Artificial pancreas system aimed at type 1 diabetes mellitus

Researchers will soon undertake one of the largest-ever long-term clinical trials of a system designed to help regulate blood sugar levels of individuals with type 1 diabetes mellitus. If the scientists’ so-called artificial pancreas system performs in patients as they hope, it could lead to commercial trials and eventual regulatory approval in the United States and abroad.

With $12.7 million in support from the National Institutes of Health (NIH), the system developed by a team of researchers from the University of Virginia (UVA) School of Medicine and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) will be tested in 240 patients at nine sites in the United States and Europe. The two six-month trials will begin early this year, in collaboration with other institutional partners.

Already one of the most common chronic disorders, the incidence of diabetes is increasing worldwide. According to the U.S. Centers for Disease Control and Prevention, 1.25 million Americans have type 1 diabetes. In people living with the disease, the body’s immune system attacks and destroys the insulin-producing beta cells of the pancreas so that little or none of the insulin needed to regulate blood glucose is produced. Diabetics must vigilantly monitor blood-glucose levels and, when necessary, administer doses of insulin via either needle injections or an infusion pump. Failure to maintain proper blood-glucose levels by managing insulin can cause life-threatening hypoglycemia, or low blood sugar, as well as other complications.

“To be ultimately successful as an optimal treatment for diabetes, the artificial pancreas needs to prove its safety and efficacy in long-term pivotal trials in the patient’s natural environment,” said principle investigator Boris Kovatchev, director of the UVA Center for Diabetes Technology. “Our foremost goal is to establish a new diabetes treatment paradigm: The artificial pancreas is not a single-function device; it is an adaptable, wearable network surrounding the patient in a digital treatment ecosystem.”

Through a match of control engineering with medical practice and behavioral science, the artificial pancreas system is designed to supply the appropriate levels of insulin by not only reacting to changes in the body, but accurately predicting future blood glucose levels.

The artificial pancreas is not a replica organ; it is an automated insulin delivery system designed to mimic a healthy person’s glucose-regulating function. The closed-loop system consists of an insulin pump, a continuous glucose monitor placed under the user’s skin, and advanced control algorithm software embedded in a smartphone that provides the engineering brains, signaling how much insulin the pump should deliver to the patient based on a range of variables, including meals consumed, physical activity, sleep, stress, and metabolism.

The artificial pancreas is not a replica organ; it is an automated insulin delivery system designed to mimic a healthy person’s glucose-regulating function.

“The idea is that this can lead to an improved quality of life for individuals with this disease — not a solution to diabetes, but a means to really extend the quality of their healthful living,” said co-principal investigator and engineering lead on the project, Francis J. Doyle III, dean and John A. and Elizabeth S. Armstrong Professor of Engineering and Applied Sciences at Harvard SEAS.

In the first of the two trials planned as part of the new NIH-funded study, 240 patients with type 1 diabetes will test the safety and effectiveness of the artificial pancreas for six months while going about their normal daily routines. The control-to-range artificial pancreas system for this trial was developed at UVA and is now licensed to TypeZero Technologies. The artificial pancreas will be compared with a standard insulin pump on two key measures: how well blood-sugar levels are controlled and whether the risk of hypoglycemia is reduced.

The second trial will follow 180 patients who completed the first study for an additional six months to test the advanced adaptive control algorithm developed by Doyle’s Harvard team. That system is based on zone model-predictive control(zone MPC), a strategy originally developed by Doyle and colleagues in a seminal paper published in 1996. Rather than regulating glucose levels to a specific point in the same way that a home thermostat keeps room temperature at a precise setting, zone MPC defines an acceptable range for an individual’s glucose levels and controls variables to stay within it.

“The biggest challenge in the design of the artificial pancreas is the inherent uncertainty in the human body,” Doyle noted. “Day to day, hour to hour, the various stresses that impact the human body change the way it responds to insulin-controlling glucose. Physical stresses, anxiety, hormonal swings will all change that balance. To be able to control for those factors we need to see longer intervals of data. This is the first trial where we’ll be looking at multi-month intervals of time with cohorts of subjects where we can actually see a long enough window to learn those patterns, to adapt and fine-tune the algorithms, and to improve the overall level of glucose control.”

In addition to UVA and Harvard, the institutions that comprise the International Diabetes Closed Loop Consortium and will participate in the clinical trials include Mount Sinai Hospital, New York; the Mayo Clinic; Stanford University; the University of Colorado; the University of Padua, Italy; Regional University Hospital Center of Montpellier, France; the Academic Medical Center, Amsterdam; and the William Sansum Diabetes Center, Santa Barbara; with coordination by the JAEB Center for Health Research in Florida.

The UVA/Harvard award is the NIH’s largest commitment under a $20 million program the agency announced in 2014 to fund advanced clinical trials to test the safety and efficacy of artificial pancreas systems. The goal is to acquire the data necessary to satisfy requirements for regulatory approval by the U.S. Food and Drug Administration (FDA) and other international agencies. The NIH announced awards to three other teams earlier this year, awarding the University of Cambridge $6.4 million, the Diabetes Wireless Artificial Pancreas Consortium (comprised of diabetes centers in Germany, Israel, and Slovenia) $2 million, and Boston University/Massachusetts General Hospital $1.5 million.

Doyle and SEAS senior researcher Eyal Dassau, who were collaborators at the University of California, Santa Barbara, before joining Harvard in the fall of 2015, are also part of a team working on a pediatric version of the artificial pancreas system as well as an implantable version of the device.

Subject Masterclass: Genetics and Biochemistry

Subject Masterclass

Genetics and Biochemistry

Aimed at academically able Year 12 students from any school/college, masterclasses offer students a true flavour of undergraduate study and an introduction to the University of Cambridge.

Masterclasses provide students with an opportunity to explore topics of interest beyond what is covered within the A Level syllabus.

Masterclass includes:

• two taster lectures delivered by leading academic members of staff from the University
• the opportunity to discuss and ask questions
• an introduction to the Cambridge admissions process
• s chance to ask your own questions about applying to Cambridge
• the opportunity to hear about life as a Cambridge student, from current undergraduates

Funded places are available for:

• Anyone eligible for the 16-19 Bursary
• Anyone eligible for Discretionary Learner Support
• Children in Care
• Any families in receipt of Income Support

If you are eligible for a funded place please make an online booking using the ’Funded place’ ticket option and then complete the verification form.

Junior Clinical Training Scholarship in Small Animal Studies x 6

Scholarship award: £14,700 per annum

4 Scholarships to start on 1 June 2016 for 13 months

2 Scholarships to start on 1 October 2016 for 13 months

Applications are invited for this one year post-graduate training programme based in the Queen's Veterinary School Small Animal Hospital.

The scholarship is designed to provide a broad but intensive clinical learning experience that acts to prepare individuals for Senior Clinical Training Programmes and potential specialisation. However, the scholarship will also benefit graduates seeking advanced training and experience prior to beginning practice. Scholars will rotate through a variety of small animal disciplines including Soft Tissue Surgery, Orthopaedics, Internal Medicine, Oncology, Neurology, Diagnostic Imaging, Anaesthesia and Clinical Pathology and will be an integral part of the out of hours care of animals within the hospital especially within the intensive care unit.

Candidates must be Members of the Royal College of Veterinary Surgeons and should have experience of small animal general practice in the UK. New graduates may be considered.

Informal enquiries: contact Matthew McMillan (programme supervisor) via email atmwm32@cam.ac.uk.

The deadline for applications is Thursday 4th February 2016.

Interviews will be held on Monday 29th February 2016.

An application form (JCTS1) and information pack can be downloaded from the link below or via the following website: https://www.vet.cam.ac.uk/

Please send a completed application form, curriculum vitae, and covering letter by email tovetmed@hermes.cam.ac.uk clearly stating which Scholarship you are applying for and preferred start date (1 June or 1 October 2016)

The University values diversity and is committed to equality of opportunity.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

Calling for help: damaged nerve cells communicate with stem cells

Nerve cells damaged in diseases such as multiple sclerosis (MS), ‘talk’ to stem cells in the same way that they communicate with other nerve cells, calling out for ‘first aid’, according to new research from the University of Cambridge.

The study, published today in the journal Nature Communications, may have significant implications for the development of future medicines for disorders that affect myelin sheath, the insulation that protects and insulates our nerve cells.

For our brain and central nervous system to work, electrical signals must travel quickly along nerve fibres. This is achieved by insulating the nerve fibres with a fatty substance called myelin. In diseases such as MS, the myelin sheath around nerve fibres is lost or damaged, causing physical and mental disability.

Stem cells – the body’s master cells, which can develop into almost any type of cell – can act as ‘first aid kits’, repairing damage to the body. In our nervous system, these stem cells are capable of producing new myelin, which, in the case of MS, for example, can help recover lost function. However, myelin repair often fails, leading to sustained disability. To understand why repair fails in disease, and to design novel ways of promoting myelin repair, researchers at the Welcome Trust-Medical Research Council Stem Cell Institute at the University of Cambridge studied how this repair process works.

When nerve fibres lose myelin, they stay active but conduct signals at much lower speed than healthy fibres. Using electrical recording techniques, a team of researchers led by Dr Thora Karadottir discovered that the damaged nerve fibres then form connections with stem cells. These connections are the same as those that connect synapses between different nerve fibres. These new synaptic connections enable the damaged fibres to communicate directly with the stem cells by releasing the glutamate, a chemical that the stem cells can sense via receptors. This communication is critical for directing the stem cells to produce new myelin – when the researchers inhibited either the nerve fibres’ activity, their ability to communicate, or the stem cells’ ability to sense the communication, the repair process fails.

“This is the first time that we’ve been able to show that damaged nerve fibres communicate with stem cells using synaptic connections – the same connections they use to ‘talk to’ other nerve cells,” says Dr Karadottir. “Armed with this new knowledge, we can start looking into ways to enhance this communication to promote myelin repair in disease.”

Dr Helene Gautier from the Department of Physiology, Development and Neuroscience, adds: "So far, the majority of the available treatments are only slowing down damage. Our research opens the possibility to enhance repair and potentially treat the most devastating forms of MS and demyelinated diseases." 

New design points a path to the ‘ultimate’ battery

Researchers have successfully demonstrated how several of the problems impeding the practical development of the so-called ‘ultimate’ battery could be overcome.

"What we’ve achieved is a significant advance for this technology and suggests whole new areas for research".  - Clare Grey.

Scientists have developed a working laboratory demonstrator of a lithium-oxygen battery which has very high energy density, is more than 90% efficient, and, to date, can be recharged more than 2000 times, showing how several of the problems holding back the development of these devices could be solved. 

Lithium-oxygen, or lithium-air, batteries have been touted as the ‘ultimate’ battery due to their theoretical energy density, which is ten times that of a lithium-ion battery. Such a high energy density would be comparable to that of gasoline – and would enable an electric car with a battery that is a fifth the cost and a fifth the weight of those currently on the market to drive from London to Edinburgh on a single charge. 

However, as is the case with other next-generation batteries, there are several practical challenges that need to be addressed before lithium-air batteries become a viable alternative to gasoline. 

Now, researchers from the University of Cambridge have demonstrated how some of these obstacles may be overcome, and developed a lab-based demonstrator of a lithium-oxygen battery which has higher capacity, increased energy efficiency and improved stability over previous attempts. 

Their demonstrator relies on a highly porous, ‘fluffy’ carbon electrode made from graphene (comprising one-atom-thick sheets of carbon atoms), and additives that alter the chemical reactions at work in the battery, making it more stable and more efficient. While the results, reported in the journal Science, are promising, the researchers caution that a practical lithium-air battery still remains at least a decade away. 

“What we’ve achieved is a significant advance for this technology and suggests whole new areas for research – we haven’t solved all the problems inherent to this chemistry, but our results do show routes forward towards a practical device,” said Professor Clare Grey of Cambridge’s Department of Chemistry, the paper’s senior author. 

Many of the technologies we use every day have been getting smaller, faster and cheaper each year – with the notable exception of batteries. Apart from the possibility of a smartphone which lasts for days without needing to be charged, the challenges associated with making a better battery are holding back the widespread adoption of two major clean technologies: electric cars and grid-scale storage for solar power. 

“In their simplest form, batteries are made of three components: a positive electrode, a negative electrode and an electrolyte,’’ said Dr Tao Liu, also from the Department of Chemistry, and the paper’s first author. 

In the lithium-ion (Li-ion) batteries we use in our laptops and smartphones, the negative electrode is made of graphite (a form of carbon), the positive electrode is made of a metal oxide, such as lithium cobalt oxide, and the electrolyte is a lithium salt dissolved in an organic solvent. The action of the battery depends on the movement of lithium ions between the electrodes. Li-ion batteries are light, but their capacity deteriorates with age, and their relatively low energy densities mean that they need to be recharged frequently. 

Over the past decade, researchers have been developing various alternatives to Li-ion batteries, and lithium-air batteries are considered the ultimate in next-generation energy storage, because of their extremely high energy density. However, previous attempts at working demonstrators have had low efficiency, poor rate performance, unwanted chemical reactions, and can only be cycled in pure oxygen. 

What Liu, Grey and their colleagues have developed uses a very different chemistry than earlier attempts at a non-aqueous lithium-air battery, relying on lithium hydroxide (LiOH) instead of lithium peroxide (Li2O2). With the addition of water and the use of lithium iodide as a ‘mediator’, their battery showed far less of the chemical reactions which can cause cells to die, making it far more stable after multiple charge and discharge cycles.

 By precisely engineering the structure of the electrode, changing it to a highly porous form of graphene, adding lithium iodide, and changing the chemical makeup of the electrolyte, the researchers were able to reduce the ‘voltage gap’ between charge and discharge to 0.2 volts. A small voltage gap equals a more efficient battery – previous versions of a lithium-air battery have only managed to get the gap down to 0.5 – 1.0 volts, whereas 0.2 volts is closer to that of a Li-ion battery, and equates to an energy efficiency of 93%. 

The highly porous graphene electrode also greatly increases the capacity of the demonstrator, although only at certain rates of charge and discharge. Other issues that still have to be addressed include finding a way to protect the metal electrode so that it doesn’t form spindly lithium metal fibres known as dendrites, which can cause batteries to explode if they grow too much and short-circuit the battery. 

Additionally, the demonstrator can only be cycled in pure oxygen, while the air around us also contains carbon dioxide, nitrogen and moisture, all of which are generally harmful to the metal electrode. 

“There’s still a lot of work to do,” said Liu. “But what we’ve seen here suggests that there are ways to solve these problems – maybe we’ve just got to look at things a little differently.” 

“While there are still plenty of fundamental studies that remain to be done, to iron out some of the mechanistic details, the current results are extremely exciting – we are still very much at the development stage, but we’ve shown that there are solutions to some of the tough problems associated with this technology,” said Grey. 

The authors acknowledge support from the US Department of Energy, the Engineering and Physical Sciences Research Council (EPSRC), Johnson Matthey and the European Union via Marie Curie Actions and the Graphene Flagship. The technology has been patented and is being commercialised through Cambridge Enterprise, the University’s commercialisation arm.

Newton, Darwin, Shakespeare – and a jar of ectoplasm: Cambridge University Library at 600

In 2016, Cambridge University Library will celebrate 600 years as one of the world's greatest libraries with a spectacular exhibition of priceless treasures – and a second show throwing light on its more weird and wonderful collections.

Older than the British Library and the Vatican Library, Cambridge University Library was first mentioned by name in two wills dated March 1416 and its most valuable contents stored in a wooden chest. The library now holds eight million books, journals, maps and magazines – as well as some of the world's most iconic scientific, literary and cultural treasures.

Its priceless collections include Newton’s own annotated copy of Principia Mathematica, Darwin’s papers on evolution, 3000-year-old Chinese oracle bones, and the earliest reliable text for 20 of Shakespeare’s plays.

But is also home to a bizarre assembly of non-book curiosities, collected over centuries, including a jar of ectoplasm, a trumpet for hearing spirits and a statue of the Virgin Mary, miraculously saved from an earthquake on Martinique.

Since 1710, Cambridge University Library has also been entitled to one copy of each and every publication in the UK and Ireland under Legal Deposit – meaning the greatest works of more than three millennia of recorded thought sit alongside copies of Woman’s Own and the Beano on more than 100 miles of shelves. With two million of its volumes on open display, readers have the largest open-access collection in Europe immediately available to them.

To celebrate the Library’s 600th birthday, a spectacular free exhibition, Lines of Thought, will open on March 11, 2016. Featuring some of Cambridge’s most iconic and best-known treasures, it investigates through six distinct themes how both Cambridge and its collections have changed the world and will continue to do so in the digital era.

As well as the iconic Newton, Darwin and Shakespeare artefacts mentioned above, items going on display include:

*Edmund Halley’s handwritten notebook/sketches of Halley’s Comet (1682)

*Stephen Hawking’s draft typescript of A Brief History of Time

*Darwin’s first pencil sketch of Species Theory and his Primate Tree

*A second century AD fragment of Homer’s Odyssey.

*The Nash Papyrus – a 2,000-year-old copy of the Ten Commandments

*Codex Bezae – 5th New Testament, crucial to our understanding of The Bible.

*A hand-coloured copy of Vesalius’ 1543 De fabrica – the most influential work in western medicine

*A written record of the earliest known human dissection in England (1564)

*A Babylonian tablet dated 2039 BCE (the oldest object in the library)

*The Gutenberg Bible – the earliest substantive printed book in Western Europe (1454)

*The first catalogue listing the contents of the Library in 1424, barely a decade after it was first identified in the wills of William Loryng and William Hunden

As well as Lines of Thought, 2016 will also see dozens of celebratory events including the library’s 17-storey tower being lit up as part of the e-Luminate Festival in February. Cambridge University Library is also producing a free iPad app giving readers the chance to interact with digitised copies of six of the most revolutionary texts held in its collections. The app analyses the context of the six era-defining works, including Darwin's family copy of On the origin of species, Newton's annotated copy of Principia Mathematica, and William Tyndale's translation of the New Testament into English, an undertaking which led to his execution for heresy.

From October 2016, an exhibition featuring some of the University Library’s most unusual curiosities and oddities will replace Lines of Thought as the second major exhibition of the sexcentenary.

Over the past 600 years, Cambridge has accumulated an extraordinary collection of objects, often arriving at the library as part of bequests and donations. Some of the library’s more unusual artefacts include children’s games, ration books, passports, prisoner art, Soviet cigarettes and cigars and an East African birthing stool.

University Librarian Anne Jarvis said: “For six centuries, the collections of Cambridge University Library have challenged and changed the world around us. Across science, literature and the arts, the millions of books, manuscripts and digital archives we hold have altered the very fabric of our understanding. Thousands of lines of thoughts run through them, back into the past, and forward into tomorrow. Our 600th anniversary is a chance to celebrate one of the world’s oldest and greatest research libraries, and to look forward to its future.

“Only in Cambridge, can you find Newton’s greatest works sitting alongside Darwin’s most important papers on evolution, or Sassoon’s wartime poetry books taking their place next to the Gutenberg Bible and the archive of Margaret Drabble. Our aim now, through our Digital Library, is to share as many of these great collections as widely as possible so that anyone, anywhere in the world, can stand on the shoulders of these giants.”

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HGSE Announces Certificate in Advanced Education Leadership

The professional education program, based on the groundbreaking Doctor of Education Leadership Program, will provide education leaders with the skills and approaches to improve their own leadership and to help make their vision a reality.

Dean James Ryan announced today a new online certificate program, Certificate in Advanced Education Leadership(CAEL), launching in February 2016. CAEL will provide current and aspiring system-level leaders with the knowledge, skills, and tools to improve their own leadership and effect meaningful systemic improvement.

“If we want to provide every child with a high-quality education, we have to ensure that there is effective leadership at every level — the classroom, the school, and systems as a whole,” Ryan said. “The online Certificate in Advanced Education Leadership will enable us to bring to scale the kind of rich and rigorous leadership development we currently provide on campus.”

CAEL, which is based on the groundbreaking Doctor of Education Leadership (Ed.L.D.) Program, provides education leaders with the skills and approaches to improve their own leadership and to help make their vision a reality. The certificate program brings together education professionals from around the world to create a dynamic community of practice. Leveraging the resources of the Harvard Graduate School of Education and the collective wisdom and expertise of program colleagues, participants will develop strategies for system-level change that can be implemented both immediately and over the long term.

“In my experience, system-level leaders have few sustained, challenging professional learning opportunities available to them, particularly ones that are connected to their own practice. And yet, we expect system-level leaders to do complex, ambiguous tasks in politically-complicated environments towards the essential goal of helping all children learn. To do their work well, leaders need to be learners, too,” said Lecturer Elizabeth City, director of the Ed.L.D. Program and chair of CAEL. “Basically, system-level leaders are tasked with supporting others’ learning, but usually don’t have much time or support to do the kind of learning they need to do in order to perform well.”

Participants must complete four, 12-week modules led by an HGSE faculty member to earn a certificate of competencies. All four modules must be completed within 24 months of beginning the certificate program. The modules are:

• Leading Learning | February 15–May 7, 2016
• Managing Evidence | May 8–July 30, 2016
• Driving Change | September 12–December 3, 2016
• Leading for Excellence and Equity | January 29–April 22, 2017

Each module is designed to be flexible and rigorous, through online activities, exercises, reading, assessments, small-group virtual discussions, professional exercises, and final projects.

“We expect that their work environments will inform and be informed by their CAEL learning,” City said. “We’ll have a collaborative learning community supported by online learning facilitators, and there will be ample opportunities for practice, feedback, reflection, and documentation of learning in an e-portfolio.”

The certificate is part of a $5 million grant from the Walton Family Foundation awarded last year that allotted for the development of online content for system-level leaders.

“With support from the Walton Family Foundation, the CAEL will help us reach even more educators in charge of districts, charter management organizations, state departments of education, and other systems — leaders who will, in turn, have a tangible impact on the lives of literally millions of learners,” Ryan said.