Researchers find secret to achieve goals

Researchers have provided new insights into why people often make unrealistic plans that are doomed to fail.

The study analysed the complex relationship between reward and effort in achieving goals and identified 2 critical stages in the decision-making process.

The researchers found that when people first decide what to do they are motivated by rewards. However, once they begin to put plans into action, their focus turns to the difficulty of the effort they need to put in.

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They suggest the key to achievable aims to consider the effort needed when deciding what to do, and then remembering to focus on the rewards once the time comes to out the effort in.

We've found that there isn't a direct relationship between the amount of reward that is at stake and the amount of effort people actually put in, said study lead author.

This is because when we make choices about what effort to put in, we are motivated by the rewards we expect to get back. But at that point at which we come actually do what we had said we would do, we focus on the level of effort we've to actually put in rather than the rewards we hoped we would get, the author added.

To investigate the relationship between effort and reward, the research team designed experiments involving 2 different forms of effort, physical and mental.

Physical effort was measured by the action of squeezing a joystick whilst the ability for participants to solve simple mathematical equations tested mental effort.

Study participants were presented with different options that combined either high or low effort with high or low financial rewards, adn asked to select which one to pursue.

The research found that when selecting options participants were guided by the level of financial reward offered , but on execution of the task their performance was determined by the actual amount of effort they needed to exert.

The team observed that the results were similar for both the physical and mental effort-based experiments.

Common sense suggests the amount of effort we put into a task directly relates to the level of reward we expect in return , the author said.

However, building psychological and economic evidence indicated that often high rewards are not enough to ensure people put in the effort they need to achieve their targets, the author added.

Scientists identify 'modifier gene' that determines severity of inherited kidney disease

Scientists have developed a new way to understand complex genetic diseases and have identified a gene that modifies the severity of inherited kidney disease, paving the way for personalised treatments.

Experts at Newcastle University, UK, have shown that the rate of kidney disease in people with Joubert syndrome is determined by the genetic makeup of the individual and each patient may respond differently to treatment.

Joubert syndrome is a complex disorder, affecting approximately one in 80,000 newborns, causing varying degrees of physical, mental and sometimes visual impairments. It is often associated with severe kidney disease that requires dialysis and ultimately transplantation.

The study, published online in the Proceedings of the National Academy of Sciences, is the first time that an explanation has been given for the difference of disease progression in Joubert syndrome patients.

Significant breakthrough

The Newcastle research has identified a second gene called BSND - a 'modifier gene' - which determines the severity of kidney disease in patients with CEP290 mutations of Joubert syndrome.

It has been assumed that these modifier genes exist, but they have never been found before in rare genetic conditions until now.

Professor John Sayer and Dr Colin Miles, from the Translational and Clinical Research Institute, Newcastle University, led the Medical Research Council-funded research.

Professor Sayer said: "We have shown, using mouse and human DNA samples, that BSND is a modifier gene for the severity of kidney disease in Joubert syndrome.

"This is the first time that a modifier gene for inherited kidney disease has been identified, and this information will improve diagnoses and will be used to develop therapies to reduce the severity of kidney disease in affected patients.

"Our research is a major step forwards and, in the future, we may be able to offer a therapy that switches on the protective modifier gene and reduces the development of genetic kidney disease.

"This work paves the way towards personalised therapies in patients with the inherited kidney disease."

The international study used mouse models and DNA samples from patients with Joubert syndrome to progress the research.

Scientists used mouse models of disease and genetic manipulation to see how the kidney disease responded to modifier gene manipulation, cross-referenced with DNA sequencing data from patients around the world to prove the modifier gene was relevant in humans.

Challenging disease
Professor Sayer, a Consultant Nephrologist at Newcastle Hospitals NHS Foundation Trust, said: "The treatment of genetic kidney disease is challenging, as this requires both the correction of the underlying gene defect and the delivery of the treatment.

"We have shown that the kidney disease in a mouse can be dramatically changed by switching on or off a modifier gene.

"This will mean that we can use this information to carry out treatments, including genetic therapies, to lessen the effects of inherited kidney diseases, such as Joubert syndrome.

"We are testing these treatments further in our model systems before we move into patient studies."

Within the next three years, research will start to test treatment of patients with modifier genes in the hope of developing personalised treatment plans.
Patient story

Siblings Emma, 11, and Ben Buckley, eight, have Joubert syndrome and both developed kidney failure before the age of eight.

They were diagnosed with Joubert syndrome from a few months of age and both have required dialysis and a kidney transplant.

They suffer from a range of medical issues due to Joubert syndrome, including visual impairment, communication problems and developmental delay.

The two children, of Whitley Bay, North Tyneside, have been instrumental in helping further the research over the years, allowing the Newcastle scientists to study the mutation in detail.

Parents Leanne and Michael say they welcome the findings of the Newcastle University-led study as it will help to give patients a chance of preventing kidney failure in the future.

Leanne said: "It is very important that research is done into Joubert syndrome and the linked kidney damage, as this will hopefully prevent patients in the future needing a kidney transplant.

"All throughout Ben and Emma's lives, they have lived with the effects of Joubert syndrome and scientists found they had a problem with the CEP290 gene.

"Both Ben and Emma have needed dialysis and kidney transplants because of their kidney problems and I would like to hope this research will help prevent kidney failure for other affected children.

"We were happy for Ben and Emma to provide samples for the study as anything that helps further understanding into the condition is well worth doing, so it's great to see the study's positive results."

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Baby gut study finds bacteria different after C-section births

A huge study of babies' stool samples has found key differences between infants born vaginally and via Caesarean section, offering clues about the development of the human immune system, researchers said on Wednesday.

Vaginally born babies got most of their gut bacteria from their mother, but C-section babies did not and had more bacteria linked to the hospital around them, the study found.

It is not clear what impact the difference may have on children's future health, and the findings should not deter women from having C-section births, the scientists leading the work said.

But the so-called "baby biome" project - the world's largest such study - had opened a window on a little-understood stage in the development of human immunity, they added.

"The first weeks of life are a critical window of development of the baby's immune system, but we know very little about it," said Peter Brocklehurst, a Birmingham University professor who co-led the study.

"We need to follow up ... these babies as they grow to see if early differences in the microbiome lead to any health issues."

The gut microbiome is a complex ecosystem of millions of microbes and is thought by scientists to be important for how the immune system develops.

Previous research has suggested that a lack of exposure to some microbes in early life is implicated in autoimmune diseases such as asthma, allergies and diabetes.

But scientists have not yet been able to work out how important the initial gut microbiome - or "baby biome" - is to future immunity and health, or how a baby's microbiome develops, or what happens to it with different modes of birth.

In this research, published in the journal Nature, scientists from University College London, Wellcome Sanger Institute and Birmingham University used DNA sequencing to analyse more than 1,600 gut bacteria samples from 175 mothers and almost 600 babies.

In samples from mothers and from the babies at four, seven and 21 days old, the team found there was a significant difference between the two delivery methods - with vaginally delivered babies having many more health-associated bacteria from their mothers than babies born by Caesarean.

In place of some of the mother's bacteria, the C-section babies had more bacteria typically found in hospitals, the researchers said, and these bugs were also more likely to be drug-resistant.

"At the moment we don't understand the long-term consequences of this," Brocklehurst said at a briefing about the results. "It's clearly complex and we're only just beginning to scratch the surface."

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Drug to replace chemotherapy may reshape cancer care

A class of drugs is emerging that can attack cancer cells in the body without damaging surrounding healthy ones. They have the potential to replace chemotherapy and its disruptive side effects, reshaping the future of cancer care.

The complex biological medicines, called antibody drug conjugates (ADCs), have been in development for decades, and are now generating renewed excitement because of the success of one ADC in late-stage testing, a breast cancer treatment called DS-8201.

The fervor over ADCs is such that AstraZeneca Plc in March agreed to pay as much as $6.9 billion to jointly develop DS-8201 with Japan’s Daiichi Sankyo Co., the British drugmaker’s biggest deal in more than a decade. The investment was widely seen to be a validation of DS-8201’s potential — and the ADC class of drugs as a whole — as an alternative for chemotherapy, the most widely used treatment, for some types of cancer.

DS-8201, which will be filed for U.S. approval by the end of September, is so well-regarded that some analysts already predict it will surpass the $7 billion in annual sales for Roche Holding AG’s breast cancer drug Herceptin, which it aims to replace.

“DS-8201 may become one of the largest cancer biologic drugs,’’ said Caroline Stewart, an analyst at Bloomberg Intelligence who estimates sales of the drug to eventually approach $12 billion globally. That’s a level that has been attained by only a handful of biologic drugs, which are produced from extracts of other living organisms.

Analysts say DS-8201 could triple the number of patients who get powerful targeted treatment for breast cancer, the most common tumor in women that kills more than half a million annually. As importantly, its ability to target cancer cells without affecting normal cells is a key advantage over the take-no-prisoners approach of chemotherapy.

Daiichi’s treatment has been seen to double survival time for advanced breast cancer patients to 20 months from 10, former UBS Securities Japan Co. analyst Atsushi Seki said in March. In trials, patients using DS-8201 experienced less nausea and hair loss compared with chemotherapy.

Magic bullet

DS-8201’s full potential is still years away, as it will take time for data to validate the drug’s efficacy in a wide range of patients. Still, the potential of ADCs is already jolting Big Pharma. Roche, whose Herceptin loses patent exclusivity in the U.S. this year, has added ADCs to its portfolio with its Kadcyla breast cancer treatment. Pfizer Inc. has Mylotarg, an ADC that treats myeloid leukemia.

About 56 pharmaceutical companies are developing ADC candidates, including ImmunoGen Inc. and Seattle Genetics Inc., and they could be targets for acquisitions or licensing deals from global pharmaceuticals anxious for a piece of the ADC pie, according to Cowen Inc.

“ADCs are being positioned as a chemo replacement,’’ Cowen analysts including Boris Peaker wrote in an April note. “There is significant potential for partnership activity.’’

The global ADC market was valued at $1.57 billion in 2017 and is projected to grow 26% every year through 2025 to almost $10 billion, according to a report by Grand View Research.

The concept behind ADCs was envisioned in 1900 by German Nobel laureate Paul Ehrlich, who formed the idea of a “magic bullet” in which a single toxic molecule would be delivered to attack a diseased cell without damaging surrounding healthy cells.

The actual use of ADCs began in 2000, but the interest in the sector cooled down as many failed to live up to expectations. The therapies belong to a broader category of cancer immunotherapies that include Merck & Co.’s Keytruda and Novartis AG’s CAR T-cell therapy Kymriah that harness the immune system to kill tumors.

Another level

Daiichi Sankyo’s drug takes ADCs to another level. Its advantage is that it carries eight payloads stably to cancer cells, double the number of the industry standard, said Toshinori Agatsuma, head of oncology research at Daiichi Sankyo who led a team that discovered the therapy.

“Currently available ADCs are far from being perfect technically because the payload linked to antibodies aren’t properly delivered to cancer cells,’’ said Agatsuma. “We wanted to challenge and improve that. We were a latecomer in biotech, but I knew it was an area where we could catch up, compete and win.’’

About 2.1 million women are diagnosed with breast cancer each year, according to the World Health Organization. Some 18% of cases are driven by a protein called HER2, and their first treatment is chemotherapy alongside Roche’s Herceptin and Perjeta, a related drug. While DS-8201 is currently in testing for later-stage cancer, the plan is to go up against the first-line treatment in the next two years.

“It would be transformative” if the drug were to become the sole first-line treatment, said David Fredrickson, president of AstraZeneca’s oncology business. “If we can eliminate the side effects associated with chemotherapy, that would be a tremendous benefit for women.”

Drugs like Herceptin only target high levels of HER2, and women with lower levels must rely on hormone therapy or chemotherapy. That’s where DS-8201 has the potential to serve far more patients, treating those with both higher and lower levels of HER2.

It’s different’

“We need more evidence, but my gut feeling is that DS-8201 is the most effective among existing medicines targeting HER2 positive patients, including Herceptin and chemotherapy,’’ said Shunji Takahashi, deputy director at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research, who took a part in an early-stage DS-8201 trial. He noted that interstitial pneumonia is a concern as a side effect, and needs to be monitored.

For Daiichi Sankyo, the development of DS-8201 has helped resurrect the Japanese company after it struggled for years to set a path for growth, weighed down by a failed acquisition of India’s Ranbaxy Laboratories Ltd. and a shortage of blockbuster products.

“A single drug has a potential to transform Daiichi Sankyo and I didn’t expect it a year ago,’’ SMBC Nikko Securities Inc. analyst Yasuhiro Nakazawa said. “Daiichi Sankyo had a track record of betraying market expectations with previous drug developments. But with this one, I can really feel that it’s different this time.’’

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Taking the pill could affect how well women recognise complex emotions

New European research has found that taking the oral contraceptive pill could very slightly impair a woman’s social judgement, making it more difficult to identify more complex emotions. Carried out by researchers, the new small-scale study recruited 95 healthy women, including 42 who took the pill and 53 who did not, and asked them to complete a special emotion recognition task.

The findings, showed that both groups of women were equally good at recognizing easy expressions and emotions, such as happiness and fear. 

However, women who took the pill were nearly 10 per cent worse on average in recognizing the most complex emotional expressions, such as pride and contempt, than women who didn’t take the pill.

The effect held true for both positive and negative expressions, and regardless of the type of pill taken. The team also found that a woman’s menstrual cycle phase had no effect on the differences in emotion recognition.

The researchers note that the effect was a subtle one, with senior author commenting that, "If oral contraceptives caused dramatic impairments in women’s emotion recognition, we would have probably noticed this in our everyday interactions with our partners."

"We assumed that these impairments would be very subtle, indicating that we had to test women’s emotion recognition with a task that was sensitive enough to detect such impairments. We, thus, used a very challenging emotion recognition task that required the recognition of complex emotional expressions from the eye region of faces"

Although the pill has been linked with a variety of physical effects, both good and bad, little is known about the psychological effects. However, Dr. added that the findings are in line with previous research.

"Coincidental findings suggest that oral contraceptives impair the ability to recognize emotional expressions of others, which could affect the way users initiate and maintain intimate relationships."

"Cyclic variations of estrogen and progesterone levels are known to affect women’s emotion recognition, and influence activity and connections in associated brain regions. Since oral contraceptives work by suppressing estrogen and progesterone levels, it makes sense that oral contraceptives also affect women’s emotion recognition, However, the exact mechanism underlying oral contraceptive-induced changes in women’s emotion recognition remains to be elucidated."

Further research is now needed to understand this area better says the Dr., and to help give women more detailed information about the potential effects of oral contraceptive use.

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