Lead investigator David C. Whiteman, MBBS, PhD, Cancer Control Group, QIMR Berghofer Medical Research Institute, and Faculty of Medicine, The University of Queensland, Brisbane, Australia, explains, “There has been a general observation in numerous populations that melanomas appear to arise at different rates in men and women. We decided to investigate this observation rigorously and assess whether these differences have been constant through time or across generations by using large-scale data from population registries to investigate long-term melanoma trends in men and women.

The research team analyzed more than 40 years of melanoma data from Queensland, Australia, the USA, and Scotland. These three populations were chosen because historically they have had high (Queensland), moderate (USA), and low (Scotland) rates of melanoma. Over time, the rates of melanoma increased in all three populations, especially among women. In women in all populations, melanomas arise most commonly on the limbs, whereas in men, melanomas arise most commonly on the trunk and head and neck. In both sexes, there has been a steady increase in melanomas on the head and neck with increasing age.

Researchers found that in virtually all investigated populations, women experience higher rates of melanoma than men in early life (up to age ~45 years), but men develop melanomas at higher rates than women later in life (from ages ≥65 years). Furthermore, these sex-specific trends reflect complex patterns of incidence across body sites that vary consistently with age. Thus, in early life, women experience higher rates of lower limb melanomas than men, which persists into older ages. Also, on the upper limbs, women experience substantially higher rates than men from young ages until middle age (45-64 years), after which men experience higher rates. In contrast, on the head and neck and the trunk, melanomas occur at higher incidence in men than in women early in life. On all body sites, the rate at which melanoma incidence rises with age is much more rapid for men than for women.

The study confirms that men and women experience melanoma in different ways. While this is most likely driven by different patterns of sun exposure between men and women, there appear to be inherent differences in the ways in which melanomas develop at different body sites in women compared with men. Understanding the underlying biological differences could provide important clues about the etiology of this enigmatic cancer.

Dr. Whiteman concludes, “Invasive melanomas are potentially lethal cancers that are increasing rapidly in incidence. We need to understand how these cancers arise, and what drives their development, if we are to find better ways to prevent them. Studies like this one suggest that we may need to target our prevention efforts differently for men and women if we are to be effective in our attempts to control this cancer.”

There is growing scientific and public interest in the AMOC, a three-dimensional system of ocean currents that act as a “conveyer belt” to distribute heat, salt, nutrients, and carbon dioxide across the world’s oceans. Changes in the AMOC’s strength could impact global and regional climate, weather, sea level, precipitation patterns, and marine ecosystems.

In this research, measurements of the Florida Current were corrected for the secular change in the geomagnetic field to find that the Florida Current, one of the fastest currents in the ocean and an important part of the AMOC, has remained remarkably stable over the past 40 years.

The study published in the journal Nature Communications, the scientists reassessed the 40-year record of the Florida Current volume transport measured on a decommissioned submarine telecommunications cable in the Florida Straits, which spans the seafloor between Florida and the Bahamas. Due to the Earth’s magnetic field, as salt ions in the seawater are transported by the Florida Current over the cable, a measurable voltage is induced in the cable. The cable measurements were analyzed together with measurements from regular hydrographic surveys that directly measure the Florida Current volume transport and water mass properties. In addition, the transport was inferred from cross-stream sea level differences measured by altimetry satellites.

“This study does not refute the potential slowdown of AMOC, it shows that the Florida Current, one of the key components of the AMOC in the subtropical North Atlantic, has remained steady over the more than 40 years of observations,” said Denis Volkov, lead author of the study and a scientist at CIMAS which is based at the Rosenstiel School. “With the corrected and updated Florida Current transport time series, the negative tendency in the AMOC transport is indeed reduced, but it is not gone completely. The existing observational record is just starting to resolve interdecadal variability, and we need many more years of sustained monitoring to confirm if a long-term AMOC decline is happening.”

Understanding the state of the Florida Current is very important for developing coastal sea level forecast systems, assessing local weather and ecosystem and societal impacts.

Since 1982, NOAA’s Western Boundary Time Series (WBTS) project and its predecessors have monitored the transport of the Florida Current between Florida and the Bahamas at 27°N using a 120-km long submarine cable paired with regular hydrographic cruises in the Florida Straits. This nearly continuous monitoring has provided the longest observational record of a boundary current in existence. Beginning in 2004, NOAA’s WBTS project partnered with the United Kingdom’s Rapid Climate Change program (RAPID) and the University of Miami’s Meridional Overturning Circulation and Heatflux Array (MOCHA) programs to establish the first trans basin AMOC observing array at about 26.5N.

The study was supported by NOAA ‘s Global Ocean Monitoring and Observing program (grant #100007298), NOAA’s Climate Variability and Predictability program (grant #NA20OAR4310407), Natural Environment Research Council (grants #NE/Y003551/1 and NE/Y005589/1) and the National Science Foundation (grants #OCE-1332978 and #OCE-1926008).

The report, published in The Lancet Planetary Health, outlines how cities and businesses have the power to play a crucial role and become the “stewards” of critical Earth systems by demonstrating how they can reduce their environmental impact on the planet. The report summarises key findings of phase one of Earth Commission, founded in 2019 with a team of 18 globally esteemed interdisciplinary scholars as commissioners, involving more than 40 researchers in various working groups.

The report builds on the Safe and Just Earth System Boundaries report published in Nature last year, which found that most of the vital limits within which people and the planet can thrive have been surpassed.

One of three lead authors, Distinguished Professor Xuemei Bai, from ANU, who led the working group on Translation, said that companies and cities have the means to act and drastically transform and reduce pressure on the planet.

“Companies and cities have a huge potential to make a difference, especially if they work towards the same goal, which is to ensure the planet can provide for everyone long-term,” she said.

“They are more nimble and flexible than states, and can reduce their pressure on the planet by setting science-based targets in line with our findings.”

Professor Stuart Bunn, from Griffith University, co-led one of the working groups, which focused on the boundaries of freshwater and nutrient pollution.

The report found the planet’s ability to provide and protect is being stretched past its limits, although it remains possible for humans to escape poverty and harm caused by Earth’s system change, if urgent action is taken.

It found the only way to provide for everyone and ensure societies, businesses and economies thrive without destabilising the planet is to reduce inequalities in how critical Earth system resources, such as freshwater and nutrients, are accessed and used, and how responsibilities, such as reducing carbon emission, are shared, alongside economic and technological transformation.

By 2050, unless urgent transformations are made, the researchers argue that Earth’s climate will deteriorate to the point where there will be no “safe and just space” left.

That means that even if everyone on the planet only had access to the resources necessary for a basic standard of living in 2050, the Earth would still be outside the climate boundary.

The researchers say earth systems face the risk of crossing dangerous tipping points, which would cause further significant harm to people around the world unless energy, food and urban systems are urgently transformed.

The paper outlines a series of recommendations to ensure Earth’s climate remains within this so-called “safe and just space.”

• Firstly, a well-coordinated, intentional effort between policymakers, businesses, civil society and communities can push for changes in how we run the economy and find new policies and funding mechanisms that can address inequality whilst reducing pressure on nature and climate.

• Secondly, fundamental to the transformation is more efficient and effective management, sharing and usage of resources at every level of society including addressing the excessconsumption of some communities, which limits access to basic resources for those whoneed them the most.

• Thirdly, investment in sustainable and affordable technologies is essential to help us use fewer resources and to reopen the safe and just space for all, particularly where there is little or no space left.

The report has been published in The Lancet Planetary Health. It is co-authored by more than 60 leading natural and social scientists from across the globe.

The Duffy-null phenotype results in relatively lower levels of white blood cells called neutrophils when measured in the blood. This is not because they have less neutrophils overall, but because they are more frequently located in other body tissues. Tests that restrict clinical trial eligibility to patients with certain blood levels of neutrophils may therefore be unfairly discriminating against patients who could potentially benefit from trial therapies.

The failure to account for Duffy-null phenotype also means that recommendations for many standard cancer drugs inappropriately call for less-effective doses for some individuals, researchers say.

Tests that count neutrophils in a blood sample are performed to ensure that patients can safely be treated with chemotherapy or other anti-cancer drugs. Levels of neutrophils, white blood cells that kill bacteria and other foreign microbes, are often reduced by cancer drugs, potentially raising the risk of infection. For patients to qualify for a clinical trial or a standard dose of many cancer drugs, their neutrophil levels need to be above a certain threshold to ensure they will retain enough of these cells following treatment.

The threshold was established by studies conducted primarily in patients of European descent who rarely have the Duffy-null phenotype. Many healthy people with the Duffy-null phenotype (mostly people of African and Middle Eastern ancestry), however, normally have lower levels of neutrophils in their blood and relatively higher levels in their other tissues.

“Natural variation in neutrophil counts between people of different ancestry has been historically described by the inaccurate and now-outdated diagnosis ‘benign ethnic neutropenia,'” says Stephen Hibbs of Queen Mary University of London, who led the study, published today by JAMA Network Open, and for which Dana-Farber’s Andrew Hantel, MD is senior author. “But since this variation was discovered to be caused by the Duffy null phenotype, we need to re-examine the ways in which neutrophil count misinterpretation can affect patient care.”

“People with the Duffy-null phenotype are equally able to fight off infections compared to others,” Hantel says. “The concern is that they’ve been excluded from clinical trials because the neutrophil blood levels that are normal for them can fall below the cut-off points for trial participation. In this study, we explored the extent to which this occurs.”

The researchers examined participation criteria for 289 major phase III trials of drugs for the five most prevalent cancers in the United States and United Kingdom: prostate, breast, colorectal, and lung cancer, and melanoma. The drugs included chemotherapy agents, targeted therapies, and hormonal therapies (which generally don’t decrease neutrophil levels).

They found that 76.5% of the trials excluded patients whose blood neutrophil counts were in the normal range for people with the Duffy-null phenotype. The trials with the highest exclusion rate — 86.4% — were for patients with colorectal cancer. Even trials of hormonal cancer therapies — which generally don’t decrease neutrophil levels — had a significant exclusion rate.

The researchers also examined the extent to which clinical trial protocols require that drug doses be modified for patients with lower neutrophil counts.

“The treatment guidelines set by the National Comprehensive Cancer Network, or NCCN, are based on the clinical trials in which those drugs were tested,” Hantel explains. “If a trial stipulates that the dosage should be lowered or delayed if a patient’s blood neutrophil count is below a certain level, doctors often use those modifications once the drug is approved as standard therapy. We know that in many cases, survival rates are lower for patients who receive lowered or delayed doses.”

The researchers reviewed 71 clinical trials that led to NCCN recommended treatment regimens. They found that more than half required reducing the drug dose, delaying its administration, or stopping it if a participant’s neutrophil count fell below a level that was still normal for people with the Duffy null phenotype. When they looked at recommended changed based on individual Food and Drug Administration labels for each therapy used, a similar rate of dose changes was seen.

“The effect of these recommendations is to inappropriately reduce the intensity of treatment for patients who would likely tolerate regular doses,” Hantel says.

Based on their findings, the researchers recommend that clinical trials of cancer drugs allow entry to patients with lower, but normal-for-them neutrophil counts. “Everyone being screened for trial entry should be tested for the Duffy-null phenotype. If they are Duffy-null and their counts are in the reference range for that group, they should be admitted,” Hantel remarks.

For current and future trials, the same principle should be used in determining whether trial participants require lower or delayed doses: people with Duffy-null phenotype whose neutrophils are in their healthy range should be eligible for full doses of the study drug. For trials that have already been completed, follow-up studies are needed to determine if administering full doses to people with Duffy-null phenotype and lower neutrophils counts are safe and effective, researchers say.

“Health inequity in cancer treatment and research has many causes, and some are more difficult to address than others. Neutrophil criteria for clinical trials and dose modifications are a hidden contributor to inequity that can be rectified. Now, action to amend these criteria is needed to ensure Duffy-null patients are not disadvantaged,” said Hibbs.

The study was funded by the National Institutes of Health, the American Society for Clinical Oncology, and the Wellcome Trust.