“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.”