Eastern hemlocks are an ecologically important tree species found from eastern Canada to the Great Lakes states and south along the entire Appalachian mountain range. The hemlock woolly adelgid — an invasive insect that was introduced to North America 70 years ago and has spread along the East Coast — can kill a hemlock tree in as little as four years.

“An integrated pest management strategy is the best approach in cases like this,” says Robert Jetton, associate professor of forest health at North Carolina State University and study co-author. “Integrated pest management utilizes multiple tactics to combat insect pests and can include chemical insecticides, seed preservation, biological control, and silviculture, or managing the surrounding forest.

“This study focused on silviculture. Is there a way to actively manage a forest to improve the health of eastern hemlocks?”

The study began in 2017. Jetton and colleagues from the U.S. Department of Agriculture selected 105 eastern hemlock trees in national and state forests along the Appalachians from Maryland to Georgia. They created small or large canopy gaps around the trees by either felling or girdling the competing trees. Felling is cutting down the tree outright, while girdling refers to killing the tree by removing its access to nutrients, but not cutting it down.

The gaps around the hemlocks ranged in size from .05 to .15 acre. Small gaps were created by felling or girdling any competing tree that overlapped the hemlock’s outermost branches, or dripline. For large gaps, they created a radius around the hemlock that was equal to the dripline plus 25% of the average tree height in the stand.

For comparison, the researchers also monitored a control group which consisted of hemlocks that didn’t have canopy gaps created around them.

The researchers collected data on the trees every six months from late 2017 through early 2021. One tree had died (due to another tree falling on it), but overall, even though all of the “canopy gap” trees in the study were infested with woolly adelgid, their health had substantially improved. By comparison, the health of the control trees continued to decline.

“The major benefit of the treatment is that the trees’ crown health improved, especially in areas where we did the large fell,” Jetton says. “Crown health refers to the tree’s foliage — its color and density. With all four gap treatments, we saw that the trees continued to produce new shoot growth annually, though this effect was greatest in the large fells. This is good news because woolly adelgids feed on branch tips, so one of the first effects of infestation is that the tree stops producing new growth.”

While the treatment’s effectiveness varied by region — it was more effective in the southernmost sites (North Carolina, Georgia and Tennessee) — the researchers believe the results are encouraging.

“The canopy gaps give the trees better access to resources like water and nutrients that help them deal with the adelgid,” Jetton says. “While it doesn’t cause the adelgid population to decrease, it may be giving trees the ability to ‘outgrow’ the insect’s impact, at least temporarily.”

The study is ongoing, and the researchers plan to focus on stands of hemlocks, rather than single trees, next.

“Our study was conducted in forests where hemlocks occurred under a canopy of primarily hardwood trees, which lose their leaves in fall and winter,” says Albert Mayfield, entomologist with the USDA Forest Service and study co-author. “So, the response of hemlocks to canopy gaps might be different in pure hemlock forests, where there is more year-round shade. But our sites were very typical of the southern Appalachian forests, where hemlock trees are usually mixed with hardwood trees.”

“We see silviculture as part of the overall pest management strategy,” says Jetton. “Hopefully it will benefit biological control efforts by allowing the adelgid’s predators to establish populations, and it may decrease our use of chemicals. But the bottom line is this study shows silviculture is another tool in the toolkit to increase the survival rate of eastern hemlocks.”

The study appears in Forest Ecology and Management and was supported by the USDA Forest Service Special Technology Development Program. Albert Mayfield of the USDA Forest Service is corresponding author. NC State research associate Andy Whittier, and USDA Forest Service members Bryan Mudder, Tara Keyser, and James Rhea, also contributed to the work.

In the largest study of its kind, researchers found that including almonds in an energy restricted diet not only helped people to lose weight, but also improved their cardiometabolic health.

Examining the effects of energy restricted diets supplemented with Californian almonds or with carbohydrate- rich snacks, researchers found that both diets successfully reduced body weight by about 7kg.

Globally, more than 1.9 billion adults are overweight (650 million with obesity). In Australia, two in three people (approximately 12.5 million adults) are overweight or have obesity.

UniSA researcher Dr Sharayah Carter says the study demonstrates how nuts can support a healthy diet for weight management and cardiometabolic health.

“Nuts, like almonds, are a great snack. They’re high in protein, fibre, and packed with vitamins and minerals, but they also have a high fat content which people can associate with increased body weight,” Dr Carter says.

“Nuts contain unsaturated fats — or healthy fats — which can improve blood cholesterol levels, ease inflammation, and contribute to a healthy heart.

“In this study we examined the effects of an almond-supplemented diet with a nut-free diet to identify any influence on weight and cardiometabolic outcomes.

“Both the nut and nut free diets resulted in approximately 9.3% reduction in body weight over the trial.

“Yet the almond-supplemented diets also demonstrated statistically significant changes in some highly atherogenic lipoprotein subfractions, which may lead to improved cardiometabolic health in the longer term.

“Additionally, nuts have the added benefit of making you feel fuller for longer, which is always a pro when you’re trying to manage your weight.”

The study was funded by the Almond Board of California. It saw 106 participants complete a nine-month eating program (a three-month energy-restricted diet for weight loss, followed by a six-month energy-controlled diet for weight maintenance). In both phases, 15% of participants’ energy intake comprised unsalted whole almonds with skins (for the nut diet) or 15% carbohydrate-rich snacks — such as rice crackers or baked cereal bars (for the nut-free diet).

The trial, called INSIGhT, is still underway testing additional therapies.

“There have been many failed attempts to find better therapies for glioblastoma,” says co-first author Rifaquat Rahman, MD, a radiation oncologist at Dana-Farber. “This new trial design meets a need for a more efficient and smarter way to find new therapies.”

Patients with glioblastoma, the most common primary brain tumor, have few effective treatment options. Those with a form of the disease called MGMT unmethylated glioblastoma fare the worst and rarely respond to the standard therapy of radiation plus chemotherapy.

Traditionally, investigational therapies for glioblastoma are tested either head-to-head against standard therapy, or on their own in a single-arm trial with no control arm.

In contrast, INSIGhT (Individualized Screening Trial of Innovative Glioblastoma Therapy) uses a shared control arm to test multiple investigational therapies at one time. So far, INSIGhT has tested a control arm of standard therapy against abemaciclib (a CDK4/6 inhibitor), neratinib (an EGFR/HER2 inhibitor), and CC-115 (a DNA-PK/mTOR inhibitor).

“This design is more economical and faster than the alternative of three separate randomized phase 2 trials, which would require many more patients and a lot more resources,” says co-senior author and principal investigator Patrick Wen, MD, Director of the Center for Neuro-Oncology at Dana-Farber.

In this first analysis of results, the trial enrolled 237 patients with newly diagnosed MGMT unmethylated glioblastoma between 2017 and 2021. Initially, patients were randomly assigned to receive one of the four treatments. Each patient had an 25% chance of receiving any one of the four options.

Once underway, the trial adapts to new information. Dana-Farber statisticians led by Lorenzo Trippa, PhD, continuously apply complex statistics to learn from each patient whether the drug they are receiving is having a likely benefit. The randomization algorithms enables future patients joining the trial to have increased odds of getting the best drug for them personally.

For instance, if patients experienced toxicities or no signs of benefit from a treatment option, future patients would be less likely to receive that treatment. If another treatment option showed benefit to patients, future patients would be more likely to be assigned to that option. The algorithm also factors in biomarkers associated with a likely benefit from a given therapeutic.

This approach, called Bayesian Adaptive Randomization, reduces the number of patients exposed to therapies that are unlikely to be successful. It also helps researchers put resources into therapies with the most promise.

“We can quickly stop pursuing drugs that are not promising and at the same time find the effective drugs and move them into phase three testing,” says Wen.

At the same time, the trial has set up an infrastructure that helps researchers learn more about why patients respond or do not respond to the therapies. This is one of the first trials in neuro-oncology to require tumor genomic sequencing up-front for all patients, which helps researchers learn more about how genetic biomarkers influence responses.

“It’s a very modern, science-enabling trial,” says co-senior author Keith Ligon, MD, PhD, a Dana-Farber pathologist and Chief of the Division of Neuropathology at Brigham and Women’s Hospital.

In this first readout of the trial, patients taking abemaciclib and neratinib experienced longer progression free survival than those receiving standard therapy or CC-115. None of the therapies extended overall survival.

The trial is designed to add new treatment arms. It is currently assigning new patients to either a novel brain penetrant chemotherapy (QBS10070S), an immunotherapy regimen consisting of a tumor vaccine VBI-1901 and a PD1 antibody, or standard therapy.

“This is a dynamic, evolving trial that will continue to test new therapies that could potentially benefit patients,” says Rahman.

Testing a drug that has the potential to benefit patients with glioblastoma may be easier to do in the context of this trial because the trial is already established. Each new arm of the trial is an amendment to the trial, not a new trial itself.

“This trial is more streamlined, but it’s also rigorous, which makes it more likely that it will produce more reliable answers about whether or not a drug is worth further investment,” says Rahman.

The study’s other co-first authors were Eudocia Quant Lee from Dana-Farber and Isabel Arrillaga-Romany from Massachusetts General Hospital, and the other co-senior author was Brian Alexander from radiation oncology.

Funding: National Brain Tumor Society, Accelerated Brain Cancer Cure, Burroughs Wellcome Fund, Celgene Corporation, Puma Biotechnology, Inc., Eli Lilly and Company, Bristol Myers Squibb/Celgene.