Wednesday, September 20, 2023

 

Researchers issue urgent call to save the world’s largest flower -Rafflesia - from extinction


Peer-Reviewed Publication

UNIVERSITY OF OXFORD

Rafflesia arnoldii interior. 

IMAGE: A RARE GLIMPSE INTO THE INTERIOR OF RAFFLESIA ARNOLDII. IMAGE CREDIT: CHRIS THOROGOOD. view more 

CREDIT: A RARE GLIMPSE INTO THE INTERIOR OF RAFFLESIA ARNOLDII. IMAGE CREDIT: CHRIS THOROGOOD.




  • New study finds that most Rafflesia species, which produce the world’s largest flowers, face extinction.
  • Lack of protection at local, national, and international levels means that remaining populations are under critical threat.
  • Researchers propose an urgent action plan to save these remarkable flowers, building on local success stories.

An international group of scientists, including botanists at the University of Oxford’s Botanic Garden, has issued an urgent call for coordinated action to save the iconic genus Rafflesiawhich contains the world’s largest flowers. This follows a new study which found that most of the 42 species are severely threatened, yet just one of these is listed in the International Union for Conservation of Nature (IUCN)’s Red List of Threatened Species. Furthermore, over two thirds (67%) of the plants’ habitats are unprotected and at risk of destruction.

Rafflesia, one of the greatest botanical enigmas, has aroused curiosity among scientists for centuries. The plant is a parasite that infects tropical vines in jungles across Southeast Asia (Brunei, Indonesia, Malaysia, the Philippines, and Thailand). For most of its lifecycle, Rafflesia is hidden from sight, existing as a system of thread-like filaments that invades its host. At unpredictable intervals, the parasite produces a cabbage-like bud that breaks through the vine’s bark and eventually forms a giant, five-lobed flower, up to a metre across. This produces a foul scent of rotting meat to attract pollinating flies, earning it the alternative name ‘corpse flower.’ 

With such an elusive lifecycle, Rafflesia remains poorly understood, and new species are still being recorded. To better understand the vulnerability of these unique plants, a group of scientists established the first coordinated global network to assess the threats facing Rafflesia.

The results of the study found that all 42 Rafflesia species are under threat: based on the criteria used by the IUCN, the scientists classified 25 as ‘Critically Endangered’, 15 as ‘Endangered’, and two as ‘Vulnerable’.* Furthermore, over two-thirds (67%) are unprotected by regional or national conservation strategies.

Rafflesia species often have highly restricted distributions, making them particularly vulnerable to habitat destruction. The study found that many of the remaining populations contain only a few individuals located in unprotected areas at critical risk of conversion for agriculture. Since attempts to propagate Rafflesia in botanic gardens have had limited success so far, this makes habitat conservation an urgent priority.

To address these threats, the researchers recommend that all Rafflesia species are immediately added to the IUCN Red List of Threatened Species. Currently just one is listed: Rafflesia magnifica.

The team propose a four-point action plan for governments, research centres, and conservation organisations:

  • Greater protection of Rafflesia habitats, targeting populations most at risk.  Habitat protection was identified as the single best tool for Rafflesia conservation. Southeast Asia has the fastest disappearing forests on the planet, and many of the known Rafflesia populations are perilously close to growing human settlements.
  • Better understanding of the full diversity of Rafflesia that exists, to inform decision-making. It is thought that Rafflesia species still remain undocumented, while others have gone extinct before they were even known to science. We cannot protect what we do not know to exist, so sampling expeditions and genetic analyses are required to understand how many Rafflesia species there really are.
  • Develop methods to successfully propagate Rafflesia outside their native habitat. These could include grafting Rafflesia-infected vines onto uninfected vines for species where habitat destruction is likely.
  • Introduce new ecotourism initiatives to engage local communities in Rafflesia conservation.  Providing funding and training for local specialist guides would be an effective way to help protect local Rafflesia populations and raise awareness of the need for conservation.

Despite the challenges, the study also highlighted valuable success stories that could offer important insights for Rafflesia conservation elsewhere. For instance:

  • Bogor Botanic Garden in West Java, Indonesia, has become a centre of excellence for Rafflesia propagation, after a series of successful blooming events, including 16 for the species Rafflesia patma. Knowledge-sharing activities would help spread best practices to regions where this is needed urgently.
  • In West Sumatra, groups of local villagers are benefitting from Rafflesia ecotourism by forming ‘pokdarwis’: tourism awareness groups linked to social media. Many of these announce Rafflesia blooming events on social media platforms to build awareness of populations, and to attract paying tourists while carefully managing the risks of, for example, trampling. These activities could be developed as a template to disseminate to areas where community involvement with Rafflesia conservation is scarce.

Dr Chris Thorogood, Deputy Director of the University of Oxford Botanic Garden and an author of the study said: ‘This new study highlights how the global conservation efforts geared towards plants – however iconic – have lagged behind those of animals. We urgently need a joined-up, cross-regional approach to save some of the world’s most remarkable flowers, most of which are now on the brink of being lost.’

Adriane Tobias, forester from the Philippines said: ‘Indigenous peoples are some of the best guardians of our forests, and Rafflesia conservation programmes are far more likely to be successful if they engage local communities. Rafflesia has the potential to be a new icon for conservation in the Asian tropics.’

Chris Thorogood with Rafflesia arnoldii, the largest flower in the world, in Sumatra. Image credit: Chris Thorogood.

Dang Zul, Village Leader, with Rafflesia bengkuluensis in Sumatra illustrated in pencil by Chris Thorogood.

Rafflesia bengkuluensis with its custodians in Sumatra. Image credit: Chris Thorogood.

Rafflesia kemumu in the rainforest of Sumatra. Image credit: Chris Thorogood.

The study ‘Most of the world’s largest flowers (genus Rafflesia) are now on the brink of extinction’ will be published in Plants, People, Planet at 00:01 BST Wednesday 20 September at https://nph.onlinelibrary.wiley.com/doi/10.1002/ppp3.10431. To view a copy of the manuscript before this, contact Dr Chris Thorogood: chris.thorogood@obg.ox.ac.uk

A series of Rafflesia images with captions to use with media articles is available at https://drive.google.com/drive/folders/1KSwZXuCMLUMbYkr999Hj0-_hizOvdogv?usp=drive_link These images may be used if the caption and credit are included.

Dr Chris Thorogood has worked for many years alongside botanists and foresters in Southeast Asia to document the huge, mysterious blooms of Rafflesia. His new book Pathless Forest tells the story of his journey to study and protect this remarkable plant – both a thrilling adventure story and an inspirational call to action to safeguard a fast-disappearing wilderness. Pathless Forest is due to be published by Penguin in April 2024.

The study involved researchers from University of Oxford Botanic Garden; Department of Biology, University of Oxford; Institute of Human Sciences, University of Oxford; University of the Philippines Los BaƱos; National Research and Innovation Agency of Indonesia (BRIN); Universitas Bengkulu (Indonesia); Forest Research Institute Malaysia; Synthetic Biology Indonesia; Genbinesia Foundation (Indonesia); Universitas Gadjah Mada (Indonesia).

*Definitions as provided by the International Union for Conservation of Nature (IUCN) Red List of Threatened Species:

  • Critically Endangered: Critically Endangered (Cr) is the highest risk category assigned by the IUCN for wild species. Critically endangered species means a species numbers have decreased, or will decrease by 80% within three generations. It is therefore considered to be facing an extremely high risk of extinction in the wild.
  • Endangered: Endangered (EN) species is a population of organisms which is at risk of becoming extinct because it is either few in numbers, or threatened by changing environmental or predation parameters. It could also mean that, due to deforestation, there may be a lack of food and/or water. It is therefore considered to be facing a very high risk of extinction in the wild.
  • Vulnerable: Vulnerable (VU) species is one which has been categorised by the IUCN as likely to become endangered unless the circumstances threatening its survival and reproduction improve. It is therefore considered to be facing a high risk of extinction in the wild.

About the Oxford Botanic Garden and Arboretum

Oxford Botanic Garden is the UK’s oldest botanic garden, founded in 1621. The Garden was first established as a physic garden for the cultivation of medicinal plants, and still occupies a unique position in terms of its history and academic location to this day. It was the birthplace of botanical science in the UK and has been a centre for plant research since the 1600s.

Oxford Botanic Garden’s mission is to share the scientific wonder of plants and the importance of plants with the world. It holds a collection of about 5,000 different types of plant, together with its sister site, Harcourt Arboretum. Some of these species exist nowhere else and are of international conservation importance.

About the University of Oxford

Oxford University has been placed number 1 in the Times Higher Education World University Rankings for the seventh year running, and number 3 in the QS World Rankings 2024. At the heart of this success are the twin-pillars of our ground-breaking research and innovation and our distinctive educational offer.

Oxford is world-famous for research and teaching excellence and home to some of the most talented people from across the globe. Our work helps the lives of millions, solving real-world problems through a huge network of partnerships and collaborations. The breadth and interdisciplinary nature of our research alongside our personalised approach to teaching sparks imaginative and inventive insights and solutions.

Through its research commercialisation arm, Oxford University Innovation, Oxford is the highest university patent filer in the UK and is ranked first in the UK for university spinouts, having created more than 300 new companies since 1988. Over a third of these companies have been created in the past five years. The university is a catalyst for prosperity in Oxfordshire and the United Kingdom, contributing £15.7 billion to the UK economy in 2018/19, and supports more than 28,000 full time jobs.

 

Probing the unimaginable: New data help to understand the nature of aphantasia



Peer-Reviewed Publication

INSTITUT DU CERVEAU (PARIS BRAIN INSTITUTE)

Aphantasia 

IMAGE: ARTISTIC DEPICTION OF THE CAPACITY TO PRODUCE MENTAL IMAGES. view more 

CREDIT: PARIS BRAIN INSTITUTE.




The ability to visualize faces, objects, landscapes, or even scenes from the past exists on a spectrum. While some can picture the layout of a city in minute detail and mentally walk through it, street by street, others have a perfectly blank internal cinema. In this case, we speak of aphantasia—the inability to voluntarily produce the visual mental image corresponding to an idea.

People whose aphantasia is congenital—i.e., not due to a stroke, brain injury, or psychiatric illness—become aware of their peculiarity reasonably late in life. Indeed, this small deficit in visualization does not cause any handicap, and they have no reason to suspect they are atypical. Nor do they realize that at the other end of the spectrum are hyperphantasic individuals who can produce mental images as precise as illustrations in a book.

Talking to these people is fascinating. We tend to think that access to visual perception, conceptualization, and memory is the same for everyone. Nothing could be further from the truth," Paolo Bartolomeo, neurologist and researcher at Paris Brain Institute, says. “Aphantasics cannot mentally picture what their parents, friends, or partner look like when they are away. But they can still describe the physical characteristics of their loved ones: this visual information has been stored, in one way or another”.

Visual mental imagery in question

There is currently a lively debate about the origin of aphantasia. Is it linked to a perceptual deficit? Emotional and psychological factors? A slight difficulty in accessing one's sensations? To answer this question, Paolo Bartolomeo and Jianghao Liu, a doctoral student in the “Neurophysiology and Functional Neuroimaging” team at Paris Brain Institute, recruited 117 volunteers—including 44 aphantasics, 31 hyperphantasics and 42 people with typical mental imagery—and gave them a mental imagery and visual perception test.

Our test, called the Imagination Perception Battery (BIP), is designed to assess the link between perception and mental imagery through the different visual qualities that enable a scene to be describedsuch as shape, color, position in space, presence of words or faces", Jianghao Liu explains.

Participants were asked to look at a blank screen. At the same time, an off-screen voice announced a visual quality (such as ‘shape’), followed by two words corresponding to concepts they had to materialize in their minds as accurately as possible (‘beaver’ and ‘fox’ for example). The voice also gave them a qualifier (such as 'long'); then, the participants were asked to decide which of the beaver or fox best matched the epithet ‘long’.

The speed and relevance of responses were recorded, and the respondents were asked to assess the quality of the mental image they had—or had not—managed to produce from the description. Finally, they had to take a perception test in which the stimuli were presented in a visual format: the long fox appeared in the form of an image accompanied by its audio description without the participants having to picture it.

When imagination takes its time

“Our results indicate that the performance of people with aphantasia is equivalent to other groups in terms of perception and the ability to associate a concept with its representation,” Liu comments. “With one exception! Aphantasics are, on average, slower than hyperphantasics and typical imagers when it comes to processing visual information, particularly shapes and colors. They also have little confidence in the accuracy of their answers”.

Previous studies have shown that aphantasics are just as quick as other people to answer questions that require manipulating abstract concepts. Therefore, only the processing of visual information is delayed for them. How can this phenomenon be explained?

“Participants in the aphantasic group perceive elements of reality accurately and show no deficits in memory and language processing. We believe that they present a slight defect of what we call phenomenal consciousness. This means that they have access to information about shapes, colors, and spatial relationshipsbut that this visual information does not translate into a visual mental image in conscious experience”, Bartolomeo says. “This peculiarity is probably compensated by other cognitive strategies, such as mental lists of visual characteristics, which allow aphantasics to remember everything they have seen.”

The future of perception

These preliminary results are limited by the data collection method, which consisted of an online questionnaire. However, they put us on a promising track to understand how visual mental imagery works. Future studies could reveal the neural mechanisms underlying these observations and, ultimately, help us to understand the visualization deficits specific to stroke patients.

We also hope to develop interventional tools for certain psychiatric illnesses, such as post-traumatic stress disorder (PTSD), which is characterized by the eruption of images from traumatic memories. If we could rid patients of these intrusive mental images, it would greatly promote their recovery”, Liu concludes.

 

A guide to Big Team Science creates a blueprint for research collaboration on a large scale


Postdoc NicolƔs Alessandroni and Professor Krista Byers-Heinlein co-author a how-to paper on managing BTS research projects


Peer-Reviewed Publication

CONCORDIA UNIVERSITY

Nicolas Alessandroni 

IMAGE: NICOLƁS ALESSANDRONI: “THERE ARE ALL THESE DIFFERENT EXPERIENCES THAT COALESCE AROUND BTS, AND THIS PROVIDES AN OPPORTUNITY TO INTEGRATE MANY PERSPECTIVES INTO A PROJECT.” view more 

CREDIT: CONCORDIA UNIVERSITY



Scientific research depends on collaboration between researchers and institutions. But over the past decade, there has been a surge of large-scale research projects involving extraordinarily large numbers of researchers, from dozens to hundreds, all working on a common project. Examples of this trend include ManyBabies, centred on infant cognition and development, and ManyManys, focused on comparative cognition and behaviour across animal taxa. These kinds of projects, known as big team science (BTS), benefit from pooled human and material resources and draw on diverse data sets to gird studies with a robustness not found in smaller ones.

However, as exciting as these projects can be, they can also be monsters to manage. Communication, team building, governance, authorship and credit are just some of the issues BTS team leaders must negotiate, along with the logistical difficulties involved in working across languages, cultures and time zones.

Fortunately, a group of BTS veterans, including two Concordia researchers, has published a how-to guide to help their fellow academics build their own projects. The article, published in the Royal Society Open Science journal, is based on expertise gained over multiple BTS projects, and it provides a road map for best practices and overcoming challenges.

“BTS is a new way of conducting research where many researchers come together to answer a common question that is crucial to their field,” says NicolĆ”s Alessandroni, a postdoctoral fellow at Concordia’s Infant Research Lab. Alessandroni works under the direction of Krista Byers-Heinlein, a professor of psychology and the Concordia University Research Chair in Bilingualism and Open Science. The two co-authored the article with researchers at Stanford University, the University of British Columbia and the University of Manitoba.

“This is important because research has traditionally been conducted in a siloed manner, where individual teams from one institution work with small, limited samples.”

Building up step by step

The authors acknowledge that no two projects are alike, and there is no one model to creating a BTS study. But success can be achieved by applying a common approach.

They suggest starting by identifying whether a research community believes the project is necessary. Consensus buy-in gets things rolling.

Once a project is a go, the authors outline how team leaders can work together to share data and collaborate on writing. The guide is designed to provide a path forward for researchers and to smooth over differences that are almost inevitable when the number of collaborators reaches three or even four digits. It touches on topics ranging from governance and codes of ethics to designated writing teams and authorship protocols.

“The beauty of big team science is that anyone can join, from undergraduates to faculty,” says Alessandroni. “There are all these different experiences that coalesce around BTS, and this provides an opportunity to integrate many perspectives into a project. You can have some people who are very seasoned researchers and others who are young students willing to collaborate and embrace this new way of doing science.”

Open to all

He admits that BTS projects are not easy to manage, but they do have clear strengths and benefits.

“Its very definition relates to important values in science: transparency, collaboration, accessibility, equity, diversity and inclusion — it touches on many important topics that have been disregarded in the practice of science traditionally. In many ways, it overlaps with the concept of open science, where data is shared openly and publications are available in open-access journals and repositories, making knowledge available without charging readers.”

Alessandroni notes that universities will have to adapt to accommodate changes in the way research is supported.

“Institutions worldwide can help foster BTS collaborations by devising new workflows, policies and incentive structures,” he says. “Naturally, this would involve important changes to the academic ecosystem, so there is much to discuss.”

Read the cited paper: “How to build up big team science: a practical guide to large-scale collaborations.”

 

Ballet of the brain: Unlocking the choreography of movement


Peer-Reviewed Publication

CHAMPALIMAUD CENTRE FOR THE UNKNOWN

Image1 

IMAGE: ZEBRAFISH HINDBRAIN CIRCUITS ACTIVE DURING EYE ROTATIONS (RED AND BLUE NEURONS) AND SWIMMING (GREEN NEURONS). view more 

CREDIT: CLAUDIA FEIERSTEIN (CCU)




The zebrafish brain, though simpler than its human counterpart, is a complex network of neurons that engage in a ceaseless dance of electrical activity. What if this neural ballet could reveal the secrets of how brains, including our own, control movement? A zebrafish study led by researchers at the Champalimaud Foundation offers a new lens through which to view the activity of neural populations, and to understand how the brain orchestrates motion.

Why we have a brain

“The brain’s primary function is movement”, explains Claudia Feierstein, lead author of the study published today in Current Biology. “Plants don’t need a brain because they don’t move. Yet, even for something as seemingly simple as eye movements, the brain’s role remains largely enigmatic. Our goal is to illuminate this ‘black box’ of motion and to decode how neural activity controls eye and body movements, using zebrafish as our model organism”.

With their tiny transparent bodies, zebrafish have become the darlings of neuroscience, offering a unique window into brain function. “Eye movement is a circuit that’s conserved across species, including humans”, notes Feierstein. “If we can understand how it works in zebrafish, we can start to understand better how human brains do movement”. Zebrafish, like humans, possess an innate ability to stabilise their vision and position in response to movement. When the world around them spins, their eyes and body move in tandem to maintain stability. This is akin to us steadying our gaze on a fixed point while on a merry-go-round.

But how does the brain coordinate this behaviour? Previous research by the team had shown that different parts of the zebrafish brain were associated with different types of movements. However, the precise relationship between these brain areas and the actual behaviour remained unclear. “While we know that neurons are involved in detecting visual stimuli (the input) and controlling muscles (the output), we remain in the dark about the processing in between”, remarks Feierstein. Complicating matters is the plethora of stimuli to which neurons respond and the staggering amount of data captured by whole-brain imaging studies. “When you have tens of thousands of neurons  and 100 different possible behaviours that they could encode, it’s not trivial to understand what is going on”.

As Michael Orger, one of the two senior authors, elaborates, “When you look at the activity of individual neurons, you find that they can respond to multiple behavioural variables. This makes it challenging to pinpoint what exactly is driving their activity”. This leads to a complex interplay between neurons and behaviour, where individual neurons can be involved in multiple types of movements.

A New Analytical Approach

To tackle this challenge, the researchers initially used a statistical method known as linear regression to explore the relationship between behavioural variables and neuronal activity. However, they quickly realised that examining neurons one by one did not provide a clear understanding of the overall picture. It was like trying to understand a grand-scale dance performance featuring hundreds of dancers by only watching one dancer's moves. “We started by looking at individual neurons but soon realised that we needed to understand the ensemble, the whole dance troupe if you will”, says Feierstein. “So we incorporated what’s known as a ‘dimensionality reduction’ step in our analysis to get a zoomed-out view of what the population of neurons is doing”.

As Christian Machens, the study’s other senior author, points out, “We wanted to know: how does the overall activity that we measure relate to behaviour? How can we boil down the activity of tens of thousands of neurons to its essential features? It took a considerable amount of time to develop the analytical approach for this. But once we managed to overcome these challenges, we could finally ask: how does the overall activity of these neurons relate to specific behaviours, like eye movement or swimming?”.

In the study, zebrafish were embedded in agarose, a gel-like substance, to keep them in a fixed position so that the researchers could image the brain. The agarose near their eyes and tails was removed to allow for movement. “We then put images on a screen below the zebrafish and recorded brain activity with a fluorescent dye through a microscope”, describes Feierstein.

Unveiling the Brain’s Choreography

By applying their analytical approach to a region of the zebrafish brain called the hindbrain, the researchers were able to condense the cacophony of neuronal activity into two main ‘features’, or patterns of activity, that corresponded to specific types of movements, and are presumably generated by separate circuits in the zebrafish hindbrain.

The first circuit they found is primarily concerned with eye movements, specifically the rotation of the eyes, either clockwise or anti-clockwise. Imagine a fish seeing something spin around in its environment. To keep a stable view of this spinning object, the fish’s eyes also rotate, and its tail may move. Essentially, this circuit helps the fish adjust its eyes to keep a constant and stable image of what it’s seeing. As Feierstein elucidates, “It’s like the brain’s way of saying, ‘Okay, the world is spinning around me, I need to move my eyes to keep track of it’”. Moreover, the researchers discovered that neurons associated with leftward and rightward rotation were anatomically segregated in the left and right hemispheres of the brain, respectively.

The second circuit is more involved in what researchers call ‘vergence’ and tail movement. Vergence is the ability of the eyes to move in opposite directions - both eyes moving towards or away from the nose - in response to stimuli. This circuit comes into play when the fish perceives a stimulus moving from back to front. Feeling as though it’s drifting backward, the fish swims forward to stabilise its position. At the same time, its eyes converge to maintain a stable image. Consequently, this circuit helps the fish adjust its body and eye movements to stay in a stable position.

As Orger summarises, “One brain circuit is primarily concerned with eye movements, particularly rotation, to maintain a stable image on the retina. The other circuit is mostly involved in body movement, particularly swimming, in response to visual stimuli to maintain a stable position in the environment. These circuits help the fish adapt to changes in their environment, allowing them to maintain a stable view and position. While the exact mechanisms are still not entirely clear, the study provides valuable insights into how separate circuits in the brain control different types of movements”.

What surprised Feierstein and her team the most was the robustness of their findings. “We found these circuits consistently across each individual fish”, she notes. The study suggests that these circuits are neither purely sensory nor purely motor but lie somewhere in between, possibly translating sensory information into motor actions. In essence, the researchers may have found two different “choreographers”, each directing their own set of movements to help the fish interact effectively with its environment.

A Simpler Perspective on Complexity

The team’s research not only enhances our understanding of how the brain controls movement but also introduces an analytical method to the field that could serve as a valuable tool for other researchers. “The nice thing about this method”, says Feierstein, “is that it can be used by other scientists to better understand the link between neural activity and behaviour”.

The study’s findings could potentially open up new avenues for understanding conditions where the translation of sensory information to motor commands might be disrupted, such as in certain neurological disorders. Furthermore, the results could inspire new approaches in robotics and machine learning, where the concept of translating sensory data into movement is a fundamental principle.

For Machens, “The analytical technique we developed underscores a critical insight: while individual neurons can be incredibly complex, at a population level, their behaviour can be distilled into simpler patterns. It’s a reminder that sometimes, to understand the intricate dance of the brain, we need to step back and view the entire ensemble”.

As for the next steps, Feierstein is keen on diving deeper. “We’ve only scratched the surface. One of the things I want to try to do next is to look at the activity of different types of neurons, such as excitatory and inhibitory neurons, to see what is happening, and how they are involved in this process”. In the grand ballet of the brain, each neuron plays a part, and thanks to this study, we’re one pirouette closer to understanding the choreography of movement.

 

Bladder transplantation in humans? Initial studies to develop technique


The Journal of Urology® reports first steps toward robotic bladder transplantation

Peer-Reviewed Publication

WOLTERS KLUWER HEALTH



September 8, 2023 – A series of pre-clinical studies provide important first steps in developing techniques of robotic bladder transplantation in humans, as reported in the October issue of The Journal of Urology®, an Official Journal of the American Urological Association (AUA). The journal is published in the Lippincott portfolio by Wolters Kluwer

"Our study is the first report of bladder auto-transplantation in heart-beating, brain-dead human research donors as a necessary preparatory step toward clinical bladder transplantation in living patients," comments Inderbir S. Gill, MD, of Keck School of Medicine, University of Southern California, Los Angeles. 

Preclinical studies to prepare for first clinical bladder transplant 

Although transplantation is an accepted treatment for many types of organ failure, human urinary bladder transplantation has never been performed. That reflects, in part, the daunting technical challenges entailed in such a procedure, including the difficulty of obtaining surgical access to the deep pelvis and the complex anatomy of the blood vessels in that area. 

Patients with terminal bladder conditions which render the bladder unusable may undergo surgery to remove the bladder (cystectomy). This is followed by some type of diversion procedure to restore urinary function, typically using a segment of the patient's own bowel tissue. Although these reconstructive procedures have a high success rate, they carry a substantial risk of short- and long-term complications. 

Dr. Gill and his team, including Dr. Nima Nassiri, performed a series of fundamental pre-clinical studies to develop the technique of robotic bladder transplantation. Their experience included three models of auto-transplantation – removing the bladder and associated tissues, including arteries, veins, and ureters; preparing it as if from a human donor; and transplanting the prepared organ back into the donor. 

  • Living animal model. Initial experiments were performed in pigs, due to the general similarity of the urinary tract and blood vessels to human anatomy. 

  • Human cadaver model. This was followed by a pulsatile human cadaver model, designed to simulate blood flow in a living patient.  

  • Beating-heart donor model. Similar techniques were then carried out in beating-heart, deceased donors who had been declared brain-dead. This phase included five subjects whose families had consented to organ donation but were ineligible due to other illnesses. 

Techniques developed in the animal and cadaver models were successfully applied to the beating-heart donors. In all three models, operative times for robotic auto-transplantation decreased with experience. In the beating-heart donors, total surgical time decreased from 10.5 to 4.7 hours. 

Bladder transplant could be a 'viable treatment option' for selected patients 

Three out of four attempts at robotic auto-transplantation in beating-heart donors were successful, resulting in good blood flow to the transplanted bladder. In one case, the donor was maintained on life support for 12 hours to confirm the continued viability of the transplanted bladder. 

Compared to open surgery, the robotic approach was felt to significantly facilitate donor cystectomy (bladder removal) surgery because of its superior technical access into the deep pelvis and blood vessel control. The online version of the article includes a link to a video where urologists can view key steps of the robotic auto-transplantation technique. Based on this rigorous pre-clinical developmental work, Dr. Gill and colleagues are preparing for the initial feasibility clinical trial of human bladder transplantation. 

If the technique of bladder transplantation can be successfully developed and refined, it could become "a viable treatment option in a minority of well-selected and well-counseled patients," the researchers conclude. They emphasize the many unanswered questions that remain – including the long-term functioning of the transplanted bladder, the need for lifelong immunosuppressive therapy to prevent organ rejection, and patient acceptance of bladder transplant versus standard urinary diversion procedures. 

Link to Paper [Robotic Bladder Autotransplantation: Preclinical Studies in Preparation for First-in-human Bladder Transplant]

Wolters Kluwer provides trusted clinical technology and evidence-based solutions that engage clinicians, patients, researchers and students in effective decision-making and outcomes across healthcare. We support clinical effectiveness, learning and research, clinical surveillance and compliance, as well as data solutions. For more information about our solutions, visit https://www.wolterskluwer.com/en/health and follow us on LinkedIn and Twitter @WKHealth

### 

About The Journal of Urology® 

The Official Journal of the American Urological Association (AUA), and the most widely read and highly cited journal in the field, The Journal of Urology® brings solid coverage of the clinically relevant content needed to stay at the forefront of the dynamic field of urology. This premier journal presents investigative studies on critical areas of research and practice, survey articles providing brief editorial comments on the best and most important urology literature worldwide and practice-oriented reports on significant clinical observations. The Journal of Urology® covers the wide scope of urology, including pediatric urology, urologic cancers, renal transplantation, male infertility, urinary tract stones, female urology and neurourology. 

About the American Urological Association 

Founded in 1902 and headquartered near Baltimore, Maryland, the American Urological Association is a leading advocate for the specialty of urology, and has more than 23,000 members throughout the world. The AUA is a premier urologic association, providing invaluable support to the urologic community as it pursues its mission of fostering the highest standards of urologic care through education, research and the formulation of health care policy. To learn more about the AUA visit: www.auanet.org 

About Wolters Kluwer  

Wolters Kluwer (EURONEXT: WKL) is a global leader in professional information, software solutions, and services for the healthcare, tax and accounting, financial and corporate compliance, legal and regulatory, and corporate performance and ESG sectors. We help our customers make critical decisions every day by providing expert solutions that combine deep domain knowledge with specialized technology and services.  

Wolters Kluwer reported 2022 annual revenues of €5.5 billion. The group serves customers in over 180 countries, maintains operations in over 40 countries, and employs approximately 20,0900 people worldwide. The company is headquartered in Alphen aan den Rijn, the Netherlands.  

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ICBM; NOT FOR TRAVEL 

New DOD-funded project will develop morphing hypersonic engine


Hypersonic speeds are those at Mach 5 and higher and could allow coast-to-coast travel from New York to L.A. in 30 mins.

Grant and Award Announcement

UNIVERSITY OF CENTRAL FLORIDA



ORLANDO, Sept. 8, 2023 – A new Naval Research Laboratory funded project led by a UCF researcher will work to create a morphing hypersonic engine for ultra-fast travel, building on UCF’s already leading edge developing hypersonic propulsion.

Hypersonic propulsion would allow for air travel at speeds of Mach 6 to 17, or more than 4,600 to 13,000 mph, and has applications in commercial and space travel. Although the technology has been around since the 1960s, countries including the U.S., Russia and China, are racing to improve the systems to achieve more efficient and longer, more sustained hypersonic flight.

The $450,000 Naval Research Laboratory grant-funded project will develop a hypersonic engine that can morph or transform its configuration during flights to optimize performance.

“Most hypersonic engines are structurally fixed due to the challenging flight environment,” says the project’s principal investigator Kareem Ahmed, a professor in UCF’s Department of Mechanical and Aerospace Engineering. “Our research will show the performance gains from an adaptable engine configuration that would self-optimize its surfaces to maximize performance power, thrust and travel distance which is the first of its kind for hypersonic engines.”

Ahmed is a leading researcher in the field of hypersonics, achieving the first stabilized and sustained rotating detonation wave for hypersonic travel and heading a $1.5 million U.S. Department of Defense award to develop high-performance fuels for hypersonic propulsion.

This new research project is based off Ahmed’s work on “scramjet”, or supersonic combustion ramjet engines. The key feature of a scramjet engine is its ability to combust air at supersonic speeds without slowing it down to subsonic speeds, as is done in traditional jet engines.

Ahmed and his research team have developed an aerothermodynamic model for the hypersonic, morphing scramjet engine and are currently in the stage of experimental testing it to assess the performance. Aerothermodynamics analyzes the interaction of gases at high speeds and elevated temperatures.

“We are very happy for being selected for the program,” Ahmed says. “Our lab has been a leader and innovator in high-speed and hypersonic propulsion and this program gives our group the opportunity to contribute and make an impact.”

Ahmed joined UCF’s Department of Mechanical and Aerospace Engineering, part of UCF’s College of Engineering and Computer Science, in 2014. He is also a faculty member of the Center for Advanced Turbomachinery and Energy Research and the Florida Center for Advanced Aero-Propulsion. He served more than three years as a senior aero/thermo engineer at Pratt & Whitney military engines working on advanced engine programs and technologies. He also served as a faculty member at Old Dominion University and Florida State University. At UCF, he is leading research in propulsion and energy with applications for power generation and gas-turbine engines, propulsion-jet engines, hypersonics and fire safety, as well as research related to supernova science and COVID-19 transmission control. He earned his doctoral degree in mechanical engineering from the State University of New York at Buffalo. He is an American Institute of Aeronautics and Astronautics associate fellow and a U.S. Air Force Research Laboratory and Office of Naval Research faculty fellow.

Writer: Mikita Nayee, UCF Office of Research

FOR PROFIT MEDICINE

What defines a safety-net hospital?


Study examines varied definitions and shared characteristics for hospitals serving low-income and uninsured populations


Peer-Reviewed Publication

NEW YORK UNIVERSITY




Safety-net hospitals have a common mission to provide care for Medicaid beneficiaries and those who are uninsured, but there’s no universal definition for these hospitals—complicating efforts to allocate funding.

In a new analysis published in JAMA Network Open and led by researchers at the NYU School of Global Public Health, the research team looked at five established definitions for safety-net hospitals and found that different criteria captured varying hospitals and characteristics. As a result, when the Centers for Medicaid and Medicare Services (CMS) use one definition to allocate funding, some hospitals are excluded and may not receive the necessary funding to continue providing care.

In an effort to characterize the safety net and inform hospital funding decisions, policymakers and researchers have developed a range of definitions for safety-net hospitals, taking into account factors such as uncompensated care costs, hospital ownership, and patients covered by Medicaid. One such definition, Disproportionate Share Hospital (DSH) payments, was developed by CMS to allocate funding to safety-net hospitals. DSH payments are calculated based on the share of care provided to patients receiving social security payments, Medicare coverage, and Medicaid coverage. 

In their analysis, the researchers looked at the characteristics of 5,955 U.S. hospitals captured in the 2020 American Hospital Association Annual Survey. They applied five different definitions of safety-net hospitals: those with the most DSH payments, Medicaid inpatient days, Medicaid inpatient days or public hospitals, public hospitals or teaching hospitals, and public hospitals. They also looked at different characteristics of the hospitals, including whether they were rural, for profit or nonprofit, number of beds, whether they were in a Medicaid expansion state, and the clinical complexity of their patients.

The analysis found that each safety-net definition encompassed a considerably different set of hospitals with varying characteristics. For instance, defining safety-net hospitals using only DSH payments accounted for 11.4% of U.S. hospitals and included the fewest rural and public facilities, while defining safety-net hospitals as public or teaching hospitals encompassed more than half (55.2%) of hospitals. 

The researchers recommend the adoption of a universal definition or safety-net hospital index to create a more precise tool to identify hospitals for funding. 

“This index should incorporate characteristics beyond financial expenditures to include community and service characteristics that can better capture which hospitals care for vulnerable populations,” said Elizabeth McNeill, a doctoral candidate at the NYU School of Global Public Health and the study’s first author. 

They also note the risk of allocating funding based on Medicaid care in light of uneven Medicaid coverage across the country. States that have not expanded Medicaid coverage may increase the proportion of uninsured individuals who need care from safety-net hospitals, driving up their costs for uncompensated care. 

“Employing a definition for safety-net hospitals based on Medicaid days will underestimate the needs of hospitals in non-expansion states,” said Ji Chang, assistant professor of public health policy and management at NYU School of Global Public Health and the study’s senior author. “A universal definition or index that includes hospital services in addition to Medicaid care would identify more facilities as safety-net hospitals in these states.” 

Additional study authors include Diana Silver of NYU School of Global Public Health, Cory Cronin and Berkeley Franz of Ohio University, and Neeraj Puro of Florida Atlantic University. The study was supported by the National Institute on Drug Abuse (R34 DA055228).

About the NYU School of Global Public Health

At the NYU School of Global Public Health (NYU GPH), we are preparing the next generation of public health pioneers with the critical thinking skills, acumen, and entrepreneurial approaches necessary to reinvent the public health paradigm. Devoted to employing a nontraditional, interdisciplinary model, NYU GPH aims to improve health worldwide through a unique blend of global public health studies, research, and practice. The School is located in the heart of New York City and extends to NYU's global network on six continents. Innovation is at the core of our ambitious approach, thinking and teaching. For more, visit: publichealth.nyu.edu