficult given the number of study subjects and years needed to detect a small number of cancers — and as yet, says Steven Hill, a circadian cancer researcher at Tulane University, “there are no published studies or active interventional studies” to that effect.

Cancer never sleeps

Logistically — and financially — it is far easier to do such trials for cancer treatment than for cancer prevention, and it’s here that many researchers are now focused. Earlier this year, for example, a team led by circadian biologist Satchidananda Panda at the Salk Institute for Biological Studies in La Jolla, California, described two novel drugs that target key clock components and kill several different types of cancer cells in a laboratory dish, as well as slow the growth of brain tumors in mice.

The drugs, by reawakening the circadian clock in cancer cells, seemed to block biological functions that tumors rely upon, including a garbage cleanup system that helps clear away toxic byproducts and a molecular pathway needed for fat synthesis. Importantly, the drugs had this therapeutic effect on tumors without causing any overt toxicity in the mice.

In fact, there’s even some data to suggest that resetting the clock in tumors could mitigate the side effects of cancer experienced elsewhere in the body. Cancer biologist Thales Papagiannakopoulos of New York University — his postdoc adviser called him “Chronos” given his Greek roots and academic interests — showed that lung tumor cells secrete a factor that travels through the blood to the liver, where it disrupts normal oscillatory patterns. Such effects, Papagiannakopoulos says, “could explain a lot of the symptoms of having cancer.”

For example, the liver is critical for draining blood from several organs, including the spleen, and altered liver rhythms could lead to splenic backups and congestion that shorten the lifespan of blood cells. This could account for common side effects of cancer, including anemia and leukopenia, the low counts of blood cells experienced by many cancer patients. And if something similar is happening in muscle tissues, circadian dysfunction could underpin cachexia, a devastating loss of body weight and strength that often afflicts people in the final stages of cancer.

A colored scanning electron micrograph of a lung cancer cell undergoing division. Tumors often have malfunctioning circadian clocks. Pic: SPL / Science Source
Dang’s own therapeutics-related research has focused mainly on showing how a notorious cancer gene named MYC  is involved in suppressing genes that lie at the very core of the mammalian clock, such as one called BMAL1. This perturbs the normal oscillatory cycles of molecular regulation inside the cell, and instead pushes protein synthesis into an aberrant, perpetual state of activity that drives tumor progression. This revealed a potential drug target — one that researchers at Texas Children’s Cancer Center have run with. Last year, they reported that a drug that indirectly stimulates BMAL1  activity could help blunt the growth of neuroblastoma, a cancer of the nerve tissue, both in cell cultures and in mouse models.

Dang, meanwhile, has recently turned his attention to a class of drugs that target NAMPT, an enzyme involved in both cancer metabolism and circadian feedback loops. Around 10 to 20 years ago, a handful of NAMPT inhibitors entered clinical testing. But they all caused such low platelet counts in recipients that they never progressed past early trials.

Now, working with mouse models of lymphoma, Dang’s team has found that administering these drugs at either 10 a.m. or 6 p.m. caused the same degree of tumor regression — with a key difference. Only at 6 p.m., when NAMPT expression was at its natural zenith in the liver, did the treatment cause low platelet counts in the mice. Inhibiting NAMPT at 10 a.m. caused no such problems whatsoever.

The work, which the group is retesting before submitting it for publication, has led Dang to think that chronotherapy could help salvage this promising class of new cancer drugs. “We may be interfering with liver function simply by giving those drugs at the wrong time,” he says.

Peaks and valleys

Another drug that doctors may currently be administering suboptimally is streptozocin, a chemotherapeutic agent that’s routinely used to treat a rare form of pancreatic cancer. In a paper published in 2017, Penn sleep medicine doctor Ron Anafi took reams of gene-activity data from both cancerous and healthy liver tissue, and then developed an algorithm that models all the molecular rhythms.

His analysis showed that activity levels of a gene called SLC2A2, which encodes a glucose transporter protein that shuttles streptozocin, cycled in a daily fashion in normal liver cells. Together with John Hogenesch, a chronobiologist at Cincinnati Children’s Hospital Medical Center, he then showed that administering streptozocin to mice at the nadir of SLC2A2  expression, when levels of streptozocin’s gatekeeper protein are low, minimized drug toxicity.

Anafi and Hogenesch hope to eventually test this time-optimized treatment schedule for streptozocin in patients with pancreatic tumors. At the moment, though, there is only one chronotherapy trial running in the United States (unlike in Europe and Asia, where these kinds of studies are more common). It’s happening at the Washington University School of Medicine in St. Louis, where neuro-oncologist Jian Campian and her colleagues have enrolled 30 people with brain cancer and given them a standard chemotherapy drug called temozolomide either at 8 a.m. or 8 p.m.

So far, says Campian, it looks as if the side effects of the drug are far worse when people take their pills in the morning. It’s too early to say anything conclusive, although animal studies from Campian’s collaborators, Erik Herzog and Joshua Rubin, suggest that the drug should work best when activity of the core clock regulator BMAL1  is highest in the tumor cells.

That would imply that the 8 p.m. dosing strategy will work better than the 8 a.m. one, at least on average. But, as Herzog points out, “people are different from each other.” We have something called a chronotype that, at its most basic level, determines whether someone is a morning person or an evening person, and that will probably affect individual responses to drugs like temozolomide.

Ideally, says Herzog, the timing of treatments would be finely tuned to a patient’s unique chronotype, and thus to the peaks and crests of their internal molecular activity. “This might end up being the ultimate personalized medicine,” he says.

But measuring something like BMAL1  activity in a tumor is no small task. It’s invasive (one has to obtain the tumor samples), expensive and unfeasible to do routinely, in real time and for many patients. In search of an easier way, a research team at Northwestern University has a 30-person pilot study looking for genomic indicators of clock status in blood and saliva.

Yet most clock researchers have settled on tracking cruder measures like skin temperature and wrist actigraphy to get a rough estimate of whether the body is in its activity or rest phase. Those are imperfect proxies, acknowledges Francis Lévi, a luminary in the field of chronotherapy from the University of Warwick in the United Kingdom. “We still need to identify better biomarkers to personalize chronotherapy.”

Even if there were an ideal biomarker, there’s still the problem of the medical system being designed around a standard working day. It’s not built to administer drugs at off hours — and there’s little financial incentive for change. So rather than bend the system to the needs of the patient, it might be easier to bend the circadian clock to the needs of the system. This may be possible simply by time-shifting eating, sleeping, exercise habits or ambient lighting to get a patient’s biological rhythms in sync with the business hours of a chemo ward.

Or perhaps the tumor’s clock itself could be reprogrammed. In a study published in 2017, Silke Kiessling, a circadian biologist who conducted the work as a postdoc at McGill University in Canada, showed that injecting tumors in mice with a steroid drug called dexamethasone reset genes like BMAL1  and induced rhythmicity in the cancer cells. Conceivably, that means a patient could take a shot of steroid a few hours before treatment so that, no matter when therapy is scheduled, that patient gets the benefit of chronotherapy without the inconvenience.

“This could be applicable for any kind of cancer you can reach with a needle,” says Kiessling, now at the Technical University of Munich in Germany. She is also thinking about making an aerosolized formulation for extending the strategy to lung cancer. “I’m more than confident that this could work, even in humans.”

Bedtime routine

For now, most of the human data come from anecdotal reports like those of Joe Kuna, who was diagnosed with metastatic colon cancer in 2014 and given two to five years to live. Four years on, the 61-year-old has beaten back a tennis-ball-size tumor in his colon and 15 lesions in his liver. Kuna, who runs a family-owned bowling alley in Johnsburg, Illinois, opted to undergo chronotherapy at the nearby Block Center for Integrative Cancer Treatment.

 “We still need to identify better biomarkers to personalize chronotherapy.” Francis Lévi

For the better part of two years after his diagnosis, Kuna would arrive at the center every other Tuesday, usually some time between 1 p.m. and 3:30 p.m., for his dose of oxaliplatin. Since different anticancer drugs kill cells in different ways, “each drug has a window of time” when it works best, says oncologist Keith Block, medical director of the clinic in Skokie, Illinois — and oxaliplatin, according to Block, seems to work best in the afternoon.

Kuna would sit in the cubicle with the palm tree painted on the wall and eat his tuna fish sandwich while the intravenous medication dripped into his veins through a port implanted over his right nipple.

Another one of the drugs in Kuna’s chemotherapeutic cocktail, fluorouracil, is considered more of a nighttime agent — which meant Kuna had to take home a special pump, about the size of a paperback novel, that he could carry around in a fanny pack or leave on the mattress next to him in bed. The pump was programmed to kick in at 10 p.m., initially as a slow trickle. The flow would ramp up until 4 a.m. before dialing back down again and finishing up at 10 in the morning.

If you ask Kuna, this unusual drug regimen, plus the diet he followed and supplements he took as directed by the clinic, is the reason he’s alive today. “I truly believe it’s why I’m still here,” he says. And although a scan from January 2018 revealed two new cancerous spots in his liver, Kuna is confident that, with surgery and more chronotherapy, he could be cancer-free once more. Doctors removed the tumors on April 26.

But there’s no proof, without controlled trials, that the therapy as Kuna received it made a difference. Notably, of the other patients whom Kuna befriended at the Block Center, none is alive today. Most chronotherapy strategies now in place are based on a limited understanding of clock biology — which frustrates experts like Dang.

“We really want to provide the mechanistic basis of why you treat at a certain time of day,” Dang says, “and not just rely on trial and error.”

It’s defining why those little tweaks to common drug regimens improve patient outcomes that captures Dang’s imagination as he stares out the window of the Amtrak train on his semiweekly commute from Philadelphia, where he lives and runs his lab, to New York, for his office job at the Ludwig. Just as a small career move reshaped his own research agenda, “it could be,” he says, “that simple adjustments make a big difference for patients.”

Elie Dolgin is a science writer in Somerville, Massachusetts. This article was originally published on The Knowable Magazine
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