In the procedure, the physician uses a handheld transducer placed on the skin to direct ultrasound waves towards the stone. The ultrasound can then be used to move and reposition the stones to promote their passage, a process called ultrasound propulsion, or the break up the stone, a technique called burst wave lithotripsy (BWL).

Unlike shock wave lithotripsy, which is the standard procedure now in use and requires sedation, this technology doesn’t hurt, said lead author Dr. M. Kennedy Hall, a UW Medicine emergency medicine doctor. “It’s nearly painless, and you can do it while the patient is awake, and without sedation, which is critical.”

The research team hopes that, with this new technology, the procedure of moving or breaking up the stones could eventually be performed in a clinic or emergency room setting, Hall added.

Stones in the ureter, which leads from the kidney to the bladder, can cause severe pain and are a common reason for emergency department visits. Most patients with ureteral stones are advised to wait to see if the stone will pass on its own. However, this observation period can last for weeks, with nearly one-fourth of patients eventually requiring surgery, Hall noted.

One in 11 Americans will have a urinary stone over the course of their lifetime. The incidence appears to be increasing, according to one UW Medicine study looking at this same technology. Up to 50% of patients with a stone event will recur within five years, the study noted.

Hall and colleagues evaluated the new technique to meet the need for a way to treat stones without surgery.

The study was designed to test the feasibility of using the ultrasonic propulsion or using BWL to break up stones in awake, unanaesthetized patients, Hall said.

Twenty-nine patients participated in the study. Sixteen were treated with propulsion alone and 13 with propulsion and burst wave lithotripsy. In 19 patients, the stones moved. In two cases, the stones moved out of the ureter and into the bladder.

Burst wave lithotripsy fragmented the stones in seven of the cases. At a two-week follow up, 18 of 21 patients (86%) whose stones were located lower in the ureter, closer to the bladder, had passed their stones. In this group, the average time to stone passage was about four days, the study noted.

One of these patients felt “immediate relief” when the stone was dislodged from the ureter, the study stated.

The next step for the researchers would be to perfom a clinical trial with a control group, which would not receive either BWL bursts or ultrasound propulsion, to evaluate the degree to which this new technology potentially aids stone passage, Hall said.

Development of this technology first started five years ago, when NASA funded a study to see if kidney stones could be moved or broken up, without anesthesia, on long space flights, such as the Mars missions. The technology has worked so well that NASA has downgraded kidney stones as a key concern.

“We now have a potential solution for that problem,” Hall said.

This study began in 2018 and was conducted on patients at Harborview Medical Center, University of Washington Medical Center-Montlake and the Northwest Kidney Stone Center at University of Washington Medical Center-Northwest. It involved the University of Washington School of Medicine’s departments of emergency medicine, urology and radiology, and the UW Applied Physics Laboratory.

Other UW Medicine trials have looked at breaking apart kidney stones inside the kidneys. This is the first trial to look at moving the stones or breaking them apart in the ureter with BWL, Hall said.

Researchers found that animal models who carry a change in DNA known as germline alteration rs55705857 developed gliomas much more frequently — and in half the time — compared to animal models without the alteration. In addition to brain tumors, the findings are relevant to other cancers and diseases.

“While we understand much of the biologic function of germline alterations within genes that code for proteins, we know very little about the biologic function of germline alterations outside of genes that code for proteins. In some way, these germline alterations interact with other mutations in cells to accelerate tumor formation,” says co-lead author Robert Jenkins, M.D., Ph.D., a genetics researcher at Mayo Clinic in Rochester. “Based on this new understanding of its mechanism of action, future research may lead to novel and specific therapies that target the rs55705857 alteration.”

The study offers new knowledge that may help clinicians determine, pre-surgery, whether a patient has a glioma.

“We expected that rs55705857 would accelerate low-grade glioma development, but we were surprised by the magnitude of that acceleration,” says co-lead author Daniel Schramek, Ph.D., a researcher at Lunenfeld-Tannenbaum Research Institute.

There are many alterations, likely thousands, outside of genes associated with the development of cancer and other diseases, but the mechanism of action is only understood for very few, Dr. Schramek says.

This study demonstrates that, with the tools of modern molecular/cell biology, it is possible to decipher much of the mechanism of action of such alterations.

Dr. Jenkins is a Ting Tsung and Wei Fong Chao Professor in Individualized Medicine Research and researcher in Mayo Clinic’s Department of Laboratory Medicine and Pathology.

Dr. Schramek is a senior investigator and holds a Kierans & Janigan Research Chair at the LTRI and is an associate professor, Department of Molecular Genetics, Faculty of Medicine, University of Toronto.

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An international team of climate scientists led by the research group of Sonia Seneviratne, Professor for Land-?Climate Dynamics at ETH Zurich, now analysed the possible influence of climate change on this extreme weather event. Their study published by the World Weather Attribution group estimates that human-caused climate change made soil moisture drought conditions in the Northern Hemisphere at least 20 times more likely, threatening crop production and adding further pressure to food prices and food security.

Intense agricultural and ecological droughts

For their study, the researchers analysed soil moisture levels in June, July and August 2022, across the whole Northern Hemisphere, excluding the tropics. They also focused on Western and Central Europe, which experienced particularly severe drought with substantially reduced crop yields. Soil moisture dryness in the top metre of soil, known as the root zone where plants extract water, is often referred to as agricultural and ecological drought.

Human-caused climate change made agricultural and ecological droughts in the North Hemisphere extratropics at least 20 times more likely, the researchers found. They calculated that drought conditions like this summer’s can be expected around once in 20 years in today’s climate. If humans had not warmed the planet, the agricultural drought conditions in the Northern Hemisphere would only have been expected around once in 400 years or less.

In the case of West-Central Europe, human-induced climate change made the agricultural and ecological drought about 3 to 4 times more likely. This does not mean that climate change has had less influence on Europe than elsewhere in the Northern Hemisphere; the different sizes of the regions mean the results cannot be directly compared.

“The 2022 summer has shown how human-induced climate change is increasing the risks of agricultural and ecological droughts in densely populated and cultivated regions of the North Hemisphere,” Seneviratne says.

High temperatures as human-made driver

The main factor driving the heightened agricultural and ecological drought risk were increasing temperatures, with changes to rainfall relatively less important. Climate change increased temperatures across the Northern Hemisphere to such an extent that a summer as hot as this year’s would have been virtually impossible without human-induced climate change, the scientists found.

“The results of our analysis also give us an insight on what is looming ahead,” says Dominik Schumacher, postdoc in Seneviratnes research group and first author of the study. “With further global warming we can expect stronger and more frequent summer droughts in the future.”

“That’s why we need to phase-out the burning of fossil fuels if we want to stabilise climate conditions and avoid a further worsening of such drought events,” concludes Seneviratne.

This article is based on a press release by the World Weather Attribution group, an international collaboration that analyses and communicates the possible influence of climate change on extreme weather events.

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In a study of the relative effects of genetics, aging and the environment on how some 20,000 human genes are expressed, the researchers found that aging and environment are far more important than genetic variation in affecting the expression profiles of many of our genes as we get older. The level at which genes are expressed — that is, ratcheted up or down in activity — determines everything from our hormone levels and metabolism to the mobilization of enzymes that repair the body.

“How do your genetics — what you got from your sperm donor and your egg donor and your evolutionary history — influence who you are, your phenotype, such as your height, your weight, whether or not you have heart disease?” said Peter Sudmant, UC Berkeley assistant professor of integrative biology and a member of the campus’s Center for Computational Biology. “There’s been a huge amount of work done in human genetics to understand how genes are turned on and off by human genetic variation. Our project came about by asking, ‘How is that influenced by an individual’s age?’ And the first result we found was that your genetics actually matter less the older you get.”

In other words, while our individual genetic makeup can help predict gene expression when we are younger, it is less useful in predicting which genes are ramped up or down when we’re older — in this study, older than 55 years. Identical twins, for example, have the same set of genes, but as they age, their gene expression profiles diverge, meaning that twins can age much differently from each other.

The findings have implications for efforts to correlate diseases of aging with genetic variation in humans, Sudmant said. Such studies should perhaps focus less on genetic variants that impact gene expression when pursuing drug targets.

“Almost all human common diseases are diseases of aging: Alzheimer’s, cancers, heart disease, diabetes. All of these diseases increase their prevalence with age,” he said. “Massive amounts of public resources have gone into identifying genetic variants that predispose you to these diseases. What our study is showing is that, well, actually, as you get older, genes kind of matter less for your gene expression. And so, perhaps, we need to be mindful of that when we’re trying to identify the causes of these diseases of aging.”

Sudmant and his colleagues reported their results this week in the journal Nature Communications.

Medawar’s hypothesis

The findings are in line with Medawar’s hypothesis: Genes that are turned on when we are young are more constrained by evolution because they are critical to making sure we survive to reproduce, while genes expressed after we reach reproductive age are under less evolutionary pressure. So, one would expect a lot more variation in how genes are expressed later in life.

“We’re all aging in different ways,” Sudmant said. “While young individuals are closer together in terms of gene expression patterns, older individuals are further apart. It’s like a drift through time as gene expression patterns become more and more erratic.”

This study is the first to look at both aging and gene expression across such a wide variety of tissues and individuals, Sudmant said. He and his colleagues built a statistical model to assess the relative roles of genetics and aging in 27 different human tissues from nearly 1,000 individuals and found that the impact of aging varies widely — more than twentyfold — among tissues.

“Across all the tissues in your body, genetics matters about the same amount. It doesn’t seem like it plays more of a role in one tissue or another tissue,” he said. “But aging is vastly different between different tissues. In your blood, colon, arteries, esophagus, fat tissue, age plays a much stronger role than your genetics in driving your gene expression patterns.”

Sudmant and colleagues also found that Medawar’s hypothesis does not hold true for all tissues. Surprisingly, in five types of tissues, evolutionary important genes were expressed at higher levels in older individuals.

“From an evolutionary perspective, it is counterintuitive that these genes should be getting turned on, until you take a close look at these tissues,” Sudmant said. These five tissues happen to be the ones that constantly turn over throughout our lifespan and also produce the most cancers. Every time these tissues replace themselves, they risk creating a genetic mutation that can lead to disease.

“I guess this tells us a little bit about the limits of evolution,” he said. “Your blood, for instance, always has to proliferate for you to live, and so these super-conserved, very important genes have to be turned on late in life. This is problematic because it means that those genes are going to be susceptible to getting somatic mutations and getting turned on forever in a bad, cancerous way. So, it kind of gives us a little bit of a perspective on what the limitations of living are like. It puts bounds on our ability to keep living.”

Sudmant noted that the study indirectly indicates the effect on aging of one’s environment, which is the impact of everything other than age and genetics: the air we breathe, the water we drink, the food we eat, but also our levels of physical exercise. Environment amounts to up to a third of gene expression changes with age.

Sudmant is conducting similar analyses of the expressed genes in several other organisms — bats and mice — to see how they differ and whether the differences are related to these animals’ different lifespans.

UC Berkeley graduate students Ryo Yamamoto and Ryan Chung are co-first authors of the paper. Other co-authors are Juan Manuel Vazquez, Huanjie Sheng, Philippa Steinberg and Nilah Ioannidis. The work was supported by the National Institute of General Medical Sciences (R35GM142916) of the National Institutes of Health.

Whereas the shortest way between two points is a straight connection, it might not be the most efficient path to follow. Complex currents often affect the motion of microswimmers and make it difficult for them to reach their destination. At the same time, making use of these currents to navigate as fast as possible is a certain evolutionary advantage. Whereas such strategies allow biological microswimmers to better access food or escape a predator, microrobots could this way be directed to perform specific tasks.

The optimal path in a given current can readily be determined mathematically, yet fluctuations perturb the motion of microswimmers and deviate them from the optimal route. Thus, they have to readjust their motion in order to account for environmental changes. This typically requires the help of an external interpreter and takes away their autonomy.

“Thanks to evolution, some microorganisms have developed autonomous strategies that enable directed motion towards larger concentration of nutrients or light,” first author of the study Lorenzo Piro explains. Inspired by this idea, the researchers from the Department of Living Matter Physics at the MPI-DS designed strategies that allow microswimmers to navigate optimally in a nearly autonomous way.

Light as a guide for autonomous navigation

When an external interpreter defines the navigation pattern, microswimmers on average follow a well-defined path. Thus, it is a good approach to guide the microswimmer along that path within the current. This can be achieved autonomously via external stimuli, despite the presence of fluctuations. This principle could be applied to swimmers that respond to variation of light, such as certain algae, in which case the optimal path can simply be illuminated. Remarkably, the resulting performances are comparable to externally supervised navigation. “These new strategies can moreover conveniently be applied to more complex scenario such as navigation on curved surfaces or in presence of random currents,” concludes Ramin Golestanian, director at MPI-DS.

Possible applications of the study thus range from targeted drug delivery at the microscale to the optimal design of autonomous micromachines.

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Up to 70 percent of mothers develop postnatal depressive mood, also known as baby blues, after their baby is born. Analyses show that this can also affect the development of the children themselves and their speech. Until now, however, it was unclear exactly how this impairment manifests itself in early language development in infants.

In a study, scientists at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig have now investigated how well babies can distinguish speech sounds from one another depending on their mother’s mood. This ability is considered an important prerequisite for the further steps towards a well-developed language. If sounds can be distinguished from one another, individual words can also be distinguished from one another. It became clear that if mothers indicate a more negative mood two months after birth, their children show on average a less mature processing of speech sounds at the age of six months. The infants found it particularly difficult to distinguish between syllable-pitches. Specifically, they showed that the development of their so-called Mismatch Response was delayed than in those whose mothers were in a more positive mood. This Mismatch Response in turn serves as a measure of how well someone can separate sounds from one another. If this development towards a pronounced mismatch reaction is delayed, this is considered an indication of an increased risk of suffering from a speech disorder later in life.

“We suspect that the affected mothers use less infant-directed-speech,” explains Gesa Schaadt, postdoc at MPI CBS, professor of development in childhood and adolescence at FU Berlin and first author of the study, which has now appeared in the journal JAMA Network Open. “They probably use less pitch variation when directing speech to their infants.” This also leads to a more limited perception of different pitches in the children, she said. This perception, in turn, is considered a prerequisite for further language development.

The results show how important it is that parents use infant-directed speech for the further language development of their children. Infant-directed speech that varies greatly in pitch, emphasizes certain parts of words more clearly — and thus focuses the little ones’ attention on what is being said — is considered appropriate for children. Mothers, in turn, who suffer from depressive mood, often use more monotonous, less infant-directed speech. “To ensure the proper development of young children, appropriate support is also needed for mothers who suffer from mild upsets that often do not yet require treatment,” Schaadt says. That doesn’t necessarily have to be organized intervention measures. “Sometimes it just takes the fathers to be more involved.”

The researchers investigated these relationships with the help of 46 mothers who reported different moods after giving birth. Their moods were measured using a standardized questionnaire typically used to diagnose postnatal upset. They also used electroencephalography (EEG), which helps to measure how well babies can distinguish speech sounds from one another. The so-called Mismatch Response is used for this purpose, in which a specific EEG signal shows how well the brain processes and distinguishes between different speech sounds. The researchers recorded this reaction in the babies at the ages of two and six months while they were presented with various syllables such as “ba,” “ga” and “bu.

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The researchers have been able to show that quantum waves behave significantly differently from their classical counterparts and can be used to increase the precision of distance measurements. Their findings also add to the discussion on physical origin of the anomalous focusing behaviour. The results are now published in the journal of Nature Photonics.

“Interestingly, we started with an idea based on our earlier results and set out to structure quantum light for enhanced measurement precision. However, we then realised that the underlying physics of this application also contributes to the long debate about the origins of the Gouy phase anomaly of focused light fields.,” explains Robert Fickler, group leader of the Experimental Quantum Optics group at Tampere University.

Quantum waves behave differently but point to the same origin

Over the last decades, methods for structuring light fields down on the single photon level have vastly matured and led to a myriad of novel findings. In addition, a better of optics’ foundations has been achieved. However, the physical origin of why light behaves in such an unexpected way when going through a focus, the so-called Gouy phase anomaly, is still often debated. This is despite its widespread use and importance in optical systems. The novelty of the current study is now to put the effect into the quantum domain.

“When developing the theory to describe our experimental results, we realised (after a long debate) that the Gouy phase for quantum light is not only different than the standard one, but its origin can be linked to another quantum effect. This is just like what was speculated in an earlier work,” adds Doctoral researcher Markus Hiekkamäki, leading author of the study.

In the quantum domain, the anomalous behaviour is sped up when compared to classical light. As the Gouy phase behaviour can be used to determine the distance a beam of light has propagated, the speed up of the quantum Gouy phase could allow for an improvement in the precision of measuring distances.

With this new understanding at hand, the researchers are planning to develop novel techniques to enhance their measurement abilities such that it will be possible to measure more complex beams of structured photons. The team expects that this will help them push forward the application of the observed effect, and potentially bring to light more differences between quantum and classical light fields.

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