Qasim Aziz

Queen Mary, University of London, Londinium, England, United Kingdom

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Publications (235)1885.14 Total impact

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    ABSTRACT: Background The processing of discomfort and pain in the central nervous system is normally studied with experimental methods, but it is mandatory that they are reliable over time to ensure that any interventions will result in valid results. We investigated reliability of rapid balloon distension in the rectum to elicit cortical evoked potentials (CEPs) to study the reliability of central processing of visceral sensation and discomfort/pain.Methods Eighteen healthy volunteers had two series of rectal balloon distensions performed on two separate days. Individualized balloon pressure, corresponding to pain detection threshold or to the maximum possible distension (30 psi), was used. Within- and between days reliability was measured in terms of amplitudes and latencies of the CEP global field power, topography and underlying brain networks.Key ResultsThere were two prominent peaks in the CEP recordings at mean latencies of 157 and 322 ms. There were no differences in latencies or amplitudes (p = 0.3) and they passed the Bland–Altman test for reproducibility. There were no differences in topographies (p > 0.7). Brain source connectivity revealed the cingulate-operculum network as the most consistent network within and between subjects. There were no differences in the location of brain sources in this network (p = 0.9) and the source coordinates were reproducible. Finally, the cingulate source generally had higher strength than operculum source (p < 0.001).Conclusions & InferencesA reliable method to study central mechanisms underlying visceral sensation and pain was established. The method may improve our understanding of visceral pain and could be an objective method for studying efficacy of analgesics on visceral pain.
    Neurogastroenterology and Motility 06/2015; 27(6). DOI:10.1111/nmo.12557 · 3.42 Impact Factor
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    ABSTRACT: Irritable bowel syndrome is a widespread disorder with a marked socioeconomic burden. Previous studies support the proposal that a subset of patients with features compatible with diarrhoea-predominant IBS (IBS-D) have bile acid malabsorption (BAM). To perform a systematic review and meta-analysis to assess the prevalence of BAM in patients meeting the accepted criteria for IBS-D. MEDLINE and EMBASE were searched up to March 2015. Studies recruiting adults with IBS-D, defined by the Manning, Kruis, Rome I, II or III criteria and which used 23-seleno-25-homotaurocholic acid (SeHCAT) testing for the assessment of BAM were included. BAM was defined as 7 day SeHCAT retention of <10%. We calculated the rate of BAM and 95% confidence intervals (CI) using a random effects model. The methodological quality of included studies was evaluated using the Quality Assessment for Diagnostic Accuracy Studies (QUADAS-2). The search strategy identified six relevant studies comprising 908 individuals. The rate of BAM ranged from 16.9% to 35.3%. The pooled rate was 28.1% (95% CI: 22.6-34%). There was significant heterogeneity in effect sizes (Q-test χ(2) = 17.9, P < 0.004; I(2) = 72.1%). The type of diagnostic criteria used or study country did not significantly modify the effect. These data provide evidence that in excess of one quarter of patients meeting accepted criteria for IBS-D have bile acid malabsorption. This distinction has implications for the interpretation of previous studies, as well as contemporaneous clinical practice and future guideline development. © 2015 John Wiley & Sons Ltd.
    Alimentary Pharmacology & Therapeutics 04/2015; 42(1). DOI:10.1111/apt.13227 · 4.55 Impact Factor
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    ABSTRACT: Background The overlap of unexplained gastrointestinal (GI) and somatic symptoms is well established in patients with functional gastrointestinal disorders (FGID). Joint hypermobility syndrome (JHS) is a non-inflammatory connective tissue disorder associated with GI and somatic symptoms. We aimed to determine whether there is an association between diagnosis of JHS and FGID and the impact of this association on comorbidities and quality of life (QOL).Methods Prospective case–control study in secondary care GI clinics over 2 years. JHS was assessed by the first author prior to consultation in 641 consecutive new patients. Diagnosis of FGID (cases, n = 336) or organic disorders (controls, n = 305) was established blind to JHS status. JHS prevalence was compared in cases (FGID patients) and controls (organic disorders patients). Extra-intestinal comorbidity and QOL were compared in FGID patients with and without JHS.Key ResultsJHS prevalence was higher in FGID compared to organic GI disorders (39.0% vs 27.5%, ORadj: 1.51, CI: 1.07–2.12, p = 0.02), and particularly associated with functional gastroduodenal disorders (44.1%, ORadj: 2.08, CI: 1.25–3.46, p = 0.005), specifically postprandial distress syndrome (51%, ORadj: 1.99, CI: 1.06–3.76, p = 0.03). FGID patients with JHS had increased chronic pain (23.2% vs 11.9%, p = 0.01), fibromyalgia (10.5% vs 3.1%, p = 0.01), somatization scores (13 vs 10, p < 0.001), urinary autonomic scores (30.5 vs 20.7, p = 0.03), and worse pain-related QOL scores (45.0 vs 63.5, p = 0.004).Conclusions & InferencesJHS is significantly associated with FGID, and this subgroup of patients have increased comorbidity and decreased QOL. Further research is required to understand the pathophysiological basis of this association.
    Neurogastroenterology and Motility 04/2015; 27(4). DOI:10.1111/nmo.12535 · 3.42 Impact Factor
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    ABSTRACT: The enzyme guanosine triphosphate-cyclohydrolase-1 (GCH-1) is a rate limiting step in the de novo synthesis of tetrahydrobiopterin (BH4) a co-factor in monoamine synthesis and nitric oxide production. GCH-1 is strongly implicated in chronic pain based on data generated using the selective GCH-1 inhibitor 2,4-diamino-6-hydroxypyrimidine (DAHP), and studies which have identified a pain protective GCH-1 haplotype associated with lower BH4 production and reduced pain. To investigate the role for GCH-1 in visceral pain we examined the effects of DAHP on pain behaviors elicited by colorectal injection of mustard oil in rats, and the pain protective GCH-1 haplotype in healthy volunteers characterized by esophageal pain sensitivity before and after acid injury, and assessed using depression and anxiety questionnaires. In rodents pretreatment with DAHP produced a substantial dose related inhibition of pain behaviors from 10 to 180 mg/kg i.p. (p < 0.01 to 0.001). In healthy volunteers, no association was seen between the pain protective GCH-1 haplotype and the development of hypersensitivity following injury. However, a substantial increase in baseline pain thresholds was seen between first and second visits (26.6 ± 6.2 mA) in subjects who sensitized to esophageal injury and possessed the pain protective GCH-1 haplotype compared with all other groups (p < 0.05). Furthermore the same subjects who sensitized to acid and possessed the haplotype, also had significantly lower depression scores (p < 0.05). The data generated indicate that GCH-1 plays a role in visceral pain processing that requires more detailed investigation. © 2015 John Wiley & Sons Ltd.
    Neurogastroenterology and Motility 03/2015; 27(5). DOI:10.1111/nmo.12538 · 3.42 Impact Factor
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    ABSTRACT: The oesophagus and stomach are responsible for transporting food from the oral cavity to the small intestine in a manner that does not compromise the safety of the airway, that is relevant to the composition of the meal, and that allows for optimal absorption of nutrients. To achieve this, several control mechanisms interact to ensure that the swallowed bolus traverses the oropharynx into the oesophageal body and enters the gastric reservoir. Here the bolus undergoes mixing and is transformed into a consistency suitable for emptying through the pylorus at a rate consistent with the maximal absorptive capacity of the small intestine.
    Medicine 03/2015; 43(5). DOI:10.1016/j.mpmed.2015.02.002 · 4.35 Impact Factor
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    Pain 03/2015; DOI:10.1097/j.pain.0000000000000160 · 5.84 Impact Factor
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    ABSTRACT: An integrated understanding of the physiological mechanisms involved in the genesis of nausea remains lacking. We aimed to describe the psychophysiological changes accompanying visually induced motion sickness, using a motion video, hypothesizing that differences would be evident between subjects who developed nausea in comparison to those that did not. A motion, or a control, stimulus was presented to 98 healthy subjects in a randomized crossover design. Validated questionnaires and visual analogue scales (VAS) were used for the assessment of anxiety and nausea. Autonomic and electrogastrographic activity were measured at baseline and continuously thereafter. Plasma vasopressin and ghrelin were measured in response to the motion video. Subjects were stratified into quartiles based on VAS nausea scores, with the upper and lower quartiles considered to be nausea sensitive and resistant respectively. 28 subjects were exposed to the motion video during functional neuroimaging. During the motion video, nausea sensitive subjects had lower normogastria:tachygastria ratio and cardiac vagal tone but higher cardiac sympathetic index in comparison to the control video. Furthermore, nausea sensitive subjects had decreased plasma ghrelin and demonstrated increased activity the left anterior cingulate cortex. Nausea VAS scores positively correlated with plasma vasopressin, left inferior frontal and middle occipital gyri activity and negatively correlated with plasma ghrelin and brain activity in the right cerebellar tonsil, declive, culmen, lingual gyrus and cuneus. This study demonstrates that the subjective sensation of nausea is associated with objective changes in autonomic, endocrine and brain networks, and thus identifies potential objective biomarkers and targets for therapeutic interventions.This article is protected by copyright. All rights reserved
    The Journal of Physiology 01/2015; 593(5). DOI:10.1113/jphysiol.2014.284240 · 4.54 Impact Factor
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    ABSTRACT: Eysenck proposed a ‘trait theory’ of personality, the dimensions of which encompass numerous individual qualities. Whilst the influence of neuroticism on the brain processing of pain is well described, the role of extraversion, to date, has not been systematically investigated. Our aim was to address this knowledge gap using functional magnetic resonance imaging (fMRI).Extraversion was measured in 33 healthy volunteers (17 males, mean age 29 years [range 20–53]) using the Eysenck Personality Questionnaire. fMRI data were acquired using a 3T MRI scanner during rest, pain anticipation, and painful oesophageal balloon distention. The effect of extraversion on fMRI responses was determined.Extraversion scores varied (range 6–22) and did not influence pain threshold or rating. High extraversion was associated with significantly greater activity in the left cuneus during rest (p ⩽ 0.001), and the right insula during both anticipation (p ⩽ 0.0002) and pain (p ⩽ 0.0008). Low extraversion was associated with significantly greater brain activity in the bilateral precuneus, bilateral lingual gyrus, right inferior temporal gyrus, left fusiform gyrus and left superior parietal lobule during pain anticipation (all p ⩽ 0.0001).These results suggest that extraversion is associated with differences in the brain processing of visceral pain. Future studies of visceral pain, using fMRI, should control for extraversion.
    Personality and Individual Differences 11/2014; 74. DOI:10.1016/j.paid.2014.10.024 · 1.86 Impact Factor
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    Adam D Farmer, Qasim Aziz
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    ABSTRACT: Summary Functional abdominal pain syndrome is characterised by frequent or continuous abdominal pain associated with a degree of loss of daily activity. It has a reported population prevalence of between 0.5% and 1.7%, with a female preponderance. The pathophysiology of functional abdominal pain is incompletely understood although it has been postulated that peripheral sensitisation of visceral afferents, central sensitisation of the spinal dorsal horn and aberrancies within descending modulatory systems may have an important role. The management of patients with functional abdominal pain requires a tailored multidisciplinary approach in a supportive and empathetic environment in order to develop an effective therapeutic relationship. Patient education directed towards an explanation of the pathophysiology of functional abdominal pain is in our opinion a prerequisite step and provides the rationale for the introduction of interventions. Interventions can usefully be categorised into general measures, pharmacotherapy, psychological interventions and 'step-up' treatments. Pharmacotherapeutic/step-up options include tricyclic antidepressants, serotonin noradrenergic reuptake inhibitors and the gabapentinoids. Psychological treatments include cognitive behavioural therapy and hypnotherapy. However, the objective evidence base for these interventions is largely derived from other chronic pain syndrome, and further research is warranted in adult patients with functional abdominal pain.
    Journal of the Royal Society of Medicine 09/2014; 107(9):347-354. DOI:10.1177/0141076814540880 · 2.02 Impact Factor
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    ABSTRACT: Chronic visceral pain affects millions of individuals worldwide and remains poorly understood, with current therapeutic options constrained by gastrointestinal (GI) side effects. Visceral pain is strongly associated with inflammation and distension of the gut. Here we report that the voltage-gated sodium channel subtype NaV1.9 is expressed in half of gut-projecting rodent dorsal root ganglia sensory neurons. We show that NaV1.9 is required for normal mechanosensation, for direct excitation and for sensitisation of mouse colonic afferents by mediators from inflammatory bowel disease tissues, and by noxious inflammatory mediators individually. Excitatory responses to ATP or PGE2 were substantially reduced in NaV1.9-/- mice. Deletion of NaV1.9 substantially attenuates excitation, and subsequent mechanical hypersensitivity, following application of inflammatory soup (bradykinin, ATP, histamine, PGE2 and 5HT) to visceral nociceptors located in the serosa and mesentery. Responses to mechanical stimulation of mesenteric afferents were also reduced by loss of NaV1.9 and there was a rightward shift in stimulus-response function to ramp colonic distension. By contrast, responses to rapid, high-intensity phasic distension of the colon are initially unaffected; however run-down of responses to repeat phasic distension were exacerbated in NaV1.9-/- afferents. Finally colonic afferent activation by supernatants derived from inflamed human tissue was greatly reduced in NaV1.9-/- mice. These results demonstrate that NaV1.9 is required for persistence of responses to intense mechanical stimulation, contributes to inflammatory mechanical hypersensitivity and is essential for activation by noxious inflammatory mediators including those from diseased human bowel. These observations indicate that NaV1.9 represents a high-value target for development of visceral analgesics.
    Pain 06/2014; 155(10). DOI:10.1016/j.pain.2014.06.015 · 5.84 Impact Factor
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    Yasser Al Omran, Qasim Aziz
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    ABSTRACT: With more than 100 studies published over the past two decades, functional brain imaging research in gastroenterology has become an established field; one that has enabled improved insight into the supraspinal responses evoked by gastrointestinal stimulation both in health and disease. However, there remains considerable inter-study variation in the published results, largely owing to methodological differences in stimulation and recording techniques, heterogeneous patient selection, lack of control for psychological factors and so on. These issues with reproducibility, although not unique to studies of the gastrointestinal tract, can lead to unjustified inferences. To obtain consistent and more clinically relevant results, there is a need to optimize and standardize brain imaging studies across different centres. In addition, the use of complementary and more novel brain imaging modalities and analyses, which are now being used in other fields of research, might help unravel the factors at play in functional gastrointestinal disorders. This Review highlights the areas in which functional brain imaging has been useful and what it has revealed, the areas that are in need of improvement, and finally suggestions for future directions.
    Nature Reviews Gastroenterology &#38 Hepatology 06/2014; 11(9). DOI:10.1038/nrgastro.2014.89 · 10.81 Impact Factor
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    ABSTRACT: Eysenck proposed 'trait theory' of personality, where the dimensions extraversion (degree of optimism and sociability) and neuroticism (degree of anxiety and fear) encompass numerous individual qualities. Whilst the influence of neuroticism on the brain processing of pain is well studied, the role of extraversion in pain processing remains to be investigated and thus this was the aim of our study using functional magnetic resonance imaging (fMRI).
    Gut 06/2014; 63(Suppl 1):A32-A33. DOI:10.1136/gutjnl-2014-307263.66 · 13.32 Impact Factor
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    ABSTRACT: The Joint hypermobility syndrome (JHS) is a non-inflammatory connective tissue disorder with a prevalence of 20%. It is characterised by joint hypermobility,chronic pain, fibromyalgia (FM) and dysautonomia. Gastrointestinal (GI) symptoms e.g., dyspepsia, reflux, bloating and constipation are present in up to 80% of affected individuals. Small studies suggest that FGID are common in these patients yet no controlled studies have systematically investigated if JHS is associated with particular GI diagnoses nor explored the effect of JHS on non-GI symptom presentation and quality of life (QOL).
    Gut 06/2014; 63(Suppl 1):A194-A195. DOI:10.1136/gutjnl-2014-307263.420 · 13.32 Impact Factor
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    ABSTRACT: Nausea is an aversive experience, which negatively impacts on quality of life, adherence to treatment and is a cause for discontinuation of the development of novel compounds. Significant knowledge gaps remain in our understanding of the cortical and psychophysiological mechanisms involved in the genesis and maintenance of nausea. We aimed to develop and validate a readily administered a visually induced motion sickness (VIMS) stimulus to examine the psychophysiological changes induced by the stimulus and characterise the changes in cortical activity using functional magnetic resonance imaging (fMRI).
    Gut 06/2014; 63(Suppl 1):A31-A32. DOI:10.1136/gutjnl-2014-307263.64 · 13.32 Impact Factor
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    ABSTRACT: Symptoms of chronic constipation are common, with a prevalence of ~14% in adults worldwide. Although increasing fibre intake is universally accepted as a first-line treatment, patient dissatisfaction is common. A systematic review is thus required in order to evaluate the quality of scientific evidence behind this management approach. The aim was to assess the effect of fibre on chronic constipation and IBS-C in adults via a systematic review of randomised controlled trials (RCTs).
    Gut 06/2014; 63(Suppl 1):A206-A207. DOI:10.1136/gutjnl-2014-307263.444 · 13.32 Impact Factor
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    ABSTRACT: Autonomic nervous system dysfunction has been implicated in visceral hypersensitivity. However, the specific contribution of the parasympathetic nervous system (PNS) is unclear. We aimed to determine whether physiological and pharmacological manipulation of parasympathetic tone influences the development of hypersensitivity in a validated model of acid-induced oesophageal pain.
    Gut 05/2014; 64(4). DOI:10.1136/gutjnl-2013-306698 · 13.32 Impact Factor
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    ABSTRACT: Heightened perception of gastrointestinal sensation is termed visceral hypersensitivity (VH) and is commonly observed in patients with gastrointestinal disorders. VH is thought to be a major contributory factor in oesophageal disease, particularly gastro-oesophageal reflux disease that does not respond to standard (proton pump inhibitor) treatment, and in functional heartburn. Clinical tools that can help phenotype according to the mechanism of chronic pain and thus allow targeted drug treatment (e.g. with pain modulator therapy) would be very desirable. A technique that produces repeatable and controllable thermal stimuli within the oesophagus could meet this need. The aims of this study were to develop a method for linear control of the heat stimulation in the oesophagus, to assess the reproducibility of this method, and obtain normal thermal sensitivity values in the distal and proximal oesophagus. The 7 mm diameter Peltier-based thermal device was investigated on 27 healthy subjects using a heating ramp of 0.2 °C s−1. The pain detection threshold (PDT) temperature was recorded. To assess the reproducibility of the device, each subject underwent the procedure twice, with a minimum of two weeks between each procedure. The mean PDT temperature measured in the distal oesophagus, was 53.8 ± 2.9 °C and 53.6 ± 2.6 °C, for visits 1 and 2 respectively. The mean PDT temperature measured in the proximal oesophagus was 54.1 ± 2.4 °C and 54.0 ± 2.8 °C, for visits 1 and 2 respectively. The reproducibility of the PDT temperature in the distal and proximal oesophagus, was good (intra-class correlation >0.6). Future studies should be aimed to determine whether oesophageal thermal sensitivity can act as a biomarker of transient receptor potential vallanoid 1 upregulation.
    Physiological Measurement 05/2014; 35(7):1265. DOI:10.1088/0967-3334/35/7/1265 · 1.62 Impact Factor
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    ABSTRACT: The parasympathetic nervous system (PNS) has been implicated in the development of visually induced motion sickness. The objective of this study was to perform a systematic review and meta-analysis of the effect of visually induced motion sickness on validated parameters of PNS tone. Methods followed PRISMA recommendations. Controlled trials reporting validated measures of PNS tone in visually induced motion sickness in healthy adults were included. One reviewer performed the screening of articles and data extraction, and two reviewers independently performed methodological evaluation. Data were synthesised using standardised mean differences (SMDs) for all relevant outcomes using a random-effects model. Publication bias was assessed via funnel plots and Egger's test. The search strategy identified seven citations comprising 237 healthy individuals. The mean quality score was 4/10 (range 3-7). There was no difference between baseline PNS tone between individuals who developed visually induced motion sickness and those that did not. Visually induced motion sickness (VIMS)-sensitive individuals had a reduction in PNS tone, following exposure to the stimulus (mean weighted SMD = -0.45, 95 % confidence interval -0.64 to -0.27, Z = -4.8, p < 0.0001). There was no evidence of heterogeneity or publication bias. These data suggest that baseline PNS parameters do not provide a useful measure of predicting the probability of developing visually induced motion sickness. However, a fall in PNS tone, as indicated by cardiac activity, is characteristic in sensitive individuals. Further work is needed to characterise these responses in clinical populations, in conjunction with improvements and standardisation in study design.
    Experimental Brain Research 05/2014; 232(8). DOI:10.1007/s00221-014-3964-3 · 2.17 Impact Factor
  • Gastroenterology 05/2014; 146(5):S-264. DOI:10.1016/S0016-5085(14)60932-X · 13.93 Impact Factor
  • Gastroenterology 05/2014; 146(5-5):S-847. DOI:10.1016/S0016-5085(14)63079-1 · 13.93 Impact Factor

Publication Stats

5k Citations
1,885.14 Total Impact Points


  • 2008–2015
    • Queen Mary, University of London
      • The Blizard Institute of Cell and Molecular Science
      Londinium, England, United Kingdom
    • The University of Sheffield
      Sheffield, England, United Kingdom
    • University of Nottingham
      • Nottingham Digestive Diseases Centre
      Nottigham, England, United Kingdom
  • 2010–2013
    • University of London
      Londinium, England, United Kingdom
    • Salford Royal NHS Foundation Trust
      Salford, England, United Kingdom
  • 2007–2013
    • KU Leuven
      • Translational Research Center for Gastrointestinal Disorders (TARGID)
      Leuven, VLG, Belgium
  • 1995–2013
    • The University of Manchester
      • Centre for Gastrointestinal Sciences
      Manchester, England, United Kingdom
    • Research Institute of Human Movement
      Santa Barbara, California, United States
  • 2012
    • Shrewsbury and Telford Hospital NHS Trust
      Shrewsbury, England, United Kingdom
  • 2005–2008
    • King's College London
      • • Institute of Psychiatry
      • • Department of Psychology
      Londinium, England, United Kingdom
  • 2006
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands
  • 1995–2004
    • Aston University
      Wheaton Aston, England, United Kingdom
  • 2003
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 1998–2003
    • London Research Institute
      Londinium, England, United Kingdom
    • University of Salford
      Salford, England, United Kingdom
  • 2001
    • Universität Konstanz
      Constance, Baden-Württemberg, Germany
  • 1998–2001
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1999
    • Dalhousie University
      • Department of Medicine
      Halifax, Nova Scotia, Canada
  • 1997
    • Uppsala University
      Uppsala, Uppsala, Sweden