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For some time now, patients in Sweden’s emergency clinics complaining of chest pain have been evaluated using the “high-sensitivity troponin T” assay. In a large-scale registry study published in the Journal of the American College of Cardiology scientists at Karolinska Institutet show how this more sensitive analytical method has improved evaluation for these patients. Since its introduction, fewer patients diagnosed with “unspecified chest pain” suffer a heart attack or die after being sent home. Chest pain is one of the most common reasons for emergency medical care. Sometimes the pain can be related to a heart attack, but most of the time the cause of the problem cannot be identified and most patients are sent home with an “unspecified chest pain” diagnosis. However, a few of these people will suffer a heart attack, others will have to undergo unplanned revascularisation, and still others will die within 30 days. The difficulty lies in ascertaining who these patients are when they go to an emergency unit with a chest pain complaint. To rule out myocardial infarction, doctors normally check the patients’ ECG and a blood test or the cardiac biomarkers troponin T or I. In recent years, however, a new and more sensitive assay has been introduced at Swedish hospitals. The method is called high-sensitivity troponin T, which has been shown by previous studies to be more diagnostically accurate, although whether this accuracy applies to clinical procedures has not been known. 65,000 patients studied To discover if high-sensitivity troponin T is associated with a lower incidence of cardiovascular events, the researchers conducted a large-scale registry study of 65,000 patients with unspecified chest pain who had been discharged from 16 Swedish emergency clinics between 2006 and 2013 in connection with the introduction of the new method. They found that the risk of suffering a serious cardiovascular event within 30 days of returning home was much lower in patients discharged from an emergency clinic when the new method was in use than in those examined with the old one. The percentage of those subsequently suffering a heart attack, dying or undergoing unplanned revascularisation dropped from 0.9 to 0.6 per cent. “Our results are of interest to other countries such as the USA, which is about to change its methods,” says Per Svensson, associate professor and senior lecturer at Karolinska Institutet’s Department of Medicine in Solna. Increased risk amongst admitted patients However, amongst the patients who had been discharged from hospital after being admitted for an unspecified chest pain diagnosis, the risk of suffering serious events increased after the change in method. In this group, 7.2 per cent of patients with the new method in use were affected, compared with 3.4 per cent who were examined in the former way. These particular patients also had a higher risk profile after the change in method. “We may conclude from the results of our study that examination using high-sensitivity troponin is associated with fewer serious cardiac events and an improvement in risk profile for patients released from emergency clinics with unspecified chest pain,” says Dr Svensson. “The opposite was observed in patients sent home after admission to hospital, which suggests that high-risk patients are identified and hospitalised more frequently. We therefore conclude that high-sensitivity troponin has helped to improve the evaluation of emergency patients with unspecified chest pain.” The study was financed by Karolinska Institutet. Publication “Outcomes in Patients With Chest Pain Discharged After Evaluation Using a High-Sensitivity Troponin T Assay” Atosa Nejatian, Åsa Omstedt, Jonas Höijer, L.O. Hansson, Therese Djärv, Kai M. Eggers, Per Svensson Journal of the American College of Cardiology (JACC), 30 May 2017, 69(21):2622-2630, doi:10.1016/j.jacc.2017.03.586

What happens in the brain when we see other people experiencing a trauma or being subjected to pain? Well, the same regions that are involved when we feel pain ourselves are also activated when we observe other people who appear to be going through some painful experience. This is shown in a study from Karolinska Institutet published in Nature Communications. But we are sensitive to different degrees to learning fear from other people and one explanation would appear to be found in the endogenous opioid system. Seeing others express pain or anxiety can give us important information about things around us that are dangerous and should be avoided. Sometimes, however, we can develop fear of situations that, rationally speaking, are not dangerous. The opioid system is supposed to alleviate pain and fear but it does not work as effectively in all of us, which might be one of the reasons why some people develop anxiety syndrome merely by seeing others experience a trauma. The opioid system affects how sensitive we are “Some people are over-sensitive to this form of social learning. Our study shows that the endogenous opioid system affects how sensitive we are and may explain why some people develop post-traumatic stress disorder (PTSD) merely by observing others who are experiencing traumatic events. After terror attacks, sensitive people might be afraid even if they themselves were not present,” says main author Jan Haaker, associated researcher at Karolinska Institutet’s Department of Clinical Neuroscience. In a double-blind study, the researchers altered the brain’s internal chemistry in 22 healthy subjects by using a pharmaceutical substance to block the opioid system. 21 subjects were given an inactive placebo. The subjects then watched a video where other people were subjected to electric shocks. Continued to react as if they were surprised The brain normally updates its knowledge of danger based on whether we are surprised, but when the opioid system was blocked, the people continued to react as if they were surprised even though they knew the electric shock would come. And the response was amplified even when they continued to watch other people being subjected to shocks. The response increased in regions of the brain such as the amygdala, the periaqueductal gray and the thalamus, which seems to indicate that the same functions as in self-perceived pain were involved. Communication also increased between these and other regions of the brain that were previously linked to the ability to understand other individuals’ experiences and thoughts. “When the people participating in the experiment were themselves subjected to threatening stimuli that they had previously associated with other people’s pain, they perspired more and displayed more fear than those who had been given a placebo. This enhanced learning was even visible three days after the social learning episode,” says research team leader Andreas Olsson, senior lecturer at Karolinska Institutet’s Department of Clinical Neuroscience. The study contributes to greater understanding of the psychology behind fear. The researchers hope that the new findings will eventually mean that people with anxiety conditions will be able to be given better, more individual-adapted clinical help. The study was financed by the European Research Council (ERC), the Knut and Alice Wallenberg Foundation and the German Research Foundation (DFG). Publication ”Endogenous opioids regulate social threat learning in humans” Jan Haaker, Jonathan Yi, Predrag Petrovic and Andreas Olsson Nature Communications, online 25 May 2017. doi:10.1038/ncomms15495

The human brain is much better than previously thought at discovering and avoiding disease, a new study led by researchers at Karolinska Institutet in Sweden reports. Our sense of vision and smell alone are enough to make us aware that someone has a disease even before it breaks out. And not only aware – we also act upon the information and avoid sick people. The study is published in the scientific journal Proceedings of the National Academy of Sciences (PNAS). The human immune system is effective at combating disease, but since it entails a great deal of energy expenditure disease avoidance should be part of our survival instinct. A new study now shows that this is indeed the case: the human brain is better than previously thought at discovering early-stage disease in others. Moreover, we also have a tendency to act upon the signals by liking infected people less than healthy ones. “The study shows us that the human brain is actually very good at discovering this and that this discovery motivates avoidance behaviour,” says principal investigator Professor Mats Olsson at Karolinska Institutet’s Department of Clinical Neuroscience. Measured brain activity By injecting harmless sections of bacteria, the researchers activated the immune response in participants, who developed the classic symptoms of disease – tiredness, pain and fever – for a few hours, during which time smell samples were taken from them and they were photographed and filmed. The injected substance then disappeared from their bodies and with it the symptoms. Another group of participants were then exposed to these smells and images as well as those of healthy controls, and asked to rate how much they liked the people, while their brain activities were measured in an MR scanner. They were then asked to state, just by looking at the photographs, which of the participants looked sick, which they considered attractive and which they might consider socialising with. “Our study shows a significant difference in how people tend to prefer and be more willing to socialise with healthy people than those who are sick and whose immune system we artificially activated,” says Professor Olsson. “We can also see that the brain is good at adding weak signals from multiple senses relating to a person's state of health”. Opposite effect in close relationships This he sees as biological confirmation of the argument that survival naturally entails avoiding infection. “Common sense tells us that there should be a basic behavioural repertoire that assists the immune system. Avoidance, however, does not necessarily apply if you have a close relationship with the person who is ill,” says Professor Olsson. “For instance, there are few people other than your children who you’d kiss when they have a runny nose. In other words, a disease signal can enhance caring behaviour in close relationships. With this study, we demonstrate that the brain is more sensitive to those signals than we once thought.” The research has been carried out in collaboration with several parties, especially with the Stress Research Institute at Stockholm University. The study was supported by the Swedish Research Council, the Swedish Foundation for Humanities and Social Sciences, the Knut and Alice Wallenberg Foundation and Deutscher Akademischer Austauschdienst. Publication “Behavioral and neural correlates to multisensory detection of sick humans” Christina Regenbogen, John Axelsson, Julie Lasselin, Danja K. Porada, Tina Sundelin, Moa G. Peter, Mats Lekander, Johan N. Lundström, Mats J. Olsson PNAS, Online 22 May 2017. doi: 10.1073/pnas.1617357114

Researchers at Karolinska Institutet in Sweden have managed to synthesise lung surfactant, a drug used in the care of preterm babies, by mimicking the production of spider silk. Animal studies reveal it to be just as effective as the biological drugs currently in clinical use. The study is published in Nature Communications. Surfactant revolutionised the care of preterm babies by reducing the surface tension in their pulmonary alveoli and allowing them to be inflated at the moment of birth. Curosurf, the most globally widespread drug, was developed by scientists at Karolinska Institutet in the 1970s and 1980s. The drug is produced by the isolation of proteins from pig lungs, a process that is expensive, complicated and potentially risky. Researchers at Karolinska Institutet and their colleagues from the University of Riga amongst other institutions, have now developed a surfactant drug that can be produced much more simply and cheaply using spider protein. “The manufacturing process is based on the method spiders use to keep their extremely easily aggregated proteins soluble for silk-spinning,” explains Professor Jan Johansson at Karolinska Institutet’s Department of Neurobiology, Care Sciences and Society. “We chose to produce lung surfactant protein C because it is probably the world’s most aggregation-inclined protein.” Used a part of the spider protein By applying this method, the researchers have managed to produce a range of potential biological drugs using the part of the spider protein that ensures that the proteins remain soluble, namely the N-terminal domain. “We had bacteria produce this part of the protein and then linked it to different protein drug candidates,” says docent Anna Rising at Karolinska Institutet’s Department of Neurobiology, Care Sciences and Society who co-led the study with Professor Johansson. Compared with the approved drug The researchers also compared their synthetic lung surfactant with the biological analogue currently on the market and found it equally effective at reducing the surface tension in an animal model of neonate respiratory disorders. “Since this production method is much simpler and cheaper, it might one day be possible to use our synthetic lung surfactant to treat more lung diseases than just preterm babies,” adds Professor Johansson. “The method will also hopefully enable the production of other biological drugs.” The study was primarily financed by the Swedish Research Council and was performed in collaboration with the Italian pharmaceutical company Chiesi Farmaceutici. Publication “Efficient protein production inspired by how spiders make silk” Nina Kronqvist, Médoune Sarr, Anton Lindqvist, Kerstin Nordling, Martins Otikovs, Luca Venturi, Barbara Pioselli, Pasi Purhonen, Michael Landreh, Henrik Biverstål, Zigmantas Toleikis, Lisa Sjöberg, Carol V. Robinson, Nicola Pelizzi, Hans Jörnvall, Hans Hebert, Kristaps Jaudzems, Tore Curstedt, Anna Rising & Jan Johansson Nature Communications , online 23 May 2017

Comment: Läkartidningen has published an interview with KI’s former vice-chancellor Harriet Wallberg following a letter she sent to KI demanding corrections to Sten Heckscher’s report on the Macchiarini case. In the interview Wallberg makes reference to a conversation with KI’s acting vice-chancellor and university director. The KI management responds here to her claims. KI’s university director and acting vice-chancellor were invited by Harriet Wallberg to a meeting following the presentation of Sten Heckscher’s report. It was pointed out at the time that the investigation was an external one commissioned by the University Board, where the investigator himself would be accountable for the content. At the same time, it was put forward that KI cannot rule out the possibility of errors in the report since it had not undergone a quality check. Contrary to Wallberg’s claim in Läkartidning, no flaws were ever found in Sten Heckscher’s report.

The expectations are high. Everyone, externally as well as internally, are asking themselves how Ole Petter Ottersen is going to lead Sweden’s most talked-about university once he takes up office as vice-chancellor of Karolinska Institutet this August. After KI’s annus horribilis, now that the university has devoted a great deal of time and energy to clearing up in the wake of the Macchiarini case many people are hoping for a fresh start. The vice-chancellor-elect is at once humble and optimistic. “We now have to make sure to use the crisis for something positive and learn from it,” says Ole Petter Ottersen. “I wouldn’t have accepted the job if I hadn’t thought that something good can come out of all this.” He makes a point of praising the work done by the acting vice-chancellor and that it means a great deal to be working alongside Karin Dahlman-Wright as pro-vice-chancellor. However, he will also be inserting new issues high up his agenda the moment he settles down at his desk. The first concerns job satisfaction. “The question of how to create job satisfaction in an organisation reeling from such challenges is one that occupies my mind a great deal, and I’m prepared to discuss it with the management, deans and departments. A lot of amazing things are happening at Karolinska Institutet, especially all the new buildings and opportunities that are emerging here. All the same, I think that academic excellence must be balanced with a solid working culture and ethical preparedness, for I think that then the university will have a fantastic future ahead of it,” he says. Leadership in Norway and internationally Professor Ottersen has a sterling academic CV and long experience of leadership in and outside Norway. He is a doctor, professor of medicine, brain researcher and, since 2009, rector of Oslo University. One could say that Professor Ottersen has taken the classic career route in his own Alma mater, as the former head of the Anatomy Department, dean of research and the Medical Faculty, and director of one of Norway’s first Centres of Excellence, the Centre for Molecular Biology and Neuroscience. In this sense he is not unlike previous vice-chancellors at KI. But what sets him apart from his predecessors is that he is to be vice-chancellor of a different university to the one he was “raised” at. Professor Ottersen is experienced in leading international university evaluations and is the former chair of the ERC, European Research Council’s Advanced Grants panel and the current chair and member of the newly established Guild of Research Intensive Universities. Amongst many other positions. Be that as it may, he admits that taking on the rectorate of KI will be a steep uphill climb, and he will have to go home to do some studying over the summer on Swedish law, on the rules governing the exercise of public authority, and on how the academic sector in Sweden operates. But he also has to gradually familiarise himself with a completely new organisation. How do you intend to inspire confidence in the employees? “I really believe in being honest and open, I suppose that’s the main thing, as is having a clear vision about where the organisation is heading,” he says. Partnership and education Aside from job satisfaction, his other priorities were proclaimed in the policy statement he presented to Karolinska Institutet when he was still being proposed as the sole final candidate for the vice-chancellor’s office. He now mentions three of them: “The most important thing is how to get the best possible partnership in place between Karolinska Institutet, the hospital and Stockholm County Council. I’m happy to see that the “Akademiska stråket” link will soon be completed so that Solnavägen will no longer be a physical barrier between the university and the university hospital. And it goes without saying that the two campuses in Flemingsberg and Solna should work well together. I also want to make sure that the status of education is raised. Karolinska Institutet’s goal is to be a world-leading research university and should also aim to be top-ranking in education too.” Oslo University has eight faculties. How different will it be to lead a medical university? “It’s surprising how many of the challenges facing KI are similar to those we have in Oslo, where we’ve created a similar partnership with the Regional Health Authority. We’ve also put a lot of work into strengthening education. So even though Karolinska Institutet is a completely different university, I’m not a stranger to these kinds of challenge. But of course, it’s a major undertaking that will require me to really get to know the organisation.” Professor Ottersen points out that even if KI is a medical university, he will actively encourage more multidisciplinary work and is keen to see closer and broader cooperation with the Royal Institute of Technology, with other universities – including Stockholm and Uppsala – and, last but not least, with Nordic medical institutions. How do you plan to go about strengthening education? “I believe that teaching at a leading university like Karolinska Institutet must carry a high status and that you need to have examinations that in themselves are part of the learning process and to go through the study programmes to see how the degrees can yield more benefit to the students. Digital degrees are often in demand from the students and this is something we’ve put a lot of effort into at Oslo University. I don’t know how far KI has come, but it’s an important area to focus on.” Why is education so often in the shadow of research? “All universities put a premium on research because it has higher kudos,” says Professor Ottersen. “But raising the status of education pays off in research terms too. Both areas benefit from it. After all, we source a lot of our researchers from amongst our own students, and it’s useful to get students involved in research as much as possible.” Professor Ottersen has himself taught for over 30 years and is a much cited researcher in his field. “I think that the combination is inspiring,” he says. “It’s a wonderful thing to research and to pass your results onto the students and get their response. It’s not without reason that education and research belong together. They’re not rivals.” Blogger and public debater His own research has focused on the brain and the neurotransmitters that allow nerve cells to “talk” to each other. He has also researched how water is transported in the brain. This said, he devotes some of his time to a completely different field: “I’m very interested in global health and have led the Lancet-University of Oslo Commission on Global Governance for Health, which has been looking at health inequality around the world and the mechanisms driving it.” Professor Ottersen is a well-known blogger and public debater in Norway. He believes that research policy should operate with a degree of consistency, and often talks about the value of foresight and endurance to research success and of having strong research funders and a higher basic appropriation for universities. “Research is time consuming, and it can sometimes take up to fifteen years for you to arrive at the goal of your investigation. Financing is very much governed by what are seen as more or less acute needs and you have to make sure to keep changing the research financing objectives.” He also sticks his neck out on the issue of whether universities should recruit researchers at the top of their careers or invest in junior doctoral graduates and postdocs by creating attractive internal career pathways. “I’ve been saying this for a long time, from the perspective of Oslo University, that the best way to recruit is to target young talent. This is a sound recruitment strategy and allows you to build strong subject fields.” The final question of the interview concerns the motto that Karolinska Institutet should have if Oslo University’s is “We are reaching for the stars”. But he chooses not to say. “It’s not up to me as vice-chancellor to dictate what the university’s motto will be. But it’s good if it signals ambition, because high ambitions are the most important driver of excellence – or frontline research, as I prefer to say. However, the ambitions must be realistic and can only be achieved brick by brick – never by taking shortcuts. I think it’s good to have the ambition to reach for the stars, to do your best to reach a little beyond your grasp.”   Text: Madeleine Svärd Huss Photo: Gustav Mårtensson

Babies born preterm run a higher risk of heart failure during childhood and adolescence than those born at full term, researchers at Karolinska Institutet in Sweden report. The registry-based study is published in The Journal of the American College of Cardiology (JACC). More and more babies survive increasingly preterm births. Babies born prematurely are exposed to life outside the womb at a time when their organs are yet to fully mature and their bodies are not entirely prepared for the radical transition from fetus to neonate. In recent years, scientists have become all the more interested in the consequences of preterm birth on, amongst other things, cardiovascular health in young adults. Complementing previous studies indicating a higher risk of hypertension, stroke and fatal cardiovascular disease, researchers at Karolinska Institutet have now uncovered a hitherto unknown connection between preterm birth and heart failure in a registry study of 2.6 million individuals born between 1987 and 2012. “We found that the risk of heart failure was higher for individuals born preterm, and inversely correlated with duration of pregnancy, in that the earlier you’re born, the greater the risk,” explains lead author Hanna Carr, doctoral student at Karolinska Institutet’s Department of Medicine in Solna. The study shows that children born before the 28th week are 17 times more likely to suffer heart failure than those born at full term. Individuals born a little later – in weeks 28 to 31 – ran just over three times the risk. This correlation held when children with birth defects were excluded from the analysis and other possible determinants, such as birth weight, socioeconomic situation and parental heart conditions, were controlled for. The results corroborate earlier studies indicating abnormal development of the cardiovascular system in people born prematurely. The researchers point out, however, that heart failure is very rare in children and young adults, so the risk of developing the condition at a young age is very small, even for people born prematurely. “It could be the case that the higher risk of heart failure remains when they grow older, in which case more people will be affected as heart failure is much more common in older people,” says associate professor Anna-Karin Edstedt Bonamy, paediatrician, who led the project. “In general the risk of heart failure can be reduced by adopting a healthy lifestyle, including refraining from tobacco use, keeping physically active, minimising your alcohol consumption and occasionally checking your blood pressure.” The study was financed by Stockholm County Council Research Service, the Karolinska Institutet Clinical Scientist Training Programme and the Swedish Heart and Lung Foundation. Publication Preterm birth and risk of Heart Failure Up to Early Adulthood Hanna Carr, Sven Cnattingius, Fredrik Granath, Jonas F. Ludvigsson, Anna-Karin Edstedt Bonamy, Journal of the American College of Cardiology, online 22 May 2017.

In diseases like cancer, diabetes, rheumatism and stroke, a disorder develops in the blood vessels that exacerbates the condition and obstructs treatment. Researchers at Karolinska Institutet now show how blood vessels can normally change their size to create a functional circulatory system and how vascular malformation during disease can occur. In the study, published in Nature Cell Biology, the researchers managed to treat vascular malformation in mice, a discovery of potential significance to numerous vascular diseases. A healthy body has a perfect balance of arteries, capillaries and veins that allow the blood to reach every cell in the body and that form what is called the “vascular tree”. New blood vessels are formed by endothelial cells, which normally coat the inside of blood vessels and which organise themselves into tubes and mature, along with other cells, into arteries, capillaries or veins. Throughout a person’s life, the vascular tree has to adapt its branches to the changing needs of body tissue, such as during growth, muscle building or wound healing. However, there are diseases that affect the endothelial cells in a way that throws the vascular tree out of balance, which exacerbates the disease and often causes haemorrhaging. In cancer, for example, it is known that the vessels leak and direct shunts form between arteries and veins, preventing drugs from reaching the tumour. To understand how arteries, veins and capillaries are created – and how the process malfunctions in the presence of disease – the researchers studied normal vascular formation and the inherited Osler-Weber-Rendu disease (HHT), which is characterised by vascular malformation and repeated haemorrhaging, with an increased risk of stroke. By switching signals on and off in the endothelial cells of genetically manipulated mice, the researchers could describe how the protein Endoglin controls vascular formation and malformation. They found that the protein acts like a sensor that detects blood flow and tells the endothelial cells to organise themselves into veins, capillaries or arteries as necessary. Cells that lacked the protein were less able to form arteries. The researchers were also able to reduce vascular malformation in the genetically manipulated mice. “Our findings contribute to the understanding of fundamental biological processes that explain how the vascular tree is formed and what causes vascular malformation,” says Lars Jakobsson, assistant professor at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics. “Drugs with a similar effect as one of those we tested are currently used to treat patients with inherited vascular malformation but are still under evaluation. Now we have another candidate and a more nuanced idea of how it works. We are now in a better position to control the formation and malformation of blood vessels and thus their function, which can eventually lead to improved treatments for a number of diseases.” The researchers at Karolinska Institutet also contributed to a parallel study, published in the same issue of Nature Cell Biology, describing how blood flow influences endothelial cell size that in turn affects vessel identity and malformation. The studies were financed by several bodies, including the William K. Bowes, Jr. Foundation, the Swedish Research Council, the Swedish Cancer Society, Karolinska Institutet, the Jeansson Foundations and the Magnus Bergvall Foundation. Publications Endoglin prevents vascular malformation by regulating flow-induced cell migration and specification through VEGFR2 signalling. Yi Jin, LarsMuhl, Mikhail Burmakin, YixinWang, Anne-Claire Duchez, Christer Betsholtz, Helen M. Arthur and Lars Jakobsson. Nature Cell Biology, online 22 May 2017 Endoglin controls blood vessel diameter through endothelial cell shape changes in response to haemodynamic cues. Wade W. Sugden, RobertMeissner, Tinri Aegerter-Wilmsen, Roman Tsaryk, Elvin V. Leonard, Jeroen Bussmann, Mailin J. Hamm, Wiebke Herzog, Yi Jin, Lars Jakobsson, Cornelia Denz, Arndt F. Siekmann. Nature Cell Biology, online 22 May 2017

Karolinska Institutet’s vice-chancellor-elect, Ole Petter Ottersen, has held his first day of meetings with representatives of the organisation, including Acting Vice-Chancellor Karin Dahlman-Wright, the chair of the university board Mikael Odenberg, the deans and University Director Per Bengtsson. He also attended a scientific meeting in the Nobel Forum. Ole Petter Ottersen takes over as vice-chancellor on 1 August 2017, at which point Karin Dahlman-Wright resumes her ordinary role as pro-vice-chancellor. Amongst the issues they discussed during his visit, which took place on 19 May, were the responsibilities that fall to them and how they are to be shared. “I’m looking forward to being a pro-vice-chancellor again, which is the job I actually applied for,” says Karin Dahlman-Wright, who admits that it came as a surprise to everyone, not least to her, for her to end up after a couple of days in the middle of all the turmoil that led to her stepping in as acting vice-chancellor. After the then vice-chancellor resigned his office following the storm of criticism over the Macchiarini case, Karolinska Institutet has been engaged not only in investigations and remedial action plans but also in a recruitment process to find a new vice chancellor. In April, the government appointed Ole Petter Ottersen as vice-chancellor at Karolinska Institutet, the only final candidate that the University Board had put forward. Starts formally on 1 August Ole Petter Ottersen will be quitting the rectorate of Oslo University this summer, but stresses that he will not have any formal role at KI before 1 August 2017. “But I’m hoping for many discussions before that,” he says. “I’ve got a very sharp learning curve to follow, given all I need to know about – Swedish law, the academic sector and, not least, the culture. It’s incredibly inspiring.” “It’s also imperative for me that Karin knows the university so well and is continuing as pro-vice-chancellor. I’m looking forward very much to working with her.” As the newly appointed pro-vice-chancellor the idea for Karin Dahlman-Wright was to be in charge of infrastructure, but this year Stefan Eriksson was made the new vice-dean of infrastructure, so it is time for a revised job description. Whether her remit will be healthcare issues, which have often landed on the pro-vice-chancellor’s desk in the past, is a matter for further discussion. “The main thing for me is to engage in new issues with the new vice-chancellor, it’s really important to move on,” says Karin Dahlman-Wright, adding: “And I can’t wait to learn some Norwegian!” Ole Petter Ottersen has his own plans for that: “I’ll try to steer clear of the very hardest words, like utdanning and overflate and say utbildning (education) and yta (space) instead,” he says.    Text: Madeleine Svärd Huss Foto: Gustav Mårtensson

Many childhood virus infections are mistaken for bacterial infection and risk being unnecessarily treated with antibiotics. A new thesis from Karolinska Institutet on respiratory infections in children shows that viruses are a more common cause of serious respiratory infection than previously believed. It is hoped that the research will help to reduce antibiotic use and contribute to new more effective drugs and diagnostic tests. By comparing the viral flora of healthy children at child health centres and children in care for serious respiratory infections, doctoral student Samuel Rhedin has found that viruses are a more common cause of respiratory infection than previously thought. He also charted the incidence of different types of virus, which can facilitate the development of more effective treatments for viral infections. “Our results suggest that we need better treatments for viruses,” says Samuel Rhedin, physician and doctoral student at Karolinska Institutet’s Department of Medicine in Solna. “They can help give the pharmaceutical industry the proper focus for the development of new antiviral drugs. Knowledge of which virus the child has can also give the parents better information on the condition’s prognosis and transmissibility.” Virus common cause of pneumonia Owing to the difficulty of differentiating between viral and bacterial infections, there is a risk that doctors will err on the side of caution and given the children antibiotics, which merely exacerbates the problem of antibiotic resistance. A total of around 1,300 children were studied from 23 child health centres, Sachs’ Children’s Hospital and Astrid Lindgren’s Children’s Hospital. The studies showed that viruses are the more common probable cause of respiratory infections in children, even in those with pneumonia, which has traditionally been considered a bacterial infection. The researchers used the routine diagnostic method PCR (polymerase chain reaction), which has revolutionised the ability to discover and isolate different viruses. The problem with PCR is that it can take days to get a result and that certain viruses are also found in healthy children. The solution to that problem was to take samples from healthy children at child health centres as controls. Evaluating a new blood test “I hope that our results will help to reduce the use of antibiotics and provide incentives to develop new diagnostic tests that are better at distinguishing between viruses and bacteria,” says Dr Rhedin. He and his research group will shortly be starting an evaluation of a new blood test that can diagnose viruses much more quickly. Samuel Rhedin defended his thesis on “Severe viral respiratory tract infections in children” on 12 May 2017. The individual studies have, however, already been frequently cited in the international scientific press.

Nils Hansson, researcher at Heinrich Heine University in Düsseldorf, is awarded the Axel Hirsch Prize 2017 for his research in Swedish and German archives on candidates for the Nobel Prize in Physiology or Medicine who were not awarded the prize. The award is made by decision of the Board of Research at Karolinska Institutet. Since 2014 Nils Hansson has written 17 articles on this theme, several of which have been published or are in press in recognised scientific journals. “This gratifying news reaches me in Berlin, where I am to give a talk at the Charité university hospital this evening – on the very topic of the history of the Nobel Prize. It’s an important recognition that will stimulate me to continue my research!,” Nils Hansson says. Nils Hansson received his PhD from Lund University in 2013, defending a thesis on medical contact between Sweden and Germany during the Nazi era.  The prize, worth SEK 50,000, will be presented during the installation ceremony on 12 October.

This year’s recipient of the Sven Gard scholarship for best thesis in virology is Eva Herweijer of the Department of medical epidemiology and biostatistics, MEB. Eva Herweijer is awarded the scholarship, worth SEK 50,000, for her thesis entitled Register-Based Evaluation of HPV Vaccination Programs, where she combines information from various Swedish quality registers and thus contributes important bases for how HPV vaccinations can best be carried out. Because Eva Herweijer’s thesis shows that HPV vaccination is effective against preliminary stages of cervical cancer it will probably lead to greater acceptance of HPV vaccination.

Although Parkinson’s disease is often associated with motor symptoms such as stiffness, poor balance and trembling, the first symptoms are often sensory and include a reduced sense of touch and smell. In a study on mice, researchers at Karolinska Institutet have now been able to identify neural circuits and mechanisms behind this loss of sensory perception. The study, which is published in the scientific journal Neuron, may open avenues to methods of earlier diagnosis. There are some 18,000 people with Parkinson’s disease in Sweden, and around 2,000 new diagnoses every year. The disease, which is one of our most common neurological conditions, is currently incurable, although its symptoms can be alleviated. When we think of Parkinson’s disease, we often focus on its motor symptoms, such as stiffness and trembling, which are caused by a gradual decrease in the dopamine supply to a brain area called the striatum, the primary input nucleus of the basal ganglia. Research on Parkinson’s disease has mainly focused on these motor impairments. However, patients are also affected by severe sensory problems, including an impaired sense of smell, touch and vision, and this area of research has remained relatively neglected. “Our study highlights the sensory aspects of basal ganglia function and presents a new approach to the mechanisms behind the sensory impairments seen in Parkinson’s disease,” says Gilad Silberberg, associate professor at Karolinska Institutet’s Department of Neuroscience. Is hoped to open the way for earlier diagnosis The researchers in the present study used a light puff of air to stimulate either the right or left whiskers of mice, some of which had an especially low number of dopamine cells, while using a new optogenetic tool called an optopatcher. Applying this technique, which enables the activity of neurons to be recorded during manipulation with light, they were able to see which neurons in the basal ganglia were active and when they transmitted signals. “By studying neuronal activity in the striatum, we found that the neurons in dopamine-depleted mice did not properly signal if it was the right or left whiskers that were being stimulated,” says Dr Silberberg. “But when we treated the mice with L-DOPA, the most commonly used Parkinson’s drug, they recovered their ability to distinguish between left and right.” It is hoped that the discovery will open the way for methods of earlier diagnosis. The study was financed by the ERC, the Knut and Alice Wallenberg Foundation, the Swedish Brain Fund, Karolinska Institutet and the Swedish Research Council.     Publication Dopamine Depletion Impairs Bilateral Sensory Processing in the Striatum in a Pathway-Dependent Manner Maya Ketzef, Giada Spigolon, Yvonne Johansson, Alessandra Bonito-Oliva, Gilberto Fisone and Gilad Silberberg, Neuron, online 17 May 2017

At a ceremony on 15 May, Karolinska Institutet returned the remains of three people from New Zealand’s indigenous population to a delegation from Te Papa Tongarewa museum. The procession entered the Hagströmer Library courtroom to the tones of a shell trumpet and traditional Maori song. Three student ushers bearing crates containing the remains were followed by representatives of Te Papa Tongarewa, Museum of New Zealand, and Karolinska Institutet. The crates were placed at the front and covered with Maori cloaks. Unit manager Eva Åhrén and docent Olof Ljungström from Karolinska Institutet’s Medical History and Heritage Unit gave a speech about the time when the remains were stolen from the indigenous people and about their efforts to repatriate them. Finally, the handover documents were signed and the Te Papa delegation invited the university’s representatives to join in a hongi, a traditional Maori greeting involving rubbing noses and foreheads. The crates were then removed and prepared for the journey home. Ceremonies are important According to Dr Olof Ljungström, it was important for KI to hold a repatriation ceremony. “It’s a tragic tale, not only in the very fact of assembling collections but also how medical science went about it. What’s done can’t be undone but we’re working hard to make what amends we can.” The Medical History and Heritage Unit was put in charge of the university’s collection of human remains in 2014, which had been stored outside KI since the 1960s. “It’s taken some detective work to identify the skulls so they could be returned,” says Dr Ljungström. Olof Ljungström and osteologist Ann Gustavsson are working on a database that will facilitate repatriation. There must be solid reasons for deciding which organisation to send human remains back to, and it is a job that requires a great deal of paperwork and a decision from the Ministry for Foreign Affairs.  One of the remains handed over at the ceremony on 15 May was a mummified head that had been presented to professor of anatomy Anders Retzius in 1862 by the British industrialist and collector  Henry Christy. The other skulls were brought to Sweden by hunter and zoologist Conrad Fristedt, who plundered a grave at Whangaroa on New Zealand’s north island in 1890. The Swedish Museum of Natural History then arranged contact with KI, which subsequently purchased the skulls. “Otherwise, direct purchases were rare and most of the material was acquired through trade with other institutions and individual scientists in the 1800s,” says Dr Ljungström. Resting place at the museum before burial When the remains arrive back in New Zealand, they will be given a temporary resting place in a consecrated space at the museum, Dr Arapata Hakiwai informs us. “We’ll then continue our investigations to ascertain where they come from so that we can give them a proper reburial.” It was Te Papa Tongarewa, Museum of New Zealand, that requested the skulls back, and the decision to do so was taken in December 2014, with ministerial approval coming the following January. “The fact that it has taken until May 2017 to effect the actual handover is because the delegation had coordinated it with other repatriations in Europe,” says Dr Ljungström. “That said, it did take too many years to make the decision. The first request from them came in 2008. They got in touch several times afterward but nothing happened. KI had an under-dimensioned registrar’s office and no clear strategy for how such cases should be handled.” Dr Hakiwai was grateful for the decision to let the ancestors return home. “It will allow healing and reconciliation,” he says. “What’s important is that they return to those who are alive today. We bear our ancestors within us. They’re part of us and our identity.”   Text: Ann Patmalnieks Photo: Erik Cronberg

An international team of researchers, led from Karolinska Institutet, has identified two receptors on the cells in the blood vessels of the brain that can be blocked and thereby prevent pneumococci from entering the brain. The study, which is published in The Journal of Experimental Medicine, shows that the use of antibodies that block the receptors can potentially be used as a new therapeutic strategy for pneumococcal meningitis. Pneumococci is the most common bacterial cause of infections in the airways and the most significant cause of meningitis in the world, a condition that affects an estimated 100,000 children under the age of 5 every year, many of them fatally. Despite antibiotic treatment, patients often develop chronic neurological complications. Bind to cerebral blood vessels In order to cause meningitis, pneumococcal bacteria have to make their way from the airways to the blood and then pass through the blood-brain barrier – the dense layer of cells surrounding the cerebral blood vessels. How the bacteria manage to penetrate this barrier has been hitherto unknown. In the present study the researchers found after examining brain tissue from patients who died from meningitis that 90–95 per cent of all pneumococci clustered around two receptors on the blood-brain barrier cells: PECAM-1 and pIgR. While it has been known that pneumococci can enter the brain, it has remained a mystery how they attach to the brain vascular cells and enter. This new paper shows how two important pneumococcal proteins, RrgA and PspC, are recognised by PECAM-1 and pIgR. “Our results suggest that these two receptors are most important for the ability of pneumococci to enter the brain,” says Birgitta Henriques-Normark, professor at Karolinska Institutet’s Department of Microbiology, Tumour and Cell Biology. The researchers then examined if antibody-mediated blocking of these two receptors could influence pneumococcal infections in mice, and found that the control group had several hundred times more bacteria in the brain than the antibody treated group. New treatment strategy The researchers also showed that antibiotics, which are the most common form of treatment, were much more efficacious when combined with antibodies – some mice were completely cured. This suggests that antibiotic-resistant bacteria might also be prevented from infecting the brain using antibodies. “We will now further study mechanisms that enable pneumococci to enter the brain via these receptors,” explains Professor Henriques-Normark. “Our findings suggest that we might be able to develop new strategies for treatment of these infections by stopping interactions between pneumococci and brain vascular cells.” The study was financed by the Knut & Alice Wallenberg Foundation, the Swedish Research Council, and the Swedish Foundation for Strategic Research, as well as through the ALF agreement with Stockholm County Council. Publication pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion Federico Iovino, Joo-Yeon Engelen-Lee, Matthijs Brouwer, Diederik van de Beek, Arie van der Ende, Merche Valls Seron, Peter Mellroth, Sandra Muschiol, J. Bergstrand, J. Widengren, Birgitta Henriques-Normark, The Journal of Experimental Medicine, online 17 May 2017

Adina Khamitova, master’s student of Public Health Sciences at KI, has been honoured with the accolade Global Swede, which is awarded by the government and the Swedish Institute to international university students in Sweden for outstanding achievements in innovation and entrepreneurship. Adina Khamitova has combined her studies with the establishment of a Swedish-Kazakhstani partnership to give people in her home region access to clean water using a Swedish innovation. “Many of the global challenges we’re currently facing require a broad partnership,” says Minister of EU Affairs and Trade Ann Linde, who presented Adina Khamitova with the award at a ceremony at the Ministry for Foreign Affairs. “Not only do overseas students bring new knowledge and perspectives, but they are also a vital resource for building bridges between Sweden and the outside world.”

Changes in the health and medical care landscape will impact Karolinska Institutet’s research and education. At a seminar on Solna Campus on 10 May, speakers described how specialist and emergency care in the future to a large extent will be carried out in primary care units. “That Karolinska Institutet is given good opportunities to conduct clinical research and education also in the healthcare of the future is not only a matter for the university but also for the health and medical care system as well as for society at large,” said acting Vice-Chancellor Karin Dahlman-Wright when she opened the seminar. The seminar background was that Karolinska Institutet believes that a highly specialised intensive emergency department at the new Karolinska University Hospital will affect both research projects and medical and nursing students’ prospects of getting sufficient training. KI has also criticised the Stockholm County Council for its lack of collaboration during the planning. “The fact that we were involved does not mean that we have always been listened to. The hope we all share is to establish a good dialogue on all levels,” Karin Dahlman-Wright continued. She pointed out that Karolinska Institutet, KI, needs health and medical care services for the students to be able to get good in-service training and enable researchers to conduct their research projects. “Have never had more resources” The remodeling at the new Karolinska University Hospital is part of the new national health and medical care landscape. Göran Stiernstedt, Associate Professor and member of Karolinska Institutet’s Board, spoke about this based on his position as the government investigator of effective care. There are many reasons to be proud of Swedish healthcare, Göran Stiernstedt stated. But there are problems. A small proportion of the population feel that healthcare works well compared to other countries. “What doesn't work is accessibility. We haven’t prioritised that aspect. The number of doctors and nurses is increasing and we have never had more resources, yet people nonetheless feel that there were more resources in the past. In the future there will be sicker patients outside the hospitals,” Göran Stiernstedt said and continued: “We’re poorly equipped for that. We need more primary care. The hospitals also need to be opened for this. Hospital healthcare needs to operate outside the hospital to a greater extent. The great potential for increased efficiency lies in the overall care of the most ill group of elderly people.” Education also in outpatient care Göran Stiernstedt emphasised that every encounter with patients is a source of development and research. Primary care must be available 24 hours a day and resources need to be transferred from specialist care. “Education must gradually become more located in outpatient care,” Göran Stiernstedt said. Stockholm County Council Chief Executive Malin Frenning spoke about the challenges Stockholm faces with among other things a substantial increase in population. The goal is a healthcare network with the individual's total needs in focus. “The care residents need must be as local and accessible as possible. We need a shift within the system so that people will go to their family doctor instead of to the emergency room. The local emergency departments will be strengthened and more spread out. Research is then more closely tied to healthcare and the endeavour will then be a more patient-oriented kind of research. But the system needs to be arranged so that we can conduct research on the patients we have even more," Malin Frenning said. Regarding prerequisites for education and research, Malin Frenning among other things points out in particular the prioritisation of 14 basic training programmes and clinical research in endemic diseases and diseases that cause great suffering, as well as the establishment of a specialist centre to support research in diabetes, neurology and rheumatological disorders. “In five years’ time I think we’ll have a cohesive structure where it is easy to access healthcare,” she said. Analysis completed by 31 May When the audience were invited to comment on what had been said during the seminar, many people had concerns about what will happen to the education and skills when specialist care is relocated. The consequences of such major relocations must be thoroughly investigated was one view. More specialist care centres were another suggestion. The seminar’s last item, KI’s opportunities and challenges in the healthcare of the future, was cancelled. Karin Dahlman-Wright said she instead would comment further on the subject after 31 May, by which time KI’s internal analysis of the consequences of an intensive emergency care department will have been completed. Text: Ann Patmalnieks

Singapore’s minister of health, Mr Gan Kim Yong, visited Karolinska Institutet on Monday 15 May, along with a delegation that included representatives of the country’s healthcare organisation. During the visit, the delegation learnt more about Karolinska Institutet’s nursing programmes, ageing research and collaboration with the healthcare sector on research and education. The visit was a joint arrangement by Business Sweden and the Swedish Embassy in Singapore. Acting Vice-Chancellor Karin Dahlman-Wright received the delegation in Aula Medica in the company of acting pro-Vice Chancellor Anders Ekbom and Deputy Vice-Chancellor for International Affairs Maria Masucci. Also present were Gunnar Nilsson, pro-dean of higher education; Ann-Langius-Eklöf, head of the nursing division/nursing subject coordinator; and Chengxuan Qiu and Anna-Karin Welmer from the Aging Research Centre. KI collaborates with Singapore on research and on education at all three levels. Its first contact with Singapore in 1999 resulted in collaborations with the National University of Singapore, Nanyang Technological University and A*STAR. Some 20 doctoral students have graduated under joint programmes with departments in Singapore, and student exchange schemes are in place for numerous study programmes, including biomedicine, medicine and public health science.

Contrary to earlier beliefs, people with severe congenital intellectual disability are sensitive to placebo-like effects, new research from Karolinska Institutet shows, published in the scientific journal Neurology. The results suggest that the influence of implicit social signals on expectancy effects has been underestimated. The placebo effect is an example of how the power of the mind may influence the functions of the body, such as when a simple sugar pill alleviates pain when the taker believes it to be a real analgesic. But placebo-like effects also occur when expectations influence the efficacy of real drugs. Until now, placebo researchers have presumed that this type of expectancy effect requires higher-order intellectual functions, such as reasoning, abstract thinking and predicting the future. But it now turns out to be more complex than that. “Our results challenge the existing ideas of how treatment expectations are formed and we can now propose other more intuitive processes as a possible basis of the placebo effect, such as the ability to internalise the expectations of the people around you,” says Karin Jensen, assistant professor at Karolinska Institutet’s Department of Clinical Neuroscience. Analysis of 24 medical studies She and her colleagues at Karolinska Institutet and Harvard Medical School analysed 24 published medical studies involving people with congenital intellectual disability (an IQ below 70), including diagnoses such as Down’s, fragile x or Prader-Willi syndrome. Half of the studies were so-called open-label, in which all participants received active drugs. The other type were placebo-controlled, in which the participants did not know whether they were being given a placebo or active drug. “We only compared the results from those who received real drugs, and found significant differences in treatment outcomes between the two groups – despite the fact that the patients had received exactly the same drugs,” says Dr Jensen. “The only difference between the groups was the likelihood of getting an active drug.” Subtle social cues could be important The conclusion is that implicit expectations conveyed by the people who administer the drugs, or who are otherwise involved in the treatment, are likely to influence the patients’ neurobiology and, ultimately, their response to treatment. In that sense, expectancy effects are not only the result of facts and suggestions but also the subtle social cues the patients pick up from the people around them. “This aspect of the placebo effect has been underestimated,” says Dr Jensen. “This means that the models we’ve created of how the placebo effect works should be revised so that the focus isn’t just on advanced cognitive functions, such as the patient’s ability to create abstract future scenarios.” The study was financed in part by the National Institutes of Health, USA. The researchers involved have no commercial stake in the results. Publication ”Certainty of genuine treatment increases drug responses among intellectually disabled patients” Karin B. Jensen, Irving Kirsch, Moa Pontén, Annelie Rosén, Kathy Yang, Randy L. Gollub, Vincent des Portes, Ted J. Kaptchuk, Aurore Curie Neurology, 16 May 2017, 88:1912-1918; published ahead of print 19 April 2017. doi: 10.1212/WNL.0000000000003934

In a new study presented in Molecular Psychiatry, researchers at Karolinska Institutet have measured how deposits of the pathological protein tau spread through the brain over the course of Alzheimer’s disease. Their results show that the size of the deposit and the speed of its spread differ from one individual to the next, and that large amounts of tau in the brain can be linked to episodic memory impairment. Already in a very early phase of Alzheimer’s disease there is an accumulation of tau in the brain cells, where its adverse effect on cell function causes memory impairment. It is therefore an attractive target for vaccine researchers. For the present study, Professor Agneta Nordberg at Karolinska Institutet’s Department of Neurobiology, Care Sciences and Society and her doctoral student Konstantinos Chiotis along with the rest of her team used PET brain imaging to measure the spread of tau deposits as well as the amyloid plaque associated with Alzheimer’s disease, and charted the energy metabolism of the brain cells. They then examined how these three parameters changed over the course of the disease. International race “There’s been an international race to measure tau spread, and we probably got there first,” says Professor Nordberg. “There are no previous reports on how tau deposits spread after 17 months into the disease. Our results can improve understanding of tau accumulation in Alzheimer’s disease, help ongoing research to quantify the effect of tau vaccines, and enable early diagnosis.” The study included 16 patients at different stages of Alzheimer’s disease from the memory unit at Karolinska Hospital in Huddinge. The patients were given a series of neurological memory tests and underwent PET scans at 17-month intervals. While all 16 participants had abundant amyloid plaque deposition in the brain, the size and speed of spread of their tau deposits differed significantly between individuals. Episodic memory impairment “We also saw a strong direct correlation between size of deposit and episodic memory impairment,” continues Professor Nordberg. “This could explain why the disease progresses at such a varying rate from one patient to the other. That said, tau doesn’t seem to have much of an effect on the global general memory, which is more reasonably related to brain metabolism.” The study was conducted in collaboration with Uppsala University, where the PET scans were performed. The study was financed by the Swedish Research Council, the Swedish Foundation for Strategic Research, Stockholm County Council (ALF funds), the Strategic Research Area in neuroscience at Karolinska Institutet, the Gamla Tjänarinnor Foundation, the Axel Linder Foundation, the Gun and Bertil Stohne Foundation, KI’s Funds, the Swedish Brain Fund, the Swedish Alzheimer’s Foundation, the Swedish Dementia Foundation, the Wenner-Gren Foundations, KTH – SCC research grants and the EU INMiND project. Publication 'Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer’s disease dementia' K Chiotis, L Saint-Aubert, E Rodriguez-Vieitez, A Leuzy, O Almkvist, I Savitcheva, M Jonasson, M Lubberink, A Wall, G Antoni och A Nordberg Molecular Psychiatry, online 16 May 2017. Doi: 10.1038/MP.2017.108