VR Can Be Used to Help Automated Driving Systems Make Ethical Traffic Decisions


The ability to engineer decision-making using machine-learning algorithms could offer an acceptable path toward handing over the car keys to self-driving systems.

 The ability to engineer decision-making using machine-learning algorithms could offer an acceptable path toward handing over the car keys to self-driving systems.
The age of self-driving cars is upon us. Companies including Google, Ford, Waymo, Lyft, Uber, and Volvo are all already testing them in cities around the world, with semi-autonomous cars already available for sale. But while the future of automated driving seems assured, so far there’s no consensus on how to incorporate moral decision-making into computer systems that would inform how they operate.
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China Just Built a 250-Acre Solar Farm Shaped Like a Giant Panda


Most solar farms align their solar arrays in rows and columns to form a grid.

A new solar power plant in Datong, China, however, decided to have a little fun with its design. China Merchants New Energy Group, one of the country’s largest clean energy operators, built a 248-acre solar farm in the shape of a giant panda.

 

The first phase, which includes one 50-megawatt plant, was completed on June 30, according to PV magazine.

The project just began delivering power to a grid in northwestern China, and a second panda is planned for later this year.

Called the Panda Power Plant, it will be able to produce 3.2 billion kilowatt-hours of solar energy in 25 years, according to the company.

That will eliminate approximately million tons of coal that would have been used to produce electricity, reducing carbon emissions by 2.74 million tons.

Panda Green Energy China 889x568China Merchants New Energy/Panda Green Energy

China Merchants New Energy Group worked with the United Nations Development Program (UNDP) to make the Panda Power Plant a reality.

The project is part of a larger effort to raise awareness among young people in China about clean energy, the UNDP wrote in a statement.

The groups hope to build more panda-shaped solar plants throughout China in the next five years.

France Is About to Make 11 Vaccines Mandatory


Of course, not everyone is pleased.

France’s Prime Minister Édouard Philippe has announced that the government will make the 11 vaccines universally recommended by health authorities mandatory from 2018 onward.

The announcement comes in response to measles outbreaks across Europe, with 79 cases reported in France in January and February alone. Philippe branded the state of affairs “unacceptable”.

 The resurfacing of diseases like measles is believed to be caused by people believing less and less in the power of vaccines.

In France, a recent survey found that 3 in 10 people don’t trust vaccines, with only 52 percent stating they believed that the benefits outweighed the risks.

Italy has also seen a worrying increase in measles infections – the number of cases in April was five times higher than the same month in 2016.

Beatrice Lorenzin, the Italian health minister, said that the rapid increase was “an emergency generated by fake news” and cited the Five Star Movement (MS5), a political party that opposes vaccines, as a contributing factor.

The shift in public perception in Italy and France is symptomatic of a Europe-wide trend that has been attributed to the growing anti-vaccine movement.

 The genesis of the skepticism was Andrew Wakefield, who stated in a 1998 research paper that there was a link between the measles, mumps, and rubella vaccine and the development of autism.

The claim has been irrefutably debunked, although dubious science and scare tactics – like those used by MS5 – are perpetuating the findings of the report.

The World Health Organization (WHO) estimates that vaccines saved more than 10 million lives between 2010 and 2015, and thanks to vaccines, we’re on the brink of completely eradicating some diseases, such as polio. Despite this, countries in both the developing and developed world remain doubtful of their effects.

In response, many countries have taken measures to increase the use of vaccines.

Italy has made 12 vaccinations obligatory for children, while Australia has introduced a financial incentive by offering parents US$129 for every child who meets recommended vaccination levels between the ages of 18 months and 24 months, with the payment being repeated if the same requirements are met between the ages of four and five.

Slovenia, in Eastern Europe, has the world’s strictest vaccination policy, with fines being issued to any parents who fail to provide their children with the nine mandatory vaccines. This has resulted in a compliance rate of 95 percent.

Dr. Farah Jameel told doctors attending the British Medical Association’s annual meeting in June that deaths in Wales from measles in 2013 were a “waste of life”.

This is arguably true for all deaths that could have been easily prevented through vaccination, especially given their ever-decreasing price and new delivery methods.

The Large Hadron Collider Just Detected a New Particle That’s Heavier Than a Proton


The Large Hadron Collider has once again done what it does best – smash bits of matter together and find new particles in the carnage.

This time physicists have come across a real charmer. It’s four times heavier than a proton and could help challenge some ideas about how this kind of matter sticks together.

 We’ve seen a lot of interesting new particles from CERN’s Large Hadron Collider “beauty” (LHCb) collaboration, which is a little sister to the ATLAS and CMS experiments that brought us the famous Higgs boson a few years back.

The experiments run in CERN’s colliders all involve accelerating matter and then bringing it to a quick stop. The resulting burst of energy results in a shower of particles with different properties, most of which we’re pretty familiar with.

Running these experiments over and over again and doing the maths on the sizes and behaviours of the particles as they form and interact with one another can occasionally provide something different.

We can now officially add a new kind of baryon to the zoo of particles, one that was already predicted to exist but never before seen.

The two baryons you’re no doubt most familiar with are the ones that make up an atom’s nucleus, called protons and neutrons.

Baryons are effectively triplets of smaller particles called quarks, which are elementary particles meaning they aren’t made up of anything smaller themselves.

 Quarks come in a variety of flavours, oddly called up, down, top, bottom, charm, and strange. It’s combinations of these that give us different bosons. Current models predict there are a bunch of ways quarks can make baryons, with some more common than others.

Protons consist of two ups and a down quark, while neutrons are two downs and an up. These quarks stick together under what’s called the strong nuclear force, which is caused by the swapping of particles called gluons. Never let it be said that physicists lack a sense of humour.

This new baryon – made when two charm quarks and a single up bound together – was given the less whimsical name Xi cc++, so they can’t all be winners.

Quarks have different masses, and charm is a beefy one. That makes this baryon a touch on the heavy side, which is good news for particle physicists.

“Finding a doubly heavy-quark baryon is of great interest as it will provide a unique tool to further probe quantum chromodynamics, the theory that describes the strong interaction, one of the four fundamental forces,” said Giovanni Passaleva, the spokesperson for the LHCb collaboration.

Seeing how this particle keeps itself together compared to the predictions made by current models will help give the going theories a good shake.

 Being made of two heavy quarks should give Xi cc++ a slightly different structure to protons and neutrons.

“In contrast to other baryons, in which the three quarks perform an elaborate dance around each other, a doubly heavy baryon is expected to act like a planetary system, where the two heavy quarks play the role of heavy stars orbiting one around the other, with the lighter quark orbiting around this binary system,” says former collaboration spokesperson Guy Wilkinson.

If you’re wondering where this baryon has been hiding all this time, like many particles it doesn’t hang around very long. It wasn’t seen directly, but was recognised by the particles it broke into.

The LHCb experiment is a champion at spotting these kinds of decay products, as well as making heavy quarks.

The discovery has a high statistical significance at 7 sigma. Physicists break out the champagne at 5 sigma, so we can be pretty confident Xi cc++ was produced.

If you’re playing Standard Model bingo, that’s one more to cross off your list.

Mars Surface Is Looking Much Deadlier Than We Previously Thought


So much for those space potatoes.

A new study has revealed that compounds present in the Martian soil can wipe out whole bacterial cultures within minutes.

Researchers have had their suspicions over whether microorganisms can actually survive on the surface of the Red Planet, and now lab tests are spelling doom for any potential little green bacteria. And yeah, growing potatoes on Mars might be more difficult than we thought.

 The problem here lies with perchlorates – chlorine-containing chemical compounds that we first detected on Mars back in 2008. These salty compounds are also what makes water on the Martian surface stay liquid, essentially turning it into brine.

Perchlorates are considered toxic for people, but they don’t necessarily pose a problem for microbes. And because they keep surface water liquid, on Mars the presence of these compounds could even be beneficial for life – or so we thought.

Researchers from the University of Edinburgh have now confirmed that when you pair the compounds with intense ultraviolet (UV) light exposure, things become grim for any life forms.

“Perchlorate, although stable at room temperature, is a powerful oxidant when activated, for instance at high temperatures,” the team writes in the study.

One way to turn a perchlorate into an oxidant is to expose it to UV light, and since Mars has a much thinner atmosphere than Earth, there’s plenty of this kind of radiation on its surface.

The scientists took a common spacecraft-loving bacteria, Bacillus subtilis, and subjected them to Mars-like conditions.

 The bacteria got a swim in a magnesium perchlorate solution of a similar concentration to how it’s found on Mars, and then got exposed to UV light of the same general wavelength as that which bathes the Martian surface.

None of the bacteria survived this test. In fact, they died within 30 seconds.

The team also exposed the bacteria to UV rays without the presence of perchlorates, but even that still wiped the colony out within about a minute.

Of course, a planet’s surface is not as barren and wet as a petri dish. With that in mind, the researchers also tested a scenario in which the microbes hung out on Mars ‘rock analogues’ made out of silica.

These conditions made it slightly easier on B. subtilis, but unfortunately most of them still died out. Which means that if there’s life on Mars to be found, it’s probably hiding quite far down beneath the surface of the planet.

“Although the toxic effects of oxidants on the Martian surface have been suspected for some time, our observations show that the surface of present-day Mars is highly deleterious to cells, caused by a toxic cocktail of oxidants, iron oxides, perchlorates and UV irradiation,” the researchers write.

 If the salty brines trickling across the rocks on Mars really are concentrated perchlorate streams, that’s not an environment fit for sustaining life. And because perchlorates are all over the Martian soil, the team says this basically renders much of the planet’s surface uninhabitable.

But there’s also a positive. If Mars soil kills Earth’s microbes on contact, that could actually be a good thing when it comes to planetary protection – there’s less of a chance that our future Mars missions could irreparably contaminate the neighbouring planet.

The scientists are hoping to do follow-up work to find out exactly how the deadly cocktail on Mars surface kills living cells.

Chocolate Boosts Your Brain Power, New Study Finds


The best excuse yet.

Italian scientists have found that a daily dose of cocoa acts as a dietary supplement to counteract different types of cognitive decline.

They found regularly eating cocoa was linked to improvements in working memory and visual information processing and cocoa could be particularly beneficial for certain people.

 Cocoa, is the dried and fermented bean from the cocoa tree used to make delicious chocolate treats. Cocoa has been studied extensively because, well, who wouldn’t want that job.

Over the years, it has been found that a range of naturally occurring chemicals in the cocoa bean have therapeutic effects.

For example, polyphenols in dark chocolate were found to increase calmness and contentedness and flavanols were able to reverse age-related memory decline.

Before you start using this an excuse to scoff as much chocolate as humanly possible, just remember that chocolate also contains theobromine, a toxic chemical. Though to be at risk of poisoning yourself, you’d have to eat about 85 full sized chocolate bars.

Despite the large number of claims about the health benefits of cocoa, there are only a limited number of randomised trials and the literature is a mixed bag of results.

In this study, the team looked through the literature for effects of acute and chronic administration of cocoa flavanols on brain activity and, more specifically, what happens if you do this over a long period of time.

The studies used to perform the review mainly required the subjects to consume a low, medium or large amount of cocoa in the form of a chocolate drink or bar for a period of between five days and three months.

The scientists found that there was enough evidence to support the health claims attributed to cocoa, and, in particular, the flavanol compounds it contains.

They noticed enhancements in working memory performance and improved visual information processing after consuming cocoa flavanols. The benefits varied depending on the demographic being tested.

For the elderly, it turns out that long term ingestion of cocoa flavanols improved attention, mental processing, working memory and verbal fluency and was most beneficial in those who had mild cognitive impairments or the beginnings of memory loss.

“This result suggests the potential of cocoa flavanols to protect cognition in vulnerable populations over time by improving cognitive performance,” wrote the researchersfrom the University of L’Aquila in Italy, including Valentina Socci and Michele Ferrara.

For healthy people, without the beginnings of memory loss, cocoa could also enhance normal cognitive functioning and have a protective role on cognitive performance. The researchers admit that you have to push the healthy subjects a little harder before that benefit starts to become significant.

One demographic in particular benefited from cocoa.

For women, eating cocoa after a night of total sleep deprivation counteracted the cognitive impairment associated with no sleep. Promising results for people that suffer from chronic sleep deprivation or work different shift patterns.

But how exactly does cocoa help with brain power?

The researchers aren’t completely sure, but do have some ideas.

“If you look at the underlying mechanism, the cocoa flavanols have beneficial effects for cardiovascular health and can increase cerebral blood volume… This structure is particularly affected by ageing and therefore the potential source of age-related memory decline in humans.”

So should you start shovelling chocolate into your mouth? Perhaps, but it comes with an obvious warning.

“Regular intake of cocoa and chocolate could indeed provide beneficial effects on cognitive functioning over time,” say the researchers.

“There are, however, potential side effects of eating cocoa and chocolate. Those are generally linked to the caloric value of chocolate, some inherent chemical compounds of the cocoa plant such as caffeine and theobromine, and a variety of additives we add to chocolate such as sugar or milk.”

Despite the risk of gaining a few extra kilograms, the scientists are happy to listen to their own advice and conduct a little bit of self-experimentation.

“Dark chocolate is a rich source of flavanols. So, we always eat some dark chocolate. Every day.”

I can’t think of health advice I’d be happier to listen to.

Untreatable Antibiotic-Resistant Strains of Gonorrhoea Are Going Global


The World Health Organisation (WHO) has issued a warning over the rise of resistant strains of the infectious bacteria responsible for gonorrhoea.

Superbugs are bad news at the best of times, but with little on the horizon by way of potential treatments for this common sexually transmitted infection (STI), we could very well be rewinding the clock on venereal disease.

 

The warning follows the discovery of several patients in France, Japan, and Spain who harboured strains of Neisseria gonorrhoeae that wouldn’t respond to any antibiotics.

WHO medical officer Teodora Wi predicts there are plenty more to come.

“These cases may just be the tip of the iceberg, since systems to diagnose and report untreatable infections are lacking in lower-income countries where gonorrhoea is actually more common,” says Wi.

Gonorrhoea is one of the most common pathogens passed around through sexual contact, largely thanks to the fact it’s often asymptomatic, meaning people often don’t even know they have the bacteria.

Decreased use of condoms and a rise in travel also contribute greatly to its spread, with an estimated 78 million people infected annually.

The bacteria not only infect the genitals of men and women, but can be found in the tissues of the throat and rectum as well, and lead to complications including infertility and increased susceptibility to catching HIV.

Since the 1930s, bacterial STIs such as gonorrhoea, chlamydia, and syphilis have been treated with a simple course of antibiotics.

“The best time to have had gonorrhoea was the eighties, since there were many drugs to treat it with,” US director of the Centre for Disease Dynamics, Economics and Policy Ramanan Laxminarayan told Nature.

While non-symptomatic cases go untreated, in the absence of an on-the-spot diagnosis kit, doctors also have a tendency to assume STI based on reported symptoms alone, prescribing antibiotics regardless of the presence of infection.

The decades since have seen an increasing number of so-called superbugs – bacteria that have acquired a resistance to numerous antibiotics.

New research has found widespread resistance to several types of antibiotics commonly prescribed for gonorrhoea.

All but 3 percent of countries surveyed between 2009 and 2014 reported Neisseria gonorrhoeae with a resistance to a common and inexpensive antibiotic called ciprofloxacin. About 66 percent of countries reported resistance to a last-resort group of antibiotics called extended-spectrum cephalosporins (ESCs).

 That’s seriously bad news, since in many countries ESCs are the only option left for treating gonorrhoea.

If we’re hoping for a miracle cure to pop up soon, we’ll be disappointed. There’s nothing much in the pipeline, with only 3 candidates being tested – one at the end of a phase 3 trial, and two that have just completed phase 2 trials.

The WHO has been vocal in the past about the reluctance of commercial companies to invest in pharmaceuticals where there is little hope of profit.

Following the 2014 outbreak of Ebola, an epidemic which claimed around 5000 lives, WHO director general Margaret Chan cited profit as the reason vaccines were slow in being developed.

“A profit-driven industry does not invest in products that cannot pay,” said Chan.

Similarly, antibiotics aren’t always appealing candidates for commercial pharmaceutical companies, since – somewhat ironically – bacteria can develop a resistance to them.

The WHO has joined forces with the Drugs for Neglected Diseases initiative to launch the Global Antibiotic Research and Development Partnership in order to address this dire issue.

“In the short term, we aim to accelerate the development and introduction of at least one of these pipeline drugs, and will evaluate the possible development of combination treatments for public health use,” says the partnership director Dr Manica Balasegaram.

Even if we develop more accurate and rapid diagnostic techniques and new antibiotics, prevention is far better than any cure.

Targeted NSCLC Therapies Go Head-to-Head


It was “fight night” at the 2017 American Society of Clinical Oncology annual meeting, with two big bouts between lung cancer therapies. In the ARCHER 1050 trial, up-and-comer dacomitinib took on the seasoned gefitinib (Iressa) in patients with advanced, EGFR-mutated non-small cell lung cancer (NSCLC). In the ALEX trial, the matchup was between alectinib (Alecensa) and crizotinib (Xalkori) in patients with treatment-naive, advanced ALK-positive NSCLC.

Which targeted therapies came out on top in these phase III trials?

ARCHER: Win by Decision

“Dacomitinib is a second-generation tyrosine kinase inhibitor [TKI] … and being second generation implies two clinical features,” explained the lead investigator, Tony Mok, MD, of the Chinese University of Hong Kong. “First it forms an irreversible bond with the receptor. Second, it [has] pan ErbB inhibition with HER1, HER2, and HER4.”

Based on positive findings from the ARCHER 1017 trial, “we thought it is likely … that dacomitinib would be superior to gefitinib, a first-generation TKI, in terms of PFS,” he added.

Mok’s group found that treatment with dacomitinib extended the time to relapse or death by 41% compared with standard gefitinib therapy.

The team randomly assigned 452 previously untreated patients with stages IIIB or IV NSCLC to receive 45 mg of dacomitinib a day or 250 mg of gefitinib a day.

 The trial’s primary endpoint was progression-free survival (PFS), which was defined as progressive disease or death. PFS was measured by an independent review committee. Objective response rates (ORR), overall survival (OS), and safety data also were analyzed.

Mok noted that the patients with central nervous system (CNS) metastases were not included in the study population. “The reason is we were not certain of the penetration of dacomitinib to the CNS at the time the study was designed,” he explained, adding that the role of gefitinib in CNS metastases is also unknown.

As for the ASCO presentation, 136 patients given dacomitinib and 179 given gefitinib had either progressed (59.9%) or died (79.6%). The median PFS for patients on dacomitinib was 14.7 months versus 9.2 months for gefitinib. The hazard ratio for progression was 0.59 in favor of dacomitinib.

The ORR for the study drug was 74.9% versus 71.6% for gefitinib. However, Mok reported that the duration of response was significantly longer for dacomitinib, at 14.8 months versus 8.3 months. OS data was not mature at the time of presentation, he added.

While dacomitinib may have won the overall “fight,” the agent was down for the count when it came to toxicity. Adverse events were as follows for dacomitinib compared with gefitinib:

  • Diarrhea: 87.2% versus 55.8%
  • Paronychia: 61.7% versus 20.1%
  • Dermatitis acneiform: 48.9% versus 28.6%
  • Stomatitis: 43.6% versus 17.9%
 In all cases, more patients on dacomitinib had grade 3 adverse events compared with gefitinib. On the other hand, gefitinib patients were more likely to have increases in alanine aminotransferase at 39.3% versus 19.4% for dacomitinib.

Given that dacomitinib does offer the more potent EGFR inhibition, the higher toxicity with the agent was not a huge surprise. Mok pointed out that “the overall total incidence of serious adverse events was similar between the two agents, but the drug-related [serious adverse events] were higher with dacomitinib,” adding that about 10% of patients had to permanently discontinue the drug, versus 7% of patients who had to discontinue gefitinib.

Because of the toxicity, dose reductions had to be used. Dacomitinib had two dose levels, a reduction of of 30 mg/day and another of 15 mg/day, while with gefitinib, there was one dose reduction to 250 mg every 2 days, Mok explained.

“The time to dose reduction was about the same, approximately 3 months, but the median duration of the dose reduction was longer with dacomitinib, at 11.3 months compared with 5.2 months with gefitinib,” he said.

Dacomitinib ultimately emerged as the victor, mainly because of its impressive PFS data, commented John Heymach, MD, chairman of the Department of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston and a designated ASCO expert. He called the extended median PFS to 14.7 months with the study drug “a really substantial advance … that would clearly put it at the front of the pack in terms of efficacy” — the “pack” being the other targeted therapies available to these patients: gefitinib, erlotinib (Tarceva), and afatinib (Gilotrif).

ALEX: A Knockout

“Chromosomal rearrangements of ALK define a distinct subset of lung cancer patients for whom small-molecule TKIs of ALK are highly effective,” noted Alice T. Shaw, MD, PhD, of Massachusetts General Hospital in Boston. “The current standard of care for patients with newly diagnosed, advanced ALK-positive NSCLC is the first-generation ALK inhibitor, crizotinib.”

But patients invariably relapse on crizotonib, and one of the common and challenging sites of relapse is the CNS, she pointed out. Alectinib is more potent and more brain penetrable than crizotinib and can retain activity against crizotonib-resistant disease, she added.

For this trial, Shaw’s group randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (at 600 mg twice daily) or crizotinib (at 250 mg twice daily). ALEX’s primary endpoint was investigator-assessed PFS, and secondary endpoints included ORR, OS, and time to CNS progression.

The results showed, the team reported, that, across the board, alectinib turned in better results than crizotinib:

  • 12-month event-free survival rate (investigator-assessed PFS): 68.4% (95% CI 61.0-75.9) versus 48.7% (95% CI 40.4-56.9)
  • Event of CNS progression: 12% versus 45% (cause-specific hazard ratio 0.16, 95% CI 0.10-0.28, P<0.001)
  • ORR: 82.9% (95% CI 76.0-88.5) versus 75.5% (95% CI 67.8-82.1, P=0.09)
  • OS: “Not estimable” for either arm (HR for death 0.76, 95% CI 0.48-1.20)

For PFS, the hazard ratio for disease progression or death was 0.47 (95% CI 0.34-0.65, P<0.001), and the median PFS with alectinib was not reached, the authors stated.

In addition, a follow-up analysis for OS will be performed when approximately 50% of the patients have died, Shaw’s group wrote in the New England Journal of Medicine.

As with dacomitinib, alectinib did stumble a bit when it came to adverse events, which occurred at a higher incidence by five percentage points or more with alectinib versus crizotinib:

  • Anemia: 20% versus 5%
  • Myalgia: 16% versus 2%
  • Increased blood bilirubin: 15% versus 1%
  • Increased weight: 10% versus 0%
  • Musculoskeletal pain: 7% versus 2%
  • Photosensitivity reaction: 5% versus 0%

However, some adverse events that were common with crizotinib were nausea, diarrhea, and vomiting.

“One of the key secondary endpoints was time to CNS progression in the total population,” Shaw stated. “We found that alectinib significantly delayed time to CNS progress compared with crizotinib, with an 84% reduction in the risk of having CNS progression as the first event.”

The results represent a “watershed moment” for the treatment of ALK-mutant NSCLC, Heymach said. “Often, studies comparing similar-type agents will show incremental improvements. This one is different. There is a dramatic difference in efficacy — more than doubling the time to progression or death. It’s also accompanied by improved tolerability.

“Finally, one of the most debilitating things that can occur in these patients with ALK-mutant disease is brain metastasis,” he continued. “What’s really impressive about this study is the dramatic reduction in the risk of brain metastasis — an 84% reduction in the likelihood, which is an absolutely striking result.”

The ARCHER 1050 trial was funded by Pfizer and SFJ Pharmaceuticals Group.

Severe asthma in humans and mouse model suggests a CXCL10 signature underlies corticosteroid-resistant Th1 bias


Abstract

We previously showed that Th1/type 1 inflammation marked by increased IFN-γ levels in the airways can be appreciated in 50% of patients with severe asthma, despite high dose corticosteroid (CS) treatment. We hypothesized that a downstream target of IFN-γ, CXCL10, which recruits Th1 cells via the cognate receptor CXCR3, is an important contributor to Th1highasthma and CS unresponsiveness. We show high levels of CXCL10 mRNA closely associated with IFNG levels in the BAL cells of 50% of severe asthmatics and also in the airways of mice subjected to a severe asthma model, both in the context of high-dose CS treatment. The inability of CS to dampen IFNG or CXCL10 expression was not because of impaired nuclear translocation of the glucocorticoid receptor (GR) or its transactivational functions. Rather, in the presence of CS and IFN-γ, STAT1 and GR were recruited on critical regulatory elements in the endogenous CXCL10 promoter in monocytes, albeit without any abatement of CXCL10 gene expression. High CXCL10 gene expression was also associated with a mast cell signature in both humans and mice, CXCR3 being also expressed by mast cells. These findings suggest that the IFN-γ–CXCL10 axis plays a central role in persistent type 1 inflammation that may be facilitated by CS therapy through GR-STAT1 cooperation converging on the CXCL10 promoter.

Introduction

Asthma is a disease with significant prevalence and morbidity throughout the developed world, affecting nearly 5%–10% of populations (1). It is increasingly recognized that asthma is a disease with multiple phenotypes, each with its own unique molecular mechanisms, natural history, and response to therapy (23). Corticosteroids (CS) have remained the mainstay of therapy, but for many patients, these therapies are ineffective (4), and research of underlying mechanisms may give insight into the etiologies of CS resistance and identify future therapeutic targets.

Our previous studies have shown that the number of Th1 cells, which produce IFN-γ, is elevated in approximately 50% of severe asthma (SA) patients and in our mouse model of SA (5), and increased IFNG mRNA levels are also evident in the airways of these subjects (6). Furthermore, IFN-γ was associated with increased airway hyperreactivity (AHR) and poor CS response (5). A high Th1/IFN-γ response in any tissue is typically induced during infections by bacteria and viruses (7). Infections by viruses (rhinovirus being the most common) and bacteria have been observed in patients with SA and can trigger asthma exacerbations (7). Several bacterial species have also been associated with severe disease (8). Once generated in lung-draining lymph nodes, Th1 cells need to be recruited to the site of infection, and the best known chemoattractant for Th1 cells is CXCL10 (9), initially cloned as an IFN-γ–induced molecule from monocytes (10). Additional chemokines that belong to the same family induced by IFN-γ include CXCL9 and CXCL11, although CXCL10 is the most studied (11). While there is significant redundancy in their effects, the expression of the 3 family members is not uniform in disease settings, including allergic disease (1112).

In this study, we sought to better understand the possible etiologies of this resistance to CS therapy, and as such, we focused on CXCL10, given its role in recruiting Th1 cells to reinforce type 1 inflammation to combat and eliminate viral and bacterial pathogens, a function that when uncontrolled can lead to significant pathology (13). The expression of CXCL10 can be induced not only by IFN-γ, but also by additional stimuli, including LPS, which can lead to differential levels of CXCL10 production and response to therapies (111416). In addition to its expression on Th1 cells, the CXCR3 receptor — which mediates chemoattraction by CXCL10 and its family members — is also present on mast cells (17), neutrophils (18), and eosinophils (19). Elevated CXCL10 levels have been detected in multiple compartments, including blood and bronchoalveolar lavage (BAL) in mild and atopic asthma (2022) and may be increased during asthma exacerbations (23). CXCL10 can be secreted by multiple cell types, including airway epithelial cells, smooth muscle cells, monocytes, and macrophages (11). However, several studies have implicated monocytes/macrophages as possible drivers of CXCL10 expression in asthma (2425).

Given its association with IFN-γ, we asked whether CXCL10 may be a contributor to steroid resistance in SA. Here, we show high levels of CXCL10 mRNA closely associated with IFNGlevels in the airways of 50% of SA subjects and in mice subjected to our SA model, both in the context of high-dose CS treatment. Our investigation of possible impairment of glucocorticoid receptor (GR) function in the presence of IFN-γ showed no such impairment with preservation of nuclear translocation and transactivational functions of GR. However, as revealed using ChIP assay, in the presence of CS and IFN-γ, we observed simultaneous enrichment of STAT1 and GR on critical regulatory elements in the endogenous CXCL10 promoter in monocytes; importantly, this did not cause inhibition of CXCL10 expression at either mRNA or protein levels. In contrast, CS inhibited LPS-induced binding of NF-κB to the CXCL10 promoter and inhibited LPS-induced CXCL10 gene expression, showing selective impairment of CS-mediated suppression in the presence of IFN-γ. High CXCL10 gene expression was also associated with markers of mast cells in the airways of severe asthmatics, consistent with known human mast cell expression of CXCR3. Taken together, these findings suggest that the IFN-γ/CXCL10 axis is prominent in CS-refractory disease. Increased expression of both IFN-γ and the chemokine that recruits IFN-γ–producing Th1 cells may establish a persistent type 1 inflammation that may actually worsen with CS therapy through GR-STAT1 cooperation in promoting CXCL10 gene expression.

Source:insight.jci.org

 

Healing the Womb: The Body’s Energetic Power Centre


As we awaken individually and collectively, we have begun the task of consciously reconnecting to two vital energy centres that are allowing us to shift out of the dualistic mind into our intuition and capacity for love. These are the pineal gland or Third Eye, and the Heart. As we embrace certain spiritual practices including certain forms of meditation, yoga and shamanic medicine work we are supporting ourselves to open and heal these two centres.

This shift into our intuitive, Heart-centred consciousness is allowing us to access multidimensional realities, forge unconditional love for ourselves and each other, and reawaken our deep connection to the unified field of consciousness that is our universe. This is already a giant leap for humanity.

However, for some of us there is an important puzzle piece missing in the story of our awakening journey. This puzzle piece is a deeper centre of power within us that I call the Womb. In women whose womb organ is present, the Womb is a centre of energy and consciousness that includes the vibrational aspect of the sexual organs and physical womb. However, all of us have an energetic centre of consciousness that we can call the Womb. This includes women who no longer have a physical womb. In men the Womb is also knows as the Hara (a Japanese energy term).

 Healing the Womb The Body's Energetic Power Centre

For the purposes of clarity in this article I will refer to “Womb” to describe this energetic centre of consciousness while any reference to the physical womb organ will be done in lower case: “womb”.

I  will also clarify that by talking about the Womb I am not referring to the “sacral chakra” even through physically the Womb and sacral chakra do coincide. My reference to the Womb is as a deep and organic centre of consciousness that operates on multiple physical, mental, emotional and energetic levels.

The Womb, as a centre of consciousness, represents our foundation of personal power during the period of our physical incarnation. The vibrational frequency of the Womb is relatively dense and sits very close to the frequency of our physical bodies. When the Womb is energetically healthy and strong, this reflects in us directly through our physical health and particularly the health of our sexual organs and the deep emotional structures of the pelvis including the Psoas (known as the muscle of the soul).

Clear and healthy Womb energy contributes to a deep sense of grounding and belonging within our physical bodies. For those of us who have been lucky enough to awaken our intuition and move into our Hearts, the Womb represents the next vital step back to ourselves: the return to fully inhabiting our bodies and our feeling of deep emotional security and groundedness in our everyday lives. The healed and compete Womb holds our divinely balanced sexual energies which are also the fountain of our creativity and inspiration.

To sum up briefly, let´s say that if the Third Eye and Heart are here to open us to the truth of the multidimensional universe and connect to it through love, then the Womb is the key to our ability to experience deeper levels of personal wellbeing in our bodies and everyday human lives, and gracefully translate our spiritual truth into the grounded and real actions that will restore humanity and the Earth to their highest potential.

Individual and Collective Womb Trauma

However, the problem is that many of us are disconnected from this foundation centre of power. The reasons for this are manifold, but one of the most fundamental reason is that the Womb has sustained multiple levels of wounding at the individual, historical and collective levels. This wounding has led to us holding embedded trauma in our Womb energy- and at a psychological level the very definition of trauma is that it´s an event that takes us beyond our ability to cope.

In our individual lifetimes many of us have sustained Womb trauma including:

  • Sexual violence and abuse, or distorted and unloving sexuality
  • Difficult childbirth, abortion, miscarriage and resulting Womb trauma and grief
  • Slavery (historically feudal peasant slavery and now debt slavery and office slavery) leading to deep survival stress and the fear of not having enough

Healing the Womb The Body's Energetic Power Centre - Trauma

Our Wombs also hold historically and collectively remembered trauma, due to the fact that each of us sits in our mother´s physical womb for 9 months, during which time we are receiving and imprinting the energy of her Womb trauma, and in turn the trauma of her mother and grandmother.

As this has happened from one generation to another all the way down our ancestral lineage, we are ultimately encoding layers of historical trauma from an incredibly violent period of human history where rape, military rape, sexual torture, war and slavery have been (and in many places still are) commonplace and normalised.

When we go deeper into the Womb we uncover the memory the original trauma of mankind – the memory of being  uprooted from our rightful sovereign and abundant relationship to the Earth and each other (see “The Fall” by Steve Taylor for a fuller historical description of this trauma). The Womb remembers this and this memory is encoded in our bodies at a cellular level.

The way that we can manifest our Womb trauma can include:

  • Unhealthy or abusive sexual relationships, and low sexual or physical drive and self-esteem
  • Being overly mind or intellect driven or “spaced out” and ungrounded
  • Physical illness in the Womb area including (in women) fibroids, endometriosis and (in men) prostate cancer

How We Avoid our Womb Trauma

The pain in the Womb can be so deep that many of us are unconsciously avoiding the pain of the Womb trauma within us. It feels unsafe to arrive in this deep centre of consciousness and power because doing so may open a Pandora´s box of unresolved emotions and energies.  We may unconsciously employ all sorts of strategies for “trauma avoidance” which compound our lack of manifestation power and leave us personally and physically ungrounded. These strategies include:

  • Adopting spiritual practices that keep us centred in our “higher” centres of consciousness but disconnected from our physical bodies
  • Absorbing ourselves in information, theories and ideas or being addicted to screens and technology
  • Avoiding dealing with key issues in our lives including our physical health, sexual relationships and wealth

In my practice I have met very few adult humans who are naturally in full conscious contact with their Womb and therefore harnessing their full creative power through a grounded connection to their sexuality, their bodies and the Earth. I have seen Womb trauma play out in manifold ways in both women and men at all ages and from all walks of life.

It´s Time to Heal Our Womb Power

However the good news is that there´s never been a better time to heal our past traumas including our Womb trauma. The individual and collective wounds that may have overwhelmed us in this lifetime and are also embedded within us from our ancestral lines are now coming to the surface – not to re-traumatise us – but to be healed. We can harness the power of our Hearts and Higher Selves to bring ourselves the deep love and wisdom that is needed to heal our deepest wounds.

Ultimately the Womb begins to heal when we hold a clear intention to heal the traumas she holds at the physical, emotional, mental and energetic levels. We need to firmly commit to arriving in this deep part of ourselves however uncomfortable that journey may be. It will require us to acknowledge the ancient pain, distortion and disconnection that we have suffered for millennia upon this planet.

However, when we dive into ourselves and complete healing Womb trauma at the subtle and cellular levels the rewards are vast and in fact endless. We are gifted with a vital sense of embodiment and power in our lives. We reprogram ourselves in our sexual and intimate relationships. We begin to harness our true creative gifts. We reconnect to our sense of fundamental security and belonging on Earth.

Healing the stored trauma of the Womb and deepening into this centre of power is the next crucial step towards declaring our human sovereignty as creator beings. Because once we learn to hold our higher vision and our love for life then our next step will be to create the healing and changes where they are most needed – here and now in our every day lives on the physical plane of our beloved planet.

Source:wakeup-world.com