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Project proposals 2019

Links to the online application forms are available under each project. Application deadline is 16 September 2019 at 23:59 (CEST)

P1: Can IASPs stimulate delayed bone healing?

Strategic criteria

      • Early recruitment of talents
      • Mobility
      • Interdisciplinary co-operation and network
      • Co-operation with the business community, university college and other external parners in municipalities

      Main supervisor

      Name: Annemarie Brüel

      Position: Professor MSO

      E-mail: mb@biomed.au.dk

      Abstract

      There are approximately 80,000 registered bone fractures each year in Denmark, and the majority heals without any problems. However, in 5-10% of the patients, healing is delayed or does not take place at all. In complicated long bone fractures, impaired healing is found in up to 25% of the patients. This is a serious problem, as these patients are often unable to return to work or resume activities of daily living. In collaboration with Erasmus MC Rotterdam, we have recently shown that a novel treatment regimen, inhibitors of the activin-receptor signaling pathway (IASPs), can increase both bone and muscle mass during immobilization in rodents. Through an international and interdisciplinary collaboration, the aim is to investigate the potential of IASPs to improve delayed fracture healing in a rodent model. IASPs are compared with PTH and GH, which are known to improve bone healing in rodents. In humans, PTH lacks effectiveness for fracture healing, and GH is not used due to side effects.

      Study 1: the efficacy of Botox and dexamethasone to delay bone healing and induce muscle atrophy.
      Study 2: compare the ability of IASPs and PTH to stimulate delayed bone healing.
      Study 3: compare the ability of IASPs and GH to stimulate delayed bone healing and muscle atrophy.

      The healing bone defects are investigated by µCT to estimate bone microstructure, skeletal muscles and fracture callus are studied by histology, bone turnover is determined using dynamic histomorphometry, qPCR is performed on relevant genes, and fracture strength is assessed by mechanical testing. In collaboration with H. Birkedal, iNANO, AU, mineralizing and nanomechanical properties of the callus will be investigated by SEM with EDX and nano indentation, respectively.

      Production of IASPs is performed in collaboration with R. Fenton, Dept. of Biomedicine and B. van der Eerden, Erasmus MC, Rotterdam, the Netherlands. The objective is to gain novel insight into how delayed bone healing can be stimulated, and may lead to new treatment regimens and increased quality of life for the patients.

      Main supervisor: Annemarie Brüel, Prof. MSO, Dept. of Biomedicine, AU.
      Co-supervisors: Jesper S. Thomsen, Ass. Prof., Dept. of Biomedicine, AU, Michael Pedersen, Prof., Dept. of Clinical Medicine, AU.
      Project supported by Jeppe Prætorius, Prof., Dept. of Biomedicine, AU and Henrik Birkedal Ass. Prof., iNANO, AU.

      Specific qualifications

      Interest and previous experience in bone, orthopedic surgery, and µCT is an advantage.

      Apply

      P2: Infection-cancer interface

      Strategic criteria

          • Early recruitment of talents
          • Mobility
          • Interdisciplinary co-operation and network
          • Co-operation with the business community, university college and other external parners in municipalities

          Main supervisor

          Name: Karthika Rajeeve

          Position: Assistant professor

          E-mail: karthikakarunakaran@gmail.com

          Abstract

          Obligate intracellular pathogens posolutely de-route signaling in eukaryotic cells for progeny formation. One such bacterium, Chlamydia trachomatis (Ct), is known as the cause of most common sexually transmitted disease with 131 million new infections per year. Being asymptomatic, Chlamydia infections are recurrent and causes Pelvic Inflammatory Disease (PID), proctitis and salpingitis, leading to sterility. Recently, Chlamydia infection has been shown associated with ovarian and cervical carcinoma.

          Chlamydia trachomatis infection is known to activate various survival signals like PI3K and MAPK in host cells and regulate anti-apoptotic proteins like IAPs and MCl-1. Most interestingly chlamydia infection is shown to destabilize the tumor suppressor p53 via miR30 axis (Siegl et al, 2014, Chowdhury et al 2017; co-authored) to unleash host pentose phosphate pathway and also prevents mitochondrial fragmentation. Research during my post-doctoral period has given me insights that strengthens chlamydia-cancer interface. Chlamydia infection destabilizes the expression of PTEN and trigger hyper-proliferation and pre-transforming lesions (manuscript in preparation). c-Myc, the proto-oncogene is stabilized throughout infection which boosted the availability of extra metabolites to the pathogen (manuscript in revision). Moreover, the recent finding that Ct evades the immune detection (Rajeeve et al., 2018: Nature Microbiology) might also fuel how this pathogen contributes to cellular transformation.

          Preliminary data shows Chlamydia infection control the fate of by-stander cells. The experiments done in primary cells isolated from fimbriae of patients showed that Ct infection can promote matrix independent growth and spheroid formation, a major finding connecting Chlamydia towards carcinoma. All these data (unpublished) urge me to investigate on the mechanism by which Chlamydia contributes to cellular transformation. The major objective is thus to investigate on the autocrine-paracrine activity/signaling during Chlamydia infection and how it leads to genomic instability. 3D tissue models and organoids derived from pateints will be used to study bacterial-host interactions and virulence factors with oncogenic potential. This study will reveal the carcinogenic potential of Chlamydia and would change the implication of policies to tackle this epidemic.

          Specific qualifications

          Highly motivated student with a strong background in microbiology and cell biology. Knowledge in biochemistry, in particular protein purification is an advantage. Should be willing to do experiments in mice.

          Apply

          P3: Investigation of the cellular mechanisms in nephrogenic diabetes insipidus

          Strategic criteria

              • Mobility
              • Interdisciplinary co-operation and network
              • Co-operation with the business community, university college and other external parners in municipalities

              Main supervisor

              Name: Birgitte Mønster Christensen

              Position: Associate Professor

              E-mail: bmc@biomed.au.dk

              Abstract

              Lithium (Li) salts are widely used drugs for patients with bipolar disorders. Li impairs urine concentration and part of the patients develop Nephrogenic Diabetes Insipidus (NDI) with polyuria. Li-NDI is associated with changes in the cellular composition of the kidney collecting duct (CD). We propose a PhD project aiming to examine if the toxic Li effect on the CD triggers differentiation of pluripotent cells disseminated in the distal nephron for tissue repair. The second part of the project will investigate if markers of Li pathophysiology identified in animal models are applicable to patients. Hypotheses:

              • Proliferating CD cells in adult kidney originate from residing renal progenitor cells
              • Cellular remodeling is reflected in urine of Li-NDI patients

              Part 1:
              Li increases the amount of intercalated cells and increases proliferation in the CD. We hypothesize that proliferating cells originate from resident renal progenitor cells. We will use Li-treated transgenic Pax8/Confetti mice (express one of four fluorescent colors in each kidney cell). In control mice, a random pattern of single colored cells exists. In the Li-Pax8/Confetti mice, we suggest that multiple neighboring cells with the same color exist in the CD showing that these cells have originated from the same clone cell and this cell may be a renal progenitor cell. Kidney tissue will be investigated by 2-photon microscopy (Søren Degn, Biomedicine). Cells will be isolated and subjected to single cell sequencing (Lin Lin, Biomedicine) to identify potential progenitor cells.

              Part 2:
              Urinary exosomes are extracellular vesicles derived from cells lining the kidney tubule system and the urinary tract. The content of exosomes reflects the composition of the origin cell and represents the physiological state of the kidney. We will perform proteomics of urinary exosomes isolated from urine pooled from Li-NDI patients and from healthy volunteers. We are collaborating with Soham Rej, McGill University, Canada on another clinical trial involving 60 Li-NDI patients and we will collect urine from these patients. Isolation of exosomes will be performed at Uni. of Campania, Italy (Francesco Trepiccione), where part of the PhD project will take place. The proteomic profile of the exosomes will be investigated by MS.

              The project is supported by S. Degn, L. Lin, and F. Trepiccione (co-supervisors).

              Specific qualifications

              The candidate must be MD, MSc or equivalent. The candidate will have to be able to work with animals. 

              Apply

              P4: Targeting Glia – A Novel Disease Modifying Strategy for Neuropathic Pain Treatment

              Strategic criteria

                  • Mobility
                  • Interdisciplinary co-operation and network
                  • Co-operation with the business community, university college and other external parners in municipalities

                  Main supervisor

                  Name: Christian Vægter

                  Position: Associate Professor

                  E-mail: cv@biomed.au.dk

                  Abstract

                  Despite great progress in Neuroscience research over the past decades, the development of novel therapeutic interventions for chronic neuropathic pain (NP) induced by injury or disease of the nervous system have been lagging behind. At the same time, the growing prevalence of NP in the population poses a growing challenge to patients and society. Current treatment strategies aiming to reduce nerve activity by blocking neuronal signaling have generally proven to be unsuccessful, showing limited efficacy and adverse side effects. Disease modification by targeting glial cells is now emerging as a promising therapeutic strategy.

                  Injury of the peripheral nervous system (PNS) and neuron-glia communication in NP is a key focus area of the Vægter lab. As partners in a consortium financed by the Innovation Fund Denmark (IFD) we are exploring a novel PNS glia-targeting drug candidate for NP treatment. The drug candidate is used as a tool compound to explore how targeting PNS glia impacts on neuronal function and how this system can be manipulated to treat NP.

                  In the proposed PhD project, we focus on Chemotherapy-Induced Peripheral Neurotoxicity (CIPN), which ranks among the most common toxicities of several widely used anticancer medications. A great number of patients suffer from CIPN years after termination of the therapy, and increased survival of cancer patients has made CIPN a medical need of increasing importance. Importantly, glial reactivity has been demonstrated in mouse models of CIPN, demonstrating involvement of these cells in chemotherapy-induced NP.

                  In a CIPN mouse model we wish to describe molecular mechanisms involved in glial reactivity, identifying specific glial pathways that may be targeted to modulate pain signaling. Glia will be isolated from in vivo models for “omics” analyses at the single cell RNA seq unit (AU-SCOMICS) as well as Center for Protein Research at UCPH, partner in the IFD consortium. The project also includes analysis of nerve tissue and functional studies in cultured cells and ex vivo explants.

                  The work will be carried out at DANDRITE and with partners of the IFD consortium. Collaborations provide excellent mobility opportunities. The IFD consortium spans academia and pharma, adding interdisciplinary co-operation.  

                  Specific qualifications

                  Experience with mouse experiments (incl. licence) and analysis of "omics" data sets is an advantage. 

                  Apply

                  P5: Beyond treatment of peritoneal metastases and advanced pelvic cancer

                  Strategic criteria

                      • Mobility
                      • Interdisciplinary co-operation and network
                      • Co-operation with the business community, university college and other external parners in municipalities

                      Main supervisor

                      Name: Lene Hjerrild Iversen

                      Position: Clinical professor, chair

                      E-mail: lene.h.iversen@clin.au.dk

                      Abstract

                      Treatment options for advanced colorectal cancer, including peritoneal metastases, emerge and survival rates improve. However, patients suffer from complex gastrointestinal dysfunction, other organ dysfunctions, pain, fatigue, and have challenged mental health. The frequency and extent of these late side effects as well as their consequences are not described in these patient groups.

                      Department of Surgery, Aarhus University Hospital (AUH) has for almost 2 decades been the single national referral centre for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastases from colorectal cancer, pseudomyxoma peritonei, among others, but also one of two national referral centres for advanced primary and recurrent pelvic cancer surgery.

                      The Pelvic Floor Unit at Department of Surgery, AUH, has for years been an international leading research unit within the field of late side effects after cancer treatment. Recently, the Pelvic Floor Unit became a chair group in the National Research Center for Survivorship and late side effects following cancer in the pelvic organs under the Danish Cancer Society. The Pelvic Floor Unit has several international collaborators that provides opportunities for research exchange abroad.

                      The research unit at Department of Surgery has multidisciplinary and interdisciplinary collaborations, among others with Department of Epidemiology, AUH, and a long track record with national population-based register-studies. Additionally, the research unit has an established cooperation with a company within software for the health care system.

                      Strategy
                      In patients who had undergone cytoreductive surgery and HIPEC for peritoneal metastases from colorectal cancer, and patients who had advanced pelvic surgery for advanced or recurrent colorectal cancer, we plan:

                      • Prospective surveillance of late side organ effects including quality of life
                      • Screening for mental disorders like depression, anxiety, sleep disturbances, pain disorder, and fatigue
                      • Examine return to labor market
                      • Offer clinical evaluation of late side organ effects
                      • Offer ‘virtual coaching’ or psychology treatment of mental disorders

                      Setting
                      Aarhus University Hospital with possibilty to collaborate with other international centres.  

                      Specific qualifications

                      Medical student or medical doctor who is motivated for research within the above mentioned field. Knowledge within the use of questionnaires and clinical knowlegde within advanced cancer surgery can be an advantage, but is not a requirement.

                      The rule concerning the age of your higher education degree (max. five years) does not apply to this project due to required experience. 

                      Apply

                      P6: Defining clinically relevant molecular and phenotypic profiles of advanced and metastatic cancer

                      Strategic criteria

                          • Mobility
                          • Interdisciplinary co-operation and network

                          Main supervisor

                          Name: Nicolai Birkbak

                          Position: Associate professor

                          E-mail: nbirkbak@clin.au.dk

                          Abstract

                          Background
                          Most cancer deaths are caused by metastasis. Beyond increased accumulation of somatic changes to the cancer genome, work to date has failed to demonstrate any defining characteristics enabling metastatic spread. However, early cancer is often curable by surgery, and phylogenetic analysis has shown metastasis is commonly of monoclonal origin from an otherwise heterogeneous tumour. This demonstrates that the capacity to metastasise is unique to advanced disease and may require specific disease biology that remains unknown.

                          Aim
                          This project aims to decipher the biology of metastatic disease and to develop clinically applicable biomarkers based on liquid biopsies that will provide treating clinicians with low-cost tools to stratify and monitor patients for precision medicine purposes.

                          Methods
                          Circulating tumour DNA (ctDNA) obtained from liquid biopsies have demonstrated a strong association with aggressive disease. This project will utilise bioinformatics approaches to analyse genomic and transcriptomic data from advanced cancer samples in order to characterise the biological and molecular phenotypes that may drive advanced disease progression. We will particularly investigate the relevance of intratumour heterogeneity, immune cell infiltration and germline variation on cancer evolution. In parallel, ctDNA from liquid biopsies will be analysed to determine the biological basis and the clinical utility of ctDNA, both to predict response to therapy and as a proxy of aggressive disease. This project will utilise data from public sources and from unique longitudinal series of early, advanced and metastatic disease available in-house and through international collaborations.

                          Strategic criteria addressed
                          This project addresses mobility and interdisciplinary collaboration and networking. It is established as a collaborative effort between the Birkbak bioinformatics lab and the translational labs of profs. Swanton and Dyrskjøt. Both Swanton and Dyrskjøt have relevant ongoing prospective clinical trials for which data access will be provided for this project (TRACERx and TOMBOLA), and a 6-12 month external stay in the Swanton lab is planned. The Swanton lab has considerable expertise in NGS and ctDNA analysis of cancer, and has agreed to provide continued supervision and ctDNA analysis of cancer, and has agreed to provide supervision and feedback.

                          Specific qualifications

                          Bioinformatics, molecular biology, medicine, or similar background. Knowledge of at least one of R, Python or similar preferred

                          Apply

                          P7: Clinical effectiveness and safety of intraoperative methadone in patients undergoing surgery

                          Strategic criteria

                              • Early recruitment of talents
                              • Mobility
                              • Interdisciplinary co-operation and network

                              Main supervisor

                              Name: Lone Nikolajsen

                              Position: Professor, chair

                              E-mail: lone.nikolajsen@clin.au.dk

                              Abstract

                              Summary
                              This PhD project includes two randomized, double-blinded, placebo-controlled trials on the use of intraoperative methadone. The PhD project will be carried out in collaboration with Washington University School Medicine, St. Louis, USA (Simon Haroutounian, MSc Pharm, Chief of Clinical Research, will act as co-supervisor). Partial funding has been obtained from Novo Nordisk Foundation (running costs).

                              The PhD project
                              Repeated intravenous doses of shorter-acting opioids, such as morphine, oxycodone and fentanyl, are typically administered to control early postoperative pain. This results in fluctuating blood concentrations, with the inherent risk of only relatively brief periods of adequate pain relief. An alternative approach to the use of shorter-acting opioids is therefore called for. In this respect, methadone is a unique opioid with pharmacological properties that may be advantageous. Most importantly, it has a half-life of 36-72 hours, and a single intraoperative administration may provide stable analgesia throughout the early postoperative period.

                              Only few studies have examined the use of methadone in patients undergoing abdominal surgery and those studies are old and suffer from small sample sizes, lack of blinding, and out-dated use of intramuscular injections. Two parallel-group, randomized, double-blinded, placebo-controlled trials are therefore planned to study the effect of intraoperative methadone on postoperative opioid requirements, pain scores and opioid-related side effects in patients undergoing bowel surgery and patients undergoing bladder surgery. The results are likely to apply to other types of surgery and will help us improve the postoperative treatment for a large number of patients.

                              Patients will be recruited at Aarhus University Hospital. Sample size calculation will be based on ongoing audits but is likely to be in the range of 80-120 patients for each study. The primary outcome will be postoperative opioid consumption within the first 6 hours after extubation. Secondary outcomes include pain, nausea and vomiting. The Hospital Pharmacy will prepare the study medication, and blood samples will be analysed for methadone and metabolites by the Department of Forensic Medicine. RedCap must be used for randomization and data handling. 

                              Specific qualifications

                              The ideal candidate is a medical doctor/pharmacist or comparable, preferably with research experience, and the candidate should know how to conduct in a hospital/operation area environment. The candidate must be fluent in English.

                              Apply

                              P8: Selection and Deferral of Fecal Microbiota Transplantation Donors

                              Strategic criterion

                                  • Interdisciplinary co-operation and network

                                  Main supervisor

                                  Name: Christian Erikstrup

                                  Position: Chair Professor/Lærestolsprofessor

                                  E-mail: christian.erikstrup@skejby.rm.dk 

                                  Abstract

                                  Fecal microbiota transplantation (FMT) has proven very efficient in the treatment of recurrent Clostridium difficile infection (rCDI). In a recently published randomised trial we reported clinical resolution among 92% of participants treated with FMT. FMT is now to be implemented in the routine treatment of rCDI. FMT has been suggested in the treatment of a range of diseases ranging from other serious diseases of the gastrointestinal tract, e.g. inflammatory bowel diseases to autoimmune or autoinflammatory diseases in other organs than, e.g. psoriasis arthritis. Extensive research is ongoing and it is mandatory that we ensure the safety of the procedure.

                                  The optimal process of donor selection is not known. In previous studies, using FMT strict criteria and extensive blood and fecal testing resulted in a very low percentage of eligible donors. The high number of positive tests, and among these false positive tests, are ethically problematic as it potentially leads to worries among the unpaid voluntary donors. Several tests are costly and constitutes the major part of the expenses related to the production of components used for FMT.

                                  At the same time, we know very little about the donor characteristics facilitating a succesful FMT and why the treatment sometimes does not work. This will be even more important for other indications than rCDI where lower cure rates have been reported. Donor characteristics, suggested to play a role in success rate, include donor microbiota composition, the prevalence of certain bacterial strains, donor diet and even tissue type matching between donor and recipient.

                                  This project will:
                                  1: Identify optimal donor deferral criteria and tests to mitigate the risk of adverse reactions in the recipient.
                                  2: Identify donor characteristics, including those of the intestinal microbiota, which are associated with clinical success or failure of FMT.

                                  The applicant will contribute to the development of the research protocol and is required to conduct independent crossdisciplinary scientific work, combining the fields of clinical immunology, clinical microbiology, and clinical medicine.

                                  Specific qualifications

                                  Experience from a clinical department of microbiology in the clinical testing for pathogens and subsequent guidance of anti-microbial treatment. Experience with clinical assessment of blood or tissue donors. 
                                  The rule concerning the age of your higher education degree (max. five years) does not apply to this project due the requirements to needed experience.

                                  Apply

                                  P9: The role of genetics in nocturnal enuresis and overactive bladder - a translational study of pathogenesis and potential treatment targets.

                                  Strategic criteria

                                      • Mobility
                                      • Interdisciplinary co-operation and network

                                      Main supervisor

                                      Name: Søren Rittig

                                      Position: Professor, Consultant

                                      E-mail: rittig@clin.au.dk

                                      Abstract

                                      Background
                                      Nocturnal enuresis (NE) is a common condition in childhood, affecting 7-10% of all 7-year old, and up to 2% of young adults. There is strong evidence suggesting a genetic risk component in NE. The pathogenesis of NE is not fully elucidated but comprise at least three important factors: a) a defect circadian rhythm of urine output; b) a reduced nocturnal bladder capacity (overactivity), and c) a sleep disorder preventing arousal when the nocturnal bladder capacity is exceeded. Center for Childhood Incontinence at Aarhus University Hospital is globally one of the leading research centers for NE especially within the areas pathogenesis and genetic aspects. Since 1995, linkage to specific gene loci has been established in large families with autosomal dominant NE. Recently, in a collaborative study based upon GWAS data from a large population-based case-cohort sample (iPSYCH2012) and from different patient registers, we have robustly implicated 6 specific common gene risk variants (in two independent loci, 5 on chromosome 6 and 1 at chromosome 13). These variants have been verified in a very large population from Iceland (Decode). The common risk variants explain app. 27% of the hereditary component of NE.

                                      The project
                                      1. Establishment of an international nocturnal enuresis biobank (INEB). We wish to establish an international biobank based upon a cohort of 200 NE children and their biological parents from each of the 8 countries worldwide. Children with mono-symptomatic NE will be included and thorough clinical characteristics including response to desmopressin treatment together with blood or spit DNA will be collected.
                                      2. GWAS of overactive bladder in iPSYCH. Identification of single-marker loci, genes and pathways involved in bladder overactivity and characterization of the genetic correlations with other phenotypes. This study will be based on all 130,000 genotyped individuals in the second wave of iPSYCH and correlated to patient diagnosis registers and national pharmacy registers.
                                      3. Expression of identified risk genes in cell and/or animal models. Establishment of translational expression models based upon the identified risk variants. Specifically, we will focus upon known pathogenic mechanisms, i.e. urine output, circadian rhythms, bladder function, and sleep as well as the autonomic nervous system. 

                                      Specific qualifications

                                      1. At least Scandinavian language skills are required as inclusion of patients in project 1 involves interaction with patients.
                                      2. Clinical paediatric experience and knowledge about nocturnal enuresis and voiding dysfunctions are preferred.

                                      Apply

                                      P10: Sentinel Node Mapping with Robotic Assisted Near Infra-Red Fluorescent Imaging in Women and Endometrial Cancer

                                      Strategic criterion

                                          • Early recruitment of talents

                                          Main supervisor

                                          Name: Pernille Tine Jensen

                                          Position: Professor

                                          E-mail: petije@clin.au.dk

                                          Abstract

                                          The present study seeks to evaluate the safety and effect of implementing the sentinel node mapping technique in women with endometrial cancer.

                                          Lymph node involvement is the main prognostic factor in patients with endometrial cancer and is observed in 6-20% of women with endometrial cancer (EC). Radical lymphadenectomy (RL) is considered the gold-standard procedure to identify lymph node metastases. RL has, per se, no survival benefit, while those patients who will stage migrate due to lymph node metastases, benefit from adjuvant treatment. The low prevalence of lymph node metastases has the consequence that >80% of the women who undergo RL will not benefit from the procedure. Several peri- and postoperative complications are related to RL: neurovascular damage, blood loss, chronic lymphedema with significant impact on quality of life.

                                          The sentinel lymph node (SLN) mapping concept is based on the principle that lymphatic drainage follows a predictable pattern to a regional lymph node basin. The SLN is the first lymph node to which the primary tumor metastasizes. If the SLN is without cancer, all lymph nodes in that region are free of cancer and RL is unnecessary. SLN mapping may have several advantages: the surgical procedure will shorten, and the incidence of intra- and postoperative complications is likely to decrease. Further, the SLN may be identified in areas, e.g. para-aortic and pre-sacral that is outside the standard lymph node dissection area. SLN mapping allows the use of pathological ultra-staging that may identify micro-metastases.

                                          In DK, all women with high-risk EC undergo FDG-PET/CT imaging before surgery. However, due to a comparatively low prevalence of lymph node metastases in this population the positive predictive value (PPV) is low. The two procedures, FDG-PET/CT and SLN mapping may supplement each-other to increase the sensitivity and the negative predictive value (NPV) or, alternatively, imaging may appear redundant.

                                          The present PhD study is a multicenter, national clinical study consisting of two sub-studies evaluating the safety, value and effect of implementing the SLN mapping technique in women with low-intermediate risk and high-risk EC. The study involves all surgical cancer centers in DK and comprises several scientific methodological aspects and research disciplines. 

                                          Specific qualifications

                                          This is a clinical research program. Applicants with 2-4 years of clinical experience will be chosen.
                                          The candidate should be able to start the PhD program in start 2020.
                                          The candidate should be interested in or already engaged in the field of gynecological cancer. 

                                          Apply

                                          P11: Is there a relationship between nutrition and orofacial pain?

                                          Strategic criteria

                                              • Early recruitment of talents
                                              • Mobility
                                              • Interdisciplinary co-operation and network

                                              Main supervisor

                                              Name: Lene Baad-Hansen

                                              Position: Associate professor

                                              E-mail: lene.hansen@dent.au.dk

                                              Abstract

                                              The project addresses the occurrence of chronic orofacial pain in Denmark and identification of possible nutritional, genetic and psychosocial risk factors for chronic pain. The project will evaluate ongoing pain, pain sensitivity, gustatory function, food preferences, psychosocial function and specific genetic polymorphisms related to pain sensitivity in a representative sample of established epidemiological cohorts on health and nutrition.
                                              General health, including orofacial health, is an important prerequisite for good quality of life. Persistent or chronic pain has a negative influence on health, function and capability for work as well as quality of life. Approximately 20% of the population suffers from chronic pain. There is emerging evidence to suggest that nutritional status may play a role in development of chronic orofacial pain, as it has recently been found that obesity is associated with an increased risk of having orofacial pain. Diet and nutrition have also been implicated as risk factors for migraine headaches. Mapping of chronic pain and risk factors will provide new and important information with the potential for prevention of chronic pain development as well as earlier and targeted interventions.

                                              The project is a collaboration between Department of Dentistry and Oral Health; Aarhus University (AU), Department of Public Health, AU and the Human Pain Genetics Lab, McGill University, Canada, and it feeds into the Faculty of Health, AUs strategic research within “Health, Food and Nutrition” and may form basis for future collaboration in the nutrition industry. Candidates shall expect to incorporate a research stay at the Human Pain Genetics Lab, McGill University, Canada.

                                              Main supervisor: Lene Baad-Hansen, Associate Professor and Deputy Head for Research and Talent Development, Section for Orofacial Pain and Jaw Function, Department of Dentistry and Oral Health, AU, Research field: Systematic pain evaluation and assessment of psychosocial risk factors.
                                              Co-supervisors: Bodil Hammer Bech, Associate Professor, Research Unit of Epidemiology, Department of Public Health, AU, Research field: Epidemiology. Luda Diatchenko, Professor, Honorary Skou Professor at Aarhus University, Human Pain Genetics Lab, McGill University, Canada, Research field: Human pain genetic variability contributing to sensitivity and pathophysiological pain states.

                                              The rule concerning the age of your higher education degree (max. five years) does not apply to this project.

                                              Apply

                                              P12: A novel technological platform for the evaluation of amphetamine pharmacology

                                              Strategic criteria:

                                                  • Early recruitment of talents
                                                  • Mobility

                                                  Main supervisor

                                                  Name: Steffen Sinning

                                                  Position: Associate professor

                                                  E-mail: stsi@forens.au.dk

                                                  Abstract

                                                  Amphetamines are substrate analogs for biogenic monoamine transporters. Here, they can exhibit differences in selectivity for dopamine transporters (DAT) vs serotonin transporters (SERT) vs norepinephrine tansporters (NE). They can also exhibit different modes of action, i.e. they can be perceived as substrates and induce reverse transport of neurotransmitters (release) or they can be perceived as transporter blockers preventing reuptake of neurotransmitters (inhibitors). Numerous amphetamine analogs enter the illicit drug market without being appropriately characterized but are classified on the basis of their chemical structure and similarities with amphetamine-like compounds, where it would be more useful to do so based on their pharmacology in terms of selectivity (DAT vs NET vs SERT) and mode of action (releasers vs inhibitors).

                                                  The project aims to develop a methodology that will allow the study of cell-based neurotransmitter influx and efflux via SERT, DAT and NET in the same setup in a homogenous real-time assay, preferentially using fluorescence. Ideally, the method can eventually be amended to work in a plate-reader. The methodology will be used to evaluate the pharmacology of new compounds with respect to selectivity and mode of action.
                                                  The project owner has established a methodology which promises to do so but invites creative solutions to the problem.

                                                  Specific qualifications

                                                  Previous experience with one of the following fields is advantageous: Fluorescence spectroscopy, cell-based assays, membrane transporter functional studies. 

                                                  Apply

                                                  P13: Does prenatal exposure to nitrate cause early puberty and poor semen quality?

                                                  Strategic criteria:

                                                      • Early recruitment of talents
                                                      • Mobility
                                                      • Interdisciplinary co-operation and network

                                                      Main supervisor

                                                      Name: Cecilia Høst Ramlau-Hansen

                                                      Position: Professor

                                                      E-mail: chrh@ph.au.dk

                                                      Abstract

                                                      In the past century, the onset of puberty ‒ which serves as an early marker of reproductive health ‒ has shifted worldwide to an earlier age in both girls and probably also in boys. This trend of decreasing age at puberty is clinically relevant, as early-onset puberty may be a predictor of several health issues in adulthood, including cardiovascular disease and cancer. Further, a high prevalence of men with a suboptimal semen quality is observed, approximately 15% of couples experience infertility and the use of technology-assisted reproduction has increased dramatically in Europe. A compelling body of evidence suggests that exposure to harmful factors in utero can predispose the child to development of diseases later in life.

                                                      The overall aim of this PhD project is to improve our understanding of how – and to what extent ‒ prenatal exposure to nitrate from drinking water and diet as well as maternal intake of nitrosatable drugs may be causes of i) altered pubertal development in sons and daughters, ii) impaired semen quality in adult sons, and iii) altered reproductive hormones in adult sons.

                                                      The PhD project will use data obtained from the Danish National Birth Cohort (DNBC), a nationwide cohort of pregnant women and their children with more than 20 years of follow-up data, including data on pubertal development (n~16,000), semen quality (n~1,000) and levels of reproductive hormones (n~1,000). Nitrate exposure levels from drinking water will be estimated using quality measurements on nitrate from Danish water supplies, where nitrate samples are available in the national database 'Jupiter'. Information on nitrate from maternal diet as well as use of nitrosatable drugs will be available from questionnaires from the DNBC. Information on prescribed medication from the Danish National Prescription Agency can be added. Causal inference methods ‒ including mediation analysis and bias analysis ‒ will be used to examine the possible causal relations between the prenatal nitrate exposure and reproductive health outcomes.

                                                      The PhD is an interdisciplinary research project involving researchers from Department of Public Health, Aarhus University; Departments of Occupational Medicine at Aarhus University Hospital and Bispebjerg Hospital; Geological Survey of Denmark and Greenland; and University of California, Los Angeles, USA. 

                                                      Specific qualifications

                                                      A Master's degree in medicine, epidemiology, biostatistics, public health or equivivalent is required. 

                                                      Apply

                                                      P14: Eating disorders among athletes: a public health concern?

                                                      Strategic criterion

                                                          • Interdisciplinary co-operation and network

                                                          Main supervisor

                                                          Name: Verner Møller

                                                          Position: Professor

                                                          E-mail: vm@ph.au.dk 

                                                          Abstract

                                                          Athletes at the highest level are willing to go far in order to fulfill their sporting ambitions. However, in their uncompromising pursuit of success they may risk their health due to concerns about weight. A 2004 study – the biggest study yet in the field – showed that three times as many athletes than controls had sub-clinical or clinical eating disorders (EDs). The prevalence of EDs among male athletes was greater in anti-gravitation sports (22%) than in ball game (5%) and endurance sports (9%; P<0.05). The prevalence of EDs among female athletes competing in aesthetic sports (42%) was higher than that observed in endurance (24%), technical (17%), and ball game sports (16%) (Sundgot-Borgen and Torstveit 2004).

                                                          The proposed study aims to explore social and systemic causes that may respectively lead to or prevent the development of eating disorders among elite and sub-elite athletes. Whereas the problem has been identified and the negative consequences for the athletes, who suffer from the condition, have been explored in previous studies, there is a lack of knowledge about prevention measures that do not compromise the athletes ability to be competitive in high performance sports.

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                                                          P15: The making of intersectoral coordination: understanding the practices of health professions

                                                          Strategic criteria

                                                              • Early recruitment of talents
                                                              • Interdisciplinary co-operation and network
                                                              • Co-operation with the business community, university college and other external parners in municipalities

                                                              Main supervisor

                                                              Name: Viola Burau

                                                              Position: Associate Professor

                                                              E-mail: viola@ph.au.dk

                                                              Abstract

                                                              Intersectoral coordination has become a primary concern of health systems across industrialised countries. More specialised hospitals and earlier discharge are shifting health services to community-based primary care settings, including prevention and rehabilitation. The issue of coordination across hospitals, general practice, other local health and social care services has come to the fore. The practice of health professions is key to the making of intersectoral coordination. Health professions are important switchboards for changing health services. They transform political programmes and administrative objectives into services for citizens. Drawing on different forms of knowledge and norms, they define the substance and organisation of health services.

                                                              Yet we know surprisingly little theoretically and empirically: about how health professions through their practice contribute to the making of intersectoral coordination. In health services research, there are many applied studies of intersectoral coordination, but they do not fully acknowledge the role health professions in changing health services. Studies are more concerned with organisational factors such as leadership, communication and professionals as individuals. This overlooks health professions as collective actors and the potentials for intersectoral coordination arising from professional practice based on self-regulation and professional ethics. Sociological studies of professions typically retain a focus on individual professional groups and only few studies analyse how professions engage in intersectoral coordination. However, the focus on professional practice enables developing a conceptual understanding of intersectoral agency of professions in processes of organisational change.

                                                              The proposed PhD project aims:
                                                              1. Theoretically, to develop a conceptual understanding of intersetcoral agency of professions in processes of organisational change.
                                                              2. Empirically, to systematically analyse health professional practices of intersectoral coordination and their contexts.
                                                              3. Practically, to develop a set of key components, which can support well functioning practices of intersectoral coordination

                                                              The PhD project is a part of an international, interdisciplinary research programme (iCoach) that investigates implementation of integrated community-based primary care.

                                                              Specific qualifications

                                                              Degree in public health/health services research or social sciences. Experience in qualitatitve research. Demonstrated interest in international, cross-country comparative perspectives. 
                                                              The rule concerning the age of your higher education degree (max. five years) does not apply to this project.

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                                                              P16: There is no place like home. An investigation of Danish home-care culture

                                                              Strategic criteria

                                                                  • Interdisciplinary co-operation and network
                                                                  • Co-operation with the business community, university college and other external parners in municipalities

                                                                  Main supervisor

                                                                  Name: Bente Martinsen

                                                                  Position: Associate Professor

                                                                  E-mail: bm@ph.au.dk

                                                                  Abstract

                                                                  This study is a cooperation between Aarhus University and The Arctic University of Norway and includes at least two professions: Nursing and social science. Since two of the supervisors take part in the EU-funded 'InnovateDignity', the study will be closely connected to the subtheme 'Home care culture' in the EU-project. Also, the student will attend the Norwegian programme 'MUNI-HEALTH-CARE' for early stage researchers in community health care.

                                                                  Background
                                                                  Due to the demographic development and the reduced length of hospital stays, Danish home care is confronting a paradigm shift these years. Hospital admissions are shortened and more care and treatment take place in the patients’ homes. This development has been going on for some years without any competence boost for home care nurses, as is the case in the other Nordic countries. Furthermore, the knowledge about Danish home care is scarce with only two scientific publications concerning the staffs’ perspective since 2011. None of them include neither social- and health helpers nor the social and health assistants who are the largest professional groups in Danish home care.

                                                                  The aim of this study is to examine Danish home care culture. The study addresses how home care nurses cope with the increasing complexity in home care; the predominant values and norms of the culture in the internal cooperation between the different professional groups. The project will adopt an ethnographic field study design using active participant observations, go along interviews, and focus group interviews to describe the home care culture in two municipalities .

                                                                  Study 1: Active participant observation. The PhD-student will be a full member of the home care staff embracing skills and customs for the sake of complete comprehension. The aim in the first part of the study will be to understand how home care is constituted and conducted in the included municipalities.
                                                                  Study 2: Go along interviews and focus group interviews. In the second part of the project the aim will be to gain insight into how caregivers in the two municipalities understand and interpret their work.
                                                                  Study 3: Individual interviews. The aim is to gain insight into how home care clients and their relatives experience to receive home care. We have a specific interest in the experience of being dependent on help from other people and technology.    

                                                                  Specific qualifications

                                                                  The ideal candidate is a Registered Nurse (RN) and has a master in nursing science, ethnography, or another area within human sciences. Due to the character of the project, the candidate must be fluent in a Scandinavian language. 

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