“This technology could be useful for a wide range of applications,” said research team member Aurora Maccarone, a Royal Academy of Engineering research fellow from Heriot-Watt University in the United Kingdom. “For example, it could be used to inspect underwater installations, such as underwater wind farm cables and the submerged structure of the turbines. Underwater lidar can also be used for monitoring or surveying submerged archaeology sites and for security and defense applications.”

Obtaining 3D images through ocean water can be challenging because it is light-limited, and any particles in the water will scatter light and distort the image. However, single-photon detection, which is a quantum-based technique, allows very high penetration and works even in low-light conditions.

In the Optica Publishing Group journal Optics Express, researchers from Heriot-Watt University and the University of Edinburgh describe experiments in which an entire single-photon lidar system was submerged in a large water tank. The new demonstrations bring the technology closer to practical applications compared to the research team’s earlier experiments with underwater single-photon detection, which were performed in carefully controlled laboratory conditions with the optical setup placed outside the water tank and data analysis performed offline. They also implemented new hardware and software developments that allow the 3D images acquired by the system to be reconstructed in real time.

“This work aims to make quantum detection technologies available for underwater applications, which means that we will be able to image the scene of interest in very low light conditions,” said Maccarone. “This will impact the use of offshore cable and energy installations, which are used by everyone. This technology could also allow monitoring without the presence of humans, which would mean less pollution and a less invasive presence in the marine environment.”

Faster low-light detection

Lidar systems create images by measuring how long it takes laser light to be reflected from objects in the scene and travel back to the system’s receiver, known as the “time of flight.” In the new work, the researchers sought to develop a way to acquire 3D images of targets that are obscured by turbid water and thus not visible to conventional lidar imaging systems.

They designed a lidar system that uses a green pulsed laser source to illuminate the scene of interest. The reflected pulsed illumination is detected by an array of single-photon detectors, which allows ultrafast low light detection and greatly reduces measurement time in photon-starved environments such as highly attenuating water.

“By taking time-of-flight measurements with picosecond timing resolution, we can routinely resolve millimeter details of the targets in the scene,” said Maccarone. “Our approach also allows us to distinguish the photons reflected by the target from those reflected by particles in the water, making it particularly suitable to performing 3D imaging in highly turbid waters where optical scattering can ruin image contrast and resolution.”

The fact that this approach requires thousands of single-photon detectors, all producing many hundreds of events per second, makes it extremely challenging to retrieve and process the data necessary to reconstruct the 3D image in a short time, especially for real-time applications. To solve this problem, the researchers developed algorithms specifically for imaging in highly scattering conditions and applied them in conjunction with widely available graphics processing unit (GPU) hardware.

The new technique builds on some important technological advances. “Heriot-Watt University has a long track record in single-photon detection techniques and image processing of single-photon data, which allowed us to demonstrate advanced single?photon imaging in extremely challenging conditions,” said Maccarone. “The University of Edinburgh has achieved fundamental advances in the design and fabrication of single-photon avalanche diode detector arrays, which allowed us to build compact and robust imaging systems based on quantum detection technologies.”

Underwater testing

After optimizing the optical setup on a laboratory optical bench, the researchers connected the lidar system to a GPU to achieve real-time processing of the data while also implementing a number of image processing approaches for three-dimensional imaging. Once the system was working properly, they moved it to a tank that was 4 meters long, 3 meters wide, and 2 meters deep.

With the system submerged in the water, the researchers added a scattering agent in a controlled manner to make the water more turbid. Experiments at three different turbidity levels demonstrated successful imaging in controlled highly scattering scenarios at distances of 3 meters.

“Single-photon technologies are rapidly developing, and we have demonstrated very promising results in underwater environments,” said Maccarone. “The approach and image processing algorithms could also be used in a wider range of scenarios for improved vision in free space such as in fog, smoke or other obscurants.”

The researchers are now working to reduce the size of the system so that it could be integrated into an underwater vehicle.Through the UK Quantum Technology Hub Network and InnovateUK, the researchers are partnering with industry to make the technology accessible for a range of underwater applications.

Five of the 60 beverages tested contained levels of a toxic metal above federal drinking water standards, according to the study from Tulane University. Two mixed juices had levels of arsenic above the 10 microgram/liter standard. A cranberry juice, a mixed carrot and fruit juice and an oat milk each had levels of cadmium exceeding the 3 parts per billion standard.

The sampled beverages, which included those commonly found in grocery stores — single and mixed fruit juices, plant-based milks, sodas, and teas — were measured for 25 different toxic metals and trace elements. Mixed-fruit juices and plant-based milks (such as oat and almond) contained elevated concentrations of toxic metals more often than other drinks, according to the findings published in the Journal of Food Composition and Analysis.

All told, seven of the 25 elements exceeded drinking water standards in some of the drinks, including nickel, manganese, boron, cadmium, strontium, arsenic, and selenium. While lead was detected in more than 93% of the 60 samples, most contained very low levels, below 1 part per billion. The highest level (6.3 micrograms/kg ) was found in a lime sports drink, though that’s below both EPA and WHO standards for drinking water.

Tewodros Godebo, lead author and assistant professor of environmental health sciences at Tulane University School of Public Health and Tropical Medicine, said the study was important because there are few peer-reviewed studies examining the contents of American beverages.

“It was surprising that there aren’t a lot of studies out there concerning toxic and essential elements in soft drinks in the United States,” Godebo said. “This creates awareness that there needs to be more study.”

These soft drinks are often consumed in smaller quantities than water, meaning the health risks for adults are most likely low. But Godebo said parents should be cautious about what drinks they offer their children.

“People should avoid giving infants and young children mixed-fruit juices or plant-based milks at high volume,” Godebo said. “Arsenic, lead, and cadmium are known carcinogens and well established to cause internal organ damage and cognitive harm in children especially during early brain development.”

Godebo said most of these elements found in beverages presumably come from contaminated soil.

“These metals are naturally occurring so it’s hard to get rid of completely,” Godebo said.

Hannah Stoner and Julia Ashmead, Tulane University students who participated in the study, said they hope the findings encourage people to think more about what they consume.

“I don’t think there needs to be fear,” Stoner said. “In toxicity, it’s the dosage that often makes the difference so everything in moderation. But this creates awareness that there needs to be more study.”

Godebo said the next step is to conduct a risk assessment based on the data collected to see the impacts of consuming toxic metals in children and adults.

“We are curious to keep exploring what’s in our drinks and foods commercially sold to the consumers,” Godebo said.

But now Northwestern Medicine scientists report results of the first in-human clinical trial in which they used a novel, skull-implantable ultrasound device to open the blood-brain barrier and repeatedly permeate large, critical regions of the human brain to deliver chemotherapy that was injected intravenously.

The four-minute procedure to open the blood-brain barrier is performed with the patient awake, and patients go home after a few hours. The results show the treatment is safe and well tolerated, with some patients getting up to six cycles of treatment.

This is the first study to successfully quantify the effect of ultrasound-based blood-brain barrier opening on the concentrations of chemotherapy in the human brain. Opening the blood-brain barrier led to an approximately four- to six-fold increase in drug concentrations in the human brain, the results showed.

Scientists observed this increase with two different powerful chemotherapy drugs, paclitaxel and carboplatin. The drugs are not used to treat these patients because they do not cross blood-brain barrier in normal circumstances.

In addition, this is the first study to describe how quickly the blood-brain barrier closes after sonication. Most of the blood-brain barrier restoration happens in the first 30 to 60 minutes after sonication, the scientists discovered. The findings will allow optimization of the sequence of drug delivery and ultrasound activation to maximize the drug penetration into the human brain, the authors said.

“This is potentially a huge advance for glioblastoma patients,” said lead investigator Dr. Adam Sonabend, an associate professor of neurological surgery at Northwestern University Feinberg School of Medicine and a Northwestern Medicine neurosurgeon.

Temozolomide, the current chemotherapy used for glioblastoma, does cross the blood-brain barrier, but is a weak drug, Sonabend said.

The paper will be published May 2 in The Lancet Oncology.

The blood-brain barrier is a microscopic structure that shields the brain from the vast majority of circulating drugs. As a result, the repertoire of drugs that can be used to treat brain diseases is very limited. Patients with brain cancer cannot be treated with most drugs that are otherwise effective for cancer elsewhere in the body, as these do not cross the blood-brain barrier. Effective repurposing of drugs to treat brain pathology and cancer require their delivery to the brain.

In the past, studies that injected paclitaxel directly into the brain of patients with these tumors observed promising signs of efficacy, but the direct injection was associated with toxicity such as brain irritation and meningitis, Sonabend said.

Blood-brain barrier recloses after an hour

The scientists discovered that the use of ultrasound and microbubble-based opening of the blood-brain barrier is transient, and most of the blood-brain barrier integrity is restored within one hour after this procedure in humans.

“There is a critical time window after sonification when the brain is permeable to drugs circulating in the bloodstream,” Sonabend said.

Previous human studies showed that the blood-brain barrier is completely restored 24 hours after brain sonication, and based on some animal studies, the field assumed that the blood-brain barrier is open for the first six hours or so. The Northwestern study shows that this time window might be shorter.

In another first, the study reports that using a novel skull-implantable grid of nine ultrasound emitters designed by French biotech company Carthera opens the blood-brain barrier in a volume of brain that is nine times larger than the initial device (a small single-ultrasound emitter implant). This is important because to be effective, this approach requires coverage of a large region of the brain adjacent to the cavity that remains in the brain after removal of glioblastoma tumors.

Clinical trial for patients with recurrent glioblastoma

The findings of the study are the basis for an ongoing phase 2 clinical trial the scientists are conducting for patients with recurrent glioblastoma. The objective of the trial — in which participants receive a combination of paclitaxel and carboplatin delivered to their brain with the ultrasound technique — is to investigate whether this treatment prolongs survival of these patients. A combination of these two drugs is used in other cancers, which is the basis for combining them in the phase 2 trial.

In the phase 1 clinical trial reported in this paper, patients underwent surgery for resection of their tumors and implantation of the ultrasound device. They started treatment within a few weeks after the implantation.

Scientists escalated the dose of paclitaxel delivered every three weeks with the accompanying ultrasound-based blood-brain barrier opening. In subsets of patients, studies were performed during surgery to investigate the effect of this ultrasound device on drug concentrations. The blood-brain barrier was visualized and mapped in the operating room using a fluorescent die called fluorescein and by MRI obtained after ultrasound therapy.

“While we have focused on brain cancer (for which there are approximately 30,000 gliomas in the U.S.), this opens the door to investigate novel drug-based treatments for millions of patients who suffer from various brain diseases,” Sonabend said.

Other Northwestern authors include: A. Gould, C. Amidei, R. Ward, K. A. Schmidt, D.Y. Zhang, C. Gomez, J.F. Bebawy, B.P. Liu, I.B. Helenowski, R.V. Lukas, K. Dixit, P. Kumthekar, V. A. Arrieta. Lesniak, H. Zhang and R. Stupp.

This work is funded by the grants 1R01CA245969-01A1 and P50CA221747 from the National Cancer Institute of the National Institutes of Health and SPORE support from the Moceri Family Foundation and the Panattoni family.

Hoarding disorder affects around 2% of the population but remains a largely misunderstood mental health condition. It was only added to the International Classification of Diseases in 2019, having previously been classified under Obsessive Compulsive Disorder (OCD).

Published in the British Journal of General Practice, the new guidance was written by Dr Sharon Morein and Dr Sanjiv Ahluwalia of Anglia Ruskin University (ARU) in Cambridge, England, to help health professionals spot the signs of hoarding disorder and intervene.

ARU experts have also organised a free conference on Wednesday, 10 May to provide the public with more information about the condition.

Hoarding disorder involves clutter in the home environment taking over living spaces, as well as excessive acquisition and difficulty discarding possessions, and affects an individual’s quality of life.

However, it typically comes to the fore only when patients seek support for other mental health or physical conditions and can then act as a barrier to treatment due to concerns about hygiene, safety, or access to the home.

People with hoarding disorder most commonly suffer from depression, while other comorbidities include Obsessive Compulsive Disorder (OCD), and Attention Deficit Hyperactivity Disorder (ADHD).

Dr Morein, an Associate Professor in Psychology at Anglia Ruskin University (ARU) and leader of the ARU Possessions and Hoarding Collective said: “Labels can be very useful in the healthcare system and can be the first stage for people receiving the support they need.

“It is really important that doctors and other frontline healthcare professionals are aware that hoarding disorder is a diagnosable medical condition and that it is usually linked to other issues so that proper support can be offered.

“Typically, hoarding disorder is something that sneaks up on people — it doesn’t happen overnight — and people don’t necessarily recognise they have a problem. One of the major difficulties with hoarding disorder is that sufferers often don’t seek help themselves, and it only presents itself to medical professionals alongside other issues. The sooner the problem is spotted, the sooner support can be provided.”

To help people understand more about hoarding disorder, the ARU Possessions and Hoarding Collective is hosting a free conference at ARU’s Cambridge campus on Wednesday, 10 May.

The event, which will feature expert speakers including Professor Nick Neave of Northumbria University, will explain more about the disorder and the latest support strategies, and is aimed at service providers who help people with hoarding as part of their role, those affected by the hoarding behaviour of others, as well as individuals who themselves are struggling with hoarding.

Dr Morein added: “The ARU Possessions and Hoarding Collective is a group of academics and professionals aiming to improve our understanding of how people interact with their possessions.

“As part of our work, we research how hoarding can affect individuals and their families, as well as how service provision is currently delivered, and how it can be improved. We are inviting all these groups to attend the event in Cambridge on 10 May as we aim to increase awareness and ultimately provide better support for all.”

In a study of mice, the researchers found that mutations in Foxp2 disrupt the formation of dendrites and neuronal synapses in the brain’s striatum, which plays important roles in the control of movement. Mice with these mutations also showed impairments in their ability to produce the high-frequency sounds that they use to communicate with other mice.

Those malfunctions arise because Foxp2 mutations prevent the proper assembly of motor proteins, which move molecules within cells, the researchers found.

“These mice have abnormal vocalizations, and in the striatum there are many cellular abnormalities,” says Ann Graybiel, an MIT Institute Professor, a member of MIT’s McGovern Institute for Brain Research, and an author of the paper. “This was an exciting finding. Who would have thought that a speech problem might come from little motors inside cells?”

Fu-Chin Liu PhD ’91, a professor at National Yang Ming Chiao Tung University in Taiwan, is the senior author of the study, which appears today in the journal Brain. Liu and Graybiel also worked together on a 2016 study of the potential link between Foxp2 and autism spectrum disorder. The lead authors of the new Brain paper are Hsiao-Ying Kuo and Shih-Yun Chen of National Yang Ming Chiao Tung University.

Speech control

Children with Foxp2-associated apraxia tend to begin speaking later than other children, and their speech is often difficult to understand. The disorder is believed to arise from impairments in brain regions, such as the striatum, that control the movements of the lips, mouth, and tongue. Foxp2 is also expressed in the brains of songbirds such as zebra finches and is critical to those birds’ ability to learn songs.

Foxp2 encodes a transcription factor, meaning that it can control the expression of many other target genes. Many species express Foxp2, but humans have a special form of Foxp2. In a 2014 study, Graybiel and colleagues found evidence that the human form of Foxp2, when expressed in mice, allowed the mice to accelerate the switch from declarative to procedural types of learning.

In that study, the researchers showed that mice engineered to express the human version of Foxp2, which differs from the mouse version by only two DNA base pairs, were much better at learning mazes and performing other tasks that require turning repeated actions into behavioral routines. Mice with human-like Foxp2 also had longer dendrites — the slender extensions that help neurons form synapses — in the striatum, which is involved in habit formation as well as motor control.

In the new study, the researchers wanted to explore how the Foxp2 mutation that has been linked with apraxia affects speech production, using ultrasonic vocalizations in mice as a proxy for speech. Many rodents and other animals such as bats produce these vocalizations to communicate with each other.

While previous studies, including the work by Liu and Graybiel in 2016, had suggested that Foxp2 affects dendrite growth and synapse formation, the mechanism for how that occurs was not known. In the new study, led by Liu, the researchers investigated one proposed mechanism, which is that Foxp2 affects motor proteins.

One of these molecular motors is the dynein protein complex, a large cluster of proteins that is responsible for shuttling molecules along microtubule scaffolds within cells.

“All kinds of molecules get shunted around to different places in our cells, and that’s certainly true of neurons,” Graybiel says. “There’s an army of tiny molecules that move molecules around in the cytoplasm or put them into the membrane. In a neuron, they may send molecules from the cell body all the way down the axons.”

A delicate balance

The dynein complex is made up of several other proteins. The most important of these is a protein called dynactin1, which interacts with microtubules, enabling the dynein motor to move along microtubules. In the new study, the researchers found that dynactin1 is one of the major targets of the Foxp2 transcription factor.

The researchers focused on the striatum, one of the regions where Foxp2 is most often found, and showed that the mutated version of Foxp2 is unable to suppress dynactin1 production. Without that brake in place, cells generate too much dynactin1. This upsets the delicate balance of dynein-dynactin1, which prevents the dynein motor from moving along microtubules.

Those motors are needed to shuttle molecules that are necessary for dendrite growth and synapse formation on dendrites. With those molecules stranded in the cell body, neurons are unable to form synapses to generate the proper electrophysiological signals they need to make speech production possible.

Mice with the mutated version of Foxp2 had abnormal ultrasonic vocalizations, which typically have a frequency of around 22 to 50 kilohertz. The researchers showed that they could reverse these vocalization impairments and the deficits in the molecular motor activity, dendritic growth, and electrophysiological activity by turning down the gene that encodes dynactin1.

Mutations of Foxp2 can also contribute to autism spectrum disorders and Huntington’s disease, through mechanisms that Liu and Graybiel previously studied in their 2016 paper and that many other research groups are now exploring. Liu’s lab is also investigating the potential role of abnormal Foxp2 expression in the subthalamic nucleus of the brain as a possible factor in Parkinson’s disease.

The research was funded by the Ministry of Science and Technology of Taiwan, the Ministry of Education of Taiwan, the U.S. National Institute of Mental Health, the Saks Kavanaugh Foundation, the Kristin R. Pressman and Jessica J. Pourian ’13 Fund, and Stephen and Anne Kott.