“If these treatments are approved by the Food and Drug Administration, our results will be practice changing,” said Stephen Freedland, MD, associate director for Training and Education and the Warschaw, Robertson, Law Families Chair in Prostate Cancer at Cedars-Sinai, and lead author of the study. “In the study, both of these new options improved metastasis-free survival while preserving quality of life.”

Cancer of the prostate, a walnut-sized gland that helps make semen, will be diagnosed in 288,300 men in the U.S. in 2023, according to American Cancer Society estimates. For some, treatment may never be needed because they have a slow-growing form of the disease, but those with more aggressive prostate cancer are often first treated with surgery or radiation therapy.

“Unfortunately, in about a third of those patients, the cancer recurs within 10 years,” Freedland said.

Patients with aggressive recurrence are treated with androgen deprivation therapy (ADT), also known as hormone therapy, which reduces the patient’s production of the male sex hormone testosterone. Testosterone helps prostate cancer cells grow and spread, and the hormone therapy effectively reduces the growth-stimulating effects. But Freedland said ADT has two downsides: It doesn’t completely eliminate testosterone, and it can cause many side effects.

“When you go on ADT, the testosterone level in the blood is reduced, but not completely eliminated,” Freedland said. “And the concern is that the testosterone that remains may still be enough to stimulate tumor growth. Also, patients don’t love the idea of being on hormones.”

In this study of 1,068 prostate cancer patients from 244 sites in 17 countries, Freedland and fellow investigators tested two experimental interventions — one to address each of these issues.

In the randomized clinical trial, one-third of the patients received ADT plus a medication called enzalutamide, which blocks the effects of testosterone. Enzalutamide keeps any testosterone remaining in the blood from stimulating the growth of cancer cells.

Another third of the patients received enzalutamide alone. This option relied on the medication to block the effects of testosterone even though testosterone levels in the patients’ blood were not reduced.

“We wanted to see whether enzalutamide on its own was so effective that we didn’t need the ADT,” Freedland said.

The final group of patients received ADT alone, which is the current standard treatment.

Investigators found that the combination of ADT plus enzalutamide reduced the risk of metastasis or death by 58% over ADT alone. They found that enzalutamide alone reduced the risk of metastasis or death by 37% over ADT alone. Both treatments maintained quality of life relative to the ADT alone.

“While the combination therapy offers greater risk reduction, some men might prefer enzalutamide alone. It does a good job of preventing cancer spread or death, with different side effects that may be more acceptable for some men,” Freedland said.

The next step is for the makers of enzalutamide to apply for FDA approval, so the experimental therapy can come into wide use, Freedland said.

“Optimizing therapy for patients with aggressive recurrence after their prostate cancer is initially treated has been an unmet need,” said Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer and the PHASE ONE Distinguished Chair. “The results of this trial point the way to two options which the study showed were more effective than current standard of care, giving these patients and their providers the opportunity to choose a potentially improved course of therapy that best meets their needs.”

Funding: The study was sponsored by Pfizer and Astellas Pharma, the co-developers of enzalutamide.

Long considered to be a myth, rogue waves strike from comparably calm surroundings, smashing oil rigs and ships in their path. Unlike tsunamis, rogue waves form by the chance combination of smaller waves in the ocean, creating an event that is very rare.

There has been a lot of research into rogue waves in recent years but now, for the first time, scientists are showing how this can be applied on a much smaller scale — nanometrically. A nanometre is a million times smaller than the thickness of the page of a book. This is a completely new approach to the behaviour of liquids on a nanometric scale, published as a Letter in Physical Review Fluids.

The holes and bumps caused by rogue waves can be manipulated to spontaneously produce patterns and structures for use in nano-manufacturing (manufacturing on a scale one-billionth of a metre). For example, patterns formed that rupture liquid films can be used to build micro-electronic circuits, which could be used in the production of low-cost components of solar cells. Furthermore, the behaviour of thin liquid layers could help to explain why millions of people worldwide suffer from dry eye. This occurs when the tear film covering the eye ruptures.

Through direct simulations of molecules and new mathematical models, the study led by the University of Warwick’s Mathematics Institute discovered how nanoscopic layers of liquid behave in counterintuitive ways. Whilst a spilt layer of coffee on a table may sit apparently motionless, at the nanoscale the chaotic motion of molecules creates random waves on a liquid’s surface. A rare event occurs when these waves conspire to create a large ‘rogue nanowave’ that bursts through the layer and creates a hole. The new theory explains both how and when this hole is formed, giving new insight into a previously unpredictable effect, by taking their large oceanic cousins as a mathematical blueprint.

The team of researchers is excited about the potential of this research in different industries; the applications are far-reaching.

Professor James Sprittles, Mathematics Institute, University of Warwick, said: “We were excited to discover that mathematical models originally developed for quantum physics and recently applied to predict rogue ocean waves are crucial for predicting the stability of nanoscopic layers of liquid.

“In future, we hope that the theory can be exploited to enable an array of nano-technologies, where manipulating when and how layers rupture is crucial. There might also be applications in related areas, such as the behaviour of emulsions, e.g. in foods or paints, where the stability of thin liquid films dictates their shelf-life.”

Water temperature is an important control for all the physical, chemical, and biological processes in rivers. It is particularly important for organisms that cannot regulate their own body temperature, such as fish. River temperature is important for human health and industrial, domestic, and recreational uses by people.

Scientists have identified three primary mechanisms that drive river water temperature increases during droughts: atmospheric energy inputs; physical habitat influences (shading and river channel shapes controlling flow); and the contributions of different water sources — groundwater tends to cool rivers in summer.

A review published in Hydrological Processes, led by University of Birmingham in collaboration with the University of Nottingham and the Scottish Government’s Marine Directorate, highlights that intense shortwave radiation during hot and dry periods is likely to be the biggest factor of high river water temperatures.

This combined with declining water levels and volumes, and slower flow velocities during droughts will warm up waters more quickly. However, the authors emphasise that cooling effects from groundwater inputs, channel shading and evaporation can offset high temperatures in certain circumstances.

Co-author David Hannah, Professor of Hydrology and UNESCO Chair in Water Sciences at the University of Birmingham, commented: “Rising river water temperatures can have significant and often detrimental implications for aquatic life, impacting both individual species and entire ecosystems.

“Drought conditions often coincide with high atmospheric temperatures and such trends will become more intense and frequent with climate change — with major implications for river water temperatures due to the combination of intense solar radiation and lower (and slower) water flows.

“However, certain management interventions such as riverside planting, and river restoration initiatives — including recreating natural channel forms and reconnecting groundwaters — could help to offset high thermal extremes during droughts if interventions are well targeted.”

The researchers note that more holistic, catchment-wide approaches to river restoration are required that consider how high river water temperature extremes can be offset while delivering other environmental and ecological benefits. The study authors call for new scientific approaches examining how the processes operating across the three mechanisms they have identified interact — helping to better inform models capable of estimating where and when high river thermal extremes are likely to occur during droughts.

Lead-author Dr James White, from the University of Birmingham, commented: “Our work highlights critical future research questions that will help us to better model river water temperature dynamics during droughts — helping river managers to work out how thermal extremes could be better managed through mitigation and adaptation strategies.”

The findings, published in the peer-reviewed journal Circulation, could lead to new therapies for heart disease and cardiac damage.

The collaborative effort with Duke-NUS Medical School in Singapore and other institutions identified an RNA splicing regulator named RBFox1, which was considerably more prevalent in adult heart cells than in newborns, based on a preclinical model. The sharp rise in RBFox1 during the maturation of heart cells was also confirmed through analyses of existing single-cell data.

“This is the first piece of evidence suggesting that RNA splicing control plays a vital role in postnatal heart cell maturation,” said study lead Jijun Huang, who conducted this research during his postdoctoral training in anesthesiology at UCLA. “While RBFox1 alone may not be sufficient to push mature fetal heart muscle cells all the way to fully matured adult cells, our findings uncover a new RNA-based internal network that can substantially drive this maturation process beyond other available approaches.”

The transformation of heart muscle cells from birth until they reach full maturity involves significant shifts in their structure, functionality, and physiological properties. The mechanisms overseeing this comprehensive maturation have been poorly understood thus far.

Although the precise mechanics associating RBFox1-mediated RNA splicing with ensuing maturation procedures and characteristics still require further exploration, the study provides proof-of-concept that modulating RNA splicing can profoundly affect cardiomyocyte maturation. This newfound knowledge hints at future therapeutic applications, pending additional research to expand upon these initial findings.

“For the first time, we’ve shown that by merely altering RNA splicing, we can encourage the significant maturation of heart cells derived from human stem cells,” said senior author Yibin Wang, director of the Cardiovascular & Metabolic Disorders Program at Duke-NUS. “These findings present a potential molecular approach to enhance heart cell maturation, which could address a major challenge in the domains of cardiac regenerative therapy and disease modeling.”

The study was funded by an American Heart Association Postdoctoral Award (18POST33990469) the National Institutes of Health (R01 HL148714, R00 HL141626) and a Department of Defense Award (PR171540).

Study co-authors are Josh Lee, Christoph Rau, Dr. Arash Pezhouman, Tomohiro Yokota, Hiromi Miwa, Tsz Kin Kong, Shreya Udani, Chen Gao, Linsey Stiles, Dr. Orian Shirihai, Dr. Reza Ardehali, and Dino Di Carlo of UCLA and others from Baylor College of Medicine, Vanderbilt University School of Medicine, Meharry Medical College, Forcyte Biotechnologies, the University of Cincinnati, the University of North Carolina, and the Agency for Science, Technology and Research (A*STAR) in Singapore.

While good fortune and circumstances can play a part, new research reveals that when it comes to start-up success, a founder’s personality — or the combined personalities of the founding team — is paramount. The study, published today in Scientific Reports, shows founders of successful start-ups have personality traits that differ significantly from the rest of the population — and that these traits are more important for success than many other factors.

“We find that personality traits don’t simply matter for start-ups — they are critical to elevating the chances of success,” says Paul X. McCarthy, lead author of the study and adjunct professor at UNSW Sydney. “A small number of astute venture capitalists have suspected this for some time, but now we have the data to demonstrate this is the case.”

Personality key to start-up success

For the study, the team, which also included researchers from Oxford Internet Institute, the University of Oxford, University of Technology Sydney (UTS), and the University of Melbourne, inferred the personality profiles of the founders of more than 21,000 founder-led companies from language and activity in their publicly available Twitter accounts using a machine learning algorithm. The algorithm could distinguish successful start-up founders with 82.5 per cent accuracy.

They then correlated the personality profiles to data from the largest directory on start-ups in the world, Crunchbase, to determine whether certain founder personalities and their combinations in cofounded teams relate to start-up success — if the company had been acquired, if they acquired another company, or listed on a public stock exchange.

The researchers found that successful start-up founders’ core Big Five personality traits — the widely accepted model of human personality measuring openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism — significantly differ from that of the population at large.

The facets distinguishing successful entrepreneurs include a preference for variety, novelty and starting new things (openness to adventure), like being the centre of attention (lower levels of modesty) and being exuberant (high activity levels).

“The greater presence of these and other personality traits in founders are related to higher chances of success,” says Dr Fabian Braesemann, co-author of the study from the Oxford Internet Institute, University of Oxford.

“We can see how this plays out in many notable examples,” Prof. McCarthy says. “The adventurousness and openness to experience of Melanie Perkins, the assertiveness and confidence of Steve Jobs, the exuberance and energy of Richard Branson, the calm under pressure Jeff Bezos, the discipline and focus of Mark Zuckerberg, and the trustworthiness of Larry Page and Sergey Brin underpin their company’s success.”

Dr. Marian-Andrei Rizoiu, a senior lecturer leading the Behavioural Data Science lab at UTS says: “We used machine learning and a variety of advanced statistical tests to reveal that there is not just one type of successful founder but indeed six types.”

“Our findings clearly show there’s not one ideal ‘founder-type’ personality,”says Associate Professor Margaret (Peggy) Kern, senior author of the study from the University of Melbourne.”Instead, the Big Five personality traits of successful start-up founders, which we can break down further across 30 dimensions, reveal six distinct types: fighters, operators, accomplishers, leaders, engineers and developers.”

While personality is crucial, Prof. McCarthy says many other factors still play a role in the ultimate success of founder-led companies, including luck, timing, and connections.

“Startups, especially during their earliest stages, before there’s any demonstrable customer traction rely to a large extent on social proof,” Prof. McCarthy says. “In other words, trust in the founders, which can sometimes present barriers for many groups including women, people who have not worked in tech before, or attended prestigious universities.”

Melanie Perkins, the co-founder of design powerhouse Canva, faced all three of these hurdles in the early days of the company, and was turned down by more than 100 investors before securing the funding they needed to build their product. In an interview, she described herself as “determined, stubborn and adventurous.”

Large, personality-diverse founding teams

The researchers also undertook multifactor modelling to measure the relative significance of personality on the likelihood of success versus other firm-level variables. They discovered a founder’s personality was more predictive of success than the industry (5 times) and the age of the start-up (2 times).

They also found start-ups with diverse and specific combinations of founder types — an adventurous’ leader’, an imaginative ‘engineer’, and an extroverted ‘developer’, for example — had significantly higher odds of success.

“Firms with three or more founders are more than twice as likely to succeed than solo-founded start-ups,” says Dr Fabian Stephany, co-author of the study from the Oxford Internet Institute, University of Oxford. “Furthermore, those with diverse combinations of types of founders have eight to ten times more chance of success than single founder organisations.”

“While all start-ups are high risk, the risk becomes lower with more founders, particularly if they have distinct personality traits,” Prof. McCarthy says. “Largely founding a start-up is a team sport and now we can see clearly that having complementary personalities in the foundation team has an outsized impact on the venture’s likelihood of success, which we’ve termed the Ensemble Theory of Success.”

The researchers say the findings have critical applications for entrepreneurs, investors, and policymakers and can inform thecreation of more resilient start-ups capable of more significant innovation and impact.

“By understanding the impact of founder personalities on start-up success, we can make better decisions about which start-ups to support and help fledgling companies form foundation teams with the best chances of success,” Prof. McCarthy says.

OpenAI cofounder Sam Altman recognised this when he led the storied start-up accelerator, Y-Combinator, observing in a lecture at Stanford University that “cofounder relationships are among the most important in the entire company.”

The findings also have implications beyond founder-led companies, highlighting the benefits of personality diversity in teams. For example, many fields, such as construction, engineering and the film industry, rely on project-based, cross-functional teams that are often new ventures and share many characteristics of start-ups.

“There are lessons here for organisations of all kinds about the importance of having a diversity of personality types in teams, which can lead to stronger performance and impact,” Prof. McCarthy says.

Just as occupation-personality maps derived from data can provide career guidance tools, information about successful entrepreneurs’ personality traits can also help people decide whether becoming a founder may be a good move for them.

“It’s not part of this study, but we estimate 8 per cent of people worldwide may have personality traits that could make them successful founders,” Prof. McCarthy says. “Likely, many are not in the entrepreneurial field right now.

“Identifying these misfits and people in roles unsuited to their personalities will be the focus of some of our follow-up studies.”